amphotericin-b and HIV-Infections

The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines.. We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.. One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).. In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Randomized Controlled Trials as Topic

The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series.. Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease.. We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs.. We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole.. Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Topics: Adult; Antifungal Agents; Central Nervous System; Female; Histoplasmosis; HIV Infections; Humans; Hydrocephalus; Itraconazole; Male; Meningitis; Vasculitis; Young Adult

Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; HIV Infections; Humans; Meningitis, Cryptococcal

Hemophagocytic lymphohistiocytosis (HLH) secondary to

Topics: Amphotericin B; Antifungal Agents; Histoplasmosis; HIV Infections; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged

Cryptococcal meningitis is a devastating brain infection cause by encapsulated yeasts of the Cryptococcus genus. Exposure, through inhalation, is likely universal by adulthood, but symptomatic infection only occurs in a minority, in most cases, months or years after exposure. Disease has been described in almost all tissues, but it is the organism's tropism for the central nervous system that results in the most devastating illness. While invasive disease can occur in the immunocompetent, the greatest burden by far is in immunocompromised individuals, particularly people living with human immunodeficiency virus (HIV), organ transplant recipients and those on glucocorticoid therapy or other immunosuppressive drugs. Clinical presentation is variable, but diagnosis is usually straightforward, with cerebrospinal fluid microscopy, culture, and antigen testing proving significantly more sensitive than diagnostic tests for other brain infections. Although disease incidence has reduced since the advent of effective HIV therapy, mortality when disease occurs remains extremely high, and has changed little in recent decades. This Therapy in Practice review is an update of a talk first given by JND at the European Congress on Clinical Microbiology and Infectious Diseases in 2019 in the Netherlands. The review contextualizes the most recently published World Health Organization (WHO) guidelines for the treatment of HIV-associated cryptococcal meningitis in terms of the data from large, randomized, controlled trials published between 1997 and 2022. We discuss the rationale for induction and maintenance therapy and the efficacy and undesirable effects of the current therapeutic armamentarium of amphotericin, flucytosine and fluconazole. We address recent research into repurposed drugs such as sertraline and tamoxifen, and potential future treatment options, including the novel antifungals fosmanogepix, efungumab and oteseconazole, and non-pharmaceutical solutions such as neurapheresis cerebrospinal fluid filtration.

Topics: Adult; Amphotericin B; Antifungal Agents; Fluconazole; Flucytosine; Glucocorticoids; HIV Infections; Humans; Meningitis, Cryptococcal; Sertraline; Tamoxifen

Single, high-dose liposomal amphotericin B (LAmB; AmBisome, Gilead Sciences) has demonstrated non-inferiority to amphotericin B deoxycholate in combination with other antifungals for averting all-cause mortality from HIV-associated cryptococcal meningitis. There are limited data on the pharmacokinetics (PK) of AmBisome. The aim of this study was to describe population PK of AmBisome and conduct a meta-analysis of the available studies to suggest the optimal dosing for cryptococcal meningoencephalitis.. Data from a Phase II and Phase III trial of high-dose, short-course AmBisome for cryptococcal meningoencephalitis were combined to develop a population PK model. A search was conducted for trials of AmBisome monotherapy and meta-analysis of clinical outcome data was performed.. A two-compartment model with first-order clearance of drug from the central compartment fitted the data best and enabled the extent of inter-individual variability in PK to be quantified. Mean (SD) population PK parameter estimates were: clearance 0.416 (0.363)  L/h; volume of distribution 4.566 (4.518) L; first-order transfer of drug from central to peripheral compartments 2.222 (3.351)  h-1, and from peripheral to central compartment 2.951 (4.070)  h-1. Data for the meta-analysis were insufficient to suggest optimal dosing of AmBisome for cryptococcal meningoencephalitis.. This study provides novel insight into the PK of AmBisome at the population level and the variability therein. Our analysis also serves to highlight the paucity of data available on the pharmacodynamics (PD) of AmBisome and underscores the importance of thorough and detailed PK/PD analysis in the development of novel antifungals, by demonstrating the challenges associated with post hoc PK/PD analysis.

Topics: Antifungal Agents; Cryptococcus neoformans; HIV Infections; Humans; Meningitis, Cryptococcal; Meningoencephalitis

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Coinfection; Darier Disease; Drug Therapy, Combination; HIV Infections; Humans; Infusions, Intravenous; Leishmaniasis, Diffuse Cutaneous; Male; Phosphorylcholine; Skin Diseases, Parasitic; Treatment Outcome; Trypanosoma cruzi

Cryptococcal meningitis causes 15% of AIDS-related deaths. Optimal management and clinical outcomes of pregnant women with cryptococcosis are limited to case reports, as pregnant women are often excluded from research. Amongst pregnant women with asymptomatic cryptococcosis, no treatment guidelines exist. We prospectively identified HIV-infected women who were pregnant or recently pregnant with cryptococcosis, screened during a series of meningitis research studies in Uganda from 2012 to 2018. Among 571 women screened for cryptococcosis, 13 were pregnant, one was breastfeeding, three were within 14 days postpartum, and two had recently miscarried. Of these 19 women (3.3%), 12 had cryptococcal meningitis, six had cryptococcal antigenemia, and one had a history of cryptococcal meningitis and was receiving secondary prophylaxis. All women with meningitis received amphotericin B deoxycholate (0.7-1.0 mg/kg). Five were exposed to 200-800 mg fluconazole during pregnancy. Of these five, three delivered healthy babies with no gross physical abnormalities at birth, one succumbed to meningitis, and one outcome was unknown. Maternal meningitis survival rate at hospital discharge was 75% (9/12), and neonatal/fetal survival rate was 44% (4/9) for those mothers who survived. Miscarriages and stillbirths were common (n = 4). Of six women with cryptococcal antigenemia, two received fluconazole, one received weekly amphotericin B, and three had unknown treatment courses. All women with antigenemia survived, and none developed clinical meningitis. We report good maternal outcomes but poor fetal outcomes for cryptococcal meningitis using amphotericin B, without fluconazole in the first trimester, and weekly amphotericin B in place of fluconazole for cryptococcal antigenemia.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Cryptococcus neoformans; Deoxycholic Acid; Disease Management; Drug Combinations; Female; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Uganda; Young Adult

HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.. We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months).. Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes.. Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region.

Topics: Adult; Africa South of the Sahara; Aged; Amphotericin B; Antifungal Agents; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic

Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear.. We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART.. We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020.. We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single-arm trials, prospective cohort studies, and single-arm cohort studies.. Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS-I tool to assess risk of bias in non-randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI).. We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low-certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high-certainty evidence). We found very low-certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died.. Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.

Topics: Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Administration Schedule; Fluconazole; Histoplasmosis; HIV Infections; Humans; Induction Chemotherapy; Itraconazole; Kidney; Liposomes; Maintenance Chemotherapy; Randomized Controlled Trials as Topic

Colonic cryptococcal infection is unusual in people living with HIV (PLWH) and even more so without concomitant neurological compromise. Published case reports describe diarrhea and other intestinal manifestations that are often confused with systemic tuberculosis infection. We describe an Peruvian woman living with HIV on antiretroviral therapy who presented hypotensive with a 6-month history of fever and epigastric pain, in addition to episodes of sporadic diarrhea. Due to the suspicion of systemic tuberculosis, antituberculosis treatment was started. Days later, without clinical improvement, colonoscopy revealed ulcers in the transverse colon. Histopathological examination of biopsied tissue was compatible with

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; HIV Infections; Humans; Hypotension; Immunosuppression Therapy; Pain; Treatment Outcome

Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM.. Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcus; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Immunologic Deficiency Syndromes; Intracranial Hypertension; Meningitis, Cryptococcal; Risk Factors

Topics: Amphotericin B; Anti-HIV Agents; Cesarean Section; Debridement; Dermatomycoses; Drug Therapy, Combination; Fungemia; Gestational Age; HIV Infections; Humans; Immunocompromised Host; Infant; Infant, Premature; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Necrosis; Prognosis; Risk Assessment; Treatment Outcome; Umbilical Veins; Umbilicus

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Topics: Africa; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcus neoformans; Developing Countries; Disease Management; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; Guidelines as Topic; HIV Infections; Humans; Income; Meningitis, Cryptococcal; Survival Analysis

Leishmaniasis is a vector-borne neglected tropical disease which manifests as visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). The current drugs are toxic, duration of treatment is long, there is regional variation in efficacy, and emergence of resistance is common.. This manuscript is based on literature derived from PubMed and reviews the current and emerging medications for the treatment of leishmaniasis. A single dose of liposomal amphotericin B (L-AmB) and multidrug therapy are the best options for VL in the Indian subcontinent (ISC), while a combination of pentavalent antimonials and paromomycin remains the treatment of choice for VL in Africa where efficacious and safe regimens are needed for HIV-VL coinfection. L-AmB at a total dose of 18-21 mg/kg is the recommended regimen for VL in the Mediterranean region, South America and for HIV-VL coinfection. Treatment of CL varies from observation, local or systemic therapy depending on severity of lesions, etiological species and its potential to develop into mucosal leishmaniasis.. The monitoring of single-dose L-AmB and combination therapy in the ISC is essential. Effective short-course combination therapy is needed for the treatment of post-kala-azar dermal leishmaniasis and HIV-VL. Better evidence for treatment is still needed along with safer and shorter treatment options for CL and MCL.

Topics: Amphotericin B; Antiprotozoal Agents; Drug Therapy, Combination; HIV Infections; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Leprostatic Agents

The recent development of highly sensitive and specific point-of-care tests has made it possible to diagnose HIV-associated cryptococcal meningitis within minutes. However, diagnostic advances have not been matched by new antifungal drugs and treatment still relies on old off-patent drugs: amphotericin B, flucytosine and fluconazole. Cryptococcal meningitis treatment is divided in three phases: induction, consolidation and maintenance. The induction phase, aimed at drastically reducing cerebrospinal fluid fungal burden, is key for patient survival. The major challenge in cryptococcal meningitis management has been the optimisation of induction phase treatment using the limited number of available medications, and major progress has recently been made. In this review, we summarise data from key trials which form the basis of current treatment recommendations for HIV-associated cryptococcal meningitis.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal

Case report We report the case of a young Cameroonian woman who presented with cough, hyperthermia, weight loss, pancytopenia, and hepatosplenomegaly. A positive HIV serology was discovered and a chest radiography revealed a 'miliary pattern'. Bone marrow aspiration pointed out yeast inclusions within macrophages. Given the morphological aspect, the clinical presentation and immunosuppression, histoplasmosis was retained as a working hypothesis. Antiretroviral and amphotericin B treatments were promptly initiated. Review Given the immigration wave that Europe is currently experiencing, we think it is important to share experience and knowledge, especially in non-endemic areas such as Europe, where clinicians are not used to face this disease. Histoplasmosis is due to Histoplasma capsulatum var. capsulatum, a dimorphic fungus. Infection occurs by inhaling spores contained in soils contaminated by bat or bird droppings. The clinical presentation depends on the immune status of the host and the importance of inoculum, varying from asymptomatic to disseminated forms. AIDS patients are particularly susceptible to develop a severe disease. Antigen detection, molecular biology techniques, and microscopic examination are used to make a rapid diagnosis. However, antigen detection is not available in Europe and diagnosis needs a strong clinical suspicion in non-endemic areas. Because of suggestive imagery, clinicians might focus on tuberculosis. Our case illustrates the need for clinicians to take histoplasmosis in the differential diagnosis, depending on the context and the patient's past history.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Bone Marrow Cells; Female; Histoplasma; Histoplasmosis; HIV Infections; Humans; Pancytopenia

Treatment of Visceral Leishmaniasis (VL), a neglected tropical disease, is very challenging with few treatment options. Long duration of treatment and drug toxicity further limit the target of achieving VL elimination. Chemotherapy remains the treatment of choice. Single dose of liposomal amphotericin B (LAmB) and multidrug therapy (LAmB + miltefosine, LAmB + paromomycin (PM), or miltefosine + PM) are recommended treatment regimen for treatment of VL in Indian sub-continent. Combination therapy of pentavalent antimonials (Sbv) and PM in East Africa and LAmB in the Mediterranean region/South America remains the treatment of choice. Various drugs having anti-leishmania properties are in preclinical phase and need further development. An effective treatment and secondary prophylaxis of HIV-VL co-infection should be developed to decrease treatment failure and drug resistance.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Clinical Trials as Topic; Drug Resistance, Multiple; Drug Therapy, Combination; HIV Infections; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Meglumine Antimoniate; Paromomycin; Phosphorylcholine; Psychodidae; Sheep; South America; Treatment Outcome

Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.

Topics: Amphotericin B; Coinfection; HIV; HIV Infections; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Public Health

There remains uncertainty about the optimum timing of antiretroviral therapy (ART) initiation in HIV-positive people with cryptococcal meningitis. This uncertainty is the result of conflicting data on the mortality risk and occurrence of immune reconstitution inflammatory syndrome (IRIS) when ART is initiated less than four weeks after cryptococcal meningitis treatment is commenced.. To compare the outcomes of early initiation of ART (less than four weeks after starting antifungal treatment) versus delayed initiation of ART (four weeks or more after starting antifungal treatment) in HIV-positive people with concurrent cryptococcal meningitis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for trials published between 1 January 1980 and 7 August 2017. We additionally searched international trial registries, including ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP), and conference abstracts from the International AIDS Society (IAS) and the Conference on Retroviruses and Opportunistic Infections (CROI) for ongoing or unpublished studies between 2015 and 2017. We reviewed reference lists of included studies to identify additional studies.. We included randomized controlled trials (RCTs) that compared early versus delayed ART initiation in HIV-positive people with cryptococcal meningitis. Children, adults, and adolescents from any setting were eligible for inclusion.. Two review authors independently applied the inclusion criteria and extracted data. We presented dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CIs). We presented time-to-death data as hazard ratios with 95% CIs. We assessed the certainty of the evidence using the GRADE approach.. Four trials including 294 adult participants met the inclusion criteria of this review. Participants were predominantly from low- and middle-income countries. Two trials treated cryptococcal meningitis with amphotericin B and fluconazole; a third trial used fluconazole monotherapy; and the fourth trial did not specify the antifungal used.Early ART initiation may increase all-cause mortality compared to delayed ART initiation (RR 1.42, 95% CI 1.02 to 1.97; 294 participants, 4 trials; low-certainty evidence). Early ART initiation may reduce relapse of cryptococcal meningitis compared to delayed ART initiation (RR 0.27, 95% CI 0.07 to 1.04; 205 participants, 2 trials, low-certainty evidence). We are uncertain whether early ART initiation increases or reduces cryptococcal IRIS events compared to delayed ART initiation (RR 3.56, 95% CI 0.51 to 25.02; 205 participants, 2 trials; I. The results of this review are relevant to HIV-positive adults with cryptococcal meningitis in low- and middle-income countries. These data suggest a higher risk of mortality among people who initiate ART within four weeks of cryptococcal meningitis diagnosis. However, it is unclear if this higher mortality risk is related to cryptococcal meningitis-IRIS.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cause of Death; Drug Administration Schedule; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Randomized Controlled Trials as Topic

Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge.. To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies.. We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South-East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018.. We included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV-associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction.. Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random-effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10-week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta-analysis using multivariate meta-regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two-week and 10-week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node-splitting approach, and global inconsistency using design-by-treatment interaction modelling. For the network meta-analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10-week mortality.. In resource-limited settings, one-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis. An all-oral regimen of two weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered. We found no mortality benefit of combination two weeks AmBd and FLU compared to AmBd alone. Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings.

Topics: Acetazolamide; Acute Disease; Adult; Amphotericin B; Antifungal Agents; Developing Countries; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; Health Resources; HIV Infections; Humans; Induction Chemotherapy; Intracranial Hypertension; Meningitis, Cryptococcal; Network Meta-Analysis

Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They report atypical signs and poor response to treatment due to impairment of T-helper and regulatory cells activity. Laboratory diagnosis is based on microscopy on bone marrow or spleen aspirates. Value of serology remains high in term of sensibility, but a positive test must be confirmed by microscopy or molecular tests. Treatment is based on Liposomal amphotericin B whose administration is associated to lower incidence of side effects, in respect to antimonials and other formulations of AmB. Use of Miltefosine needs further investigation when L. infantum is the causative agent. Frequent relapses are observed in co-infected HIV who can benefit of a second cycle.

Topics: Amphotericin B; HIV Infections; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Phosphorylcholine; Recurrence

Topics: Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Drug Resistance, Fungal; Fluconazole; Fungal Capsules; Fungal Polysaccharides; Fungal Proteins; Gene Expression Regulation, Fungal; HIV Infections; Humans; Melanins; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Pigmentation; Polyploidy

Cryptococcus neoformans is a fungal pathogen associated with advanced HIV disease and other disorders associated with immune dysfunction. The pulmonary and the central nervous system are the most common manifestations of the disease. Localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. Herein, we present five cases of Cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. We also identified 84 additional cases of isolated cryptococcal osteomyelitis in the literature. Using these data, we have made some general recommendations regarding an approach to treatment of this uncommon clinical entity.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child, Preschool; Cryptococcosis; Cryptococcus neoformans; Female; Hepatitis C; HIV Infections; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Sarcoidosis; Tomography, X-Ray Computed; Young Adult

Visceral Leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Typically, VL is classified as a zoonotic infection when Leishmania infantum is the causative agent and as an anthroponotic one when L. donovani is the causative agent. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They may present atypical signs and poor response to the treatment due to a compromission of T-helper and regulatory cells activity. Also pregnancy can be considered a condition predisposing to Leishmania reactivation and to the changes in immune response, due to a switch toward a Th2 response reported in this condition of the life. Laboratory diagnosis is based on microscopy for parasites detection on bone-marrow or spleen aspirates. Value of serology remains high in term of sensibility, but a positive test has to be confirmed by microscopy or molecular tests. Hypergammaglobulinemia and pancytopenia are the main alteration identified by blood examination. Treatment is based on use of liposomal amphotericin B (L-AmB) whose administration is associated to lower incidence of side effects, in respect to antimonials and other formulations of AmB. Use of Miltefosine needs further investigation when L. infantum is the causative agent. Relapses to treatment are observed in coinfected HIV patients. They can benefit of a second cycle, but cumulative efficacy of the treatment can be low.

Topics: Amebicides; Amphotericin B; Animals; Guidelines as Topic; HIV Infections; Humans; Immunocompromised Host; Italy; Leishmania infantum; Leishmaniasis, Visceral; Recurrence; Treatment Outcome

Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality, primarily caused by Cryptococcus neoformans and Cryptococcus gattii. In China, C. neoformans var. grubii (especially molecular type VNI) is the most common variety in the environment and responsible for the majority of cryptococcal infections. C. gattii infections are quite rare in China and the primary molecular type is VGI, which is closely related to C. gattii isolates in Australia. Interestingly, the majority of cryptococcosis in China were reported in the HIV-uninfected patients (especially immunocompetent hosts). This unique phenomenon may be attributed to multiple polymorphisms in the genes encoding mannose-binding lectin (MBL) and Fc-gamma receptor 2B (FCGR2B) in the Han population, the major ethnic group in China. Compared to immunocompromised patients, immunocompetent patients with cryptococcal meningitis often presented with more intense inflammatory responses and more severe neurological complications, but less fungal burdens and disseminated infection. The overall prognosis, which is independently associated with amphotericin B-based initial therapy, is similar between immunocompetent and immunocompromised patients. In addition, intrathecal administration of amphotericin B has been proved to be an effective adjunctive treatment for cryptococcosis in China.

Topics: Amphotericin B; Antifungal Agents; China; Cryptococcosis; Cryptococcus neoformans; Genotype; HIV Infections; Humans; Injections, Spinal; Molecular Epidemiology; Mycological Typing Techniques; Survival Analysis; Treatment Outcome

Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.

Topics: Adult; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Cerebrospinal Fluid; HIV Infections; Humans; Itraconazole; Male; Meningitis, Fungal; Microbiological Techniques; Rhodotorula; Treatment Outcome

Immunocompromised patients are at increased risk of disseminated cryptococcal infection, often presenting as a primary respiratory infection with yeast cells originating from bird excreta. Because Cryptococcus neoformans has a tropism for cerebrospinal fluid, most patients suffer from meningitis or meningoencephalitis. Symptoms of cryptococcal meningitis are non-specific: headache, fever, nausea, or altered mental state and behaviour. Case descriptions of a renal transplant recipient and an HIV patient illustrate the non-specific presentation of cryptococcal meningitis. Lumbar puncture seemed to be critical in establishing the diagnosis. Cerebrospinal fluid, blood and other tissues were tested for C. neoformans by microscopy, culture and antigen tests. The patients were successfully treated with amphotericin B or liposomal amphotericin B intravenously and flucytosine intravenously or orally, followed by long-term fluconazole. The mortality rate for cryptococcal meningitis is 41% among renal transplant recipients and 20% in HIV patients.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Immunocompromised Host; Kidney Transplantation; Male; Meningitis, Cryptococcal; Spinal Puncture; Treatment Outcome

Treatment guidelines recommend combination antifungal therapy with amphotericin B (AmB) as an induction therapy for cryptococcal meningitis. The objective of this study was to compare the survival benefit between 5-FC (flucytosine) and fluconazole as second-line drugs given in combination with AmB. We carried out a systematic review and meta-analysis of prospective controlled studies reporting early combination treatment for human immunodeficiency virus (HIV)-associated cryptococcal meningitis. We searched MEDLINE, EMBASE and the Cochrane Library up to October 2013. Randomised trials and prospective cohort studies were selected. The primary outcome was mortality in the first 14 and 70 days. The secondary outcome was early fungicidal activity (EFA) in the first 2 weeks. Four trials were included in our study. All included studies could be considered to be of fair quality in their methodology. The meta-analysis suggested that mortality was lower in patients who were given AmB and 5-FC at the 2 weeks point (Fig. 2); the overall reduction in mortality with the 5-FC combination group was 44% [risk ratio (RR) 0.56, 95% confidence interval (CI) 0.33-0.95, p = 0.03]. EFA was significantly shorter in patients receiving AmB plus 5-FC [mean difference (MD) -0.10 log10 colony-forming units (CFU) per day, 95 % CI -0.11-0.09, p < 0.00001]. Mortality was no different between the 5-FC and fluconazole groups at the 3 months time point (p = 0.15) (Fig. 4). Adverse events occurred with similar frequency between the two treatment groups. There was no statistically significant difference in the survival rate between AmB in combination with high-dose fluconazole and the current standard of AmB plus 5-FC therapy for HIV-associated cryptococcal meningitis.

Topics: Amphotericin B; Antifungal Agents; Coinfection; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Immunocompromised Host; Meningitis, Cryptococcal; Treatment Outcome

Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

Topics: Africa, Eastern; Amphotericin B; Anti-Retroviral Agents; Antiprotozoal Agents; Coinfection; HIV Infections; Humans; Leishmaniasis, Visceral; Phosphorylcholine; Prevalence

We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals.. The outcomes of interest were clinical and parasitological cure, mortality, and adverse events.. PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available.. Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb(v)). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin.. Available evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antimony; Antiprotozoal Agents; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Survival Analysis; Treatment Outcome; Young Adult

Current, widely accepted guidelines for the management of HIV-associated cryptococcal meningoencephalitis (CM) recommend amphotericin B combined with flucytosine (5-FC) for ≥2 weeks as the initial induction treatment of choice. However, access to flucytosine in Africa and Asia, where disease burden is greatest, is inadequate at present. While research into identifying effective and well-tolerated antifungal combinations that do not contain flucytosine continues, an ever-increasing body of evidence from in vitro, in vivo and clinical studies points to the benefits of flucytosine in the treatment of CM in both intravenous combinations with amphotericin B and oral combinations with high-dose fluconazole. This article provides an up-to-date review of this evidence, and the current issues and challenges regarding increasing access to this key component of combination antifungal therapy for cryptococcosis.

Topics: Africa; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Asia; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal

Cryptococcal meningitis most commonly occurs in advanced HIV. Although diminishing in the developed world with antiretroviral therapy (ART), it remains a major problem in resource-limited settings. ART rollout will improve long-term HIV survival if opportunistic infections are effectively treated. Considering cryptococcal meningitis in that context, this review addresses excess morbidity and mortality in developing countries, treatment in areas of limited drug availability and challenges posed by combined anticryptococcal and HIV therapy.. From Early Fungicidal Activity (EFA) studies, amphotericin B-flucytosine is best induction therapy but often unavailable; high dose amphotericin B monotherapy may be feasible in some settings. Where fluconazole is the only option, higher doses are more fungicidal. Serum cryptococcal antigen testing may identify patients at highest disease risk and primary prophylaxis is effective; the clinical role of such interventions needs to be established. Timing of ART introduction remains controversial; early initiation risks Immune Reconstitution Disease (IRD) delays may increase mortality.. Amphotericin B based treatment is appropriate where possible. More studies are needed to optimize fluconazole monotherapy doses. Other research priorities include management of raised intracranial pressure, appropriate ART initiation and IRD treatment. Studies should focus on developing countries where problems are greatest.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Developing Countries; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal

Despite the advent and increasingly wide availability of antiretroviral therapy, cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with HIV infection in resource-limited settings. The ideal management of CM remains unclear. The aim of this review is to assess the evidence for deciding on which antifungal regimen to use as well as other modalities of management to utilise especially resource poor settings in order to achieve the best possible outcome and enable an individual with CM to survive their acute illness and benefit from antiretroviral therapy.. To determine the most effective initial and consolidation treatment strategy for CM in HIV infected adults.. The Cochrane HIV/AIDS group search strategy was used. Key words in the search included, meningitis, cryptococcus neoformans, treatment, trial, human immunodeficiency virus, acquired immunodeficiency syndrome, antifungal agents, amphotericin, flucytosine, fluconazole, azole, lumbar puncture, cerebrospinal fluid (CSF) pressure and acetazolamide.. Randomised of HIV-infected adults with a first episode of CM diagnosed on CSF examination, by India ink staining, CSF culture or cryptococcal antigen testing.. Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software.. Six studies are included in the review. Five of the studies compared antifungal treatments and one study addressed lowering intracranial pressure. This study was stopped early due to excess adverse effects. The results of the other five studies as summarised as follows.Mayanja-Kizza 1998 compared fluconazole to fluconazole with 5 flucytosine. The dose of fluconazole used 200mg initially is lower than the recommended initial dose of 400mg. No survival advantage was found with the use of 5 flucytosine in addition to fluconazole.Two studies Brouwer 2004 and van der Horst 1997 compared Amphotericin (AmB) to AmB with 5 flucytosine. Both drugs were given at currently recommended doses for 2 weeks. No survival difference was found at 14 days or at 10 weeks (only recorded in Brouwer 2004). There were significantly more patients with sterile CSF cultures at 14 days in the group that received AmB with flucytosine.Brouwer 2004 compared AmB given alone to AmB given with flucytosine and fluconazole alone or in combination. This was a small study and no differences in mortality were noted between the groups.Bicanic 2008 compared high to standard dose AmB both with flucytosine. There was no difference in mortality between the two groups or adverse events.Leenders 1997 compared standard AmB to liposomal AmB. There was no difference in death rates between the two groups. But there were significantly fewer side effects in the group treated with liposomal AmB.. The main aim of this review was to determine the best treatment for cryptococcal meningitis in resource-limited settings. In these settings usually only AmB and fluconazole are available. No studies suitable for inclusion in the review were found that compared these two drugs. Therefore we are unable to recommend either treatment as superior to the other. The recommended treatment for CM is a combination of AmB and flucytosine. The optimal dosing of AmB remains unclear. Liposomal AmB is associated with less adverse events than AmB and may be useful in selected patients where resources allow.Future research into the management of cryptococcal meningitis in resource-limited settings should focus on the most effective use of medications that are available in these settings.Flucytosine in combination with AmB leads to faster and increased sterilisation of CSF compared to using AmB alone. As Flucytosine is often not available in developing countries, policy makers and national departments of heath should consider procuring this drug for HIV treatment programmes.

