amphotericin-b and Acute-Disease

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

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Facial Dermatoses; Female; Hepatomegaly; Humans; Itraconazole; Lung Diseases, Fungal; Molluscum Contagiosum; Paracoccidioides; Paracoccidioidomycosis; Paraguay; Pleural Effusion; Spores, Fungal; Young Adult

The urinary tract is a common source for life-threatening infections. Most patients with sepsis or septic shock from a urinary source have complicated urinary tract infection. This article explains the epidemiology, risk factors, and treatment. Effective management, appropriate collection of microbiology specimens, prompt initiation of antimicrobial therapy, source control, and supportive therapy are described.

Topics: Acute Disease; Aminoglycosides; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Catheters, Indwelling; Community-Acquired Infections; Cross Infection; Deoxycholic Acid; Drug Combinations; Female; Fluconazole; Humans; Male; Prognosis; Risk Factors; Shock, Septic; Urinary Tract; Urinary Tract Infections

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

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Humans; Leukemia, Myeloid; Rhizopus; Triazoles; Zygomycosis

We describe a case of primary aspergillosis involving the tongue of a patient with acute myeloid leukemia. Intraoral aspergillosis is very rare and we found only 23 cases reported in the English literature. Clinically it was a 2-cm, ulcerated, grayish lesion on the dorsum of the tongue. Microscopically there was invasion of the epithelium, connective tissue and muscle of the tongue by fungal hyphae branching at 45 degrees angle. The large hyphae were easily seen by H & E stain, and were strongly positive for periodic acid-Schiff and Grocott methenamine. The patient was successfully treated with intravenous amphotericin B. Based on clinical, microscopic and culture data, the diagnosis of primary aspergillosis of the tongue was established. Invasive oral aspergillosis is a potentially lethal disease and it should be considered in immunosuppressed patients.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Humans; Hyphae; Immunocompromised Host; Leukemia, Myeloid; Male; Tongue Diseases

Various adverse effects have been reported with the use of amphotericin B. The respiratory adverse effects include dyspnea, tachypnea, bronchospasm, hemoptysis, and hypoxemia. Stridor has not been previously reported with the use of amphotericin B.. To review the mechanism of action and reports of respiratory adverse effects for amphotericin B, the liposomal preparations of amphotericin B, and the differential diagnosis of stridor.. A MEDLINE search from 1966 to 2002 was performed to review the current literature for possible mechanisms and immunoregulatory effects related to the infusion of amphotericin B.. Amphotericin B has been shown to increase tumor necrosis factor alpha (TNF-alpha) concentrations in macrophages. In addition, it induces prostaglandin E2 synthesis and increases the production of interleukin 1beta (IL-1beta) in mononuclear cells. The immunoregulatory effects of amphotericin B include increases in apoptosis, production of monocyte chemoattractant protein 1, superoxide anion, nitric oxide, and intercellular adhesion molecule 1 expression.. Amphotericin B induces the production of TNF-alpha, interferon-gamma, and IL-1beta, which may potentiate its toxic effects. Some liposomal preparations induced lower levels of TNF-alpha and nitric oxide and may be useful in patients unable to tolerate amphotericin B deoxycholate.

Topics: Acute Disease; Aged; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Drug Compounding; Drug Hypersensitivity; Humans; Leukemia, Myeloid; Male; Respiratory Hypersensitivity; Respiratory Sounds

Geotrichum capitatum sepsis are rare, occurring exclusively in immunocompromised patients.. We report the case of a patient with acute leukemia, presenting with chemotherapy-induced neutropenia and hospitalized in an intensive care unit for a severe sepsis. In spite of an antibiotic and antifungal treatment, the patient died of cardiorespiratory failure. Later on, blood cultures proved to be positive for Geotrichum capitatum.. If fungal infections are common in neutropenic patients, Geotrichum capitatum sepsis remain exceptional. The portal of entry is digestive or respiratory, and the invasion is favored by immunodepression and suppression of the normal microbial flora. Induced lesions can be multiorganic. The treatment is not well established, and the association of either amphotericine B and 5-fluorocytosine or amphotericine B and itraconazole would lead to better results. Nevertheless, the prognosis is still unfavorable, with a mortality rate of approximately 75%.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Combinations; Fatal Outcome; Flucytosine; Geotrichosis; Humans; Immunocompromised Host; Itraconazole; Leukemia; Male; Middle Aged; Neutropenia; Opportunistic Infections

