deoxycholic-acid and Histoplasmosis

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

Fungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).. An 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable.. H. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.

Topics: Administration, Intravenous; Administration, Oral; Aged, 80 and over; Amphotericin B; Antifungal Agents; Asia; Deoxycholic Acid; Drug Combinations; Female; Histoplasma; Histoplasmosis; Humans; Itraconazole; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Treatment Outcome

Histoplasma capsulatum has not typically been associated with sinusitis in either immunocompetent or immunocompromised hosts. We report a case of sinusitis caused by H. capsulatum in a patient with chronic lymphocytic leukemia and discuss the reported cases of this rare clinical manifestation of histoplasmosis in the medical literature.

Topics: Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Histoplasma; Histoplasmosis; Humans; Immunocompromised Host; Itraconazole; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Sinusitis; Treatment Outcome

Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fluconazole; Flucytosine; Fungemia; Histoplasmosis; Humans; Immunocompromised Host; Mycoses; Zygomycosis

A 48-year-old male patient living with HIV presented to our hospital with fever and weight loss. On evaluation, he was found to have pancytopenia, deranged liver and kidney function. CD4 count was 13 cells/uL. Bone marrow examination done because of pancytopenia showed yeast forms of histoplasmosis. Although liposomal amphotericin B is preferred for induction, he was treated with deoxycholate amphotericin B despite poor kidney function because of financial constraints. He was treated for 12 days with intravenous amphotericin, during which his clinical condition significantly improved. He was discharged on oral itraconazole.

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Histoplasmosis; Humans; Kidney; Male; Middle Aged

The therapeutic efficacy of daily amphotericin B infusion is related to its maximum concentration in blood; however, trough levels may be useful in intermittent regimens of this antifungal drug.. : High performance liquid chromatography (HPLC) was used to determine the minimum concentration (Cmin) of amphotericin B in the serum of patients receiving deoxycholate (D-Amph) or liposomal amphotericin B (L-AmB) for the treatment of cryptococcal meningitis (n=28), histoplasmosis (n=8), paracoccidioidomycosis (n=1), and leishmaniasis (n=1).. Daily use of D-Amph 30 to 50 mg or L-AmB 50 mg resulted in a similar Cmin, but a significant increase ocurred with L-AmB 100 mg/day. The geometric mean Cmin tended to decrease with a reduction in the dose and frequency of intermittent L-AmB infusions: 357 ng/mL (100 mg 4 to 5 times/week) > 263 ng/mL (50 mg 4 to 5 times/week) > 227 ng/mL (50 mg 1 to 3 times/week). The impact on Cmin was variable in patients whose dose or therapeutic scheme was changed, especially when administered the intermittent infusion of amphotericin B. The mean Cmin for each L-AmB schedule of intermittent therapy was equal or higher than the minimum inhibitory concentration of amphotericin B against Cryptococcus isolates from 10/12 patients. The Cmin of amphotericin B in patients with cryptococcal meningitis was comparable between those that survived or died.. By evaluating the Cmin of amphotericin B, we demonstrated the therapeutic potential of its intermittent use including in the consolidation phase of neurocryptococcosis treatment, despite the great variability in serum levels among patients.

Topics: Amphotericin B; Antifungal Agents; Chromatography, High Pressure Liquid; Deoxycholic Acid; Histoplasmosis; Humans; Leishmaniasis; Meningitis, Cryptococcal; Paracoccidioidomycosis

Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Biopsy; Colon; Colonoscopy; Deoxycholic Acid; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Histoplasma; Histoplasmosis; Humans; India; Male; Middle Aged; Prognosis; Retrospective Studies; Time Factors

In patients with acquired immunodeficiency syndrome (AIDS), advanced immunosuppression is associated with atypical presentation of dermatological conditions. Our patient presented with a single crusted plaque over the lower lip and large tender cervical lymphadenopathy. The enzyme-linked immunosorbent assay for human immunodeficiency virus was found to be positive, and his CD4+ lymphocyte cell count was 4 cells/mm

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Biopsy; CD4 Lymphocyte Count; Deoxycholic Acid; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Histoplasma; Histoplasmosis; Humans; Itraconazole; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Treatment Outcome

Topics: Adolescent; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Dermatomycoses; Drug Combinations; Fever; Histoplasmosis; Humans; Itraconazole; Lung Diseases, Fungal; Male; Nepal; Rural Population