Topics: Acetazolamide; Acute Disease; Adult; Amphotericin B; Antifungal Agents; Antihypertensive Agents; Developing Countries; Fluconazole; Flucytosine; Health Resources; HIV Infections; Humans; Intracranial Hypertension; Meningitis, Cryptococcal

Coccidioidomycosis is a recognized opportunistic infection in those with HIV-1 infection. The major risk factor is immunodeficiency, particularly when the peripheral blood CD4 T lymphocyte count is below 250/muL. There are many manifestations of coccidioidomycosis during HIV-1 infection, including diffuse, reticulonodular pneumonia, focal primary pneumonia, and disease disseminated beyond the thoracic cavity. Diagnosis is based on serology, culture and histopathologic identification. Two therapeutic modalities are currently available, the polyene antifungal amphotericin B and the triazole antifungals. Of the latter, the most experience is with the triazoles fluconazole and itraconazole. There are increasing data regarding drug interactions between triazoles and antiretroviral agents. The duration of treatment of coccidioidomycosis in those with HIV-1 infection is not established and in many patients it is either prolonged or life-long. Adherence to antiretroviral therapy is important in preventing recurrence.

Topics: Amphotericin B; Antifungal Agents; CD4-Positive T-Lymphocytes; Coccidioidomycosis; HIV Infections; HIV-1; Humans; Patient Compliance; Recurrence; Triazoles

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antiretroviral Therapy, Highly Active; Histoplasmosis; HIV Infections; Humans; Immunosuppressive Agents; Itraconazole; Male; Risk Factors; Skin Diseases, Papulosquamous

Treatment of visceral leishmaniasis in HIV patients encounters inefficacy and relapse due to drug resistance, toxicity and immunodepression. Our goal was to evaluate treatment of these patients by liposomal amphotericin B (L-AmB). Since 1998, five clinical files were exploitable out of 13 patients. Protocols used bolus doses ranging between 2.9 and 4.1 mg/kg dispatched on 5-24 days, followed by maintenance dose ranging from 2.7 to 3.8 mg/kg every 15 days. Attack treatment involved high bolus dose (cumulated doses ranging from 60 to 86 mg/kg at day 30) and allowed favorable clinical and biological results with healing in four patients. Secondary prophylaxis with L-AmB has been efficacious and well tolerated in three patients. Although literature and study results cannot indicate a standard therapeutic care in these patients, an initial treatment by L-AmB at doses higher than marketing-approved doses with a secondary prophylaxis by L-AmB associated with an antiretroviral treatment seem to be major asset in order to obtain healing. Expanding this study to a multicenter trial should allow to better define the frequency and duration of the secondary prophylaxis and to evaluate the risk of therapeutic escape as well as the life-span increase.

Topics: Adult; Amphotericin B; Animals; Antiprotozoal Agents; Drug Combinations; Drug Evaluation; Female; HIV Infections; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Phosphatidylcholines; Phosphatidylglycerols; Recurrence; Retrospective Studies; Substance Abuse, Intravenous; Treatment Outcome

Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Once established, the clinical course of untreated disease leads to death. Recent, large-scale epidemics in east Africa and India and the emergence of a new epidemic in patients infected with HIV makes VL a priority for the World Health Organization. Pentavalent antimonials have been the mainstay of the treatment for > 60years. The progressive appearance of antimonial resistance, the developments of lipid formulations of amphotericin B and a new oral administered drug (miltefosine) have changed the pattern of VL treatment. The prohibitive cost of new therapies leads to different treatment practices according to the socioeconomic and cultural status of each region.

Topics: Amphotericin B; Animals; Antiprotozoal Agents; Developing Countries; HIV Infections; Humans; Leishmaniasis, Visceral; Mice; Phosphorylcholine; World Health Organization

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Cryptococcosis; Cryptococcus neoformans; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV; HIV Infections; Humans; Itraconazole; Lung Diseases, Fungal; Meningitis, Cryptococcal; Randomized Controlled Trials as Topic

In 1903, Leishman and Donovan separately described the protozoan now called Leishmania donovani in splenic tissue from patients in India with the life-threatening disease now called visceral leishmaniasis. Almost a century later, many features of leishmaniasis and its major syndromes (ie, visceral, cutaneous, and mucosal) have remained the same; but also much has changed. As before, epidemics of this sandfly-borne disease occur periodically in India and elsewhere; but leishmaniasis has also emerged in new regions and settings, for example, as an AIDS-associated opportunistic infection. Diagnosis still typically relies on classic microbiological methods, but molecular-based approaches are being tested. Pentavalent antimony compounds have been the mainstay of antileishmanial therapy for half a century, but lipid formulations of amphotericin B (though expensive and administered parenterally) represent a major advance for treating visceral leishmaniasis. A pressing need is for the technological advances in the understanding of the immune response to leishmania and the pathogenesis of leishmaniasis to be translated into field-applicable and affordable methods for diagnosis, treatment, and prevention of this disease.. This paper discusses the pathogenesis and clinical management of leishmaniasis. Leishmaniasis is a vector-borne disease caused by obligate intramacrophage protozoa, characterized by diversity and complexity. It is endemic in areas of the tropics, subtropics, and southern Europe, in settings ranging from rain forests in Americas to deserts in western Asia, and from rural to periurban areas. Several clinical syndromes are categorized under the term leishmaniasis: most notably visceral, cutaneous, and mucosal leishmaniasis, which result from replication of the parasite in macrophages of the mononuclear phagocyte system, dermis, and naso-oro-pharyngeal mucosa, respectively. These syndromes are caused by a total of about 21 leishmanial species, which are transmitted by about 30 species of phlebotomine sandflies. Clinical manifestation of the disease depends on the type of leishmaniasis, which could be life-threatening systemic infection (visceral), chronic skin sores (cutaneous), or dreaded metastatic complications, which causes facial disfigurement (mucosal). Clinical management is directed to prevent death from visceral leishmaniasis and morbidity from cutaneous and mucosal leishmaniasis. Also included in its management is the ongoing research on immunoregulation of leishmaniasis in the understanding of the immune response to intracellular pathogens and rationalizing vaccine development. General principles on the disease diagnosis and treatment are outlined in this paper.

Topics: Amphotericin B; Animals; Antimony; Antiprotozoal Agents; Drug Administration Schedule; Female; HIV Infections; Humans; Leishmania; Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral; Male

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Azoles; Cryptococcosis; Female; Histoplasmosis; HIV Infections; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mouth Diseases; Mucormycosis; Mycoses; Sinusitis

A 39-year-old woman infected with human immunodeficiency virus had disseminated histoplasmosis that presented with nodules on her tongue. This is the seventh reported case of biopsy- and/or culture-proven oropharyngeal histoplasmosis in patients with acquired immunodeficiency syndrome. We review those previous reports and discuss the clinical features of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Biopsy; Female; Histoplasmosis; HIV Infections; Humans; Tongue Diseases

Cryptococcosis is a major cause of illness and death among persons infected with human immunodeficiency virus (HIV). Its management must include both initial and maintenance treatment. Although most authorities favor an initial period of therapy with amphotericin B for acute cryptococcosis, the triazoles play a role in both the management of acute disease and subsequent maintenance therapy. AIDS surveillance data collected by the Centers for Disease Control and Prevention document the occurrence of cryptococcosis in more than 17,000 (6.2%) of adults with AIDS in the United States, although this figure is known to be an underestimate. The risk of cryptococcosis among HIV-infected persons is highest at CD4+ lymphocyte counts of < 100/microL. Although cryptococcosis is especially frequent among AIDS patients who are black, male, or injection drug users, the explanations for these patterns remain unclear. Whether geographic differences in rates of cryptococcosis result from variations in the environmental distribution of Cryptococcus neoformans as well as in the distribution of HIV infection is also unclear. Although exposure to pigeon feces is the best known of the putative exposure-related risk factors, proof is lacking that avian excreta are the primary environmental source of the organism in most cases of cryptococcosis. Prophylaxis with triazoles can prevent cryptococcosis and may be considered for adults and adolescents with CD4+ counts of < 50/microL. However, it is uncertain whether prophylaxis will affect survival, be cost-effective, or have an adverse impact on the susceptibility of a variety of fungi to antifungal drugs. Vaccines and monoclonal antibodies designed to prevent or modify cryptococcosis in HIV-infected persons are in the experimental stage.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; HIV Infections; Humans; Incidence; Male; Risk Factors; United States

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Ganciclovir; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Product Surveillance, Postmarketing; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The AmBisome Therapy Induction Optimization (AMBITION-cm) trial, conducted in eastern and southern Africa, showed that a single, high dose (10 mg/kg) of liposomal amphotericin B, given with an oral backbone of fluconazole and flucytosine, was noninferior to the World Health Organization (WHO)-recommended regimen of 7 days of amphotericin B deoxycholate plus flucytosine for treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis and has been incorporated into WHO treatment guidelines. We believe that the trial also has important implications for the treatment of HIV-associated cryptococcal meningitis in high-income settings. We advance the arguments, supported by evidence where available, that the AMBITION-cm trial regimen is likely to be as fungicidal as the currently recommended 14-day liposomal amphotericin-based treatments, better tolerated with fewer adverse effects, and confer significant economic and practical benefits and, therefore, should be included as a treatment option in guidance for HIV-associated cryptococcal treatment in high-income settings.

Topics: Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV; HIV Infections; Humans; Meningitis, Cryptococcal

The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.. In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant predetermined safety or efficacy concerns. In Stage-2, the 1200mg dose was excluded per protocol because of increased mortality, and participants were randomised to 1600mg, 2000mg FCZ or AMB in a 1:1:1 ratio.. One hundred and sixty eight participants were enrolled with 48, 50, and 48 in the AMB, 1600mg and 2000mg cohorts. The Kaplan Meier proportion for mortality (90% CI) at 10 and 24 weeks for AMB was 17% (10, 29) and 24% (15, 37), compared to 20% (12, 32) and 30% (20, 43) for 1600mg, and 33% (23, 46) and 38% (27, 51) for 2000mg/day FCZ. With the exception of a higher incidence of gastrointestinal side effects in the 2000mg cohort, both induction doses of FCZ were safe and well tolerated. There were no life-threatening changes in electrocardiogram QTc which were similar across all doses of FCZ and AMB. The median (IQR) change in log10 cryptoccal colony forming units (CFU) from week 0 to week 2 was -8(-4.1,-1.9) for AMB; -2.5(-4.0, -1.4) for 1600mg FCZ and -8 (-3.2, -1.0) for 2000mg FCZ. The proportion (90% CI) CSF CM negative at 10 weeks was 81%(71,90) for AMB; 56%(45,69) for 1600mg FCZ and 60%(49,73) for 2000mg FCZ.. Induction phase weight and renal-adjusted doses of 1600mg and 2000mg/day FCZ for CM were safe and well tolerated except for increased GI side effects in the 2000mg/day dose, and had similar times to achieve CSF sterilization, but took significantly longer than AMB. The WHO recommended 1200mg FCZ was associated with a high mortality. While not statistically significant, mortality was numerically lower in the AMB compared to 1600mg and 2000mg FCZ These data make a case for a phase 3 study of higher doses of FZC.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Treatment Outcome

Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent.. This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations.. Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.. Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations.. Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r).

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Coinfection; Drug Therapy, Combination; HIV; HIV Infections; Humans; India; Leishmaniasis, Visceral; Pharmaceutical Preparations; Phosphorylcholine; Recurrence; Treatment Outcome

Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.. In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.. A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log. Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).

Topics: Administration, Oral; Africa South of the Sahara; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Administration Schedule; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Meningitis, Cryptococcal

Visceral leishmaniasis (VL) treatment in HIV patients very often fails and is followed by high relapse and case-fatality rates. Hence, treatment efficacy assessment is imperative but based on invasive organ aspiration for parasite detection. In the search of a less-invasive alternative and because the host immune response is pivotal for treatment outcome in immunocompromised VL patients, we studied changes in the whole blood transcriptional profile of VL-HIV patients during treatment.. Embedded in a clinical trial in Northwest Ethiopia, RNA-Seq was performed on whole blood samples of 28 VL-HIV patients before and after completion of a 29-day treatment regimen of AmBisome or AmBisome/miltefosine. Pathway analyses were combined with a machine learning approach to establish a clinically-useful 4-gene set.. Distinct signatures of differentially expressed genes between D0 and D29 were identified for patients who failed treatment and were successfully treated. Pathway analyses in the latter highlighted a downregulation of genes associated with host cellular activity and immunity, and upregulation of antimicrobial peptide activity in phagolysosomes. No signs of disease remission nor pathway enrichment were observed in treatment failure patients. Next, we identified a 4-gene pre-post signature (PRSS33, IL10, SLFN14, HRH4) that could accurately discriminate treatment outcome at end of treatment (D29), displaying an average area-under-the-ROC-curve of 0.95 (CI: 0.75-1.00).. A simple blood-based signature thus holds significant promise to facilitate treatment efficacy monitoring and provide an alternative test-of-cure to guide patient management in VL-HIV patients.. Project funding was provided by the AfricoLeish project, supported by the European Union Seventh Framework Programme (EU FP7).

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Coinfection; Endoribonucleases; Female; Gene Expression Regulation; HIV; HIV Infections; Host-Pathogen Interactions; Humans; Interleukin-10; Leishmania donovani; Leishmaniasis, Visceral; Male; Phagosomes; Phosphorylcholine; Receptors, Histamine H4; Recurrence; Serine Proteases; Transcriptome; Treatment Failure

We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana.. Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day.. Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated.. Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial.. ISRCTN 10248064.

Topics: Adult; Amphotericin B; Antifungal Agents; Botswana; Cerebrospinal Fluid; Cryptococcus neoformans; Female; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Tanzania; Treatment Outcome

Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.. An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment. Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45-87%) in the unadjusted analysis, and 50% (95% CI 27-73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67-90%) and 67% (95% CI 48-82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32-78%) in the monotherapy arm, and 88% (95% CI 79-98%) in the combination arm. No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.. The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.. www.clinicaltrials.gov NCT02011958.

Topics: Adult; Amphotericin B; Anti-Retroviral Agents; Antiprotozoal Agents; Coinfection; Drug Therapy, Combination; Ethiopia; Female; HIV Infections; Humans; Leishmania donovani; Leishmaniasis, Visceral; Male; Middle Aged; Parasite Load; Phosphorylcholine; Treatment Outcome; Young Adult

Amphotericin-induced phlebitis is a common infusion-related reaction in patients managed for cryptococcal meningitis. High-quality nursing care is critical component to successful cryptococcosis treatment. We highlight the magnitude and main approaches in the management of amphotericin-induced phlebitis and the challenges faced in resource-limited settings.. We prospectively determined the incidence of amphotericin-induced phlebitis during clinical trials in Kampala, Uganda from 2013 to 2018. We relate practical strategies and challenges faced in clinical management of phlebitis.. Overall, 696 participants were diagnosed with HIV-related cryptococcal meningitis. Participants received 7-14 doses of intravenous (IV) amphotericin B deoxycholate 0.7-1.0 mg/kg/day for induction therapy through peripheral IV lines at a concentration of 0.1 mg/mL in 5% dextrose. Overall, 18% (125/696) developed amphotericin-induced phlebitis. We used four strategies to minimize/prevent the occurrence of phlebitis. First, after every dose of amphotericin, we gave one liter of intravenous normal saline. Second, we rotated IV catheters every three days. Third, we infused IV amphotericin over 4 h. Finally, early ambulation was encouraged to minimize phlebitis. To alleviate phlebitis symptoms, warm compresses were used. In severe cases, treatment included topical diclofenac gel and oral anti-inflammatory medicines. Antibiotics were used only when definite signs of infection developed. Patient/caregivers' education was vital in implementing these management strategies. Major challenges included implementing these interventions in participants with altered mental status and limited access to topical and oral anti-inflammatory medicines in resource-limited settings.. Amphotericin-induced phlebitis is common with amphotericin, yet phlebitis is a preventable complication even in resource-limited settings.. The ASTRO-CM trial was registered prospectively. ClincalTrials.gov : NCT01802385 ; Registration date: March 1, 2013; Last verified: February 14, 2018.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Health Resources; HIV Infections; Humans; Incidence; Infusions, Intravenous; Male; Meningitis, Cryptococcal; Phlebitis; Poverty Areas; Uganda

Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (P = 0.52).

Topics: Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Coinfection; Cryptococcus neoformans; Drug Resistance, Fungal; Drug Therapy, Combination; Female; Fluconazole; HIV; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Multilocus Sequence Typing; Treatment Outcome; Uganda

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.

Topics: Adult; Amphotericin B; Anemia; Antifungal Agents; Blood Cell Count; Coinfection; Creatinine; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Female; Flucytosine; Hemoglobins; HIV; HIV Infections; Humans; Hypokalemia; Induction Chemotherapy; Kidney; Male; Meningitis, Cryptococcal; Neutropenia; Survival Analysis; Treatment Outcome

Interferon-gamma (IFNγ) is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. We performed a randomized controlled trial to determine whether addition of IFNγ to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated cryptococcal meningitis.. Patients were randomized to amphotericin B 1 mg/kg per day and 5FC 100 mg/kg per day for 2 weeks (standard therapy), standard therapy and IFNγ1b 100 μg days 1 and 3 (IFNγ two doses), or standard therapy and IFNγ1b 100 μg days 1, 3, 5, 8, 10 and 12 (IFNγ six doses). Primary outcome was rate of clearance of cryptococcus from the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival.. Rate of fungal clearance was significantly faster in IFNγ containing groups than with standard treatment. Mean EFA [log colony forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with IFNγ two doses, and -0.64 with IFNγ six doses. Difference in EFA was -0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard treatment and IFNγ two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006) between standard treatment and IFNγ six doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated.. Addition of short-course IFNγ to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFNγ are as effective as six doses.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiviral Agents; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Female; Flucytosine; HIV Infections; Humans; Interferon-gamma; Male; Meningitis, Cryptococcal; Treatment Outcome

The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections.. A randomized trial was conducted in HIV-infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas-liquid chromatography.. Sixty-four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively).. High fluconazole dosage (800 mg/day) for the treatment of HIV-associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success.

Topics: Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Biological Availability; Chromatography, Gas; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Models, Biological; Risk Factors; Time Factors; Treatment Outcome

Cryptococcosis is a life-threatening infection among patients with human immunodeficientcy virus (HIV) infection. Therapeutic options for the treatment of central nervous system cryptococcosis are limited, especially in resource-limited settings.. We conducted a randomized, open-label, phase II trial in Thailand and the United States that compared the safety and efficacy of intravenous amphotericin B deoxycholate (AmB) 0.7 mg/kg (the standard therapy) with that of AmB 0.7 mg/kg plus fluconazole 400 mg (the low-dosage combination) or AmB 0.7 mg/kg plus fluconazole 800 mg (the high-dosage combination) administered daily for 14 days, followed by fluconazole alone at the randomized dosage (400 or 800 mg per day) for 56 days. The primary safety end point was the number of severe or life-threatening treatment-related toxicities; the primary efficacy end point was a composite of survival, neurologic stability, and negative cerebrospinal fluid culture results after 14 days of therapy.. A total of 143 patients were enrolled. There were no differences in treatment-related toxicities among the 3 arms. Toxicity was predictable and was most often related to AmB, and it included electrolyte abnormalities, anemia, nephrotoxicity, and infusion-related events. At day 14, 41%, 27%, and 54% of patients in the standard therapy, low-dosage combination, and high-dosage combination therapy arms, respectively, demonstrated successful outcomes. A trend towards better outcomes in the combination therapy arms was seen at days 42 and 70.. AmB plus fluconazole administered at a dosage of 800 mg for 14 days, followed by fluconazole administered at a dosage of 800 mg daily for 56 days, is well-tolerated and efficacious among HIV-positive patients with central nervous system cryptococcosis. These results have significant treatment implications and should be validated in a randomized phase III trial.

Topics: Adult; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Survival Analysis; Thailand; Treatment Outcome; United States

Topics: Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal

Animal studies and case series have demonstrated the dose-dependent efficacy and long half-life of amphotericin B deoxycholate (ABd), providing the rationale for our randomized controlled study to compare once-daily (OD) (1 mg/kg) and alternate-d (AD) (2 mg/kg) administration of ABd in the treatment of cryptococcal meningitis in patients with AIDS hospitalized at King Chulalongkorn Memorial Hospital, Thailand, from 2003 to 2004. Of 28 patients, 15 and 13 received OD and AD administration, respectively. There was no significant difference between the 2 groups regarding the demography, clinical features, and laboratory data. After 2 weeks of the intensive-phase treatment, there was no significant difference in the clinical response between the OD (80%) and AD (76.9%) groups. Mycological response was observed in 33.3% and 10% of patients in the OD and AD groups, respectively (p = 0.3). There was no difference in nephrotoxicity and infusion-related events. In conclusion, this is the first randomized controlled study comparing OD and AD administration of ABd in the treatment of cryptococcal meningitis. Although our study was not sufficiently powered to draw conclusions on clinical efficacy and toxicities, the results are encouraging and should warrant further clinical trials evaluating the efficacy and adverse effects with a larger sample size.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Deoxycholic Acid; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; HIV Infections; Hospitalization; Humans; Male; Meningitis, Cryptococcal; Thailand; Treatment Outcome

Visceral leishmaniasis (VL) in HIV-positive patients is characterized by a chronic course with frequent relapse. The aim of this study was to evaluate the efficacy and safety of amphotericin B lipid complex (ABLC) in preventing VL relapses in HIV-infected patients.. This was a multicentre, open-label (with blinded centralized randomization), parallel, no-treatment, controlled clinical trial. HIV-infected patients, with at least one previous treated episode of VL and with negative bone marrow aspirate for Leishmania parasites prior to the study, were randomized to receive either ABLC 3 mg/kg/day every 21 days (ABLC) or no treatment (NT). Patients were followed-up every 9 weeks for up to 12 months, and the efficacy was measured as the proportion of patients remaining free (non-relapse) of VL at 1 year of follow-up. The primary analysis was performed on an intention-to-treat basis.. One hundred and fifteen patients were screened, but only 17 were randomized: eight in the ABLC group and nine in the NT group. The intention-to-treat analysis of data showed 50% of patients remaining free of VL at 12 months of follow-up (95% CI = 15.7%, 84.3%) in the ABLC group, and 22.2% (95% CI = 2.8%, 60.0%) in the NT group. The non-relapse odds ratio was 3.5 (95% CI = 0.30%, 52.0%) favouring ABLC. ABLC was well tolerated: patients only presented infusion-related mild adverse events. No patients from either group discontinued treatment or died during follow-up.. ABLC, administered every 21 days for 12 months, is useful as secondary prophylaxis in preventing VL relapse in HIV-infected patients, and is well tolerated.

Topics: Adult; Amphotericin B; Antifungal Agents; Double-Blind Method; Drug Combinations; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Phosphatidylcholines; Phosphatidylglycerols

Optimal treatment for HIV-related visceral leishmaniasis (VL) has still to be established. A pilot clinical trial was carried out in 57 HIV-VL coinfected patients to compare the efficacy and safety of amphotericin B lipid complex (ABLC) versus meglumine antimoniate. The patients were randomized to receive either ABLC 3 mg/kg/day for 5 days (ABLC-5, 18 patients), ABLC 3 mg/kg/day for 10 days (ABLC-10, 20 patients) or meglumine antimoniate 20 mg Sbv /kg/day for 28 days (19 patients). Treatment was considered successful if parasites were not detected in a bone marrow aspirate after treatment. Parasitological cure was attained in 33% (95% CI: 13%-59%) of the ABLC-5 group, in 42% (95% CI: 16%-62%) of the ABLC-10 group and in 37% (95% CI: 16%-62%) of the meglumine antimoniate group (P = 0.94). Eight out of 19 patients administered antimoniate discontinued treatment prematurely following serious adverse events, compared with one in the ABLC groups (P = 0.0006). The efficacy of ABLC is similar to meglumine antimoniate, but the severity of toxicity in the treatment of HIV-VL is lower with ABLC.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Bone Marrow; Double-Blind Method; Drug Combinations; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Phosphatidylcholines; Phosphatidylglycerols; Pilot Projects; Treatment Outcome

A prospective descriptive study was designed to determine the impact of highly active antiretroviral therapy (HAART) in the evolution of visceral leishmaniasis (VL) in HIV-1 infected patients. Thirty-two patients were treated with meglumine antimoniate or amphotericin B in lipid formulations. Patients who had undergone previous HAART at study entry (n=17) continued with therapy while receiving treatment for VL. Patients who had never undergone HAART started it after VL treatment finished (n=15). Ten patients were lost to follow-up. All of the remaining patients (n=20) continued to receive HAART and were followed for an average of 441 days. Relapses were observed in 5 of 20 patients. These results indicate that HAART neither prevents the incidence of VL relapse nor modifies the clinical picture described in the pre-HAART era.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Europe; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Prospective Studies

Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood measurements of AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Area Under Curve; Chromatography, High Pressure Liquid; Drug Combinations; Drug Interactions; Half-Life; HIV Infections; Humans; Kidney Diseases; Leishmaniasis, Mucocutaneous; Mycoses; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Reference Values

To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis.. Non-blind randomised controlled trial.. University hospital; tertiary clinical care.. 22 HIV positive patients with oral candidiasis.. Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion).. Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin.. 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose.. Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis, Oral; Deoxycholic Acid; Drug Combinations; Excipients; Fat Emulsions, Intravenous; Glucose; HIV Infections; Humans; Infusions, Intravenous; Middle Aged

Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions. The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted. These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antifungal Agents; Fluconazole; HIV; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Inflammation; Male; Meningitis, Cryptococcal

This study aimed to investigate antifungal resistance in oral Candida isolates and the efficacy of chitosan, a natural polymer, against drug-resistant Candida.. Oral Candida isolates were collected from HIV-infected and healthy individuals in our previous study (n = 66 isolates/group). The minimum-inhibitory-concentration (MIC) of amphotericin-B and fluconazole was determined by Epsilometer test. Minimal-fungicidal-concentration (MFC) of 3 chitosan derivatives: high-molecular-weight chitosan (HMWC, 150-200 kDa), oligomer (7-9 kDa) and polymer (900-1000 kDa) chitosan, were investigated by agar dilution method. Statistical analysis was performed using Chi-square or Fisher's exact tests as appropriate.. Fluconazole-resistant C. albicans were significantly more prevalent in HIV-infected than in healthy individuals (P = 0.02), while amphotericin-B-resistant C. parapsilosis were more common in healthy individuals (P = 0.03). The majority of Candida isolates were killed by HMWC at ≤ 40 mg/ml, as well as by oligomer and polymer chitosan at ≤ 6 mg/ml. Remarkably, chitosan was effective against most antifungal drug-resistant isolates.. Antifungal drug resistance was prevalent among oral C. albicans isolates from HIV-infected individuals. Chitosan could serve as a complementary antifungal agent against drug-resistant strains.

Topics: Amphotericin B; Antifungal Agents; Candida; Chitosan; Drug Resistance, Fungal; Fluconazole; HIV Infections; Humans; Microbial Sensitivity Tests

Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally.. In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities.. Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine.. Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Topics: Amphotericin B; Antifungal Agents; HIV; HIV Infections; Humans; Meningitis, Cryptococcal; Retrospective Studies

American cutaneous leishmaniasis is an infectious disease caused by the protozoa of the genus Leishmania. Clinical manifestations vary according to the virulence of the parasite speciesand the host's immune response. We report a case of a 2-year-old girl vertically exposed to HIV who presented painful and itchy papules throughout her lower limbs with further dissemination of vegetative ulcers all over the body and scalp. The histopathological examination evidenced the amastigote form of Leishmania and the polymerase chain reaction was positive for Leishmania sp. in the tissue sample. The patient was treated with amphotericin B and demonstrated improvement of lesions. Despite successful treatment for American cutaneous leishmaniasis, she developed osteomyelitis related to a bacterial secondary infection over the site of a previous ulcer on the left ankle and required a 6-week course of intravenous antimicrobial treatment. Children with vertical exposure to HIV, even without seroconversion, are at greater risk of infections if compared to non-exposed children. This is perhaps the reason for such an exuberant and rare case of complicated eishmaniasis.