Pancreatic infection remains a significant clinical problem, with substantial morbidity and mortality. Published case reports of Candida species identified in these infections prompted a review of 17 consecutive patients recently treated for peripancreatic infection by scheduled relaparotomy. Six patients were transferred from other hospitals, all having undergone prior operative intervention (median stay elsewhere: 58 days). The 11 other patients underwent initial operation an average of 14 days after admission. Candida species were identified in the initial operative cultures of 5 patients (29%), three of whom had undergone previous drainage at other hospitals. Two patients (11.7%) had Candida identified at subsequent operation. Six patients were treated with Amphotericin B for a median of 12 days (range 6-32) and a median dosage of 420 mg (range 225-830 mg). All patients were cleared of their Candida infection, but three subsequently died, for an overall mortality of 17.6%. Candida infected patients suffered a 42 per cent mortality. Our series supports the suspicion that Candida is much more frequent (41% of patients) than previously recognized in peripancreatic sepsis, and is commonly acquired after the initial operation. Amphotericin B therapy is effective in clearing Candida infection, but affected patients have a high associated mortality.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candidiasis; Chronic Disease; Combined Modality Therapy; Drainage; Female; Humans; Incidence; Length of Stay; Male; Middle Aged; Necrosis; Pancreatitis; Reoperation; Severity of Illness Index; Survival Rate; Treatment Outcome

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Carbon; Coloring Agents; Cryptococcus neoformans; Drug Administration Schedule; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Prognosis; Serotyping; Spinal Puncture; Staining and Labeling; Tomography, X-Ray Computed

This review has traced chemotherapy of coccidioidomycosis from its unsuccessful beginnings through the present time. Although in vitro susceptibilities give initial impressions of activity of many drugs, and although animal studies identify the diseases targeted for initial trials, ultimately it is the patient in whom the benefits and risks of a new agent must be weighed. For this reason, considerations have been limited to clinical studies, with no review of animal data or immunologic forms of therapy such as transfer factor. In this review, amphotericin B has been found to be the first active antifungal agent in coccidioidomycosis. Although responses clearly occurred, even in meningitis, the vagaries of disease and investigators prevented a really hard assessment of how many patients really were "cured" versus how many relapsed again and again. Responses were given in broad ranges and the term "remission" came to be considered a more accurate definition for this illness than "cure." The azole antifungals, though fungistatic, gave us, for the first time, the ability to treat a patient indefinitely with an oral preparation; the advantages of this cannot be overstated. Although all of these drugs act by similar mechanisms, the differences in potency, pharmacokinetics and toxicities have brought fluconazole and itraconazole to the fore. Which of the two is superior (if either is) cannot be defined with the limited data available. The role of SCH39304 is, at present, unclear. Other agents such as nikkomycin and modified polyenes may enter a role in clinical evaluation of coccidioidomycosis, but for the next five years the drugs described in the preceding pages, or combinations, are likely to constitute the pharmaceutical arsenal against C. immitis. While we now have much more to offer the heirs of Domingo Escurra and Jose Furtado-Silveira than gentian violet and carbolic acid, we still have response rates of less than 75% for extrameningeal disease and we have not yet identified a drug that will guarantee a cure without later relapse. There is still a way to go.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Chronic Disease; Coccidioidomycosis; Humans; Ketoconazole; Lung Diseases, Fungal

Dr. William G. Powderly provides a comprehensive review of the state of our knowledge regarding cryptococcal infection in persons with infection due to human immunodeficiency virus type 1. The introduction of fluconazole and itraconazole increased insight into prognostic factors affecting these patients. The need to suppress this fungal infection in individuals with impaired immunity has greatly altered the management of cryptococcal meningitis; therapy for this condition was established by the landmark study conducted by the Mycosis Study Group in 1979 (Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in treatment of cryptococcal meningitis. N Engl J Med 1979;301:126-31). In this AIDS commentary Dr. Powderly clearly outlines the progress made through clinical investigations and the problems that remain to be resolved.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Fluconazole; HIV-1; Humans; Meningitis, Cryptococcal; Prognosis