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

To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.. 目的：比较肺型与进展播散型组织胞浆菌病的临床特点、诊断及预后差异。 方法：回顾性分析中南大学湘雅医院2009年2月至2015年10月期间收治的组织胞浆菌病住院患者12例，其中肺型4例，进展播散型8例。从临床表现、影像学、确诊途径及预后等方面分析两者之间的差异性。 结果：肺型组织胞浆菌病临床表现轻微，干咳多见。进展播散型患者全身症状明显，极易出现反复高热、全身浅表淋巴结肿大、肝脾肿大，可合并咳嗽、腹痛、关节痛、皮肤改变等。实验室检查示全血细胞减少、肝功能异常、凝血功能异常等。1例肺型患者给予了左下肺切除术，其余3例肺型及6例进展播散型患者分别给予两性霉素B脱氧胆酸盐、伊曲康唑、伏立康唑或氟康唑抗真菌感染治疗，好转出院，1例播散型确诊后暂未治疗即出院，1例播散型因合并重症肺炎及活动性肺结核治疗无效死亡。结论：组织胞浆菌病临床少见，极易漏诊或误诊，依靠骨髓涂片、病理组织切片特殊染色明确病原学是目前确诊的主要依据，推荐两性霉素B脂质体、两性霉素B脱氧胆酸盐及伊曲康唑抗感染治疗。.

Topics: Abdominal Pain; Amphotericin B; Antifungal Agents; Biopsy; Cough; Death; Deoxycholic Acid; Diagnostic Errors; Drug Combinations; Fever; Hepatomegaly; Histoplasma; Histoplasmosis; Humans; Invasive Fungal Infections; Itraconazole; Lung; Lung Diseases, Fungal; Pneumonia; Recurrence; Retrospective Studies; Splenomegaly; Treatment Outcome; Tuberculosis

Disseminated histoplasmosis is an invasive fungal infection documented in patients with impaired cellular immunity coming from endemic areas (America, Asia, Africa). We report two cases of disseminated histoplasmosis in AIDS patients paradigmatic of the multifaceted nature of the disease, which may be an expression either of an advanced state of immunosuppression or the immune reconstitution inflammatory syndrome (IRIS).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brazil; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Female; Hepatitis B, Chronic; Hepatitis D, Chronic; Histoplasmosis; Homosexuality, Male; Humans; Immunocompromised Host; Invasive Fungal Infections; Italy; Male; Risk Factors; Thailand; Treatment Outcome; Voriconazole

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Brain Damage, Chronic; Brain Edema; Child; Delayed Diagnosis; Deoxycholic Acid; Diagnostic Errors; Drug Combinations; Histoplasma; Histoplasmosis; Humans; Hydrocephalus; Immunocompetence; Itraconazole; Liposomes; Male; Meningitis; Meningitis, Viral; Prognosis; Stroke, Lacunar; Tuberculosis, Meningeal; Ventriculoperitoneal Shunt

Abstract. Coinfection with tuberculosis in some countries occurs in 8-15% of human immunodeficiency virus (HIV) -infected patients who have histoplasmosis. This coinfection interferes with prompt diagnosis, and treatment is difficult because of drug interactions. We retrospectively reviewed the cases of 14 HIV-infected patients who had concomitant tuberculosis and histoplasmosis. The most frequent clinical manifestations were weight loss (85.7%), asthenia (78.5%), and fever (64.2%). The diagnosis of histoplasmosis was made primarily by histopathology (71.4%), and the diagnosis of tuberculosis was made by means of direct microscopic examination (71.4%). Death occurred in two patients, and relapse of both infections occurred in one patient. Moxifloxacin was substituted for rifampicin in six patients, with good outcomes noted for both infections. The clinical presentation does not readily identify acquired immunodeficiency syndrome (AIDS) patients who have tuberculosis and histoplasmosis. The use of a fluoroquinolone as an alternative agent in place of rifampicin for tuberculosis allows effective therapy with itraconazole for histoplasmosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Coinfection; Deoxycholic Acid; Drug Combinations; Female; Histoplasmosis; Humans; Itraconazole; Male; Middle Aged; Retrospective Studies; Risk Factors; Tuberculosis

Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20%-40% and the relapse rate is as high as 50%; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML), that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Chronic Disease; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fluconazole; Histoplasmosis; Humans; Immunocompromised Host; Leukemia, Myeloid; Male; Meningitis, Fungal; Treatment Outcome

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fungemia; Hepatitis B, Chronic; Hepatomegaly; Herpes Zoster; Histoplasmosis; Humans; Male; Splenomegaly; Toxoplasmosis; Ultrasonography; Uremia