Topics: Amphotericin B; Brazil; Child; Child, Preschool; Female; HIV Infections; Humans; Leishmania; Leishmaniasis, Cutaneous; United States

Here we tested the correlation between minimum inhibitory concentrations (MICs) of major antifungal agents and sequence types (STs) within Cryptococcus neoformans VNI isolates, and explored the ERG11 gene of included strains.. We analysed 23 C. neoformans strains categorised into two groups according to the distribution of the ST profile in Kinshasa clinics (Democratic Republic of Congo): major ST [ST93 (n = 15)], and less common STs [ST659 (n = 2), ST5 (n = 2), ST4 (n = 1), ST 53 (n = 1), ST31 (n = 1), and ST69 (n = 1)]. The MICs of the major antifungal agents [amphotericin B (AMB), 5-fluorocytosine (5FC) and fluconazole (FCZ)] were determined following EUCAST guidelines. ERG11 gene sequences were extracted from whole genome sequence of the isolates and compared with the wild-type gene sequence of the C. neoformans VNI.. Although major ST isolates appeared to have lower median MICs for AMB and 5FU than less common ST isolates (0.50 vs. 0.75 mg/L for AMB, 2 vs. 4 mg/L for 5FU, respectively), FCZ susceptibility was similar in both groups (4 mg/L) (p-value >0.05). The susceptibility profile of C. neoformans strains separately considered did not significantly affect the patients' clinical outcomes (p-value >0.05). Furthermore, two structural modalities of the ERG11 gene were observed: (1) that of the reference gene, and (2) that containing two exonic silent point substitutions, and one intronic point substitution located in a sequence potentially involved in pre-mRNA splicing (c.337-22C > T); with no association with the MICs of the isolates (p-value >0.05).. The lack of association/correlation found in this study calls for further investigations to better understand the mechanisms of C. neoformans resistance to antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Democratic Republic of the Congo; Drug Resistance, Fungal; Fluconazole; Flucytosine; Fluorouracil; HIV Infections; Humans; Microbial Sensitivity Tests; Polymorphism, Genetic

Malassezia is a lipophilic and lipid-dependent yeast genus belonging to the skin microbiota of humans and other animals. However, due to dysbiosis processes or other factors in the host, this yeast can cause different pathologies, ranging from skin diseases, such as seborrheic dermatitis, to fungemia. Isolation of Malassezia furfur has been reported in HIV-positive patients with or without skin lesions. Due to its opportunistic nature and its variable resistance to antifungal compounds, it is relevant to know the Malassezia sensitivity profiles.. To determine the sensitivity to different antifungal agents, of clinical isolates of M. furfur obtained from HIV-positive or negative patients, with or without seborrheic dermatitis.. Assessment of isolates sensitivity to itraconazole, voriconazole, fluconazole, and amphotericin B was performed by two techniques: (1) Broth microdilution using Clinical and Laboratory Standards Institute (CLSI) protocol M27-A3 with modifications; and (2) agar tests using Etest®.. Isolates obtained from HIV patients showed an increase in the minimum inhibitory concentration of fluconazole, voriconazole, and amphotericin B, compared with those of non-HIV patients. Itraconazole was the antifungal with the lowest minimum inhibitory concentration (MIC) in most isolates.. We observed differences in the sensitivity profiles of M. furfur isolates according to the context of the patient. High MIC of antifungals like fluconazole, commonly used for treating pathologies caused by Malassezia, were identified.. Malassezia es un género de levaduras lipofílicas que dependen de los lípidos y hacen parte de la microbiota de la piel de humanos y otros animales. No obstante, debido a procesos de disbiosis u otros factores en el huésped, esta levadura puede llegar a causar diferentes enfermedades: desde cutáneas (como dermatitis seborreica) hasta fungemias. Se han reportado aislamientos de Malassezia furfur en pacientes positivos para HIV, con lesiones cutáneas o sin ellas. Por su carácter oportunista y sensibilidad variable a los compuestos antifúngicos, es relevante conocer los perfiles de sensibilidad.. Determinar la sensibilidad a diferentes antifúngicos de aislamientos clínicos de M. furfur obtenidos de pacientes positivos o negativos para HIV, con dermatitis seborreica o sin ella.. La sensibilidad de los aislamientos a itraconazol, voriconazol, fluconazol y anfotericina B, se determinó mediante dos técnicas: microdilución en caldo según el protocolo M27-A3 del Clinical & Laboratory Standards Institute (CLSI), con modificaciones, y pruebas en agar mediante Etest®.. Los aislamientos obtenidos de pacientes con HIV mostraron aumento de la concentración inhibitoria mínima a fluconazol, voriconazol y anfotericina B, en comparación con los de pacientes sin HIV. Por otro lado, al evaluar la mayoría de los aislamientos, el itraconazol fue el antifúngico con la menor concentración inhibitoria mínima.. Se evidencian diferencias en los perfiles de sensibilidad de los aislamientos de M. furfur, según el contexto del paciente, y elevadas concentraciones inhibitorias mínimas de antifúngicos como el fluconazol, usados comúnmente para el tratamiento de las enfermedades causadas por Malassezia spp.

Topics: Amphotericin B; Animals; Antifungal Agents; Dermatitis, Seborrheic; Fluconazole; HIV Infections; Humans; Itraconazole; Malassezia; Saccharomyces cerevisiae; Voriconazole

This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis.. A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020.. The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance.. ChiCTR1900021195. Registered 1 February 2019.

Topics: Amphotericin B; Anemia; Antifungal Agents; HIV Infections; Humans; Induction Chemotherapy; Leukopenia; Prospective Studies; Thrombocytopenia

Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons.We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/μL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at ${\\$}$16.25 to ${\\$}$40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted.In South Africa, at ${\\$}$16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost ${\\$}$475, ${\\$}$220, or ${\\$}$136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at ${\\$}$24 per vial cost.Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher.. We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.

Topics: Amphotericin B; Animals; Antifungal Agents; Antigens, Fungal; CD4 Lymphocyte Count; Cost-Benefit Analysis; Developing Countries; Fluconazole; HIV Infections; Meningitis, Cryptococcal; Prospective Studies; Uganda

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare, virally-induced malignancies that occur almost exclusively in immunocompromised individuals. We report a very rare case of a dura-based EBV-SMT with superimposed local cryptococcal infection.. An adult male with a history of untreated acquired immunodeficiency syndrome presented to our hospital with worsening headaches, diarrhea, and diffuse myalgias.. Blood cultures were positive for methicillin-resistant Staphylococcus aureus and Cryptococcus neoformans serum antigen. Magnetic resonance imaging revealed 2 adjacent enhancing masses in the right temporal lobe, perilesional edema, and mass effect of the right lateral ventricle. Histological examination and immunohistochemical stains of the surgical specimen were consistent with EBV-SMT. Cryptococcus organisms were identified within the neoplasm.. The patient underwent complete tumor resection, received an extended course of amphotericin and flucytosine, and was restarted on antiretroviral therapy.. The patient was discharged from the hospital with no focal neurological deficits.. Epstein-Barr virus associated smooth muscle tumors are rare malignancies that occur in immunocompromised patients. Prognosis is largely dependent on immune reconstitution and treatment of concomitant infections.

Topics: Adult; Amphotericin B; Antiretroviral Therapy, Highly Active; Cryptococcus neoformans; Epstein-Barr Virus Infections; Flucytosine; Herpesvirus 4, Human; HIV Infections; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Methicillin-Resistant Staphylococcus aureus; Opportunistic Infections; Smooth Muscle Tumor; Superinfection; Temporal Lobe

Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection.. Describe general aspects and challenges of this disease and its association with HIV.. Review of literature.. Articles found using different combinations of terms including "disseminated histoplasmosis" and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database.. We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients.. Histoplasmosis is caused by. Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Histoplasma; Histoplasmosis; HIV Infections; Humans

The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.. A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.. Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.. Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.. Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Topics: Amphotericin B; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Infertility; Meningitis, Cryptococcal; Prospective Studies; Voriconazole

The AMBITION-cm trial for HIV-associated cryptococcal meningitis demonstrated that a single, high-dose of liposomal amphotericin (AmBisome) plus 14-days of oral flucytosine and fluconazole was non-inferior in terms of all-cause mortality to 7-days of amphotericin B deoxycholate and flucytosine followed by 7-days of fluconazole (Control). The AmBisome regimen was associated with fewer adverse events. We explored the acceptability of the AmBisome regimen from the perspective of participants and providers.. We embedded a qualitative methods study within the AMBITION-cm sites in Botswana and Uganda. We conducted in-depth interviews with trial participants, surrogate decision makers, and researchers and combined these with direct observations. Interviews were transcribed, translated, and analysed thematically.. We interviewed 38 trial participants, 20 surrogate decision makers, and 31 researchers. Participant understanding of the trial was limited; however, there was a preference for the AmBisome regimen due to the single intravenous dose and fewer side effects. More time was required to prepare the single AmBisome dose but this was felt to be acceptable given subsequent reductions in workload. The AmBisome regimen was reported to be associated with fewer episodes of rigors and thrombophlebitis and a reduction in the number of intravenous cannulae required. Less intensive monitoring and management was required for participants in the AmBisome arm.. The AmBisome regimen was highly acceptable, being simpler to administer despite the initial time investment required. The regimen was well tolerated and associated with less toxicity and resultant management. Widespread implementation would reduce the clinical workload of healthcare workers caring for patients with HIV-associated cryptococcal meningitis.

Topics: Antifungal Agents; Botswana; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Uganda

Progressive disseminated histoplasmosis remains a major but neglected cause of death among patients with advanced HIV. Recently, aiming to reduce avoidable deaths, the Pan American Health Organization issued the first diagnosis and treatment guidelines for HIV-associated histoplasmosis. But what proportion of progressive disseminated histoplasmosis in HIV-infected patients is severe is currently not known. Because this proportion influences treatment needs, we aimed to estimate this in a cohort of 416 patients in French Guiana.. We used the definition in the recent PAHO/WHO guidelines for severity. We used regression modelling to predict the impact of CD4 count on the proportion of severe cases. In a territory where treatment cost is not a limiting factor and where histoplasmosis is well known, we assumed that clinicians' initial treatment reflected their perception about the severity of the case and therefore, the needs for different treatments.. Using these definitions, since the beginning, there were 274 (65.9%) severe/moderately severe cases and 142 (34.1%) mild cases. In practice 186 cases were treated with deoxycholate or liposomal amphotericin B (44.7%) and 230 (55.3%) cases treated with itraconazole as first line treatment. The Kappa concordance measure between the guideline definition and the actual treatment given was 0.22. There was a 9% risk difference for death within 30 days of antifungal treatment initiation between severe/moderately severe and mild cases. Over threequarters (77%) of early deaths were attributed to severe/moderately severe cases.. This is the only rigorous estimate of the proportion of severe/moderately severe cases of progressive disseminated histoplasmosis in symptomatic HIV patients on the largest published cohort. These numbers may help defend budget needs for rapid diagnostic tests and liposomal amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole

Topics: Amphotericin B; Cost-Benefit Analysis; HIV Infections; Humans; Meningitis, Cryptococcal

HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis.. The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed.. The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda.. The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays.. European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research.. For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.

Topics: Amphotericin B; Cost-Benefit Analysis; HIV Infections; Humans; Malawi; Meningitis, Cryptococcal

Cryptococcal meningitis remains a common cause of mortality in low- and middle-income countries, where amphotericin B deoxycholate (amphotericin) plus fluconazole is the most common treatment. Flucytosine is almost uniformly absent as is outcome data on flucytosine use in routine care. The main goal of this study was identified the cumulative mortality at 2, 4, and 10 weeks after hospital admission.. We conducted a retrospective, observational cohort study among HIV-infected adults with cryptococcal meningitis receiving amphotericin plus flucytosine as induction therapy in Brazil. We assessed cumulative mortality at 2, 4, and 10 weeks and the cumulative proportion discontinuating amphotericin or flucytosine due to toxicity at 2 weeks. We performed multiple logistic regression to identify variables associated with in-hospital mortality.. In total, 77 individuals (n = 66 men) were included with median baseline CD4 of 29 (IQR, 9-68) cells/mcL. Twenty (26%) had at least one concurrent neurological disease diagnosed. Sixty (78%) patients received at least 14 days of amphotericin plus flucytosine. Cumulative mortality was 5% (4/77) at 2 weeks, 8% (6/77) at 4 weeks, and 19% (15/77) at 10 weeks. Cumulative proportion of patients that discontinuated amphotericin or flucytosine due to toxicity was 20% (16/77) at 2 weeks. In addition, in-hospital mortality was associated with receiving ≤ 10 days of induction therapy (odds ratio = 4.5, 95% CI 1.2-17.1, P = 0.028) or positive cerebrospinal fluid fungal culture after 2 weeks (odds ratio = 3.8, 95% CI 1.1-13.5, P = 0.035).. In this "real-world" study, amphotericin plus flucytosine shows low early mortality of patients with HIV-associated cryptococcal meningitis. Early discontinuation due to adverse events was moderate. More effective and safe antifungals are needed in order to improve the outcome of cryptococcal meningitis.

Topics: Adult; Amphotericin B; Antifungal Agents; Brazil; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Referral and Consultation; Retrospective Studies

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Female; Flucytosine; Global Health; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Middle Aged

Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4. During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4. During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.

Topics: Adult; Amphotericin B; Antibodies, Protozoan; Brazil; CD4-Positive T-Lymphocytes; Deoxycholic Acid; Drug Combinations; Female; HIV Infections; Humans; Immunoglobulin G; Interleukin-6; Leishmania; Leishmaniasis, Visceral; Male; Middle Aged; Recurrence

We report on a 22-years-old Thai male patient with congenital HIV infection. Due to his non-adherence to antiretroviral treatment he developed disseminated

Topics: Amphotericin B; Anterior Chamber; Antifungal Agents; Fungemia; Granuloma; HIV Infections; Humans; Male; Mycoses; Talaromyces; Uveitis, Anterior; Young Adult

Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antitubercular Agents; Bacteremia; Catheter-Related Infections; Central Venous Catheters; Drug Therapy, Combination; Female; Fluconazole; HIV; HIV Infections; Humans; Immunocompromised Host; Middle Aged; Neutropenia; Trichosporon; Trichosporonosis; Tuberculosis, Pulmonary

In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks.. We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days.. Mortality through 18 weeks was 37% for EFA > = 0.60 (n = 170), 36% for 0.40-0.59 (n = 182), 39% for 0.30-0.39 (n = 112), 35% for 0.20-0.29 (n = 87), and 50% for those with EFA < 0.20 CFU/mL/day (n = 187). The hazard ratio for 18-week mortality, comparing those with EFA < 0.20 to those with EFA > = 0.20, was 1.60 (95% confidence interval, 1.25, 2.04; P = .002). The lowest EFA group had lower median CD4 T-cell counts (P < .01) and lower proportion of patients with CSF pleocytosis (P < .001).. EFA is associated with all-cause mortality in cryptococcal meningitis. An EFA threshold of > = 0.20 log10 CFU/mL/day was associated with similar 18-week mortality (37%) compared to 50% mortality with EFA < 0.20. This EFA threshold may be considered a target for a surrogate endpoint. This builds upon existing studies to validate EFA as a surrogate endpoint.

Topics: Amphotericin B; Antifungal Agents; Biomarkers; Cerebrospinal Fluid; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal

We report a retroviral positive patient who presented to us with recurrent skin lesions along with intermittent, colicky periumbilical abdominal pain associated with non-projectile, postprandial vomiting. Contrast-enhanced CT (CECT) of abdomen and pelvis was suggestive of proximal jejunal obstruction. Double balloon enteroscopy done which showed extensive deep ulceration with surrounding nodular surface and friable mucosa at 60 cm from pylorus with luminal narrowing. The biopsy from this region as well as the skin lesion on the forehead grew

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Enteral Nutrition; Female; HIV Infections; HIV Seropositivity; Humans; Intestinal Obstruction; Itraconazole; Jejunostomy; Mycoses; Nutritional Status

Visceral leishmaniasis (VL) is a public health threat for several tropical countries, including Brazil. Therapy failures and relapses aggravate VL morbidity and mortality. Our study aimed at identifying predictors of relapse and thus contributes to directing therapeutic options and patient follow-up.. A nonconcurrent cohort of 571 subjects who completed successful therapy for VL in the city of Bauru, São Paulo State, Brazil, was followed for 24 months in order to identify the incidence and predictors of relapse. Extensive review of medical charts and laboratory files was conducted. Univariate and multivariable Cox regression models were used to identify predictors for the outcome of interest. A hierarchical strategy was used for variable selection in multivariable models.. Relapses occurred in 6.8% of treated subjects, after a median of 6 months (interquartile range, 4-9). In a comprehensive multivariable model, relapse was associated with: HIV-coinfection (hazard ratio [HR], 7.47; 95% confidence interval [CI], 2.58-21.55); the presence of lower limb edema (HR, 6.06; 95%CI, 1.38-26.77) and low platelet count upon admission (HR for platelet count × 1000, 0.99; 95%CI, 0.98-0.99) ; and secondary pneumonia (HR, 5.49; 95%CI, 1.49-20.18). On the other hand, therapy with Liposomal Amphotericin (as opposed to Antimoniate) was not independently associated with relapse (HR, 5.97; 95%CI, 0.63-56.29).. Besides reinforcing the impact of HIV coinfection on the outcome of VL, our study points to clinical and laboratory findings that characterize patients who were more likely to relapse. Those groups should be more closely followed, and possibly could benefit from novel therapeutic options.

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Cohort Studies; Coinfection; Edema; Female; HIV Infections; Humans; Infant; Infant, Newborn; Leishmaniasis, Visceral; Linear Models; Male; Middle Aged; Recurrence; Treatment Outcome

Clinical worsening or new manifestation of cryptococcal disease following initiation of anti-retroviral therapy (ART) in an HIV patient is a hallmark of cryptococcal immune reconstitution inflammatory syndrome (C-IRIS). However, it can be difficult to distinguish IRIS from worsening or new infection. Here, we present a case of severe C-IRIS involving multiple cerebellar, spinal, and intradural abscesses and spinal arachnoiditis 7 months after ART initiation in an AIDS patient with uncertain prior ART compliance. He had multiple prior episodes of cryptococcal meningitis with complications necessitating ventriculoperitoneal shunt placement and was on suppressive fluconazole when he developed worsening brain manifestations. He received empiric anti-cryptococcal re-induction without improvement. All cerebrospinal fluid cultures remained sterile, with negative

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anti-Inflammatory Agents; Anti-Retroviral Agents; Antifungal Agents; Arachnoid; Arachnoiditis; Biopsy; Brain; Brain Abscess; Brain Edema; Cerebellar Diseases; Empyema, Subdural; Fluconazole; Flucytosine; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Magnetic Resonance Imaging; Male; Meningitis, Cryptococcal; Middle Aged; Prednisone; Recurrence

We report a case of visceral leishmaniasis (VL)/HIV coinfection in a patient undergoing regular antiretroviral therapy and treatment with thalidomide for erythema nodosum leprosum. He presented at a health service with high fever, chills, asthenia, pale skin, lower limb edema, hepatomegaly, and splenomegaly. Visceral leishmaniasis was confirmed by direct examination, and serological and molecular tests. Serum levels of Th1/Th2 cytokines were measured. The patient began treatment with liposomal amphotericin B, with good clinical response; however, VL recurred 6 months later. Treatment was reinitiated, maintaining secondary prophylaxis with liposomal amphotericin B. The patient showed clinical improvement with important recovery of CD4

Topics: Adult; Amphotericin B; Anti-Retroviral Agents; Coinfection; Erythema Nodosum; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Recurrence; Treatment Outcome

Gastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient.. A 25-year-old Thai woman with a well-controlled HIV infection and Grave's disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital - Thailand's largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1-5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy's lesion and succumbed to her disease on day 33 of her admission.. Diagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed.

Topics: Adult; Amphotericin B; Antifungal Agents; DNA, Fungal; Fatal Outcome; Female; Gastrointestinal Tract; Graves Disease; HIV Infections; Humans; Mucormycosis; Rhizopus; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes; Syndrome; Thailand

Talaromyces marneffei is a thermally dimorphic fungus endemic in south-east Asia. It predominantly occurs in both immunocompromised and immunosuppressed patients and can be fatal if diagnosis and treatment are delayed. The clinical manifestations of T. marneffei infection are nonspecific and rapid diagnosis of T. marneffei infection remains challenging.. A 24-year-old man came to our outpatient department with the sign of common skin lesions. The lesions were cuticolor follicular papules with or without central umbilication, nodules and acne-like lesions, which are common in syringoma, steatocystoma multiplex and trichoepithelioma. A dermatoscopy examination was performed to differentiate these skin lesions. The dermatoscopic images revealed circular or quasi-circular whitish amorphous structure with a central brownish keratin plug, providing the diagnostic clues of T. marneffei infection. Therefore, a skin scrapings culture, skin biopsy and serological detection for human immunodeficiency virus (HIV) were performed. The final diagnosis of this patient was T. marneffei and HIV co-infection.. Rapid diagnosis of T. marneffei infection is clinically challenging since presenting clinical manifestations are nonspecific with significant overlap with other common conditions. This case highlights that dermatoscopy is a promising tool for the rapid diagnosis of T. marneffei infection in patients with nonspecific skin lesions, assisting clinicians to avoid delayed diagnosis or misdiagnosis.

Topics: Amphotericin B; Anti-HIV Agents; Antifungal Agents; China; Dermoscopy; HIV Infections; Humans; Itraconazole; Male; Mycology; Mycoses; Talaromyces; Young Adult

Topics: Amphotericin B; Antifungal Agents; Biopsy; Brain; Brain Neoplasms; CD4 Lymphocyte Count; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole; Magnetic Resonance Imaging; Male; Middle Aged; Polymerase Chain Reaction; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Brain; Cerebrospinal Fluid; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Pilot Projects; Sertraline; Uganda

Neuromeningeal cryptococcosis is a common and severe opportunistic fungal infection caused by the encapsulated yeast Cryptococcus neoformans. It commonly occurs in immunocompromised patients, in particular in subjects with advanced stage HIV while it is rare in immunocompetent patients. We report 40 cases of neuromeningeal cryptococcosis (NMC) diagnosed at the Mycology-Parasitology Department of the Ibn Sina hospital in Rabat, over a 21-year period (1993-2014). The diagnosis was based on nested-PCR-based assay for the detection of Cryptococcus neoformans after staining with China ink and culture on Sabouraud agar without actidione as well as on the identification of soluble cryptococcal antigens. Thirty-five patients had HIV infection, 2 patients were apparently immunocompetent and 3 were immunocompromised patients without HIV (30 men and 10 women). The average age of patients was 38 years; neuromeningeal cryptococcosis was indicative of HIV infection in 13 cases. In 22 cases it was a complication of AIDS. Twenty-seven patients of our series were treated with fluconazole monotherapy. Amphotericin B was used in 13 patients. Outcome was favorable in 13 patients (32.5%) while 3 patients had complications (7.5%). Eighteen patients died (45%) and 6 were lost to follow-up (15%). The tests to diagnose a Cryptococcus neoformans infection should be performed systematically in patients with neurological signs for early diagnosis.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Female; Fluconazole; HIV Infections; Humans; Immunocompromised Host; Male; Meningitis, Cryptococcal; Middle Aged; Morocco; Young Adult

Genetic diversity analyses were performed by sero-genotyping and multi-locus sequence typing on 252 cryptococcal isolates from 13 HIV-positive Ivorian patients followed-up for cryptococcal meningitis. Antifungal susceptibility analyses were performed according to the CLSI M27A3 method. The majority (67.8%) of the isolates belonged to the Cryptococcus neoformans (serotype A) species complex, with 93% being VNI and 7% being VNII. Cryptococcus deuterogattii VGII (serotype B) represented 16.7% of the strains, while C. neoformans/C. deneoformans VNIII (serotype AD) hybrids accounted for 15.1% of the strains. One strain (0.4%) was not identifiable. Nine different sequence types (STs 5, 6, 23, 40, 93, 207, 311, and a new ST; 555) were identified in the C. neoformans population, while the C. deuterogattii population comprised the single ST 173. The distribution of the strains showed that, while the majority of patients (9/13) harboured a single sequence type, 4 patients showed mixed infections. These patients experienced up to 4 shifts in strain content either at the species and/or ST level during their follow-up. This evolution of diversity over time led to the co-existence of up to 3 different Cryptococcus species and 4 different ST within the same individual during the course of infection. Susceptibility testing showed that all strains were susceptible to amphotericin B while 3.6% of them had a none-wild type phenotype to 5-flucytosine. Concerning fluconazole, 2.9% of C.neoformans serotype A strains and 2.4% of C. deuterogattii had also respectively a none-wild type phenotype to this molecule. All C. neoformans x C. deneoformans serotype AD hybrids had however a wild type phenotype to fluconazole. The present study showed that mixed infections exist and could be of particular importance for care outcomes. Indeed, (i) the different Cryptococcus species are known to exhibit different virulence and different susceptibility patterns to antifungal drugs and (ii) the strains genetic diversity within the samples may influence the susceptibility to antifungal treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Coinfection; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; Follow-Up Studies; Genetic Variation; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Mycological Typing Techniques

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Oral; Diagnosis, Differential; Fatal Outcome; Female; HIV Infections; Humans; Infant; Palate, Hard

Visceral leishmaniasis (VL) is a protozoan infection caused by

Topics: Adult; Amphotericin B; Atovaquone; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Middle Aged; Recurrence; Secondary Prevention; Treatment Outcome

Topics: Amphotericin B; Antiretroviral Therapy, Highly Active; Aspergillosis, Allergic Bronchopulmonary; Asthma; Hepatitis B; HIV Infections; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

Deoxycholate amphotericin B (d-AMB) has a higher rate of acute kidney injury (AKI) in comparison of lipid formulations. However, lipid amphotericin B has high costs in developing countries. The aim of this study is to assemble a model of cost-minimization of amphotericin B lipid complex (ABLC) in patients with cryptococcal meningitis. This is a retrospective study done in a cohort of patients with cryptococcal meningitis to study the economic impact of its use in developing countries. Cost analysis were based on direct cost of different antifungal therapies, chronic dialysis after discharge, and survival of patients based on a retrospective cohort of 102 patients infected with human immunodeficiency virus with confirmed diagnosis of cryptococcal meningitis. From 102 patients treated with d-AMB, 60.78% developed any grade of AKI and 10.78% developed AKI demanding hemodialysis. The percentage of patients with meningeal cryptococcosis treated with d-AMB that requeired chronic HD was 2.39%. The same model was performed for patient that would be treated with ABLC, which resulted in 0.20% of patients demanding chronic HD due to its lower nephrotoxicity. When the model is applied in 100 patients, the total costs with d-AMB would be US$ 184,543 and with ABLC would be US$ 1,640,109 in 5 years. Treatment with ABLC would be cost saving in comparison to d-AMB treatment, if early switch of treatment occurred in patients presenting AKI. The change should be as soon as possible to avoid further complication, like dialysis, which is associated with a lower life expectancy.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Cost of Illness; Costs and Cost Analysis; Deoxycholic Acid; Drug Combinations; HIV Infections; Humans; Meningitis, Cryptococcal; Renal Dialysis; Retrospective Studies

We describe a Venezuelan visitor to Japan who was diagnosed with hemophagocytic lymphohistiocytosis (HLH). The patient was also diagnosed with human immunodeficiency virus (HIV) and Epstein-Barr virus infection by the Western blot and polymerase chain reaction (PCR) tests, respectively. The cause of HLH was considered to be these two infections at first; however, the patient did not recover with antiretroviral/anti-herpes virus therapy. Thereafter, diagnosis of disseminated histoplasmosis was confirmed with an antigen detection test, culture, and PCR test of blood, urine, and bone marrow, and the patient improved gradually after the initiation of liposomal amphotericin B. This case highlights the importance of ruling out endemic mycosis as a cause of HLH even if other probable causes exist in patients from endemic areas.