Four patients with underlying diseases including multiple trauma, aortic graft infection, and complex fistulae developed acute acalculous cholecystitis with bile cultures positive only for Candida albicans. The primary site of the candida infection included urinary tract, gastrointestinal tract, and an aortic graft in one patient each and was undetermined in the trauma victim. All had received broad-spectrum antibiotics; three of the four were in the intensive care unit (ICU) with organ failure. Ultrasonography showed a thickened gallbladder wall in three patients and sludge in one. Hepato-iminodiacetic acid scans were nonvisualizing in these three patients. Operative findings included gangrenous cholecystitis in two patients and edematous cholecystitis in one. The fourth patient was treated with percutaneous cholecystostomy and interval cholecystectomy. The interval from the onset of symptoms to recognition of the need for operation was an average of 7 days. Two of the four patients died of ongoing sepsis. Candida cholecystitis is a life-threatening complication of critical surgical illness. Risk factors are similar to those for candida infection elsewhere and include antibacterial therapy, complex fistulae, disseminated malignancy, immunosuppression, and prolonged ICU stay. A high index of suspicion for this fungal pathogen and aggressive surgical therapy offer the only chance for a favorable outcome.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candidiasis; Cholecystectomy; Cholecystitis; Cholecystostomy; Cholelithiasis; Critical Illness; Disease; Female; Humans; Male; Middle Aged; Postoperative Complications; Risk Factors; Surgical Procedures, Operative

We have presented the case of a postpartum woman with a pseudocyst infected with C albicans and have reviewed the relevant literature. The patient did well with surgical drainage of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogens, and the patient should receive aggressive therapy.

Topics: Acute Disease; Adolescent; Amphotericin B; Candidiasis; Combined Modality Therapy; Female; Humans; Pancreatic Cyst; Pancreatic Pseudocyst; Puerperal Infection; Tomography, X-Ray Computed

Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad-spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations.

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Bacterial Infections; Clinical Trials as Topic; Fever; Humans; Leukemia; Mycoses; Neutropenia; Remission Induction

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Catheters, Indwelling; Female; Hepatic Artery; Humans; Leukemia; Liver Abscess; Male; Mycoses; Portal Vein; Splenic Artery; Splenic Diseases

Aspergillus produces diverse pulmonary manifestations, its clinical spectrum extending from harmless saprophytic colonization to universally lethal disseminated infection. Management of the conditions produced by Aspergillus is also diverse and may consist of either observation or treatment with corticosteroid agents or amphotericin B. The factors that influence the expression of Aspergillus into a specific clinical entity are not well understood, but are believed to be related to immune status, both pulmonary and systemic, and the genetic composition of the host.

Topics: Acute Disease; Adrenal Cortex Hormones; Alveolitis, Extrinsic Allergic; Amphotericin B; Antibodies, Fungal; Antifungal Agents; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Diagnosis, Differential; Hemoptysis; Humans; Immunoglobulin G; Lung; Lung Diseases, Fungal; Radiography; Spores, Fungal; Sputum

Topics: Acute Disease; Adrenal Cortex Hormones; Amphotericin B; Aspergillosis; Blood Transfusion; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Iron; Leukemia; Leukemia, Lymphoid; Lymphoma; Mucor; Multiple Myeloma; Mycoses; Neutropenia; Rhizopus

To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP).. Seventy patients with SAP admitted from Jan. 1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were compared.. The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16% vs 30%, P<0.05 and 9% vs 30%, P<0.01, respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole group.. Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with SAP. But once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective.