Topics: Amphotericin B; Antiviral Agents; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Histoplasma; Histoplasmosis; HIV; HIV Infections; Humans; Japan; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Travel; Venezuela

Cryptococcosis is a common opportunistic infection in patients infected by Human Immunodeficiency Virus (HIV) and is the second leading cause of mortality in Acquired Immunodeficiency Syndrome (AIDS) patients worldwide. The most frequent presentation of cryptococcal infection is subacute meningitis, especially in patients with a CD4+ T Lymphocytes count below 100 cells/μL. However, in severely immunosuppressed individuals Cryptococcus neoformans can infect virtually any human organ, including the bone marrow, which is a rare presentation of cryptococcosis.. A 45-year-old HIV-infected male patient with a CD4+ T lymphocyte count of 26 cells/μL who presented to the emergency department with fever and pancytopenia. Throughout the diagnostic evaluation, the bone marrow aspirate culture yielded encapsulated yeasts in budding, identified as Cryptococcus sp. The bone marrow biopsy revealed a hypocellularity for age and absence of fibrosis. It was observed presence of loosely formed granuloma composed of multinucleated giant cells encompassing rounded yeast like organisms stained with mucicarmine, compatible with Cryptococcus sp. Then, the patient underwent a lumbar puncture to investigate meningitis, although he had no neurological symptoms and neurological examination was normal. The cerebrospinal fluid culture yielded Cryptococcus sp. The species and genotype identification step showed the infection was caused by Cryptococcus neoformans var. grubii (genotype VNI). The patient was initially treated with amphotericin B deoxycholate plus fluconazole for disseminated cryptococcosis, according to guideline recommendations. However, the patient developed acute kidney injury and the treatment was switched for fluconazole monotherapy. The symptoms disappeared completely with recovery of white blood cells and platelets counts. Cerebrospinal fluid cultures for fungi at one and two-weeks of treatment were negative.. Bone marrow infection caused by Cryptococcus neoformans is a rare presentation of cryptococcosis. The cryptococcal infection should be included for differential diagnosis in HIV-infected patients with fever and cytopenias, especially when CD4+ T lymphocytes count is below 100 cells/μL.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Fluconazole; Genotype; HIV Infections; Humans; Male; Meningitis; Middle Aged

Topics: Adult; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; HIV Infections; Humans; Leishmaniasis, Diffuse Cutaneous; Male

Cryptococcal meningitis (CM) carries a high risk of mortality with increasing incidences in immune competent hosts. Current treatments are not well tolerated, and evaluation of other treatments is needed. Fluconazole and 5-flucytosine in treating immune competent hosts have not been characterised. To evaluate the efficacy of fluconazole and 5-flucytosine in treating non-HIV- and non-transplant-associated CM. We performed a retrospective cohort study of the outcomes in immune competent patients with CM treated with fluconazole and 5-flucytosine or deoxycholate-amphotericin B and 5-flucytosine. The primary outcome was treatment response evaluated at the 12th week after initiation of antifungal therapy. A total of 43 and 47 patients received amphotericin B deoxycholate and 5-flucytosine or fluconazole and 5-flucytosine, respectively. A total of 38 (88.4%) patients cannot tolerate recommended doses of amphotericin B deoxycholate and 5-flucytosine (patients needed dose reduction during the treatment). Patients given fluconazole and 5-flucytosine had higher baseline cryptococcal burdens (median 3632 versus 900 cryptococci/mL, P = 0.008). No significant differences were seen in cryptococcus clearance (74.4% vs 70.2%, P = 0.814), treatment time (39 days, 20-69 days vs 21 days, 7-63 days, P = 0.107) and successful response (including complete and partial responses) rates (69.7% vs 72.3%, P = 0.820). Fluconazole and 5-flucytosine treatment had lower total adverse events (19.1% vs 90.7%, P < 0.001). Fluconazole and 5-flucytosine had relatively high efficacy with few adverse events in treating CM. Fluconazole and 5-flucytosine therapy is promising in patients that do not tolerate or are not suited for amphotericin B deoxycholate treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcus; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Immunocompetence; Male; Meningitis, Cryptococcal; Middle Aged; Organ Transplantation; Retrospective Studies; Treatment Outcome

The aim of this study was to assess the biotope of the Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast, and clarify the possible epidemiological relationship between environmental and clinical strains.. Samples from Eucalyptus camaldulensis (n=136), Mangifera indica (n=13) and pigeon droppings (n=518) were collected from different sites close to the living environment of Ivorian HIV patients with cryptococcosis (n=10, 50 clinical strains). Clinical and environmental strains were characterized by molecular serotyping and genotyping [RFLP analysis of the URA5 gene, (GACA)4, (GTG)5 and M13 PCR fingerprinting] and compared.Results/Key findings. Environmental strains were recovered only from the pigeon droppings. In vitro susceptibility profiles showed that all strains were susceptible to fluconazole, flucytosine and amphotericin B. All environmental strains consisted of C. neoformans (A, AFLP1/VNI), whereas clinical strains included C. neoformans (A, AFLP1/VNI), C. neoformans x Cryptococcus deneoformans hybrids (AD, AFLP3/VNIII) and Cryptococcus deuterogattii (B, AFLP6/VGII). Two patients were co-infected with both C. neoformans and C. neoformans x C. deneoformans hybrids. We noticed a low genetic diversity among the environmental samples compared to the high diversity of the clinical samples. Some clinical strains were genetically more similar to environmental strains than to other clinical strains, including those from the same patient.. These results provide new information on the ecology and epidemiology of the C. neoformans/C. gattii species complex in Ivory Coast.

Topics: Adult; Amphotericin B; Antifungal Agents; Chloramphenicol; Cote d'Ivoire; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; DNA, Fungal; Environmental Microbiology; Female; Fluconazole; Flucytosine; Genotype; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Mycological Typing Techniques; Prospective Studies; Serotyping; Young Adult

Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Bone Marrow; Communicable Diseases, Imported; Cote d'Ivoire; Fatal Outcome; Female; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole; Microscopy; Respiratory Distress Syndrome; Tunisia

Talaromyces marneffei (T. marneffei) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to investigate the susceptibility of 189 T. marneffei clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase. The MICs of anidulafungin, micafungin, caspofungin, posaconazole, itraconazole, voriconazole, fluconazole, and amphotericin B were 2 to > 8 μg/ml, >8 μg/ml, 2 to > 8 μg/ml, ≤ 0.008 to 0.06 μg/ml, ≤ 0.015 to 0.03 μg/ml, ≤ 0.008 to 0.06 μg/ml, 1 to 32 μg/ml, and ≤ 0.12 to 1 μg/ml, respectively. The MICs of all echinocandins were very high, while the MICs of posaconazole, itraconazole, and voriconazole, as well as amphotericin B were comparatively low. Notably, fluconazole was found to have a higher MIC than other azoles, and exhibited particularly weak activity against some isolates with MICs over 8 μg/ml. Our data in vitro support the use of amphotericin B, itraconazole, voriconazole, and posaconazole in management of talaromycosis and suggest potential resistance to fluconazole.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Echinocandins; HIV Infections; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mycoses; Reagent Kits, Diagnostic; Talaromyces; Voriconazole

The Brazilian municipality of Rondonópolis, Mato Grosso State, represents an important visceral leishmaniasis (VL) endemic area. This study described epidemiological and clinical aspects of the occurrence, VL/HIV coinfection and lethality related to VL in Rondonópolis. Data from autochthonous cases reported between 2011 and 2016 were obtained from official information systems. During this period, 81 autochthonous cases were reported, with decreasing incidence through 2016. Contrastingly, the lethality rate was 8.6% overall, but varied widely, reaching a peak (20%) in 2016. Almost 10% of patients had VL/HIVcoinfection. The occurrence of VL prevailed among men (56.8%), brown-skinned (49.4%), urban residents (92.6%), aged 0-4 years (33.3%). Housewives or retired (29.6%) were the most affected occupational groups. Lower age was the main difference among the total VL cases and those who were coinfected or died. Clinically, fever, weakness and splenomegaly were more frequent among all VL cases and VL/HIV coinfected individuals. Bacterial infections (p=0.001) and bleeding (p<0.001) were associated with death due to VL. Pentavalent antimonial and liposomal amphotericin B were the first choices for treatment among all VL cases (71.6%) and those who died (71.4%), respectively. VL/HIV patients were equally treated with both drugs. These findings may support control measures and demonstrate the need for further investigations.

Topics: Adolescent; Adult; Age Factors; Amphotericin B; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Coinfection; Female; HIV Infections; Humans; Incidence; Infant; Infant, Newborn; Leishmaniasis, Visceral; Male; Middle Aged; Retrospective Studies; Sex Factors; Socioeconomic Factors; Young Adult

Topics: Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Choroiditis; Cryptococcosis; Cryptococcus gattii; Drug Therapy, Combination; Eye Diseases; Eye Infections, Fungal; Fluconazole; Flucytosine; HIV Infections; Humans; Infusions, Intravenous; Male; Meningitis, Cryptococcal; Retinitis; Tomography, Optical Coherence; Vitreous Body

Epidemiological cut-off values (ECVs) have been used as a tool to detect the acquisition of resistance mechanisms to antifungal drugs. In this context, the objective of this study was to determine the ECVs for classic antifungals against Histoplasma capsulatum var. capsulatum isolates from human immunodeficiency virus (HIV)-infected patients with a diagnosis of disseminated histoplasmosis. First, minimum inhibitory concentrations (MICs) for amphotericin B (AmB), itraconazole (ITR), fluconazole (FLU), voriconazole (VCZ) and caspofungin (CAS) were determined against 138 H. capsulatum isolates in the filamentous form by the broth microdilution method; antifungal ECVs were then calculated. MIC ranges were 0.0078-1 µg/mL for AmB, 0.0005-0.0625 µg/mL for ITR, 2 to ≥256 µg/mL for FLU, 0.0078-1 µg/mL for VCZ and ≤0.0156 to ≥32 µg/mL for CAS. The obtained ECVs were 0.5, 0.0313, 128, 0.5 and 16 µg/mL for AmB, ITR, FLU, VCZ and CAS, respectively. The percentage of wild-type isolates was 96.4% for AmB, 98.6% for ITR and 99.3% for FLU, VCZ and CAS. Although these results do not cover all phylogenetic species of H. capsulatum, they bring important information on strains from Brazil. In addition, the assessed isolates were from HIV-positive patients, which may not reflect the antifungal ECVs against isolates from immunocompetent individuals or from other sources. Finally, this study pioneers the initiative of establishing ECVs for five antifungal agents against H. capsulatum var. capsulatum, providing a criterion for the interpretation of susceptibility results as well as a monitoring strategy for the emergence of antifungal resistance.

Topics: Amphotericin B; Antifungal Agents; Brazil; Caspofungin; Echinocandins; Fluconazole; Histoplasma; Histoplasmosis; HIV; HIV Infections; Humans; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Retrospective Studies; Voriconazole

Cryptococcus neoformans is a ubiquitous encapsulated environmental yeast that can cause severe central nervous system disease, primarily in immune compromised hosts. In patients with AIDS, the spectrum of cryptococcal central nervous system disease includes meningitis, cystic lesions, and mass-like cryptococcomas. We report a fatal case of meningitis and cerebritis caused by C. neoformans in an AIDS patient refractory to multiple courses of liposomal amphotericin B despite immune recovery with antiretroviral therapy. This case highlights ongoing diagnostic and therapeutic challenges in the face of treatment failure for cryptococcal meningitis and reinforces the need for improved treatment approaches.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antiretroviral Therapy, Highly Active; Brain; Cryptococcus neoformans; Fatal Outcome; Fever; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Meningitis, Cryptococcal; Middle Aged

North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients.. We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6-88.6); death rate 12.7% (95% CI, 8.5-18.5) and parasitological failure rate 3.5% (95% CI, 1.6-7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001).. Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Coinfection; Drug Therapy, Combination; Ethiopia; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Phosphorylcholine; Retrospective Studies; Treatment Outcome; Young Adult

The number of new cases of emerging fungal infections has increased considerably in recent years, mainly due to the large number of immunocompromised individuals. The objective of this study was to evaluate the susceptibility of emerging fungi to fluconazole, itraconazole and amphotericin B by disk diffusion method. In 2015, 82 emerging fungi were evaluated in IPB-LACEN/RS and 13 (15.8%) were resistant: 10/52 were from superficial mycoses and 3/30 from systemic mycoses. The data from the study point to the need for permanent vigilance regarding the careful evaluation in the prescription and clinical and laboratory follow-up of patients affected by fungal infections.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Drug Resistance, Fungal; Female; Fluconazole; Fungi; HIV Infections; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Mycoses

Oropharyngeal candidiasis is the commonest mucocutaneous infection in HIV-positive individuals. Herein, samples were taken from oral cavities of 150 HIV-infected patients and cultured on Sabouraud-dextrose agar; 89 (59·3%) of 150 patients had positive culture for Candida and presented clinical sign of classical oral candidiasis. Totally, 102 morphologically distinct colonies were isolated from Candida positive cultures and subsequently identified by polymerase chain reaction and sequencing assay, presenting the following frequency: 54 C. albicans (52·9%), 16 C. dubliniensis (15·7%), 12 C. tropicalis (11·8%), 9 C. glabrata (8·8%), 7 C. kefyr (6·9%) and 4 C. africana (3·9%). Additionally, multiple Candida species were co-isolated from 13·5% (12/89) patients. Regarding the antifungal susceptibility test, which was performed by CLSI protocol (M27-A3/M27-S3), all Candida isolates were susceptible to amphotericin B and caspofungin, while some of them were resistant to fluconazole (17·6%; 16 C. albicans, 1 C. dubliniensis and 1 C. glabrata), itraconazole (16·7%; 15 C. albicans, 1 C. dubliniensis and 1 C. tropicalis) and voriconazole (5·9%; 5 C. albicans and 1 C. tropicalis). Collectively, our findings reinforce the urgent necessity to find new therapeutic agents to treat oral candidiasis in HIV-positive patients, especially due to the high incidence of azole-resistant Candida strains and the increased frequency of non-C. albicans species.. The Candida species recovered from oral cavity of 150 Iranian HIV/AIDS patients and their antifungal susceptibility profiles were reported. Candida albicans was the commonest Candida species, followed by C. dubliniensis, C. tropicalis, C. glabrata, C. kefyr and C. africana. All Candida isolates were susceptible to amphotericin B and caspofungin, while resistance to azoles was detected. The growing drug-resistance profile reported in clinical isolates of C. albicans and non-C. albicans strains is a serious problem in hospitals worldwide. Consequently, the suitable antifungal choice to treat the HIV/AIDS population with oral candidiasis needs to be rethought and new therapeutic options must urgently arise.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis, Oral; Caspofungin; Drug Resistance, Multiple, Fungal; Echinocandins; Female; Fluconazole; HIV Infections; Humans; Incidence; Iran; Itraconazole; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Mouth; Prevalence; Young Adult

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antigens, Fungal; Child; Cryptococcus; Deoxycholic Acid; Drug Combinations; Fluconazole; Flucytosine; HIV Infections; Humans; Maintenance Chemotherapy; Meningitis, Cryptococcal; Practice Guidelines as Topic; World Health Organization

The first-line combination therapy for HIV-associated cryptococcal meningitis (CM), a condition of high mortality particularly in the first two weeks of treatment, consists of amphotericin B plus flucytosine (5-FC). Given that 5-FC remains unavailable in many countries, the knowledge of factors influencing mycological clearance in patients treated with second-line therapy could contribute to effective management.. To determine the factors associated with the clearance of Cryptococcus sp. from the cerebrospinal fluid by the second week of effective antifungal therapy (early mycological clearance) in HIV-associated CM.. Retrospective cohort study based on secondary data corresponding to HIV-associated CM cases hospitalized at a tertiary health care center in Lima, Peru where 5-FC remains unavailable. Risk factors associated with early mycological clearance were analyzed by generalized linear regression models.. From January 2000 to December 2013, 234 individuals were discharged with a diagnosis of HIV-associated CM; in 215 we retrieved the required data. The inpatient mortality was 20% (43/215), 15 of them in the first two weeks of treatment. In the final model (157 cases), adjusted for age, previous episode of CM, ART use, type of antifungal treatment, raised intracranial pressure, frequency of therapeutic lumbar punctures, baseline fungal burden and treatment period, the factors associated with early mycological clearance were: Amphotericin B deoxycholate plus fluconazole as combination therapy (RR, 1.56; 95% CI, 1.14-2.14); severe baseline intracranial pressure (≥35 cm H2O) (RR, 0.57; 95% CI, 0.33-0.99); and baseline fungal burden over 4.5 log10 CFU/mL (RR, 0.61 95% CI: 0.39-0.95).. In a setting without access to first-line therapy for CM, the combination therapy with amphotericin B deoxycholate plus fluconazole was positively associated with early mycological clearance, while high fungal burden and severe baseline intracranial pressure were negatively associated, and thus related to failure.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Colony Count, Microbial; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; Humans; Immunocompromised Host; Male; Meningitis, Cryptococcal; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Diagnosis, Differential; Female; Histoplasmosis; HIV Infections; Humans; Itraconazole

To characterize the clinical and epidemiological profiles of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (LAmB) and to identify prognostic factors for death from VL in 2008-2012 in the state of Minas Gerais, Brazil.. A historical cohort study was conducted using data obtained from treatment requests forms, Brazilian Notifiable Disease Information System and the Mortality Information System. Case-fatality rates of patients with VL treated with LAmB were compared with patients treated with other therapies. Logistic regression analysis was used to identify prognostic factors for death.. The overall case-fatality rate of the 577 patients treated with LAmB was 19.4%. Prognostic factors for death from VL were age between 35 and 49 years (OR 2.7; 95% CI 1.3-5.4) and above 50 years (OR 2.6; 95% CI 1.3-4.9), jaundice (OR 2.2; 95% CI 1.2-3.7), kidney disease (OR 2.8; 95% CI 1.6-4.9), presence of other infections (OR 2.4; 95% CI 1.5-4.1), edema (OR 2.0; 95% CI 1.1-3.4), platelet count below 50.000/mm3 (OR 3.6; 95% CI 2.1-6.0), AST higher than 100 U/L (OR 2.2; 95% CI 1.3-3.8), and assistance in non-specialized institutions (OR 1.9; 95% CI 1.0-3.5).. Case-fatality rates were higher than that observed among patients with VL treated with other therapies. Identification of prognostic factors of death from VL may allow early diagnosis of patients prone to such outcome and prompt an expeditious and appropriate management of VL to reduce fatality rates.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Cohort Studies; Comorbidity; Edema; Female; Heart Diseases; HIV Infections; Humans; Infant; Jaundice; Leishmaniasis, Visceral; Liver Failure; Male; Middle Aged; Prognosis; Renal Insufficiency; Risk Factors; Young Adult

Topics: Amphotericin B; Antifungal Agents; Brain; Cryptococcus gattii; Cryptococcus neoformans; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Early Diagnosis; Fluconazole; HIV Infections; Humans; Immunocompromised Host; Meningitis, Cryptococcal; Patient Care Management

We describe four cases of histoplasmosis indigenous to Himachal Pradesh (India) that will be of considerable public health interest. A 48-year-old human immunodeficiency virus (HIV)-negative man with cervical and mediastinal lymphadenopathy, hepatosplenomegaly, adrenal mass, and bone marrow involvement was treated as disseminated tuberculosis without benefit. Progressive disseminated histoplasmosis was diagnosed from the fungus in smears from adrenal mass. Another 37-year-old HIV-positive man was on treatment of suspected pulmonary tuberculosis. He developed numerous erythema nodosum leprosum-like mucocutanous lesions accompanied by fever, generalized lymphadenopathy, and weight loss. Pulmonary histoplasmosis with cutaneous dissemination was diagnosed when skin lesions showed the fungus in smears, histopathology, and mycologic culture. Both were successfully treated with amphotericin B/itraconazole. Third patient, a 46-year-old HIV-negative man, had oropharyngeal lesions, cervical lymphadenopathy, intermittent fever, hepatosplenomegaly, and deteriorating general health. Progressive disseminated oropharyngeal histoplasmosis was diagnosed from the fungus in smears and mycologic cultures from oropharyngeal lesions and cervical lymph node aspirates. He died despite initiating treatment with oral itraconazole. Another 32-year-old man 3 months after roadside trauma developed a large ulcer with exuberant granulation tissue over left thigh without evidence of immunosuppression/systemic involvement. He was treated successfully with surgical excision of ulcer under amphotericin B/itraconazole coverage as primary cutaneous histoplasmosis confirmed pathologically and mycologically. A clinical suspicion remains paramount for early diagnosis of histoplasmosis particularly in a nonendemic area. Most importantly, with such diverse clinical presentation and therapeutic outcome selection of an appropriate and customized treatment schedule is a discretion the treating clinicians need to make.

Topics: Adult; Amphotericin B; Antifungal Agents; Fatal Outcome; Fever; Histoplasma; Histoplasmosis; HIV Infections; Humans; India; Itraconazole; Lung; Lung Diseases, Fungal; Male; Middle Aged; Treatment Outcome

Cryptococcus spp. is a rare cause of ventriculoperitoneal shunt (VPS) infection, with a variable clinical presentation. Diagnosis and treatment of this entity are challenging.. A cryptococcal VPS infection occurred in a human immunodeficiency virus-infected patient with an excellent immunovirologic status, with an abdominal mass as the only clinical sign at presentation. Microbiologic diagnosis was confirmed when Cryptococcus neoformans was isolated in 4 cerebrospinal fluid samples on different days. The patient was treated with dual antifungal therapy (liposomal amphotericin B plus flucytosine). The VPS was initially externalized and then removed. At 12-month follow-up, the patient remained asymptomatic, and no replacement VPS was required.. This is the first reported case of cryptococcal VPS infection in a patient with human immunodeficiency virus infection. Clinical outcome was excellent after dual antifungal therapy plus device withdrawal. Diagnosis and treatment of this entity remain a challenge for clinicians.

Topics: Abdominal Abscess; Adult; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Catheter-Related Infections; Device Removal; Flucytosine; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Ventriculoperitoneal Shunt

AbstractSeveral case reports of autochthonous leishmaniasis in Thailand have been published since 1996. Most of the previous cases presented with visceral leishmaniasis (VL) and were mostly reported in southern part of Thailand. Recently, it has been evident that

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Antiviral Agents; Coinfection; Dermis; DNA, Ribosomal Spacer; Female; HIV; HIV Infections; Humans; Itraconazole; Leishmania; Leishmaniasis, Diffuse Cutaneous; Protozoan Proteins; RNA Polymerase II; Sequence Analysis, DNA; Thailand

AbstractReported herein is the first case of

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Coinfection; Cytochromes b; Fatal Outcome; HIV; HIV Infections; Humans; Leishmania guyanensis; Leishmaniasis, Diffuse Cutaneous; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Protozoan Proteins; Sequence Analysis, DNA; Shock, Septic; Skin; Treatment Failure

In Brazil, the rates of mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) decreased from 20% to 1-2% in some regions. However, the country contains 90% of individuals infected with visceral leishmaniasis (VL) in Latin America, and the west region of São Paulo state faces an alarming expansion of the disease. We describe the epidemiological aspects of the expanding infection of VL and a case report of an HIV-VL-co-infected child from the west region of São Paulo state. The patient was an AIDS-C3 with low levels of CD4, high viral load, severe diarrhea, oral and perineal candidiasis, severe thrombocytopenia, and protein-caloric malnourishment. She evolved with sepsis, renal and cardiac failure. An rK rapid diagnosis test, indirect fluorescent antibody test (IFAT), and bone marrow aspirate were performed for VL. Her symptoms improved significantly after liposomal amphotericin B administration. From the 45 municipalities that compose the Regional Health Department of Presidente Prudente, Lutzomyia longipalpis vectors were found in 58% of them. VL infected dogs were found in 33% of those municipalities, infected dogs and humans were found in 29%, 20% are starting and 33% of the municipalities are preparing VL investigation. It is likely, in this patient, that VL advanced the clinical progression of the HIV disease and the development of AIDS severity. Supported by favorable conditions, the region becomes a new frontier of VL in Brazil.

Topics: Amphotericin B; Animals; Antiparasitic Agents; Brazil; Child; Coinfection; Dog Diseases; Dogs; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Psychodidae; Sepsis; Treatment Outcome

Cryptococcal meningitis is uncommon in children, particularly in infants. A 2-day-old boy was admitted with signs suggestive of meningitis. Lumbar puncture confirmed meningitis and cryptococcal infection (cryptococcal antigen and Indian ink stain-positive). His mother was HIV-negative. This is thought to be the youngest case of cryptococcal meningitis to be reported. Cryptococcal infection should be considered in children of all ages with meningitis where there is possible immunodeficiency or failure to respond to initial treatment with antibiotics.

Topics: Amphotericin B; Cryptococcus neoformans; HIV Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis, Cryptococcal

The effect of tenofovir and amphotericin coadministration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4 weeks after diagnosis in Ugandans undergoing cryptococcal meningitis therapy and classified as not receiving antiretroviral therapy (ART), receiving nontenofovir ART or receiving tenofovir-based ART. Longitudinal creatinine changes and grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks after diagnosis, creatinine was 0.25 mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin coadministration did not increase the risk of kidney dysfunction.

Topics: Adult; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Creatinine; Deoxycholic Acid; Drug Combinations; Female; Glomerular Filtration Rate; HIV Infections; Humans; Kidney; Male; Meningitis, Cryptococcal; Middle Aged; Tenofovir

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p = 0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p = 0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004-0.262, p = 0.02], impaired consciousness (OR 5.09, 95 % CI 1.477-17.522, p = 0.01), and hospitalization length (OR 0.98, 95 % CI 0.977-0.999, p = 0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Blood Glucose; Child; Child, Preschool; Chronic Disease; Consciousness Disorders; Cryptococcus; Deoxycholic Acid; Drug Combinations; Female; Glucose; HIV Infections; Hospitalization; Humans; Infant; Infectious Encephalitis; Male; Meningitis, Cryptococcal; Meningoencephalitis; Middle Aged; Retrospective Studies; Risk Factors; Young Adult

Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml(-1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Argentina; Cryptococcosis; Cryptococcus neoformans; Drug Resistance, Fungal; Epidemiologic Methods; Fluconazole; Flucytosine; HIV Infections; Humans; Itraconazole; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Triazoles; Voriconazole

Opportunistic infections have been reported infrequently in primary HIV infection. We report a case of cryptococcemia in primary HIV infection. To our knowledge there has not been such a case reported. Our case highlights the need for clinicians to be wary of other opportunistic infections, including cryptococcosis, in primary HIV infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diabetes Mellitus; Fluconazole; Hepatitis B; HIV Infections; Humans; Liver Function Tests; Male; Syphilis; Treatment Outcome

To describe an unusual clinical presentation of visceral leishmaniasis affecting the colon.. We report the case of an HIV-positive patient with visceral leishmaniasis. We describe the clinical case, the procedures performed, the treatment provided and the patient's evolution. A comparative table of previously reported similar cases is shown.. Visceral leishmaniasis with intestinal involvement is an uncommon process. Nevertheless, this possibility should be taken into consideration in the differential diagnosis of immunosuppressed patients with symptoms of diarrhea, as a favorable prognosis depends on early diagnosis and appropriate treatment.

Topics: Amphotericin B; Antiprotozoal Agents; Colonic Diseases; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Histoplasma; Histoplasmosis; HIV Infections; Humans; Treatment Outcome; Uganda

We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities.. Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 -February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly.. Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524).. AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; HIV Infections; Hospitalization; Humans; Male; Meningitis, Cryptococcal; Prevalence; Retrospective Studies; South Africa

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus; Fluconazole; HIV Infections; Humans

To report the cases of neuromeningeal cryptococcosis and to describe the clinical, paraclinical, therapeutic and outcomes of patients.. Retrospective study of 43 patients infected with HIV admitted from January first 2010 to June 30th 2015 in the infectious disease unit of UHC Ibn Rochd, for neuromeningeal cryptococcus.. Neuromeningeal cryptococcosis remains a severe opportunistic infection in HIV patients with a heavy mortality rate.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Female; HIV Infections; HIV-1; Hospitalization; Hospitals, University; Humans; Incidence; Male; Meningitis, Cryptococcal; Middle Aged; Morocco; Retrospective Studies; Survival Analysis

Cryptococcus neoformans is an important opportunistic pathogen that causes serious mortality and morbidity in AIDS patients. Although its incidence has decreased with proper antiretroviral treatment (ART), it is still a major concern in areas with low socioeconomic HIV endemic countries with poor sources of therapy. In our country, pediatric HIV infection and so, HIV-related opportunistic infections are very rare. In order to pay attention to this unusual collaboration; herein, we presented a pediatric case who was diagnosed with HIV and disseminated cryptococcus infection concomitantly. A 6.5-year-old previously healthy girl has admitted to our hospital with the complaints of prolonged fever, cough and hemoptysis. On her physical examination she had oral candidiasis, generalized lymphadenopathy and hepatosplenomegaly. Laboratory findings were as follows; white blood cell count: 3170 µL (neutrophil: 2720 µL, lymphocyte: 366 µL), hemoglobin level: 7.8 gr/dl, hematocrit: 25.5% platelets: 170.000 µL, CRP: 15.2 mg/L and serum IgG level: 1865 mg/dl. Her anti-HIV test yielde,d positive result and confirmed by Western blot assay, together with a high viral load (HIV-RNA: 3.442.000 copies/ml). She was started ART (lamivudine, zidovudine and lopinavir/ritonavir combination) with the diagnosis of stage 3 HIV infection (AIDS). Posteroanterior chest radiograph showed mediastinal extension and nodular parenchyma. Since the patient was suspected to have pulmonary tuberculosis based on the clinical and radiological findings, empirical antituberculosis therapy was started. Because of the insistance of fever, three different blood specimens, bone marrow and gastric aspirates were collected for culture, in which all of them yielded C.neoformans growth. She was then diagnosed as disseminated cryptococcosis and treated with liposomal amphotericin B and fluconazole successfully. Although pediatric HIV infection is usually diagnosed secondary to maternal disease, it can rarely be presented later in life with opportunistic infections. In the case of unusual infectious diseases, in addition to primary immune deficiency syndromes, HIV infection should also be kept in mind. Herein, we discussed a pediatric case with two rare infectious agents reported in our country and wanted to focus on secondary immune deficiency related with pediatric HIV infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Child; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; Humans; Tuberculosis, Pulmonary

Visceral leishmaniasis (VL) is a zooanthroponosis affecting both rural and periurban areas, and can also spread into urban areas. VL has emerged in many countries in the world, presenting new cases in new countries of occurrence. Thus, studies concerning epidemiological aspects in different world regions are very meaningful.. With this purpose, this study analyzed 89 cases of VL, treated between June 2006 and June 2014 at Eduardo de Menezes Hospital (HEM), a Reference Center of Infectious Diseases situated in Belo Horizonte, in Minas Gerais state, Brazil.. According to the results, it was observed that males are mostly infected (84%/n=75) and the most affected age range was 20-49 years old (83%/n=74). The treatment liposomal amphotericin B (33%/n=29) was mostly used. Recurrences were more frequent in patients treated with Glucantime® (17%/n=9). No side effects were reported among the 29 patients treated with liposomal amphotericin B. On the other hand, there were 23 cases related to the occurrence of acute renal failure (ARF) and the use of conventional amphotericin B, both when it was administered alone or in combination with other drugs. Additionally, we observed a close relationship between the VL and HIV infection, observing a coinfection rate of 28.1% (n=25).. From the survey data, it was possible to conclude that the majority of VL patient treated at HEM is male, classified as brown racial group, economically active, and may be drug addicts, chronic alcoholics and/or smokers. They may present some Non-communicable diseases (NCD), such as hypertension, diabetes mellitus, dyslipidemia and/or obesity and, predominantly present a great chance of being a carrier of the Human Immunodeficiency Virus, associated or not with tuberculosis. As symptoms, these patients possibly will present hepatosplenomegaly, fever and pronounced weight loss.

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Coinfection; Female; HIV Infections; Humans; Infant; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence; Retrospective Studies; Sex Distribution; Young Adult

Visceral leishmaniasis (VL) is a protozoan disease that is invariably fatal if left untreated. The disease is found in 70 countries with incidence of 0.2 - 0.4 million cases. The mainstay of treatment in resource limited countries like Ethiopia is antimonials, while use of liposomal amphotericin B is reserved for treatment of complicated VL cases. The aim of this study was to assess the safety and efficacy of liposomal amphotericin B in HIV negative VL patients diagnosed with complications.. A retrospective chart review was conducted involving records of patients admitted between January 2009 and December 2014. Baseline sociodemographic, clinical, and treatment outcome data were collected. The doses of liposomal amphotericin B and adverse events related to treatment were retrieved. Categorical and continuous variables respectively were analyzed by Chi-square and Mann-Whitney U tests. A p-value of less than 0.05 was considered statistically significant.. A total of 147 patients with severe VL were treated with liposomal amphotericin B in total dose ranges of 20 mg/kg to 35 mg/kg. In the overall treatment outcome analysis, initial cure (30 days after start of treatment) was observed in 128 (87.1 %), treatment failures in 10 (6.8 %), interruptions in 2(1.4 %) and deaths in 7 (4.8 %) patients. Initial cure rate at high dose (24-35 mg/kg total dose) was 96.7 % (59/61) versus 80.2 % (69/86) at lower doses (<24 mg/kg); which was significantly higher (P < 0.01), OR = 4.56: 95 %, Confidence Interval (CI) = 1.17 - 20.78). Ten cases (11.8 %) of treatment failure occurred in the low dose treatment group. The most common adverse events (AEs) were hypokalemia in 39 cases (26.5 %) and infusion related reactions in 16 (10.9 %). The frequency of hypokalemia and infusion related reactions were not significantly different between the low and high dose liposomal amphotericin B.. In HIV negative complicated VL patients, high dose of liposomal amphotericin B was found to have high cure rate at the end of treatment. The appropriate dose for better efficacy needs to be determined. Monitoring serum potassium level during treatment with liposomal amphotericin B should be an essential component of the clinical management of VL.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Drug Administration Schedule; Ethiopia; Female; Follow-Up Studies; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Retrospective Studies; Treatment Outcome

We report 7 HIV-infected children with cryptococcosis. Median age and CD4 counts were 9.3 years and 12 cells/mm, respectively. Two children died early. Of 4 children requiring prolonged amphotericin B and fluconazole at a dosage above 12 mg/kg/d, 3 presented with meningitis and 1 with fever. Immune reconstitution inflammatory syndrome contributed to morbidity through exacerbations at the primary site and elsewhere.

Topics: Adolescent; Age Distribution; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Child; Cryptococcosis; Female; Fluconazole; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Retrospective Studies

Visceral leishmaniasis (VL) in north-west Ethiopia is causing an overwhelming case load among adult migrant workers that masked the disease burden in children. This study describes the clinical profile and explores comorbidities in paediatric VL patients.. A prospective study at two hospitals in this region (Gondar and Humera) was conducted in a year period, 2011-2012. The clinical manifestations and comorbidities such as malnutrition, intestinal parasitosis and vitamin D deficiency and HIV infection were assessed, and treatment outcomes noted.. A total of 122 children with VL were detected during the study period with median age of 8.5 years (IQR 5-12 years); 23% were under 5 years. Eighty-five (69.7%) cases were male. The clinical manifestations were similar to the adult patients. High rates of malnutrition, intestinal parasitosis (47.5%) and hypovitaminosis D (56.4%) were detected. The proportion of stunting and wasting was 63% and 22.2% in children aged under five years, and 50.5% and 75.9% in 5-year and older children, respectively, using WHO standard growth curves. Only one child had HIV infection. In 95% of the cases, sodium stibogluconate (20 mg/kg/day for 30 days) was used for treatment. The treatment success rate at end of therapy was 98.3%, but the definitive outcome at 6 months could not be determined because of a high loss to follow-up (80.2%).. While HIV co-infection was rare, malnutrition, intestinal parasitosis and vitamin D deficiency were frequent indicating the need for further research on their role in the pathophysiology. Meanwhile, systematic assessment and management of malnutrition and intestinal parasitosis in VL programmes is recommended.

Topics: Amebicides; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Ethiopia; Female; HIV Infections; Humans; Intestinal Diseases, Parasitic; Leishmaniasis, Visceral; Male; Malnutrition; Paromomycin; Prospective Studies; Treatment Outcome; Vitamin D Deficiency

There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen.. This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART).. 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse.. In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Amphotericin B; Coinfection; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; India; Leishmaniasis, Visceral; Male; Middle Aged; Phosphorylcholine; Recurrence; Retrospective Studies; Risk Factors; Treatment Failure; Treatment Outcome; Young Adult

Immune reconstitution inflammatory syndrome (IRIS) is an immuno-pathologic reaction to quiescent opportunistic microbial pathogens upon restoration of underlying immune defects. Here we report a Honduran patient with HIV/AIDS who developed a facial rash worsening on antiretroviral therapy and increasing CD4 count. Culture and PCR analysis from the skin biopsy identified Leishmania panamensis, which was effectively treated with long-term liposomal amphotericin B. This is the first report of mucocutaneous leishmaniasis (MCL)-associated IRIS due to L. panamensis.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antiprotozoal Agents; Female; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Leishmania; Leishmaniasis, Mucocutaneous; Polymerase Chain Reaction

Topics: Adult; AIDS Serodiagnosis; Amphotericin B; Antifungal Agents; Fungemia; Histoplasma; Histoplasmosis; HIV Infections; Humans; Male; Skin

The aim of this study was to report the patient profile and treatment outcomes, including relapses, of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (AmBisome) in Gedaref, Sudan.. AmBisome was offered to two groups of patients: primary VL patients with specific criteria (age ≤2 or ≥45 years, advanced clinical disease, pregnancy, HIV co-infection and contraindications for antimonials) and VL relapses. AmBisome was given at a total dose of 30 mg/kg, over 10 days. Slow responders received up to 50 mg/kg. Treatment failure was confirmed parasitologically. Standardised treatment outcomes were assessed.. Between March 2010 and June 2012, a total of 281 (74%) patients with primary VL and 98 (26%) patients with VL relapses received AmBisome (54% male, median age = 11 years, interquartile range 2-30). End-of-treatment outcomes for primary VL were 260 (92%) initial cure including three (1%) slow responders, three (1%) treatment failures, 14 (5%) deaths and four (1%) unknown outcomes. Outcomes for VL relapses were 92 (94%) initial cure with five (5%) slow responders, four (4%) treatment failures, one (1%) death and one (1%) unknown outcome. At 6 months, there were 19 (7%) relapses amongst primary VL and 10 (10%) VL relapses had a new relapse. Loss to follow-up in both groups was 38%. None of the deaths that occurred during the study period was attributed to AmBisome.. AmBisome appears to be effective for initial cure of VL and the drug seems safe, but is expensive (400 USD/treatment). Sustained mechanisms to allow improved access of this expensive drug particularly in East Africa are urgently needed. Relapses and losses to follow-up require specific investigation.

Topics: Adolescent; Adult; Amphotericin B; Child; Child, Preschool; Female; HIV Infections; Humans; Infant; Leishmania donovani; Leishmaniasis, Visceral; Lost to Follow-Up; Male; Middle Aged; Neglected Diseases; Pregnancy; Pregnancy Complications, Parasitic; Recurrence; Sudan; Treatment Failure; Treatment Outcome; Trypanocidal Agents; Young Adult

The polyene antifungal agent Amphotericin B exhibits potent and broad spectrum fungicidal activity. However, high nephrotoxicity can hinder its administration in resource poor settings. Quantification of early fungicidal activity in studies of HIV patients with cryptococcosis demonstrate that 5-Fluorocytosine therapy in combination with Amphotericin B results in faster clearance than with Amphotericin B alone. In vitro synergy between the two drugs has also been reported but the mechanism by which 5-Fluorocytosine synergizes with Amphotericin B has not been delineated. In this study we set out to investigate the effect of genetic mutation or pharmacologic repression of de novo pyrimidine and purine biosynthesis pathways on the Amphotericin B susceptibility of Cryptococcus neoformans. We demonstrate that a ura- derivative of wild type Cryptococcus neoformans strain H99 is hypersensitive to Amphotericin B. This sensitivity is remediated by re-introduction of a wild type URA5 gene, but not by addition of exogenous uracil to supplement the auxotrophy. Repression of guanine biosynthesis by treatment with the inosine monophosphate dehydrogenase inhibitor, mycophenolic acid, was synergistic with Amphotericin B as determined by checkerboard analysis. As in Cryptococcus neoformans, a ura(-) derivative of Candida albicans was also hypersensitive to Amphotericin B, and treatment of Candida albicans with mycophenolic acid was likewise synergistic with Amphotericin B. In contrast, neither mycophenolic acid nor 5-FC had an effect on the Amphotericin B susceptibility of Aspergillus fumigatus. These studies suggest that pharmacological targeting of nucleotide biosynthesis pathways has potential to lower the effective dose of Amphotericin B for both C. neoformans and C. albicans. Given the requirement of nucleotide and nucleotide sugars for growth and pathogenesis of Cryptococcus neoformans, disrupting nucleotide metabolic pathways might thus be an effective mechanism for the development of novel antifungal drugs.

Topics: Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Cryptococcosis; Cryptococcus neoformans; Flucytosine; HIV Infections; Humans; Microbial Sensitivity Tests; Mycophenolic Acid; Nucleotides

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV-infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological work-up showed that this is the first report of R. glutinis isolation from our institute.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; HIV Infections; Humans; Male; Meningitis; Middle Aged; Retrospective Studies; Rhodotorula

Use of the PLEX-ID system can lead to a rapid molecular diagnosis in microbiology. To illustrate the clinical implications of this new diagnostic tool, we present the case of a 46-year-old patient admitted with severe respiratory failure and septic shock. Cryptococcal pneumonia was diagnosed by Fungi-Fluor™ staining of the bronchoalveolar lavage (BAL) and the patient tested positive for HIV. Unfortunately, he died 12h after admission despite intensive care support and treatment with broad-spectrum antibiotics, amphotericin B, and flucytosine. Retrospective use of the PLEX-ID on the BAL, bronchial aspirate, and blood yielded Cryptococcus neoformans in all fluids tested. Rapid molecular diagnosis with PLEX-ID, especially when performed on the blood of septic patients, may reduce the time to adequate treatment and limit the number of diagnostic procedures needed.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bronchoalveolar Lavage Fluid; Coinfection; Cryptococcosis; Cryptococcus neoformans; Fatal Outcome; Female; Flucytosine; HIV Infections; Humans; Male; Middle Aged; Nucleic Acid Amplification Techniques; Pneumonia

In Western French Guiana, there was a dramatic increase in HIV prevalence between 1990 and 2000. The present study describes the causes of fever among HIV patients hospitalized in the medical ward of the only hospital in the western part of French Guiana. A retrospective descriptive study was conducted between 1 January 2008 and 30 June 2010 in the department of medicine of Saint Laurent du Maroni Hospital. The main characteristics of 67 patients having presented with fever in the first 48 hours of hospitalization were described. Among patients with CD4 <200/mm(3)the main febrile opportunistic infection was disseminated histoplasmosis (41.1%). Among patients with CD4 counts <50/mm(3)and fever without focal points 85.7% had disseminated histoplasmosis. Three patients died and all had disseminated histoplasmosis. Disseminated histoplasmosis is the most common febrile opportunistic infection in western French Guiana. Primary prophylaxis with itraconazole among immunocompromised patients seems warranted.

Topics: Adolescent; Adult; Age Distribution; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; CD4 Lymphocyte Count; Coinfection; Female; Fever; French Guiana; Histoplasma; Histoplasmosis; HIV Infections; Hospitalization; Humans; Immunocompromised Host; Itraconazole; Male; Middle Aged; Prevalence; Retrospective Studies; Sex Distribution; Weight Loss; Young Adult

Topics: Adult; Amphotericin B; Anorexia; Antifungal Agents; CD4 Lymphocyte Count; Emergencies; Endemic Diseases; Guyana; Hallucinations; Histoplasma; Histoplasmosis; HIV Infections; Humans; Incidental Findings; Itraconazole; Leukocytes; Male

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy, Fine-Needle; Botswana; Cryptococcus neoformans; Female; Fluconazole; HIV Infections; Humans; Lymph Nodes; Lymphadenitis; Neck; Treatment Outcome

Penicillium marneffei is a thermally dimorphic pathogenic fungus that causes systemic infection similar to disseminated cryptococcosis. P. marneffei is endemic in Southeast Asia, usually infecting HIV-infected individuals; infection of HIV-negative individuals is extremely rare. Here, we describe a disseminated P. marneffei infection within an osteolytic lesion in an HIV-negative patient. A 40-year-old Chinese woman presented with intermittent fever, generalized lymphadenopathy, and a skin rash. Following a sternum biopsy, the patient was diagnosed with P. marneffei infection. An emission computed tomography bone scan revealed the presence of increased radioactivity in the left clavicle and sternum, indicative of an osteolytic lesion. In addition to reporting this very rare case, we also present a brief review of the literature, highlighting the differences in clinical manifestations between HIV-positive and HIV-negative patients infected with P. marneffei as it applies to our case.

Topics: Adult; Amphotericin B; Antifungal Agents; Asia, Southeastern; Asian People; Female; HIV Infections; Humans; Mycoses; Osteolysis; Penicillium; Tomography, Emission-Computed

Visceral Leishmaniasis (VL) is an opportunistic infection amongst HIV-infected people in several endemic countries, and the clinical management of this co-infection poses several challenges. Here we describe a co-infected patient in India who failed to respond to miltefosine monotherapy and subsequently relapsed following two further (different) regimens of liposomal amphotericin B. He was then successfully treated with a combination of 30 mg/kg liposomal amphotericin B and 14 days of 100mg/day oral miltefosine.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Coinfection; HIV Infections; Humans; India; Leishmaniasis, Visceral; Male; Phosphorylcholine; Recurrence; Treatment Outcome

Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.. Intravenous AmBisome (20-25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4-10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4-51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7-14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64-66% reduced risk of mortality and 75% reduced risk of relapse.. This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-HIV Agents; CD4 Lymphocyte Count; Child; Cohort Studies; Coinfection; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Treatment Outcome

Secretion of hydrolytic enzymes such as hemolysin is considered an important virulence attribute of the opportunistic pathogenic fungus Candida. It is known that Candida spp. isolated from HIV-infected patients produce copious hemolysins. As common antifungal agents may perturb the production of extracellular enzymes, we evaluated the effect of three antifungals nystatin, amphotericin B and fluconazole on the hemolytic activity of Candida albicans and Candida tropicalis isolates from HIV-infected individuals. The impact of antimycotics on hemolytic activity was assessed by a previously described in vitro plate assay, after exposing ten isolates each of C. albicans and C. tropicalis recovered from HIV-infected individuals to sub-minimum inhibitory concentrations (sub-MIC) of nystatin, amphotericin B and fluconazole. All Candida isolates showed a significant reduction in hemolytic activity. The reduction was highest for amphotericin B-exposed C. albicans and C. tropicalis followed by nystatin and fluconazole. The effect of antimycotics was more pronounced on the hemolytic activity of C. tropicalis compared to that of C. albicans. Commonly used antifungal agents significantly suppress hemolysin activity of Candida species. This implies that the antifungals, in addition to their lethality, may modulate key virulence attributes of the yeast. The clinical relevance of this phenomenon in HIV disease and other similar pathologies remains to be determined.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candida tropicalis; Candidiasis, Oral; Fluconazole; Hemolysin Proteins; HIV Infections; Humans; Microbiological Techniques; Nystatin; Virulence Factors

Topics: Adult; Amphotericin B; Antifungal Agents; Asia, Southeastern; Bone Marrow Examination; CD4 Lymphocyte Count; Diagnosis, Differential; Drug Administration Routes; Female; HIV; HIV Infections; Humans; Itraconazole; Mycoses; Penicillium; Travel; Treatment Outcome; Viral Load

Topics: Adult; Amphotericin B; Antifungal Agents; Blood Specimen Collection; CD4 Lymphocyte Count; Diagnosis, Differential; Erythrocytes, Abnormal; Fungemia; Histoplasma; Histoplasmosis; HIV Infections; Humans; Itraconazole; Male; Viral Load

The goal of this study was to determine the degree to which the persistence of cryptococcosis, overall 1-year mortality, and 1-year mortality due to cryptococcosis were influenced by initial antifungal treatment regimen in a cohort of adults with cryptococcosis treated at a tertiary care medical center. Risk factors, underlying conditions, treatment, and mortality information were obtained for 204 adults with cryptococcosis from Duke University Medical Center (DUMC) from 1996 to 2009. Adjusted risk ratios (RR) for persistence and hazard ratios (HR) for mortality were estimated for each exposure. The all-cause mortality rate among patients with nonsevere disease (20%) was similar to that in the group with disease (26%). However, the rate of cryptococcosis-attributable mortality with nonsevere disease (5%) was much lower than with severe disease (20%). Flucytosine exposure was associated with a lower overall mortality rate (HR, 0.4; 95% confidence interval [CI], 0.2 to 0.9) and attributable mortality rate (HR, 0.5; 95% CI, 0.2 to 1.2). Receiving a nonrecommended antifungal regimen was associated with a higher relative risk of persistent infection at 4 weeks (RR, 1.9; 95% CI, 0.9 to 4.3), and the rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher than that of those receiving recommended dosing (HR, 2.3; 95% CI, 1.0 to 5.0). Thus, the 2010 Infectious Diseases Society of America (IDSA) guidelines are supported by this retrospective review as a best-practice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between all-cause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Administration Schedule; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Incidence; Male; Practice Guidelines as Topic; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal

Molecular methods have been proposed as an alternative tool for the diagnosis of visceral leishmaniasis (VL), but no data are available regarding use for monitoring clinical outcome. A prospective cohort study of human immunodeficiency virus-(HIV) and VL-coinfected patients was conducted in a university-affiliated hospital in Barcelona, Spain. Leishmania parasite load was monitored using a real-time polymerase chain reaction (PCR) at baseline and every 3 months. Cutoff values for PCR were determined using receiver operating characteristic (ROC) curves. Overall, 37 episodes were analyzed, and 25 of these episodes were considered as relapsing episodes. A significant decrease of parasite load measured 3 months after treatment could predict the clinical evolution of VL. A parasite load over 0.9 parasites/mL measured 12 months after treatment could predicts relapse with a sensitivity of 100% and a specificity of 90.9%. Monitoring parasite load by an ultrasensitive quantitative Leishmania PCR is useful to predict the risk of relapse after a VL episode in HIV-infected patients.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; CD4 Lymphocyte Count; Coinfection; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Prospective Studies; Real-Time Polymerase Chain Reaction; Recurrence; ROC Curve

A 50-year-old man with HIV infection (first diagnosed > 20 years ago) presented at our hospital with fulminant oral mucositis. Antiretroviral therapy (tenofovir, emtricitabine, raltegravir) had been started 2 months ago. Previously he had no opportunistic infections and no other pre-existing illnesses. He had not travelled outside Europe but stayed in Spain for several weeks during summer.. Physical examination revealed swelling of the lips and severe ulcerative mucositis of the gums and pharynx. The patient complained of painful swallowing. The blood-chemistry showed no abnormalities. The microscopical analysis of a smear and a biopsy of the buccal mucosa revealed amastigotes of leishmania. By means of PCR technique, Leishmania donovani complex was specified.. The patient was treated with liposomal amphotericin B (1 mg/kg) for 21 days. Because of the immunosuppression he was put on maintenance therapy afterwards (liposomal amphotericin B every 3 weeks). However, 4 months later there was a clinical relapse of the mucositis and a new cultural and PCR detection of leishmania in a buccal biopsy. After another course of 21 days with liposomal amphotericin B (3 mg/kg) and miltefosine (150 mg/d), the mucositis subsided. Therapy with liposomal amphotericin B (3 mg/kg single dose every 3 weeks) has since been maintained. The antiretroviral therapy was changed meanwhile to lamivudin, abacavir and raltegravir because of kidney failure with elevated urea and creatinine. The patient has been clinically stable ever since without any other HIV-related problems. The latest CD4 count was 456/µl and the HIV load 340 copies/ml.. Leishmaniasis is a severe infection in HIV-positive patients. Clinical manifestations can be atypical in immunosuppressed patients and the treatment is complicated with HIV coinfection. This is also due to a lifelong persistence of the parasite with potential reactivation especially in patients with suppressed CD4 cells. Therefore maintenance therapy after standard therapy of leishmaniasis is mandatory at least for a CD4 count below 350/µl. Especially in HIV patients with a leishmaniasis relapse lifelong maintenance therapy should be considered.

Topics: Amphotericin B; Anti-Retroviral Agents; Antiprotozoal Agents; HIV Infections; Humans; Leishmaniasis; Male; Middle Aged; Stomatitis; Treatment Outcome

Topics: Adult; Amphotericin B; Anti-HIV Agents; Female; Histamine Antagonists; HIV Infections; Humans; Leishmaniasis, Visceral; Stevens-Johnson Syndrome

Topics: Adult; Amphotericin B; Anti-HIV Agents; Antiprotozoal Agents; Cytomegalovirus Retinitis; Drug Resistance, Viral; HIV; HIV Infections; Honduras; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male; Toxoplasmosis, Cerebral

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Biopsy; Dermatomycoses; Histoplasma; Histoplasmosis; HIV Infections; Humans; Male; Middle Aged; Skin Ulcer; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fatal Outcome; Fever; Flucytosine; HIV Infections; Humans; Male; Multiple Organ Failure; Respiratory Distress Syndrome

Histoplasmosis of the central nervous system (CNS) is seen in 10% to 20% of patients with disseminated histoplasmosis and/or in association with immunocompromised patients. Meningitis, arachnoiditis, and hydrocephalus are the most common clinical manifestations of CNS histoplasmosis. Patients with CNS histoplasmosis present similarly to other infectious etiologies, and confirmatory diagnosis is important in the management of these patients. However, diagnosis of CNS histoplasmosis can be difficult, and sometimes performing a parenchymal biopsy is necessary to confirm the diagnosis.. We describe the case of a 41-year-old man with HIV/AIDS who presented with the signs, symptoms, and radiologic evidence of basal meningitis and hydrocephalus. Cerebrospinal fluid (CSF) analysis from multiple lumbar punctures was negative. The patient underwent a neuroendoscopic procedure with diagnostic and therapeutic goals. Internal CSF diversion (endoscopic third ventriculostomy) and biopsy of the floor of the third ventricle and subarachnoid space were performed; surgical biopsies identified noncaseating granulomas, and ventricular CSF was positive for Histoplasmosis antibodies. The patient was treated with liposomal amphotericin B and itraconazole. The patient had resolution of his symptoms immediately after surgery, and 1-month follow-up computed tomography of the head demonstrated resolution of the hydrocephalus. At the last follow-up 12 months postoperatively, the patient has not required insertion of a ventriculoperitoneal shunt.. Clinicians should maintain a high index of suspicion for fungal basal meningitis in patients with AIDS and hydrocephalus. With nondiagnostic lumbar CSF sampling, neuroendoscopy can be considered as an alternative for diagnosis and treatment of basal meningitis and hydrocephalus.