Topics: Acute Disease; Adult; Aged; Allyl Compounds; Amphotericin B; Antifungal Agents; Disulfides; Female; Fluconazole; Humans; Incidence; Male; Middle Aged; Mycoses; Pancreatitis; Prospective Studies; Treatment Outcome

Fungal infections remain a major cause of treatment failure and death in acute leukemia. New liposomal preparations of amphotericin B are now available. While less toxic, their comparative efficacy and toxicity profiles are unknown. In this study the comparative efficacy and safety of ABLC vs. AmBisome was evaluated in seventy-five patients with leukemia who developed 82 episodes of suspected or documented mycosis, and were treated (1:1) with either ABLC (n=43) or AmBisome (n=39). Both drugs were dosed accordingly from 3 to 5 mg/kg/day. Using an intent-to-treat analysis, the overall response to therapy was 27/43 (63%) for ABLC and 15/39 (39%) for AmBisome (p=0.03). Median dose and duration of treatment was 10 days at 3 mg/kg for ABLC and 15 days at 4 mg/kg for AmBisome. Acute, not dose-limiting infusion side effects were seen in 70% vs. 36% (p=0.002), ABLC vs. AmBisome. Increase of bilirubin > 1.5 times from baseline was 38% vs. 59%, ABLC vs. AmBisome (p=0.05). ABLC and AmBisome were equally effective for the treatment of suspected or documented fungal infections. While, acute infusion-toxicity was greater with ABLC, infusion toxicity requiring discontinuation was similar for both drugs. AmBisome was better tolerated than ABLC but was associated with mild abnormalities in liver function tests at the end of therapy.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Combinations; Humans; Leukemia; Mycoses; Phosphatidylcholines; Phosphatidylglycerols

Invasive fungal infections have increasingly become a matter of concern with regard to patients receiving intensive myelosuppressive therapy for hematologic malignancies. Such infections, especially prolonged neutropenia systemic fungal infections, may contribute substantially to infectious complications and early death. Measures for early detection and effective prophylactic strategies using active and nontoxic antifungal agents are therefore urgently needed.. The current randomized study was initiated to assess the efficacy of oral fluconazole as systemic antifungal prophylaxis for high risk patients with recurrent acute myeloid leukemia undergoing intensive salvage therapy.. Of 68 fully evaluable patients, 36 were randomized to fluconazole in addition to standard prophylaxis with oral co-trimoxazol, colistin sulphate, and amphotericin B suspension, and 32 were randomized to standard prophylaxis only. No major differences between the two groups were observed in the number of episodes of fever of unknown origin (61% vs. 50%) or clinically defined infections (56% vs. 50%). Microbiologically defined infections were more frequent in the fluconazole group (50% vs. 31%), mainly due to a higher incidence of bacteremias (42% vs. 22%). There were two cases of proven invasive fungal infections in each group. Systemic amphotericin B was administered more frequently to patients receiving fluconazole prophylaxis (56% vs. 28%). Fluconazole prophylaxis had no impact on the rate of early death or overall survival.. For patients with high risk recurrent acute myeloid leukemia undergoing intensive salvage therapy, antifungal prophylaxis with fluconazole was not superior to standard prophylaxis only.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Female; Fluconazole; Humans; Immunocompromised Host; Leukemia, Myeloid; Male; Middle Aged; Mycoses; Prospective Studies; Recurrence; Risk Factors; Salvage Therapy

The authors report the clinical and microbiological findings of a 6-month follow-up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg-1 day-1 i.v. plus flucytosine at doses of 100 mg kg-1 day-1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day-1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day-1 p.o. indefinitely. During the 6-month follow-up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three-drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6-month follow-up. The two patients with haematogenous cryptococcosis did not relapse after the 6-month follow-up.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antigens, Fungal; Chronic Disease; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Follow-Up Studies; Humans; Itraconazole; Meningitis, Cryptococcal

We analyzed the 67 of 278 patients with newly-diagnosed AML or 'high-risk' MDS, treated in 1994 and 1995, who developed pneumonia during course 1 of their induction therapy. Pneumonia responded to treatment in 66%, but outcome depended on when pneumonia was diagnosed. Patients with pneumonia diagnosed during week 1 or 2 (group 2 patients) had the lowest response rate (43%). Patients who developed pneumonia in the 3rd week after treatment initiation had the best outcome with all 16 patients recovering. Patients presenting with pneumonia had an intermediate response rate (75%). The different patient groups were comparable with regard to age, underlying disease, prophylactic therapy, and G-CSF application. Although a lower CR rate was not entirely responsible for the lower response rate in group 2, failure to achieve CR predicted unsuccessful treatment of pneumonia in all groups. Fungal pathogens appeared more common in group 2 patients. However, in these patients, administration of amphotericin B was associated with a significantly higher failure rate (15/21 failures vs 2/9 who received no amphotericin B). We conclude that patients who develop pneumonia during week 1 or 2 are a high-risk group, and that use of amphotericin B indicates a particularly poor prognosis, although we present data suggesting that earlier use of amphotericin might be beneficial. Furthermore, since achievement of CR was an important prognostic factor in all groups, WBC transfusions particularly from donors given G-CSF should be considered as a therapeutic option. Finally, since time to failure of induction therapy and time to CR were similar in high-risk patients, new chemotherapy regimens could potentially improve both the CR rate and the outcome of pneumonia.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid; Middle Aged; Myelodysplastic Syndromes; Pneumonia, Bacterial; Remission Induction; Risk Factors

The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated. Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions). There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy. During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01). A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001). We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Antigens, Fungal; Biomarkers; Cryptococcus neoformans; Fluconazole; Fungemia; Humans; Meningitis, Cryptococcal; Polysaccharides; Prognosis; Treatment Outcome

Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.. Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.. Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).. At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Blast Crisis; Female; Fluconazole; Humans; Kidney Diseases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mycoses; Premedication; Prospective Studies; Remission Induction

To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.. A randomized, controlled, multicenter trial.. 30 hematologic units in tertiary care or university hospitals.. 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.. Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.. An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.. Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).. Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Mycoses; Neutropenia; Patient Compliance; Treatment Outcome

In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Mycoses; Prospective Studies; Remission Induction

Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B (ampho B) alone or in combination with 5-Fluorocytosine (5-FC). Because of the potential myelosuppressive side effects of 5-FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5-FC treatment for proven or suspected systemic fungal infections. The study population comprised 87 patients who were treated by standard chemotherapy for acute myeloid leukemia (AML) at first diagnosis or relapse. Twenty-two patients underwent systemic antifungal therapy consisting of ampho B (3 to 10 mg/kg/d) and 5-FC (150 mg/kg/d) for 3 to 33 days (median, 12 days). The remaining 65 patients served as controls to assess the hematologic recovery time (TR) as defined by the interval between the onset of chemotherapy and the post-treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm. In patients receiving antifungal therapy, a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days (P = 0.0016) for the control group. No correlation was found between TR and the total dose of either ampho B or 5-FC or the type of antileukemic regimen. A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5-FC treatment was started in patients with proven or only suspected fungal infections, causing a similar delay of TR in both groups. The present data strongly suggest a myelosuppressive effect of ampho B/5-FC antifungal treatment in patients after intensive chemotherapy for acute leukemias.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Agents; Candidiasis; Drug Administration Schedule; Drug Therapy, Combination; Flucytosine; Hematopoiesis; Humans; Immune Tolerance; Leukemia, Myeloid; Middle Aged; Random Allocation

In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cephalosporins; Enterobacteriaceae Infections; Female; Flucytosine; Humans; Leukemia; Male; Middle Aged; Oxacillin; Penicillins; Prospective Studies; Staphylococcal Infections; Streptococcal Infections

Fifty-two patients with nonlymphocytic leukaemia were studied during remission induction treatment in a randomized trial to ascertain the effect of prophylactic oral trimethoprim-sulfamethoxazole on infection and fever rate. A decrease in the total number of acquired infections was found (16 infections in the group given trimethoprim-sulfamethoxazole versus 31 in the control group, p less than 0.01). The number of patients without any infection in the trimethoprim-sulfamethoxazole group was 13 compared to only three in the control group (p less than 0.01). Patients in the trimethoprim-sulfamethoxazole group needed parenteral antibiotics during 33% of the days they were granulocytopenic compared to 61% of these days for patients in the control group. However, six of nine bacteriologically documented infections in the trimethoprim-sulfamethoxazole group were caused by resistant microorganisms compared to two out of 20 in the control group.