Topics: Adult; Amphotericin B; Antibodies, Fungal; Antifungal Agents; Arachnoiditis; Biopsy; Central Nervous System Fungal Infections; Cerebral Ventricles; Histoplasmosis; HIV Infections; Humans; Hydrocephalus; Itraconazole; Male; Neuroendoscopy; Neurologic Examination; Neurosurgical Procedures; Paresis; Spinal Puncture; Subarachnoid Space; Tomography, X-Ray Computed; Ventriculostomy

Renal involvement is a rare complication in HIV-1-infected patients leading to various pathologies and clinical symptoms. In addition to the classic HIV-1-associated nephropathy with collapsing-type focal segmental glomerulosclerosis and characteristic tubulocystic changes, which is more common in Afro-American than in Caucasian HIV-1 patients, immune complex GNs such as membranous GN and membranoproliferative GN are particularly common renal manifestations. Besides HIV-1 itself, a number of opportunistic infections may cause renal disease in HIV-1-infected patients. In this study, we report an unusual case of HIV-1 infection with a severe renal manifestation of systemic leishmaniasis that developed years after repeated visits to Mediterranean countries. The case presents several remarkable clinical, pathologic, and therapeutic aspects that may be important for daily clinical practice.

Topics: Amphotericin B; Anti-HIV Agents; Biopsy, Needle; Follow-Up Studies; HIV Infections; Humans; Immunohistochemistry; Kidney; Kidney Function Tests; Leishmaniasis; Male; Middle Aged; Nephrotic Syndrome; Risk Assessment; Treatment Outcome

Topics: Amphotericin B; Antiprotozoal Agents; Bone Marrow; HIV; HIV Infections; Humans; Immunophenotyping; Kidney; Leishmania infantum; Leishmaniasis, Visceral; Liver; Lymphoma, B-Cell, Marginal Zone; Macrophages; Male; Middle Aged; Multimodal Imaging; Phosphorylcholine; Positron-Emission Tomography; Splenic Neoplasms; Tomography, X-Ray Computed

A 43-year-old HIV-positive Ethiopian immigrant presented with persistent diarrhoea, hepatosplenomegaly and pancytopaenia. Visceral leishmaniasis was diagnosed by multiple gastrointestinal tract biopsies. Blood polymerase chain reaction (PCR) was positive for Leishmania donovani. Despite highly active antiretroviral therapy (HAART) and multiple courses of antileishmanial treatments, including liposomal amphotericin and sodium stibogluconate, the patient had multiple relapses. CD4 counts remained at 40-60 cells/µL although viral loads were undetectable. Splenectomy resulted in resolution of the patient's pancytopaenia and in rising CD4 levels, which enabled a long-lasting remission.

Topics: Adult; Amphotericin B; Anti-HIV Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Blood; CD4 Lymphocyte Count; DNA, Protozoan; Emigrants and Immigrants; HIV; HIV Infections; Humans; Israel; Leishmania donovani; Leishmaniasis, Visceral; Male; Polymerase Chain Reaction; Recurrence; Splenectomy; Treatment Outcome; Viral Load

Cryptococcus species are the most common causative agents of fungal meningitis. Different populations may show different clinical manifestations and outcomes. In this retrospective study, we investigated these differences in patients with and without HIV infection.. From 1995 to 2009, we collected data from HIV-infected or HIV-uninfected patients aged 18 years or over who had cryptococcal meningitis (CM) in a medical center in Taiwan. We reviewed and analyzed their demographic data, clinical manifestations, therapeutic strategies and outcomes.. Among the 72 patients with CM, 19 HIV-infected patients were predominantly younger males, and all of them had AIDS status when CM was diagnosed. In contrast, the 53 HIV-uninfected patients were mostly older males with underlying diseases. The time from initial symptoms to diagnosis was shorter in HIV-infected patients (median 10 vs. 18 days, p = 0.048). The HIV-infected patients presented with less pleocytosis (p = 0.003) and lower protein levels in the cerebrospinal fluid (CSF), but a higher proportion had positive results for cryptococci in the CSF (90% vs. 60%, p = 0.02) and blood (53% vs. 21%, p = 0.009) cultures. Surgical drains and repeated lumbar punctures for the management of increased intracranial pressure were performed in 47% of the HIV-infected patients and 38% of the HIV-uninfected patients. A lower mortality rate was observed in the HIV-infected patients (p = 0.038). On multivariate analysis, initial CD4 count ≤20/mm(3) was an indicator of death or relapse in HIV-infected patients. In the HIV-uninfected group, the initial high cryptococcal antigen titer in the CSF (≥1:512) and hydrocephalus were related to unsatisfactory outcomes.. In addition to well-known differences, we found a lower mortality in HIV-infected patients than in HIV-uninfected patients. Cryptococci and inflammation in the central nervous system may play important roles in the pathogenesis of CM. Low intensity of inflammation and effective surgical CSF drains for increased intracranial pressure and cryptococci removal may contribute to lower mortality in HIV-infected patients.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; CD4 Lymphocyte Count; Cryptococcus; Female; Flucytosine; Follow-Up Studies; HIV; HIV Infections; Humans; Hydrocephalus; Intracranial Hypertension; Male; Meningitis, Cryptococcal; Retrospective Studies; Spinal Puncture; Taiwan; Treatment Outcome

Penicillium marneffei may cause life-threatening systemic fungal infection in immune-compromised patients and it is endemic in Southeast Asia. A 39-yr-old HIV-infected male, living in Laos, presented with fever, cough, and facial vesiculopapular lesions, which had been apparent for two weeks. CT scans showed bilateral micronodules on both lungs; Pneumocystis jirovecii was identified by bronchoscopic biopsy. Despite trimethoprim-sulfamethoxazole and anti-tuberculosis medications, the lung lesions progressed and the facial lesions revealed central umbilications. Biopsy of the skin lesions confirmed disseminated penicilliosis, with the culture showing P. marneffei hyphae and spores. The P. marneffei was identified by rRNA PCR. A review of the bronchoscopic biopsy indicated penicilliosis. The patient completely recovered after being prescribed amphotericin-B and receiving antiretroviral therapy. This is the first case of penicilliosis in a Korean HIV-infected patient. It is necessary to consider P. marneffei when immunocompromised patients, with a history of visits to endemic areas, reveal respiratory disease.

Topics: Adult; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Bronchoscopy; Dermatomycoses; HIV Infections; Humans; Immunocompromised Host; Laos; Lung Diseases; Male; Penicillium; Pneumocystis carinii; Tomography, X-Ray Computed

At present, few data are available on the prevalence and antifungal susceptibility of Candida parapsilosis complex isolates from HIV-infected individuals. The C. parapsilosis complex comprises three species, C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. Fifteen of 318 Candida isolates were identified as members of the C. parapsilosis complex by PCR and restriction fragment length polymorphism (RFLP). The prevalence of C. parapsilosis complex isolates was 4.7 %, 2.2 % being identified as C. parapsilosis sensu stricto and 2.5 % as C. metapsilosis, while no C. orthopsilosis was isolated. This is believed to be the first study that has identified isolates of C. metapsilosis obtained from the oral cavity of HIV-infected individuals. Antifungal susceptibility tests indicated that all the isolates were susceptible to amphotericin B (AMB), fluconazole (FLC), ketoconazole (KTC), itraconazole (ITC), voriconazole (VRC) and caspofungin (CASPO). Although isolates of C. parapsilosis sensu stricto and C. metapsilosis were susceptible to FLC, isolates of C. metapsilosis showed a tendency for higher MICs (≥1.0 µg ml(-1)). Based upon the frequency of candidiasis and the fact that certain isolates of the C. parapsilosis complex respond differently to FLC therapy, our data may be of therapeutic relevance with respect to susceptibility and potential resistance to specific antifungal agents. Our data suggest that C. metapsilosis can be a human commensal; its importance as a pathogen has yet to be confirmed.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Oral; Caspofungin; Echinocandins; Female; Fluconazole; HIV Infections; Humans; Lipopeptides; Male; Microbial Sensitivity Tests; Mouth; Mycological Typing Techniques; Polymorphism, Restriction Fragment Length; Pyrimidines; Triazoles; Voriconazole

We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and 9 months, respectively, of standard treatment. Both patients were treated successfully with a salvage regimen consisting of the combination of liposomal amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant interferon γ-1b (200 μg thrice weekly). Voriconazole was administered at an increased dose (5 mg/kg, twice daily) to overcome interactions with co-administered ritonavir. In both patients, resolution of clinical signs and symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after 10 weeks of salvage therapy. No major side effects were encountered. At the end of treatment, both patients were placed on maintenance therapy with oral fluconazole; no recurrence has been observed after 4 years of follow-up.

Topics: Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; HIV Infections; Humans; Interferon-gamma; Male; Meningitis, Cryptococcal; Middle Aged; Pyrimidines; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Cryptococcus neoformans; Disease Management; Fatal Outcome; Fluconazole; Health Resources; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Meningitis, Cryptococcal; Recurrence; Uganda

An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.

Topics: Abdomen; Amphotericin B; Antifungal Agents; Antigens, Fungal; Brain; Child; Cryptococcosis; Cryptococcus neoformans; Fluconazole; Histocytochemistry; HIV Infections; Humans; Lymphadenitis; Male; Microscopy; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

Nigeria is a West African country of more than 150 million persons with the second highest case of HIV/AIDS infected patients in the world. The species spectrum of oral yeast colonization and the susceptibility to a wide range of antifungal agents is poorly understood in Nigeria especially in the south east, south south, and the northern axis. This study evaluates the species spectrum of oral colonization by Candida species in HIV-infected patients in Nigeria and the in vitro susceptibility pattern of the Candida isolates to a broad range of antifungal agents.. Two hundred oropharyngeal swabs from HIV-infected patients and 100 age-matched healthy controls were screened for yeast isolates using standard procedures and confirmed by the analytical profile index 20C along with other biochemical tests. In vitro susceptibility testing of the yeast isolates to antifungals were performed using the broth microdilution method protocol recommended by the Clinical Laboratory Scientific Institute.. Of 200 patients screened, 120 (60%) were colonized by yeasts. C albicans was the dominating species in both groups with 54 (45%) isolated from HIV subjects. The non-albicans Candida species accounted for 55% with C tropicalis 22 (18.3%) showing the highest frequency. We observed that 11.7% of all yeasts isolates were resistant to fluconazole, 8.3% to flucytosine, 7.5% to itraconazole, and 1.7% to voriconazole. All isolates were susceptible to amphotericin B and most of them demonstrated very low voriconazole minimal inhibitory concentrations. Apart from C albicans, C tropicalis and C parapsilosis isolates were also recovered from apparently healthy control subjects.. Although C albicans continues to be the dominant Candida species in oral Candida carriage of HIV-infected patients in Nigeria, the nonalbicans Candida species are increasing. Furthermore, the finding of resistant isolates in our study emphasizes the need for antifungal susceptibility testing whenever antifungal treatment is desired especially in HIV-infected subjects.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida; Candidiasis, Oral; Drug Resistance, Fungal; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Mycological Typing Techniques; Nigeria; Pyrimidines; Triazoles; Voriconazole

To explore linkage to and retention in HIV care after an episode of cryptococcal meningitis (CM) in rural South Africa. Design. A retrospective case series of adult individuals (> or = 16 years old) with laboratory-confirmed CM from January - December 2007 at Hlabisa Hospital--a district hospital in northern KwaZulu-Natal.. Inpatient mortality and associated risk factors were analysed. The proportion alive and on antiretroviral therapy (ART) at 2 years was determined by linkage to the HIV treatment programme.. One hundred and four individuals were identified with laboratory diagnosis of CM; 74/104 (71.2%) with complete records were included in the analysis. Inpatient mortality was high (40.5%) and was significantly associated with reduced conscious level (aHR 3.09, 95% CI 1.30 - 7.33) and absence of headache (aHR 0.33 for headache, 95% CI 0.13 - 0.87). Only 8 individuals (10.8% of all study subjects) were alive and receiving ART 2 years after the CM episode.. Long-term outcomes of CM are poor in routine practice. Interventions to strengthen linkage to HIV treatment and care and continuation of secondary fluconazole prophylaxis are critical.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Prognosis; Rural Population; South Africa; Treatment Outcome

Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India.. The study included all patients with newly diagnosed VL-HIV coinfection and initiating treatment with liposomal amphotericin B (20-25 mg/kg in 4-15 days) between July 2007 and September 2010. Kaplan-Meier estimates of the cumulative incidence of death/treatment failure were calculated.. Fifty-five patients were included (83.6% male; median age, 35 years; 62% migrant laborers; median follow-up, 1 year). The median CD4 cell count at VL diagnosis was 66 cells/μL (interquartile range, 38-112). Twenty-seven patients (49.1%) presented with VL relapse of VL. The overall tolerance of liposomal amphotericin B was excellent, with no interrupted treatment. Survival by 1 and 2 years after VL treatment was estimated at 85.5%. No patients had initial treatment failure. The probabilities of VL relapse were 0%, 8.1%, and 26.5% at 0.5, 1, and 2 years after VL treatment, respectively; relapse rates were similar for primary VL and VL relapse. CD4 counts <200 cells/μL at 6 months after cART initiation were predictive of subsequent relapse. The mean CD4 cell counts at 6 and 24 months after cART initiation were 187 and 261 cells/μL, respectively. The rate for retention in HIV care was 83.6%.. Good long-term survival and retention rates were obtained for VL-HIV-coinfected patients treated with liposomal amphotericin B and cART. Although the initial VL treatment response was excellent, VL relapse within 2 years remained frequent.

Topics: Adolescent; Adult; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; India; Leishmaniasis, Visceral; Male; Recurrence; Survival Analysis; Treatment Failure; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Dermatomycoses; Histoplasma; Histoplasmosis; HIV Infections; Humans; Immunocompromised Host; Male; Shock, Septic; Silver Staining

Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV).. We used clinical data obtained from January 2007 to January 2009 to compare outcomes by HIV status and VL episode (primary vs relapse) and to identify risk factors for treatment failure among patients treated with AmBisome monotherapy at a total dose of 30 mg/kg in 6 doses on alternate days, a higher dose than recommended by the World Health Organization (20 mg/kg).. Among 94 HIV-negative severely ill VL patients, 93% had initial cure and 6% died. Among 195 HIV-positive patients (116 primary, 79 relapse VL), 60% had initial cure, 7% died, and 32% were parasitological failures. AmBisome was less effective in the 79 HIV-positive VL relapse patients (38% initial cure, 5% mortality, 56% parasitological failure) than in the 116 HIV-positive primary VL patients (74% initial cure, 8% mortality, 16% parasitological failure). Sodium stibogluconate (SSG) rescue treatment increased the overall cure rate among all HIV-positive VL patients from 60% to 83%, but 16% (9 of 59) of rescue treatment patients died, mainly due to SSG toxicity.. High-dose AmBisome for VL is safe and effective in severely ill HIV-negative patients, and safe but less effective in HIV-positive patients. Combining AmBisome with another drug may enhance its effectiveness in HIV-positive VL patients. SSG should be avoided for treatment of VL in HIV-positive patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antiprotozoal Agents; Child; Child, Preschool; Ethiopia; Female; HIV Infections; Humans; Infant; Leishmaniasis, Visceral; Male; Middle Aged; Pregnancy; Risk Factors; Treatment Failure; Treatment Outcome; Young Adult

The aim of this study was to identify baseline prognostic factors for poor clinical outcome of HIV-associated cryptococcal meningitis. We conducted a trial in Thailand and the USA comparing low- and high-dose concomitant use of amphotericin B and fluconazole for HIV-associated cryptococcal meningitis to amphotericin B followed by fluconazole. Subjects who were either alive and cerebrospinal fluid (CSF) culture-positive or dead were considered to have a poor outcome. At day 14, baseline characteristics associated with poor outcome included: low weight, high CSF cryptococcal antigen (CrAg) titre and low CSF white blood cell (WBC) count. At day 70, the associated baseline characteristics included: CSF CrAg titre >1:1024 and low Karnofsky performance status. Overall, consistent with published findings, low weight, high CSF CrAg titre and low CSF WBC counts at baseline were predictors for poor clinical outcome. In addition, we found that low Karnofsky performance status was predictive of poor outcome. Prompt management with appropriate antifungal therapy for this particular group of patients may improve the outcomes.

Topics: Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Prognosis; Survival Analysis; Thailand; Treatment Outcome; United States

We measured fungicidal activity of continuous infusion of amphotericin B deoxycholate plus 5'flucytosine using quantitative cultures of cerebrospinal fluid (CSF) obtained from lumbar punctures of human immunodeficiency virus (HIV)-infected patients with neurocryptococcosis during 14 days of treatment. Glomerular renal function was preserved in all patients. Mycological efficacy with progressive reduction in CSF cryptococcal colony-forming units was comparable to standard 4-h infusion of amphotericin B.

Topics: Adult; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; Colony Count, Microbial; Cryptococcus; Deoxycholic Acid; Drug Combinations; Female; Flucytosine; HIV Infections; Humans; Infusions, Intravenous; Male; Meningitis, Cryptococcal; Microbial Viability; Middle Aged; Treatment Outcome; Young Adult

Gastric leishmaniasis was diagnosed in a 43-year-old HIV infected patient by histopathology as an accidental diagnostic finding. Leishmania HIV co-infections have increasingly been reported recently as a result of intensive travelling and an increase in geographical extension. Nevertheless, Leishmania gastritis is a rare disease which can occur without clinical symptoms and in the absence of endoscopic abnormalities. In this case microscopic detection of the pathogen in macrophages of the gastric mucosa resulted in the correct diagnosis.

Topics: Adult; Amebicides; Amphotericin B; Female; Gastric Mucosa; Gastritis; HIV Infections; Humans; Leishmania; Leishmaniasis

Since the advent of combination antiretroviral therapy, the incidence of opportunistic infections has declined and the life expectancy of HIV-infected people has significantly increased. However, opportunistic infections, including fungal diseases, remain a leading cause of hospitalizations and mortality in HIV-infected people. With the availability of several new antiretroviral and antifungal agents, drug-drug interactions emerge as a potential safety concern.. Relevant literature was identified using a Medline search of articles published up to March 2010 and a review of conference abstracts. Search terms included HIV, antifungal agents and drug interactions. Original papers and relevant citations were considered for this review.. Readers will gain an understanding of the pharmacokinetic properties of antiretroviral and antifungal agents, and insight into significant drug-drug interactions which may require dosage adjustments or a change in therapy.. Azole antifungal drugs, with the exception of fluconazole, pose the greatest risk of two-way interactions with antiretroviral drugs through CYP450 enzymes effects. Limited studies suggest the risk of interactions between antiretroviral drugs and echinocandins is much lower. The combination of tenofovir and amphotericin B should be used with caution and close monitoring of renal function is required.

Topics: Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Azoles; Biotransformation; Cytochrome P-450 Enzyme System; Drug Interactions; Echinocandins; HIV Infections; Humans; Kidney; Microsomes, Liver; Mycoses

Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.

Topics: Acquired Immunodeficiency Syndrome; Aged; Amphotericin B; Fatal Outcome; HIV Infections; Humans; Kidney; Leishmania infantum; Leishmaniasis, Visceral; Male; Nephritis, Interstitial; Spain; Tunisia

A 5-week-old infant presented with a fever, and was diagnosed with congenital human immunodeficiency virus and histoplasmosis. Both infections were likely transmitted vertically. The child was effectively treated with antifungal medications and highly active antiretroviral therapy. This represents the first case of delayed presentation of vertically transmitted histoplasmosis, and the first case in a nonendemic area.

Topics: Amphotericin B; Antifungal Agents; Female; Guatemala; Histoplasma; Histoplasmosis; HIV Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Itraconazole; Mothers

Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome.. A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome.. 57 patients were studied. Cryptococcus neoformans var grubii molecular type VN1 caused 70% of infections; C. gattii accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age > or = 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for C. neoformans var grubii compared with C. gattii (p < 0.001 and p = 0.01 respectively).. In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to C. neoformans var grubii. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cryptococcus gattii; Cryptococcus neoformans; Female; Flucytosine; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Treatment Outcome; Vietnam; Young Adult

CIyptococcal meningitis is an important opportunistic funimgal infection that became very common after the era of HIV infection.. To determine the magnitude of Clyptococcal meningitis and study the clinical pattern among inpatients with HV infection at Gondar Hospital.. A descriptive study was done among ELISA confirmed admitted HIV patients. Clinically suspected cases of meningitis underwent lumbar puncture and cerebrospinal fluid analysis. The clinical profile and outcomes of the confirmed Cryptococcal meningitis cases were described.. Among 375 HIV serology positive patients 31 were confirmed to have Cryptococcal meningitis. Their median age was 29 years (range 16-64); and 22 were males. The major manifestation at presentation included headache and fever each in 90% malaise (65%), stiffness of the neck (48%), altered Mentation (32%) and nausea and vomiting (32%), photophobia (23%) and seizure (3.6%). Median duration of illness was 16 days; ranging from 1-40 days. Temperature was above 38.4 degreees C in 80%. Meningial signs were observed in 32% altered Mentation was noted in 29% and focal neurologic deficit in 19% Cerebrospinal fluid examination revealed visually increased pressure (measured opening pressure >200 mmH2O in six patients) in 81% glucose < 50 mg/dl (50-70 mg/ dl) in 55% Protein >40 mg/dl (15-40 mg/dl) in 35% leukocytes count < 20/mm3 (poor prognostic sign) in 58% Indian ink staining detected encapsulated yeasts in 71% C. neoformans was cultivated in 90% of sample. Highest case fatality rate of the disease was observed during the pre HAART era.. Cryptococcal Meningitis is common among patients with immune-suppression. It could be the initial manifestation of HIV infection and should be suspected in any potential HIV infected patient with neurological symptoms especially headache and fever. As it has highest case fatality rate, early diagnosis and prompt therapy is strongly recommended Better treatment options like boosting their immunity with HAART should also be investigated

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cerebrospinal Fluid; Cryptococcus neoformans; Dose-Response Relationship, Drug; Ethiopia; Female; HIV Infections; HIV-1; Humans; Incidence; Male; Meningitis, Cryptococcal; Middle Aged; Retrospective Studies; Young Adult

Disseminated penicilliosis-an AIDS-indicator disease in Southeast Asian countries -but not Japan- is a systemic fungal infection caused by Penicillium marneffei. A 30-year-old HIV-positive Japanese man visiting Southeast Asia three months before admission and reporting fever, general fatigue, and enlarged lymph nodes lasting over one month was admitted for detailed tests. Blood culture and fine-needle aspiration lymph node biopsy a led to a diagnosis of disseminated penicillioisis, later cured by several anti-fungal agents. Caution is thus recommended regarding the possibility of this disease, given the large number of travelers visiting overseas, geographical proximity to Southeast Asia, and increasing numbers of HIV patients in Japan.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Asian People; HIV Infections; Humans; Male; Mycoses; Penicillium; Thailand; Travel

Candida oral flora from 52 Brazilian HIV-infected children was characterized while they received antiviral monotherapy therapy and subsequently, HAART with the use of protease inhibitor. There was a significant increase in non-C. albicans Candida isolates from 9.6-28.8% (P=0.005) after the children were placed on protease inhibitor therapy. Although Candida albicans still remained the most commonly isolated species, relative presence of C. tropicalis (n=9) followed by C. parapsilosis (n=8) markedly increased in association with protease inhibitor therapy. Furthermore, rare Candida species including C. dubliniensis, C. norvegensis, C. humicula and C. rugosa also appeared after the onset of protease inhibitor therapy. Subsequent investigation of the antifungal sensitivity of these diverse isolates, derived during protease inhibitor therapy, demonstrated some variation in antifungal sensitivity. With notable exceptions, the majority were sensitive to amphotericin B while most C. albicans and non-C. albicans Candida isolates were also susceptible to fluconazole, itraconazole and ketoconazole. Amongst exceptions was a single C. tropicalis isolates which was resistant to fluconazole (MIC>64 microl/ml) and one C. albicans-B isolate which showed cross-resistance to all azoles and amphotericin.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Azoles; Brazil; Candida; Candidiasis, Oral; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Microbial Sensitivity Tests; Species Specificity

Zygomycosis and aspergillosis are two serious opportunistic fungal infections that are commonly seen in immunocompromised patients. Since both these fungi invade vessels of the arterial system, an early and rapid diagnosis by direct examination of KOH mounts of the relevant clinical sample can confirm the diagnosis. Here, we present an unusual case of a diabetic patient who presented with nasal blockade and bleeding for 2 months, along with occasional haemoptysis for 15 days. On investigation, the patient was diagnosed with a case of rhinocerebral zygomycosis and was treated with amphotericin B (1 mg kg(-1) day(-1)), which was subsequently replaced with liposomal amphotericin B (2 mg kg(-1) day(-1)). However, the patient did not completely respond to therapy as haemoptysis continued. Further investigations revealed the presence of Aspergillus flavus in respiratory specimens. Thus, a final diagnosis of rhinocerebral zygomycosis with pulmonary aspergillosis in a non-HIV-infected patient was made, but due to infection of two vital sites by these fungi, the patient could not be saved.

Topics: Amphotericin B; Antifungal Agents; Diabetes Mellitus, Type 2; Female; HIV Infections; Humans; India; Middle Aged; Paranasal Sinus Diseases; Pulmonary Aspergillosis; Zygomycosis

Topics: Amphotericin B; Antiprotozoal Agents; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Leishmaniasis, Visceral; Male; Middle Aged

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Fluconazole; HIV Infections; Humans; Meningitis, Cryptococcal; Treatment Outcome

Nervous system infections by Cryptococcus neoformans may occur not only in congenital or acquired immunodeficiency syndromes, but also in immunocompetent hosts. Neurological manifestations of C. neoformans infection include meningitis and, less commonly, parenchymal CNS granulomatous disease. This paper provides detailed clinical descriptions of highly unusual neurological manifestations of cryptococcal nervous system infections. Medical records and diagnostic data including magnetic resonance imaging, histopathology, serology, and CSF analysis were reviewed. A conus medullaris abscess was found in a patient infected with the human immunodeficiency virus (HIV). A patient with Hodgkin's disease was diagnosed with cryptococcal meningitis and dermatitis mimicking ophthalmic zoster. An immunocompetent patient presented with recurrent cerebral infarctions in the setting of cryptococcal meningitis. Cryptococcal infections of the nervous system can cause severe neurological disability when diagnosis is delayed. Sensitive and specific tests are readily available and should be considered when an unusual clinical presentation is encountered.

Topics: Abscess; Adult; Aged; Amphotericin B; Anticoagulants; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Cryptococcosis; Cryptococcus neoformans; HIV Infections; Hodgkin Disease; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Spinal Diseases; Tomography, X-Ray Computed; Warfarin

AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

Topics: Amphotericin B; Amyloidosis; Anti-HIV Agents; Antiprotozoal Agents; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Young Adult

Cases of visceral leishmaniasis (VL) in the course of human immunodeficiency virus (HIV) infection have regularly been recorded, mainly in southern Europe. HIV infection can increase the risk of VL development by 10-100 times in endemic areas. We describe the occurrence of this co-infection in 15 patients from Brazil. The mean age of the patients was 38 +/- 8.8 yr, with 86.6% males. The mean time between HIV diagnosis and the onset of visceral leishmaniasis was 44 +/- 39 mo. The main signs and symptoms presented at admission were splenomegaly (73%), weight loss (73%), cough (67%), fever (67%), asthenia (60%), and diarrhea (60%). The mean T CD4+ lymphocyte count was 173.7 +/- 225.6 cells/mm3, and viral load was 51,030 +/- 133,737/mm3. Treatment consisted of pentavalent antimonials (67% of cases). Most (87%) patients recovered from VL infection; death occurred in 1 patient due to septic shock. VL is an important opportunistic infection in HIV patients, which is potentially fatal, even when correct treatment is completed. Treatment should be done with pentavalent antimonials or amphotericin B in the case of relapse. Although there is no consensus, secondary prophylaxis should be considered in severe cases.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Asthenia; Bone Marrow; Brazil; CD4 Lymphocyte Count; Cough; Diarrhea; Female; Fever; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Pancytopenia; Retrospective Studies; Splenomegaly; Time Factors; Weight Loss

To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM).. Case series.. The Aga Khan University Hospital, Karachi, from December 1995 to December 2005.. Patients with a confirmed diagnosis of TBM or CCM were included in this study. The signs and symptoms, laboratory findings and other variables of patients were entered and analyzed by Statistical Package for Social Sciences (SPSS) Software version 14.. We compared 16 patients of TBM with 11 of CCM. None of the patients with TBM were Human Immunodeficiency Virus (HIV) positive while 4 patients with CCM had HIV. The common initial signs and symptoms in patients with TBM were fever, altered mental status and headache; and in patients with CCM were fever, headache and cough. The mean CSF glucose level decreased according to the Medical Research Council (MRC) stage in TBM. The mean CSF RBCs, WBCs, glucose and protein in TBM were 2010/mm3, 228/mm3, 52.32 mg/dL and 289.48 mg/dl respectively and in CCM were 178.54/mm3, 529.54/mm3, 32.63 mg/dL and 432.18 mg/dL respectively.. TBM and CCM should be suspected in all cases that present with symptoms of chronic meningitis. Patients with TBM are more likely to have altered mental status and higher CSF RBCs; those with CCM are more likely to have headache, cough and higher CSF WBCs.

Topics: Amphotericin B; Anti-Bacterial Agents; Biomarkers; Cerebrospinal Fluid; Diuretics, Osmotic; Female; HIV Infections; Humans; Male; Mannitol; Meningitis, Cryptococcal; Middle Aged; Pakistan; Prevalence; Treatment Outcome; Tuberculosis; Tuberculosis, Meningeal

The indirect impact of the known comparator drug in double-blind comparative clinical trials of novel agents is underappreciated, despite its potentially pernicious effects. This hypothesis-generating analysis illustrates potential spillover effects of a comparator (amphotericin) in the evaluation of the first member (caspofungin) of a novel class (echinocandins) of antifungal drugs. Reported rates of drug-related fever in the first 3 studies of caspofungin for the treatment of mucosal candidiasis in patients with advanced human immunodeficiency virus infection were retrospectively analyzed. We compared patients who received 50 mg of caspofungin per day in a double-blind trial that used fluconazole as the comparator with patients who received the corresponding dosage in 2 similar earlier studies that used amphotericin as the comparator. With respect to the incidence of drug-related fever, the difference between the concurrent caspofungin and fluconazole groups was less than the difference between caspofungin groups from studies that used different comparators. In phase II/III blinded, active-control trials, the reporting of adverse experiences attributed to a first-in-class drug might be confounded to a variable degree by expectations regarding a well-known comparator.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Double-Blind Method; Echinocandins; Fever; Fluconazole; HIV Infections; Humans; Lipopeptides; Randomized Controlled Trials as Topic

An HIV-infected patient started combination antiretroviral therapy with 13 CD4+ cells/microL. Despite sustained virological suppression over the following four years, the anemia did not resolve, and the CD4+ cell counts always remained below 200/microL until co-infection with Leishmania was diagnosed in October 2006 when the patient started complaining of persistent mild fever and asthenia. Once treatment for leishmaniasis was started with miltefosine, CD4+ cell count rose above 400/microL. A new drop in CD4+ cell count was observed when Leishmania DNA turned out again to be positive, but treatment with liposomal amphotericin-B restored immune recovery.

Topics: Adult; Amphotericin B; Anti-Retroviral Agents; Antiprotozoal Agents; CD4 Lymphocyte Count; HIV Infections; Humans; Leishmaniasis; Male; Phosphorylcholine

Topics: Amphotericin B; Antibiotic Prophylaxis; HIV Infections; Humans; Leishmaniasis, Visceral; Liposomes

Topics: Amphotericin B; Animals; Anti-Retroviral Agents; Antibodies, Protozoan; Antiretroviral Therapy, Highly Active; Diagnosis, Oral; Gingiva; Gingivitis, Necrotizing Ulcerative; HIV; HIV Infections; Humans; Leishmania; Leishmaniasis; Male; Middle Aged

Topics: Adult; Amphotericin B; Animals; Anti-HIV Agents; Antiprotozoal Agents; Female; HIV Infections; Humans; Leishmania infantum; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Uveitis

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Drug Carriers; HIV Infections; Humans; Leishmaniasis, Visceral; Liposomes; Male; Paromomycin; Pentamidine; Treatment Failure

Atypical presentations of cryptococcal infection have been described as clinical manifestations of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients following commence of antiretroviral therapy (ART). The authors describe a patient presenting with cryptococcal meningoradiculitis two weeks after initiation of ART. In patients with advanced HIV disease, immune reconstitution induced by ART can precipitate onset of atypical clinical manifestations in those patients with latent cryptococcal infection of the central nervous system.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Retroviral Agents; Ceftriaxone; Ciprofloxacin; Female; HIV Infections; Humans; Lamivudine; Meningitis, Cryptococcal; Nevirapine; Radiculopathy; Stavudine

In Sudan, two treatments are currently registered for visceral leishmaniasis: sodium stibogluconate (SSG) as first line and liposomal amphotericin B (AmBisome) as second line. We present 64 patients (52 relapse cases to SSG, 12 new but complicated cases) treated with AmBisome in eastern Sudan. AmBisome was administered at 2.5-8.2mg/kg (15-49mg/kg in total) per dose six times (days 1, 2, 3, 5, 10, 15) as an intravenous infusion. We measured outcome according to clinical response and parasitological clearance (lymph node aspiration). Patient outcomes fell into three groups: group 1, clinical responders (cured) with a negative test of cure (n=35); group 2, clinical responders with a positive test of cure (n=19); group 3, clinical non-responders (failures) with a positive test of cure (n=10). Of the 10 failures, six were already relapse cases. All of group 3, and 15 from group 2, were also treated with additional SSG (20mg/kg intramuscularly daily for 30-50 d) with resulting clinical and parasitological improvement. Parasite persistence and clinical failure were associated with a higher parasite density on admission (P<0.002) and underlying immunosuppressive disease: tuberculosis (three cases) or HIV (two cases). Because AmBisome monotherapy may fail in Sudan, a combination of AmBisome and SSG is recommended for relapse cases.

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; HIV Infections; Humans; Infant; Infusions, Intravenous; Leishmaniasis, Visceral; Male; Risk Factors; Treatment Failure; Tuberculosis

The following case illustrates an ileal perforation and reactive hemophagocytic syndrome (RHS) resulting from disseminated histoplasmosis in a patient with Human Immunodeficiency Virus (HIV) from Puerto Rico. Although the diagnosis was established by histopathologic findings and a positive bone marrow culture, Histoplasma capsulatum-specific real-time Polymerase Chain Reaction (PCR) allowed to confirm the diagnosis from formalin-fixed, paraffin-embedded tissue. Interestingly, the Histoplasma antigens in both serum and urine samples were falsely negative. Amphotericin B lipid complex (Abelcet), followed by oral itraconazole, led to a successful response and resolution of symptoms. A short review of the clinical signs and symptoms, diagnostic tests, and therapeutic options for disseminated histoplasmosis is done, with emphasis on the role of Histoplasma-specific real-time PCR as a molecular diagnostic tool and the efficacy of treatment with one of the lipid formulations of amphotericin B.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Combinations; Histoplasma; Histoplasmosis; HIV Infections; HIV-1; Humans; Ileum; Intestinal Perforation; Lymphohistiocytosis, Hemophagocytic; Male; Phosphatidylcholines; Phosphatidylglycerols; Puerto Rico; Treatment Outcome

A patient with Candida albicans thrush and oesophagitis was treated with high doses of caspofungin but treatment eventually failed. Four C. albicans isolates were serially recovered before and after caspofungin treatment. A microbiological study was performed to characterize these four isolates.. In vitro antifungal susceptibility testing was performed by the EUCAST reference method in RPMI and AM3 and by Etest. Molecular typing of the four isolates was done by sizing three polymorphic microsatellite markers. To look for specific mutations, sequencing of a region of the gene encoding the 1-3-beta-D-glucan synthase was performed for the four isolates.. In vitro antifungal susceptibility testing showed an increase in both caspofungin and micafungin MICs for the two isolates recovered after caspofungin treatment failure. The best discrimination between the pre-treatment and post-treatment isolates was obtained with Etest. Molecular typing of the four isolates showed that the post-treatment isolates with reduced susceptibility were identical to a susceptible pre-treatment isolate, suggesting the acquisition of caspofungin resistance. Sequencing of the gene encoding the 1-3-beta-D-glucan synthase showed a mutation responsible for an amino acid change at Phe-641 that could confer reduced susceptibility to both echinocandins.. Our results indicate that is it useful to perform in vitro susceptibility testing in the cases of clinical failure during caspofungin therapy.

Topics: Adult; Amino Acid Sequence; Amino Acid Substitution; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Genotype; HIV Infections; HIV-1; Humans; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides, Cyclic; Pyrimidines; Treatment Failure; Triazoles; Voriconazole

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brain; Brain Diseases; HIV Infections; Humans; Liposomes; Lymphoproliferative Disorders; Magnetic Resonance Imaging; Male; Middle Aged; Mucormycosis; Radiography; Sphenoid Sinus; Sphenoid Sinusitis; Treatment Outcome

In a prospective observational study of 54 patients with human immunodeficiency virus-associated cryptococcal meningitis, the early fungicidal activity of amphotericin B (1 mg/kg/day) was significantly greater than that of fluconazole (400 mg/day). Compared with antiretroviral therapy-naive patients, patients developing cryptococcal meningitis while already receiving antiretroviral therapy had lower baseline fungal burdens and a longer median duration of survival, but there were no differences observed in fungal clearance, cerebrospinal fluid proinflammatory cytokines, or 10-week mortality.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Drug Therapy, Combination; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome

Rhodotorula spp. are common saprophytes but may be responsible for systemic infections in immunocompromised patients. Meningitis caused by Rhodotorula spp. in human immunodeficiency virus (HIV) infected patients has been reported only rarely. We present a case of meningitis caused by Rhodotorula rubra in HIV infected patient. The presumptive diagnosis of cryptococcal meningitis was made on the basis of India ink preparation, Gram staining and latex agglutination test (LAT) for cryptococcal antigen. The final diagnosis was confirmed by isolation of Rhodotorula rubra from cerebrospinal fluid on culture. LAT was considered false positive. Amphotericin B and 5-fluorocytosine were administered but the patient succumbed to his illness.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cerebrospinal Fluid; False Positive Reactions; Fatal Outcome; Flucytosine; HIV Infections; Humans; Latex Fixation Tests; Male; Meningitis, Fungal; Rhodotorula

Visceral leishmaniasis (VL) is characterized by frequent relapses in HIV-infected patients, even in those who receive secondary prophylaxis. The aim of our study was to evaluate the efficacy of liposomal amphotericin B (L-AMB) for secondary prophylaxis of VL in HIV-infected patients.. From January 2001 to December 2005, 17 HIV patients, with at least one previous episode of VL who received L-AMB as secondary prophylaxis for VL, were included in the study. Efficacy was measured as the proportion of patients remaining free (non-relapse) of VL at different time points. Relapses were analysed as time-to-relapse distribution and were evaluated by survival analysis using the Kaplan-Meier method.. Twenty-one episodes of VL were diagnosed and nine relapsed. The median follow-up time was 14 (5-44) months. The probability of remaining free of relapse at 6 months was 89.7% (95% CI, 76.2-100); at 12 months, the probability was 79.1% (95% CI, 61-97.2) and at 24 and 36 months, the probability was 55.9% (95% CI, 30.5-81.3). In the non-relapsing group, patients had a significant increase in CD4 cell levels of 102 (10-174) and 126 (4-159) cells/mm(3) at 12 and 24 months, respectively (P = 0.037), whereas in the relapsing group, no significant increase was observed. Prophylaxis with L-AMB was well tolerated and only three patients had a mild impairment of renal function without requiring any change in treatment.. L-AMB is well tolerated and useful for secondary prophylaxis of VL.

Topics: Adult; Amphotericin B; Antiprotozoal Agents; CD4 Lymphocyte Count; Chemoprevention; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Survival Analysis; Time Factors

We describe drug-drug interactions (DDIs) encountered with antifungals in clinical practice.. Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug-drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI.. There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug-drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%).. In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Cyclosporine; Drug Interactions; Female; Fluconazole; France; Furosemide; HIV Infections; Hospitals, University; Humans; Hydrocortisone; Hypokalemia; Intensive Care Units; Itraconazole; Kidney Diseases; Leukemia; Male; Middle Aged; Neoplasms; Retrospective Studies

The purpose of this study was to evaluate in a retrospective analysis, cases of Mediterranean visceral leishmaniasis (VL) diagnosed in adults during a 20-year period in a department of infectious diseases. Demographic data, clinical and laboratory features and therapeutic findings were considered. During the study period, 22 cases of VL were diagnosed, and 6 (27%) were associated with HIV infection. Fever and splenomegaly were observed in all cases. Anaemia was constant. The anti-leishmanial IF titer was positive among 21 patients (95%). Smears from bone marrow aspiration were positive at microscopy in 95% of cases. Zymodeme analysis was carried out in nine isolates. L. infantum zymodeme MON-1 was characterized in all cases. Seventeen patients (77%) received meglumine antimoniate (MA) (20 mg SbV/kg per day) and 5 (23%) patients amphotericin B (AB) (0.5-1 mg/kg per day) for an average period of 25 days (10-49 days). Adverse events occurred in 7 patients (32%), among them 4 received AB. Clinical cure was achieved with success in 21 patients (95%). After a successful MA treatment of the initial episode, VL relapse was observed in one HIV-positive patient. Only one HIV-positive patient died from neurological disorders. VL is rare in adults. However, its incidence is increasing everywhere in the world, because of HIV-related cases. Its prognosis depends on the precocity of diagnosis and treatment.

Topics: Adult; Amphotericin B; Anemia; Animals; Antimony; Antiprotozoal Agents; Fever; HIV Infections; Humans; Leishmania infantum; Leishmaniasis, Visceral; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Recurrence; Retrospective Studies; Splenomegaly; Treatment Outcome; Tunisia

To study survival time and risk factors of mortality among HIV-infected patients who had cryptococcal meningitis.. Retrospective cohort study.. Patients' medical records of those who had HIV-infection with newly diagnosed cryptoccocal meningitis between January 2002 and December 2004 were reviewed. Each patient was classified into one of two groups, according to their anti-retroviral status (ART).. Five hundred and forty nine patients enrolled in the present study: 281 (51.2%) in the ART+ group and 268 (48.8%) in the ART-group. The mean age was 33.4 +/- 6.9 years old in the ART + group and 33.6 +/- 7.0 years old in the ART-group. There were more male in both groups: 207 males and 74 females in the ART+ group, and 195 males and 73 females in the ART-group. Baseline CD4 cell count of both groups was 20 (6-74) cells/mL and 24 (9-72) cells/ml. About 30% of both groups of patients experienced major opportunistic infection before cryptococcal meningitis. All patients were treated by standard amphotericin B for a 2-week duration followed by fluconazole for an additional 8 weeks. There were no differences of baseline characteristics between the two groups (p > 0.05). The survival rates at 12, 24, and 36 months were 92.8%, 87.4%, and 85.4% in the ART+ group and 55.3%, 42.2%, and 36.8% in the ART- group, respectively (p < 0.01). The median survival time in the ART- group was 15 months. From the Cox regression model, the hazard ratio for "not received ART" was 4.87 (95%CI = 2.48-9.44, p < 0.01).. The present study demonstrated the substantial increasing of survival time of HIV-infected patients with cryptococcal meningitis by initiated ART even in a resource limited setting (no flucytosine, local combined antiretroviral drugs with NVP based regimens).

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; CD4 Lymphocyte Count; Comorbidity; Female; Fluconazole; HIV Infections; Humans; Male; Meningitis, Cryptococcal; Retrospective Studies; Risk Factors; Survival; Time Factors

We present a 42-year-old man who was admitted with worsening of his general condition and facial skin lesions. He had previously been diagnosed with HIV infection and visceral leishmaniasis (VL). Diagnostic work-up revealed a new relapse of VL paralleled by the diagnosis of post-kala-azar dermal leishmaniasis (PKDL). The patient was treated with IV liposomal amphotericin B as well as sodium stibogluconate followed by oral hexadecylphosphocholine (miltefosine) over a period of 9 months. PKDL lesions began to disappear after 8 months of treatment. In addition, severe and relapsing VL so far remains in remission. This case demonstrates successful treatment of PKDL and relapsing VL in a Western European patient with HIV infection.

Topics: Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Europe; Germany; HIV Infections; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Liposomes; Male; Phosphorylcholine; Recurrence; Treatment Outcome

To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients.. HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed.. During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%.. Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diabetes Complications; Female; Fluconazole; Health Surveys; HIV Infections; HIV Seronegativity; Hospitals, University; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Male; Middle Aged; Neoplasms; Retrospective Studies; Thailand; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis, Oral; Drug Resistance, Fungal; Female; Fluconazole; HIV Infections; Humans

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antiprotozoal Agents; CD4 Lymphocyte Count; Diagnosis, Differential; Drug Resistance; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Nose; Skin Diseases, Parasitic

The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Flucytosine; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Predictive Value of Tests; Prognosis; Treatment Outcome

Topics: Amphotericin B; Anti-HIV Agents; HIV Infections; Humans; Inflammation; Leishmaniasis; Male; Middle Aged

To evaluate clinical and immunological parameters, interleukin (IL)-15 production and outcome of patients with visceral leishmaniasis (VL), including HIV positive patients, we analyzed 48 cases of VL. Clinical manifestations and response to therapy were similar in VL/HIV- and VL/HIV+ patients. However, relapses were more frequent in patients with HIV infection. Low levels of IL-15 concentrations were found in HIV+ patients without VL. These levels were comparable to concentrations obtained in healthy donors. We found a relationship between response to therapy and IL-15 levels. We found increased levels of IL-15 in VL/HIV- and VL/HIV+ patients with clinical and parasitological response to therapy. Our data demonstrate that VL in HIV-infected patients occurs in subjects with severe immunodeficiency and presents high rate of relapses. Low levels of IL-15 in illness patients and restored production in cured persons suggest that this cytokine could play a central role in immune responses during Leishmania/HIV co-infection.

Topics: Adult; Amphotericin B; Animals; Antimony; Antiprotozoal Agents; Female; HIV; HIV Infections; Humans; Interleukin-15; Leishmania; Leishmaniasis, Visceral; Longitudinal Studies; Male

A 20-year (1985-2004) retrospective review of 39 patients with imported visceral leishmaniasis found that tourism to Mediterranean countries and HIV infection were associated with visceral leishmaniasis. Diagnosis was often delayed. Treatment with liposomal amphotericin B has improved prognosis. Visceral leishmaniasis should be made a reportable disease.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Child; Child, Preschool; Female; HIV Infections; Humans; Leishmania; Leishmaniasis, Visceral; Liposomes; Male; Middle Aged; Prognosis; Travel; United Kingdom

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Biopsy; Female; Histoplasma; Histoplasmosis; HIV Infections; HIV Protease Inhibitors; Humans; Itraconazole; Lopinavir; Pyrimidinones; Skin; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Diagnosis, Differential; Drug Therapy, Combination; Facial Dermatoses; Female; Flucytosine; HIV Infections; Humans; Pruritus; Radiography

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Fluconazole; Flucytosine; HIV Infections; Humans; Immunologic Memory; Lamivudine; Lopinavir; Male; Meningitis, Cryptococcal; Pyrimidinones; Recurrence; Ritonavir; Syndrome; T-Lymphocyte Subsets; Zidovudine

The incidence of Candida dubliniensis in immunocomprimised patients in Turkey has not yet been determined. In this study the presence of C. dubliniensis in oral rinse samples of human immunodeficiency virus (HIV)-positive patients and healthy controls were investigated. Phenotypic tests like inability of growth at 45 degrees C, colony formation on Staib agar, intracellular beta-D-glucosidase activity, carbohydrate assimilation profiles and polymerase chain reaction with species-specific primers (DUBF and DUBR) were carried out for differentiation of C. dubliniensis. Of the 35 patients, four (11.4%) had C.dubliniensis in their oral cavity. Antifungal susceptibility testing of these C. dubliniensis isolates showed fluconazole MICs ranging from <0.06 to 32 microg ml(-1) and amphotericin B from <0.06 to 0.25 microg ml(-1). One isolate was dose-dependently susceptible to fluconazole (32 microg ml(-1)). This study demonstrates C. dubliniensis in HIV-positive patients from Turkey.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis, Oral; Female; Fluconazole; HIV Infections; Humans; Immunocompromised Host; Male; Microbial Sensitivity Tests; Middle Aged; Mycological Typing Techniques; Oropharynx; Polymerase Chain Reaction; Turkey

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Disease Susceptibility; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Treatment Outcome

Acanthamoeba infection is a rare, difficult-to-treat, and often fatal, opportunistic parasitic infection in immunocompromised hosts, such as patients infected with HIV. We describe an aggressive nasal and sinus infection by Acanthamoeba spp. in a person with AIDS. The resolution of this Acanthamoeba infection was secondary to a multidisciplinary treatment approach involving a combination of surgery as well as high-dose amphotericin B plus 5-fluorocytosine. In the era of the HIV/AIDS pandemic, the present report underscores the need for early identification and prompt aggressive treatment to ensure successful management of this rare but potentially fatal opportunistic infection.

Topics: Acanthamoeba; Adult; AIDS-Related Opportunistic Infections; Amebiasis; Amebicides; Amphotericin B; Animals; Flucytosine; HIV Infections; Humans; Male; Rhinitis; Sinusitis; Treatment Outcome

Anti-Candida activity by oral epithelial cells is considered one of several innate mucosal defense mechanisms against oropharyngeal candidiasis (OPC). OPC is the most common fungal infection in HIV disease. Previously we reported that oral epithelial cell anti-Candida activity is reduced in those with OPC, potentially representing a contributing factor to OPC. However, testing clinical epithelial cells possessing high levels of Candida has been limiting due to high background in the assay controls. HIV+ smokers often develop OPC sooner than non-smokers during progression to AIDS, suggesting additional immune aberrations. The purpose of this study was to design a means to reduce Candida associated with epithelial cells collected from saliva without affecting their in vitro growth inhibitory activity, and to employ that approach to evaluate antifungal activity in HIV+ smokers. To do so, oral epithelial cells with and without known levels of Candida were subjected to various treatments including azole, polyene, or echinocandin antifungal drugs or fixation followed by the standard growth inhibition (GI) assay. The results indicated that antifungal drugs, while effectively reducing cell-associated Candida, also affected epithelial cell function. In contrast, fixation with paraformaldehyde eliminated cell-associated Candida and had minimal effects on epithelial cell anti-Candida activity. Employing the fixation design that allowed a broad range of patients to be evaluated showed no difference in oral epithelial anti-Candida activity between HIV+ smokers and non-smokers. Therefore, oral epithelial cell antifungal activity does not appear compromised in those who smoke, reducing it as a contributing factor in susceptibility to premature OPC.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida; Candidiasis, Oral; Caspofungin; Echinocandins; Epithelial Cells; Fixatives; Fluconazole; HIV; HIV Infections; Humans; Lipopeptides; Mouth Mucosa; Peptides, Cyclic; Smoking

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; HIV-1; Humans; Magnetic Resonance Imaging; Male; Meningitis, Cryptococcal

To evaluate in a retrospective analysis cases of Mediterranean visceral leishmaniasis (VL) diagnosed in HIV-negative adults during a 7-year period.. Demographic data, previous or underlying diseases, clinical and laboratory features and therapeutic findings were considered.. A total of 64 patients were included, of whom 10 (16%) had underlying diseases and two were pregnant. Fever and hepatosplenomegaly were the main presenting symptoms, whereas pancytopenia and an elevated erythrocyte sedimentation rate were observed in all cases. Smears from bone marrow aspirate were positive at microscopy in 62 cases (97%). Twenty-four patients received meglumine antimoniate (MA) given during 21 consecutive days (20 mg/kg per day), and 40 patients liposomal amphotericin B (l-AmB) given at days 1-5 and 10 (3 mg/kg per day). Both groups' clinical and laboratory findings improved, but patients on l-AmB therapy had a faster recovery (85% on l-AmB therapy and 50% on MA therapy showed defervescence at day 5, P < 0.01). Treatment failures were observed in five cases, three (12%) on MA and two (5%) on l-AmB therapy. No significant toxicity was observed in patients treated with l-AmB, whereas three (12%) patients treated with MA showed electrocardiographic abnormalities.. l-AmB therapy may be considered the treatment of choice for any adult patients with Mediterranean VL, since it permits a faster recovery, has a lower incidence of side effects and is useful also in immunosuppressed patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Chi-Square Distribution; Drug Combinations; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Mediterranean Region; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies

Topics: Adult; Amphotericin B; Antifungal Agents; Diabetes Complications; Diabetes Mellitus; Diagnosis, Differential; Female; HIV Infections; Humans; Lung Diseases, Fungal; Mucormycosis

Subgingival colonization by Candida albicans has been described in human immunodeficiency virus (HIV)-infected individuals, but subgingival isolates have scarcely been characterized, particularly with respect to genotype and antifungal susceptibility. A series of 29 subgingival strains of C. albicans isolated from nine HIV-infected individuals was typed by electrophoretic karyotyping and tested for susceptibility to fluconazole, itraconazole, the new investigational triazole posaconazole and amphotericin B. DNA typing showed genetic heterogeneity within subgingival isolates, as almost every individual harbored his/her own specific isolate. Genetic identity was usually demonstrated within oral and subgingival isolates simultaneously collected from the same individual, but a number of DNA types were found to be unique to subgingival strains. These findings suggest that colonization is not just the result of Candida spreading from oral surfaces, and that subgingivally adapted strains could be involved. All isolates were susceptible to all the triazole drugs tested and amphotericin B. Additional studies on subgingival Candida colonization and further characterization of subgingival isolates are now required to clarify the role of Candida as opportunistic periodontal pathogen.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Dental Plaque; DNA, Fungal; Drug Resistance, Fungal; Female; Fluconazole; Genetic Heterogeneity; HIV Infections; Humans; Itraconazole; Karyotyping; Male; Microbial Sensitivity Tests; Mycological Typing Techniques; Triazoles

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anemia; Animals; Blood Cell Count; Bone Marrow Examination; Canada; Diagnosis, Differential; Fever; Guyana; HIV Infections; Humans; Leishmania; Leishmaniasis, Visceral; Male; Middle Aged; Physical Examination; Splenomegaly; Thrombocytopenia; Trypanocidal Agents

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antimony; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Drug Administration Schedule; HIV Infections; Humans; Immunocompromised Host; Leishmaniasis, Visceral; Prospective Studies; Recurrence; Spain; Viral Load

The clinical presentation of visceral leishmaniasis, or kala-azar, is variable but usually includes fever, severe cachexia, lymphadenopathy and hepatosplenomegaly. In immunocompromised patients the clinical course of the disease is even less specific and the diagnosis is often made by means of incidental detection of the parasites at atypical sites such as the gastrointestinal tract, peripheral blood, lungs and cerebrospinal fluid. We describe a case of pericardial leishmaniasis in an HIV-infected patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antifungal Agents; Antiprotozoal Agents; Candida albicans; Candidiasis; HIV Infections; Humans; Leishmania; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pericarditis

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antiprotozoal Agents; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Leishmaniasis; Lopinavir; Male; Pyrimidinones; Renal Dialysis; Renal Insufficiency; Ritonavir

A wide spectrum of oral lesions has been associated with human immunodeficiency viral infection (HIV), or AIDS. This report describes the case of an HIV-infected patient who developed a case of disseminated sporotrichosis whose first clinical sign was the presence of orofacial lesions. A histopathological study of this patient's biopsy specimens taken from the oropharyngeal lesions revealed a number of rounded and/or oval free-spore forms of Sporothrix schenkii, the identification of which was corroborated by culturing skin lesion exudate on Sabouraud's glucose agar. To the best of our knowledge to date, this is the first time a case of the oral manifestation of sporotrichosis in association with HIV infection has been described in the dental literature.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Facial Dermatoses; Gingival Hyperplasia; HIV Infections; Humans; Male; Mouth Diseases; Oropharynx; Periodontal Diseases; Pharyngeal Diseases; Sporothrix; Sporotrichosis

The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml, <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage--44%(7/16)--exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Analysis of Variance; Antifungal Agents; Candida albicans; Candidiasis, Oral; China; Cohort Studies; Drug Resistance, Microbial; Ethnicity; Female; Fluconazole; Follow-Up Studies; HIV Infections; Humans; Ketoconazole; Male; Middle Aged; Oropharynx; Pharyngeal Diseases; Recurrence

Oropharyngeal candidiasis (OPC) is the most frequent AIDS-associated opportunistic infection, as up to 90% of HIV-infected individuals suffer at least one episode during the course of their disease. Various in vivo and in vitro procedures have been used to assess the effectiveness of antifungal agents used in HIV infection. In the present study, we evaluated in vitro the minimum inhibitory concentration (MIC) and the post-antifungal effect (PAFE) of two polyenes, two azoles and one DNA-analogue against 10 oral isolates of Candida albicans and 10 of Candida tropicalis, all from HIV-infected individuals, in order to obtain basic data on the pharmacodynamics of these drugs. One-hour exposure to twice the MIC of all the drugs, except fluconazole, elicited a consistently high PAFE in both Candida species. Furthermore, the PAFE elicited by the antifungals (except fluconazole) was significantly prolonged for C. tropicalis compared with C. albicans. This speedy recovery of C. albicans isolates exposed to transient low concentrations of antifungals appeared to reflect its virulence compared with lesser potent species, such as C. tropicalis. Taken together, the current data, while confirming the existence of PAFE in a non-albicans species of Candida, also provide further clues for the recalcitrance of C. albicans species in the face of antifungal therapy for oropharyngeal candidiasis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis, Oral; Fluconazole; Flucytosine; HIV Infections; Humans; Ketoconazole; Microbial Sensitivity Tests; Nystatin; Oropharynx; Pharyngeal Diseases; Statistics as Topic; Time Factors; Virulence

A 33-year-old Hispanic woman with newly diagnosed human immunodeficiency virus (HIV) infection, a CD4 T-lymphocyte count of 2, viral load of 730,000 copies/mL, candidal esophagitis, seizure disorder, a history of bacterial pneumonia, and recent weight loss was admitted with tonic clonic seizure. On admission, her vital signs were: pulse of 88, respiration rate of 18, temperature of 37.7 degrees C, and blood pressure of 126/76. Her only medication was phenytoin. On examination, the patient was found to have multiple umbilicated papules on her face, as well as painful, erythematous, large, punched-out ulcers on the nose, face, trunk, and extremities of 3 months' duration (Fig. 1). The borders of the ulcers were irregular, raised, boggy, and undermined, while the base contained hemorrhagic exudate partially covered with necrotic eschar. The largest ulcer on the left mandible was 4 cm in diameter. The oral cavity was clear. Because of her subtherapeutic phenytoin level, the medication dose was adjusted, and she was empirically treated with Unasyn for presumptive bacterial infection. Chest radiograph and head computed tomography (CT) scan were within normal limits. Sputum for acid-fast bacilli (AFB) smear was negative. Serologic studies, including Histoplasma antibodies, toxoplasmosis immunoglobulin M (IgM), rapid plasma reagin (RPR), hepatitis C virus (HCV), and hepatitis B virus (HBV) antibodies were all negative. Examination of the cerebrospinal fluid was within normal limits without the presence of cryptococcal antigen. Blood and cerebrospinal cultures for bacteria, mycobacteria, and fungi were all negative. Viral culture from one of the lesions was also negative. The analysis of her complete blood count showed: white blood count, 2300/microl; hemoglobin, 8.5 g/dL; hematocrit, 25.7%; and platelets, 114,000/microl. Two days after admission, the dermatology service was asked to evaluate the patient. Although the umbilicated papules on the patient's face resembled lesions of molluscum contagiosum, other infectious processes considered in the differential diagnosis included histoplasmosis, cryptococcosis, and Penicillium marnefei. In addition, the morphology of the ulcers, particularly that on the left mandible, resembled lesions of pyoderma gangrenosum. A skin biopsy was performed on an ulcer on the chest. Histopathologic examination revealed granulomatous dermatitis with multiple budding yeast forms, predominantly within histiocytes, with few organisms resid

Topics: Adult; Amphotericin B; Antifungal Agents; Biopsy; Dermatomycoses; Female; Histoplasma; Histoplasmosis; HIV Infections; Humans; Pyoderma Gangrenosum

Topics: Adult; Amphotericin B; Antifungal Agents; HIV Infections; Humans; Leishmaniasis, Mucocutaneous; Male

To evaluate the ability of liposomes bearing anti-HLA-DR Fab' fragments (immunoliposomes) and containing amphotericin B (AmB) to target and neutralize cell-free HIV-1 particles and virally-infected cells.. The effect of AmB on the attachment and fusion of HIV-1(NL4-3) to Jurkat E6.1 cells has been evaluated using a p24 enzymatic assay. The ability of AmB to inhibit HIV-1-based luciferase reporter viruses pseudotyped with HXB2, AML-V and VSV-G envelopes has been evaluated in Jurkat E6.1 cells. The efficacy of free and immunoliposomal AmB to inhibit cell-free HIV, that have incorporated or not HLA-DR molecules, has been evaluated in HLA-DR/negative (NEG) 1G5 T cells and HLA-DR/positive (POS) Mono Mac 1 cells.. AmB inhibited HIV infectivity independently of the nature of viral envelope proteins. Pretreatment of HIV with AmB had no major effect on viral attachment and fusion process to Jurkat E6.1 cells. Immunoliposomal AmB (0.5 microg/ml) led to a 77% inhibition of replication of HLA-DR/POS HIV-1 with no cell toxicity, whereas free AmB had no significant antiviral activity at this concentration. A complete inhibition of viral replication was observed following incubation of viruses with immunoliposomal AmB (2.5 microg/ml). Anti-HLA-DR immunoliposomes containing AmB had no effect on the infectivity of HLA-DR/NEG HIV-1 particles in HLA-DR/NEG T lymphoid cells but completely inhibited replication of viruses in an HLA-DR/POS monocytic cell line.. The incorporation of neutralizing agents in anti-HLA-DR immunoliposomes could represent a novel therapeutic strategy to specifically target cell-free HIV particles and virally-infected cells to treat HIV infection more efficiently.

Topics: Amphotericin B; Antibodies; Antibody Specificity; Cell Line; Drug Delivery Systems; HIV Infections; HIV-1; HLA-DR Antigens; Humans; Immunoglobulin Fab Fragments; Jurkat Cells; Liposomes

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Animals; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Chemoprevention; Female; HIV Infections; Humans; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence; Treatment Outcome

Human immunodeficiency virus (HIV) and hepatitis B and hepatitis C viruses have emerged as major blood-borne infections. Several cases of infections through the use of unsterile injection needles also are on record. Kala-azar, or visceral leishmaniasis, is a hemoparasitic disease caused by Leishmania donovani. All the anti-kala-azar medications require multiple intramuscular injections of the anti-leishmanial drugs. To find whether these patients were at higher risk of contracting blood-borne infection, than those who were not on medication, a community-based study was conducted in the kala-azar-endemic state of Bihar, India.. Five villages (4050 families) of three highly endemic districts of Bihar were included in this study. The sociodemographic data of the affected families and their annual income were determined as per Government of India guidelines. The diagnosis of kala-azar and its sequelae, post-kala-azar dermal leishmaniasis (PKDL), was made, and their therapeutic details were noted. All the leishmania-infected patients, their spouses, family members, and villagemates were tested for hepatitis B surface antigen, hepatitis C virus antibodies, and anti-HIV (1 + 2) antibodies, using commercially available kits.. Of the 4050 families, 61 (1.5%) were found affected with kala-azar or PKDL. These 61 families had 77 cases of leishmaniasis, of which 64 (83%) had kala-azar and 13 (17%) PKDL. The most affected (4.5%) age group was 11 to 40 years. Of the 61 families, 57 (93.4%) families belonged to so-called untouchable castes, and 9 of them could not afford to have any anti-kala-azar treatment. Only 64 patients received treatment in the form of injectables. The number of injections received by these patients ranged from 3 to 120. Hepatitis B and C viral infections were found to be significantly more prevalent in those who received multiple injections. Compared to their male counterparts infected with L. donovani, females who received injectable medicines were at higher risk of contracting hepatitis B infections (20% vs. 11.3%) and hepatitis C virus infection (26.7% vs. 18.9%). Overall, hepatitis C virus infections were more common (20.6%) than hepatitis B virus infection (13.2%) in this group of patients. Villagemates with a history of injections for other ailments also were found to have a high rate of infection with hepatitis viruses. One patient with kala-azar was found to be co-infected with HIV, although probably not related to injections.. The treatment of Indian kala-azar and post-kala-azar dermal leishmaniasis consists of multiple intramuscular injections of sodium stibogluconate, pentamidine, or amphotericin B. Though the original disease gets cured, all these therapeutic regimens were found to carry a significantly high risk of transmitting yet more dangerous blood-borne infections, such as HIV and hepatitis B and C viruses, through the shared use of unsterile injection needles. All needles should be appropriately sterilized, if they are to be re-used.

Topics: Adolescent; Adult; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Equipment Contamination; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis C Antibodies; HIV Antibodies; HIV Infections; Humans; India; Injections, Intramuscular; Leishmaniasis, Visceral; Male; Needles; Pentamidine; Prevalence; Social Class

Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candida; Candidiasis, Oral; Fluconazole; Genotype; HIV Infections; Humans; Itraconazole; Microbial Sensitivity Tests; Mouth; North America; Pharynx; Phenotype; Pyrimidines; Triazoles; Voriconazole

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Antiviral Agents; Cidofovir; Clinical Trials as Topic; Cytomegalovirus Retinitis; Cytosine; HIV Infections; Humans; Isoquinolines; Nelfinavir; Nevirapine; Organophosphonates; Organophosphorus Compounds; Protease Inhibitors; Pyridines; Ritonavir; Sulfonic Acids

The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Neoplasms; HIV Infections; Humans; Itraconazole; Logistic Models; Male; Middle Aged; Multivariate Analysis; Opportunistic Infections; Prognosis; Prospective Studies; Risk Factors; Survival Analysis

The aim of the present study was to evaluate the utility of the E test in determining the antifungal susceptibility of Candida albicans. Reproducibility of the E test was determined for amphotericin B, fluconazole, and itraconazole using three different solid media: RPMI 1640, Casitone, and yeast nitrogen base agar. Minimum inhibitory concentrations (MICs) were comparable (results at +/- 2 dilutions) in 92% of the tests for amphotericin B and in 100% for fluconazole and itraconazole. Determination of MIC endpoints was easiest on Casitone agar. Candida albicans isolates from 23 patients undergoing fluconazole therapy for oropharyngeal candidiasis were tested for fluconazole susceptibility. Good correlation was obtained between the MICs of fluconazole and clinical outcome. Clinical failure was associated with strains for which MICs were > or = 48 micrograms/ml. These results suggest that the E test has potential utility for fluconazole susceptibility testing of clinical yeast isolates.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis, Oral; CD4 Lymphocyte Count; Fluconazole; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Itraconazole; Microbial Sensitivity Tests; Reproducibility of Results; Sensitivity and Specificity

Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable disease, there is evidence that the actual number of cases is higher than that reported. In 1987, a regional reference center for active surveillance of VL was established and it recorded a total of 284 cases through 1995, a mean of 31.5 cases/year and about four-fold more than previously reported. Of the 284 cases, 150 (53%) were children (< or = 14 years of age), and of the 134 adults, 39 (29%) were coinfected with human immunodeficiency virus (HIV). The commonest viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%) of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280 patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects), 254 (91%) were treated with meglumine antimoniate alone or in combination with other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional or in liposomal form; and three terminally ill patients were not treated. Among the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%) (seven adults) died during the course of antimonial treatment. None of the 35 HIV-positive patients was definitively cured, although mortality was apparently associated with other opportunistic infections.

Topics: Adolescent; Adult; Age Distribution; Aged; Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence; Sex Distribution; Sicily

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Delivery of Health Care; Drug Therapy; Guatemala; Histoplasmosis; HIV Infections; HIV-1; Humans; Itraconazole; Male; Retrospective Studies; Risk Factors

We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC). PC was the first AIDS-defining manifestation in nine patients. HIV infection was identified simultaneously with the onset of PC in 4 patients. The CD4+ lymphocyte count was low in all cases (median, 24/m3). Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases. In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient. For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans. Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture. Serum cryptococcal antigen was detected in all 15 patients. Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients. First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients. Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Fluconazole; HIV Infections; Humans; Lung Diseases, Fungal; Male; Middle Aged; Pneumonia, Pneumocystis; Radiography, Thoracic; Retrospective Studies

We report on a 32-year old HIV-infected male patient who was admitted to the hospital in a comatose state. A cryptococcus neoformans septicemia with meningoencephalitis was diagnosed. Intravenous treatment with amphotericin B was initiated and replaced three weeks later by fluconazole per os. With this therapy the patient recovered quite well. However, following two grand mal epileptic seizures he suddenly fell into a deep coma 22 days after admission to the hospital. The cause of the encephalopathy remained unclear, and the patient died 2 days later. Autopsy revealed a severe meningoencephalitis and a pneumonia due to cryptococcus neoformans. Departing from this case we discuss diagnosis, clinical presentation and treatment of cryptococcus meningoencephalitis.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcus neoformans; Epilepsy, Tonic-Clonic; Fatal Outcome; Fluconazole; HIV Infections; Humans; Injections, Intravenous; Male; Meningoencephalitis; Pneumonia, Bacterial; Sepsis

The microbiology, epidemiology, clinical features, and treatment of aspergillosis are discussed. Aspergillosis is a fungal infection that is increasingly found in patients with advanced HIV disease. The lung is involved in almost 75 percent of aspergillus infections. The central nervous system is the second most commonly infected site, occurring in about 10 to 15 percent of reported cases. Sinus involvement is recognized as a feature of aspergillosis, accounting for about 75 percent of all cases of fungal sinusitis seen in AIDS patients. While these infections are more than likely localized, dissemination to many organs can occur. The prognosis of patients with aspergillosis is poor, and its treatment is difficult. Treatment with amphotericin B is considered the gold standard, but responses are limited, with only 20 to 30 percent of patients responding in most cases. Itraconzole is approved as a second-line therapy. Surgery may also be appropriate for some cases of aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Central Nervous System Diseases; HIV Infections; Humans; Itraconazole; Lung Diseases; Sinusitis

Coccidioides immitis is a dimorphic fungus primarily found in the soil in a limited region of the southwestern United States. When this fungus causes an infection (coccidioidomycosis), it is due to the spores being inhaled and causing an inflammation of the respiratory tract. In most cases, the infection is self-limiting and is controlled by cell-mediated immunity. In HIV-infected patients, it is thought that the infection may be newly acquired, or reactivated, from a former incident. Patients with a CD4 count under 250 are at highest risk for becoming infected, and may present with pneumonia, fever, weight loss, night sweats, cough, and dyspnea. The infection can also become disseminated, and upon autopsy, widespread disease is found in the majority of patients that die of coccidioidomycosis. Chest x-rays show a diffuse reticulonodular infiltrate, then diagnosis is made by culturing the organism. The treatment of choice for disseminated disease is amphotericin B and alternative therapies including itraconazole and fluconazole, with possible lifelong treatment necessary. There is no current evidence that coccidioidomycosis can be prevented by any of these drugs.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Fluconazole; HIV Infections; Humans; Itraconazole; Risk Factors; Southwestern United States

New approaches to the diagnosis, treatment, and prevention of fungal infections were discussed at Focus on Fungal Infections in 1997. This article examines the use of early presumptive treatment for candida fungemia, the cause of and treatment for recurrent vulvovaginal candidiasis, and the treatment and prevention practices for invasive aspergillosis. The efficacy of using amphotericin B lipid complex, amphotericin B in colloidal dispersion, and liposomal amphotericin B in patients with fungal infections is also discussed. Concluding comments address how serious a problem antifungal resistance is in choosing treatment regimens and the new and upcoming strategies for treating coccidioidomycosis in patients who are immunosuppressed.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Coccidioidomycosis; Dosage Forms; Drug Carriers; HIV Infections; Humans; Liposomes; Mycoses

The case of a 30-year-old, female, HIV-positive intravenous drug user who suffered from isolated cerebral mucormycosis is reported. Treatment with amphotericin B at an accumulative dose of 5.5 grams led to significant recovery, and there was no recurrence of disease over a follow-up period of six months. Patients with isolated cerebral mucormycosis in whom surgery would be a high-risk or impossible procedure could be managed medically with prolonged courses of intravenous amphotericin B.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain; Female; HIV Infections; Humans; Mucormycosis; Radiography; Substance Abuse, Intravenous

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Drug Resistance, Microbial; HIV Infections; HIV-1; Humans; Mouth

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Carriers; Epiglottis; HIV Infections; Humans; Laryngeal Diseases; Liposomes; Lung Diseases, Fungal; Male

A case study is presented of a mid-20's, HIV-infected male visitor from Thailand who became increasingly ill with tuberculosis-like symptoms. The question addressed is whether the patient should be treated for miliary tuberculosis or for disseminated Mycobacterium avium complex (MAC) infection pending further evaluation. It is argued that due to the frequency with which Penicillium marneffei infection occurs in Thai AIDS patients and the similarity of the symptoms to MAC infection, such treatment is not warranted. Following isolation of P. marneffei, the patient was treated with high dose amphotericin B and responded well, defervescing within a week.

Topics: Adult; Amphotericin B; Antifungal Agents; Diagnosis, Differential; HIV Infections; Humans; Male; Mycoses; Penicillium; Thailand; Tuberculosis; United States

Histoplasmosis is a fungal infection caused by the organism Histoplasma capsulatum. Disseminated disease usually occurs in immunosuppressed patients or in patients with chronic illnesses. Although relatively uncommon, histoplasmosis has been reported in patients with AIDS, and oral lesions have been noted on multiple sites and in various clinical presentations. We present two HIV-positive cases with oral lesions as the initial signs of histoplasmosis. Both patients responded well to IV amphotericin B but later suffered recurrences despite being maintained on systemic antifungal therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Histoplasmosis; HIV Infections; Humans; Ketoconazole; Male; Mouth Diseases

Within the upper aerodigestive tract, histoplasmosis often mimics carcinoma, making prompt and accurate diagnosis imperative. More severe and potentially lethal infections with Histoplasma capsulatum are now being seen as the numbers of patients at the extremes of age, as well as those with compromised immune systems, increase. We reviewed the cases of 115 hospitalized patients with disseminated histoplasmosis. Of these, 9 patients were identified with otolaryngologic manifestations: 4 were infected with human immunodeficiency virus (HIV), 1 was diabetic, and 3 were renal transplant patients. Sites of involvement included the larynx (in 2 cases) and the oral cavity and oral pharynx (in 7 cases). Eight of the 9 patients had a positive biopsy result; the other, a positive culture. Treatment with amphotericin B was generally effective, while the use of newer azole anti-fungal agents were less effective. As the number of immunocompromised patients continues to increase in modern clinical practice, histoplasmosis will undoubtedly be encountered more frequently in the head and neck area.

Topics: Amphotericin B; Histoplasmosis; HIV Infections; Humans; Itraconazole; Laryngeal Diseases; Laryngeal Neoplasms; Laryngoscopy; Male; Middle Aged; Retrospective Studies; Stomatognathic Diseases; Treatment Outcome

Topics: Acute Disease; Adult; Amphotericin B; Antimony Sodium Gluconate; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Pancreatitis

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Meningitis, Cryptococcal; Mycoses

Topics: Amphotericin B; HIV Infections; Humans; Leishmaniasis, Visceral; Prospective Studies; Recurrence

Topics: Adrenal Cortex Hormones; Amphotericin B; Controlled Clinical Trials as Topic; Cryptococcosis; Fluconazole; HIV Infections; Humans; Isoniazid; Pneumonia, Pneumocystis; Prospective Studies; Tuberculosis

Preliminary observations have shown that AmBisome, a liposomal formulation of amphotericin B (Vestar Inc.), is effective and non-toxic in animal and human visceral leishmaniasis. The activity of multiple doses of this drug on Leishmania infantum, in BALB/c mice was investigated, and amphotericin B concentration in liver and spleen was determined. Groups of infected mice were treated intravenously with 3, 5, or 7 doses of AmBisome (3 mg/kg) over 3, 10 and 25 days, respectively. The antileishmanial activity of the drug was compared with that of meglumine antimoniate (28 mg Sbv/kg per day over 21 days). Three consecutive daily doses of AmBisome were sufficient to clear all parasites from the liver of mice, while antimony did so only after 21 doses. Twenty-four-48 h after their last dose all the AmBisome-treated mice showed very high amphotericin B concentrations in liver (61.2-76.2 micrograms/g) and spleen (39.8-72.1 micrograms/g) with no overt signs of toxicity. Mice that received 2 or 4 doses at intervals of 5 to 8 days, maintained drug levels as high as those detected after 3 consecutive doses over 11 and 26 days, respectively. This should enable visceral leishmaniasis treatment on an intermittent or outpatient basis, thereby reducing overall treatment costs.

Topics: Amphotericin B; Animals; Cricetinae; HIV Infections; Humans; Infant, Newborn; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Liver; Meglumine; Meglumine Antimoniate; Mice; Mice, Inbred BALB C; Organometallic Compounds; Spleen; Tissue Distribution

From June 1990 to August 1991, 21 patients infected with the human immunodeficiency virus (HIV) presented with systemic mycosis caused by Penicillium marneffei. Between August 1987 and August 1991, only five patients were observed who had P. marneffei infection but not HIV infection. The clinical presentation included fever, cough, and generalized papular skin lesions. For 11 of these 21 patients, the presumptive diagnosis of P. marneffei infection could be made by microscopic examination of Wright's-stained bone marrow aspirate and/or touch smears of skin specimens obtained by biopsy several days before the results of culture were available. Initial clinical response to treatment with either parenteral amphotericin B or oral itraconazole was favorable in most patients. Epidemiological and clinical evidence suggest that this systemic mycosis is caused by an important opportunistic pathogen and that it should be included in the differential diagnosis of AIDS, at least for countries in areas of endemicity, i.e., Southeast Asia and China.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; HIV Infections; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Mycoses; Opportunistic Infections; Penicillium; Retrospective Studies; Thailand; Treatment Outcome

We present four cases of C. neoformans meningitis (CNM) in patients with Human Immunodeficiency Virus (HIV) infection treated with fluconazole p.o. at an initial dose of 400 mg followed by 200 mg/day during a follow up period ranging from 3 to 12 months, and who presented an excellent clinical evolution. When comparing them to our previous cases who were treated with Amphotericin-B in combination with 5-fluorocytosine, a decrease in mean hospital stay (p less than 0.001) and a smaller incidence of secondary effects were observed. Treatment with fluconazole seems to be an effective alternative in treatment of CNM. Future greater studies are needed to confirm this findings.

Topics: Administration, Oral; Adult; Amphotericin B; Drug Therapy, Combination; Female; Fluconazole; Flucytosine; Follow-Up Studies; HIV Infections; Humans; Length of Stay; Male; Meningitis, Cryptococcal; Time Factors

The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no significant effect on infection, the compounds in combination were potent inhibitors of HIV as evaluated by reduction in HIV antigen production and HIV induced cytopathic effect. These results indicate that a combination therapy employing compounds with different modes of action like AZT and AME may have synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV.

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Antifungal Agents; Cells, Cultured; Drug Synergism; Drug Therapy, Combination; HIV; HIV Infections; Humans; Zidovudine

Isolation of HIV from cultures of CD4+ lymphocytes purified from peripheral blood by indirect panning was optimized and evaluated. Infectious HIV was isolated by single isolation attempts in 98% of 102 HIV-antibody-positive patients (55 had AIDS or ARC and 47 were clinically healthy). The average culture time required for positive cultures was largely independent of the CD4 count of the patients and 87% of the positive isolation cultures from both groups of patients became positive within 14 days of culture. An evaluation of the possible influence of media additives on propagation of HIV showed that: amphotericin-B had a suppressive effect on HIV replication at concentrations recommended for anti-fungal activity; recombinant and human interleukin-2 were equally suitable for both isolation cultures and for propagation of HIV, and polybrene, at a concentration of 2 micrograms/ml in the culture medium had a beneficial effect.

Topics: Amphotericin B; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Hexadimethrine Bromide; HIV; HIV Antigens; HIV Infections; Humans; Interleukin-2

Topics: Adult; Amphotericin B; Antiprotozoal Agents; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pentamidine; Spain; Treatment Outcome

In 20 HIV-patients (17 male homosexuals, 1 male and 1 female i.v. drug abuser and 1 female patient with M. Willebrand-Jürgens) Candida esophagitis was diagnosed by esophagogastroduodenoscopy. Clinically they presented retrosternal pain or an exacerbation of oral candidosis under local antimycotics. The diagnosis of Candida esophagitis was based on histopathologic examination and culture studies of biopsy specimen from macroscopically suspect lesions. Candida antigen was found in the serum of 30% of the patients, immunofluorescence was positive for Candida antibodies in 25%. A CMV- or HSV-esophagitis could be ruled out by direct immunofluorescence, in situ hybridoma experiments and by virus culture assays. In 11/20 patients the Candida esophagitis was the first manifestation of full blown AIDS. 10 patients were treated daily with a combination of amphotericin B 0.4 mg/kg KG and flucytosine 150 mg/kg/KG and 10 patients by oral administration of fluconazole 400 mg/d each for 8 days. Secondary prophylaxis was carried out with 2.4 g/d (24 ml) amphotericin B as oral suspension in the amphotericin group and with 50 mg/d fluconazole p.o. in the fluconazole group. Both therapy regimens showed a complete remission in a control esophagogastroduodenoscopy after 10 days. Side effects were only moderate. After an observation period between 7-24 months there were three relapses in the amphotericin group and four in the fluconazole group. After 24 months 10 patients had died, a rate comparable to that after Pneumocystis carinii pneumonia. In total, there is no difference between both therapy regimens, the oral administration of fluconazole once a day allowed treatment as an outpatient and was appreciated by the patients.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Esophagitis; Female; Fluconazole; Flucytosine; HIV Infections; HIV-1; Humans; Male

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Clindamycin; Communicable Diseases; Fluconazole; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Arizona; California; Coccidioidomycosis; Dermatomycoses; Female; Follow-Up Studies; HIV Infections; Humans; Ketoconazole; Leukocyte Count; Liver Diseases; Lung Diseases, Fungal; Lymphatic Diseases; Male; Meningitis; Retrospective Studies; T-Lymphocytes, Helper-Inducer

Three patients with generalized histoplasmosis and the acquired immunodeficiency syndrome (AIDS) are described. Symptoms of generalized histoplasmosis in patients with AIDS are not specific and concomitant opportunistic infections frequently occur. Two patients suffered from an infection by Mycobacterium tuberculosis, one patient had Pneumocystis carinii pneumonia, and one had cerebral toxoplasmosis. One patient had serological results positive for Histoplasma capsulatum. Two of the three patients showed rapid clinical improvement on amphotericin B but this was temporary and all patients died within 5 months.

Topics: Adult; Amphotericin B; Female; Histoplasmosis; HIV Infections; Humans; Male; Middle Aged

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Topics: Amphotericin B; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Flucytosine; HIV Infections; Humans; Meningitis; Recurrence

Topics: Adult; Amphotericin B; Blastomyces; Blastomycosis; Diabetes Mellitus, Type 1; HIV Infections; Homosexuality; Humans; Lung Diseases, Fungal; Male; Opportunistic Infections