Topics: Acute Disease; Agranulocytosis; Amphotericin B; Drug Combinations; Drug Therapy, Combination; Fever; Humans; Infection Control; Infections; Leukemia; Middle Aged; Random Allocation; Sulfamethoxazole; Trimethoprim

Candida lusitaniae is an uncommon pathogen that accounts for approximately 1% of patients with candidiasis. In this report, we present the case of a 24-year-old woman with severe pancreatitis who was emergently admitted to Northern Yokohama Hospital. We started treating the pancreatitis and infections according to her culture results. However, her symptoms, accompanied by a necrotic pancreas, did not improve. Finally, C. lusitaniae was detected in the blood and catheter samples. We started antifungal treatment according to the culture results, but the patient died. Generally, the mortality rate for acute pancreatitis ranges from 3% for patients with interstitial edematous pancreatitis to 17% for those who develop pancreatic necrosis. Although we chose appropriate antibiotics and antifungal agents based on the culture results, the treatments failed. Early detection, sufficient doses of antimicrobials and frequent monitoring using sample culture are crucial because infection control may be inadequate, especially in tissues with low blood flow, such as necrotic tissues.

Topics: Acute Disease; Adult; Antifungal Agents; Candida; Candidiasis; Female; Humans; Pancreatitis; Young Adult

Acute invasive fungal rhinosinusitis (AIFRS) is a fatal infection associated with high morbidity and mortality. Although it is a rare disease, upsurge of AIFRS was noticed during the second wave of COVID-19 disease. Early diagnosis and management is the cornerstone for good outcomes. However, management of AIFRS is challengeable especially in developing countries due to limited resources and high prices of antifungal agents. No previous studies have been conducted to evaluate the outcomes of management of AIFRS in Syria. The purpose of this study is to report the results of management of AIFRS with low doses of liposomal amphotericin B in our tertiary hospital in Syria.. The outcomes of management of AIFRS cases were followed through a prospective observational study between January 2021 and July 2022. The required medical data were collected for each individual. Three-month mortality rate was studied. SPSS v.26 was used to perform the statistical analysis. Pearson Chi-square test was used to study the associations between different variables and mortality. Survival curves were plotted by the Kaplan-Meier to compare the survival probability. Log Rank (Mantel-Cox) test and Cox regression were conducted to evaluate the factors affecting survival within the follow up period.. Of 70 cases, 36 (51.4%) were males and 34 (48.6%) were females. The mean age of patients was 52.5 years old. The most common underlying risk factor was diabetes mellitus (84.3%). The used dose of liposomal amphotericin B ranged between 2-3 mg/kg per day. The overall 3-month mortality rate was 35.7%. Significant association was found between survival and the following variables: Age, orbital involvement, stage, and comorbidity.. The overall mortality rate was close to other studies. However, survival rate was worse than comparable studies in selected cases of AIFRS (older ages, involved orbits, advanced stages, and chronic immunodeficiency). Therefore, low doses of liposomal amphotericin B could be less effective in such cases and high doses are recommended.

Topics: Acute Disease; Antifungal Agents; COVID-19; Female; Hospitals, University; Humans; Male; Middle Aged; Mycoses; Rhinitis; Sinusitis; Syria

Topics: Academic Medical Centers; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Child; Child, Preschool; Comorbidity; Early Diagnosis; Endoscopy; Female; Fungi; Humans; Male; Middle Aged; Mycoses; Retrospective Studies; Rhinitis; Sinusitis; United States; Young Adult

Topics: Acute Disease; Aged; Amphotericin B; Antifungal Agents; Blindness; Debridement; Diabetes Mellitus, Type 1; Eye Infections, Fungal; Eye Pain; Fatal Outcome; Humans; Intraocular Pressure; Magnetic Resonance Imaging; Male; Mucormycosis; Orbital Diseases; Rhinitis; Slit Lamp Microscopy; Tomography, X-Ray Computed; Visual Acuity

The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc).. A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT.. The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample.. Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up.. With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.

Topics: Acute Disease; Administration, Intravenous; Aftercare; Amphotericin B; Antifungal Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Fungal; Mucorales; Mucormycosis; Respiratory Distress Syndrome; Scleroderma, Diffuse; Scleroderma, Systemic; Transplantation, Autologous; Treatment Outcome; Young Adult

Topics: Acute Disease; Amphotericin B; Animals; Antiprotozoal Agents; Biopsy; Dogs; Hepatitis; Humans; Leishmania infantum; Leishmaniasis, Visceral; Liver; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Zoonoses

Continuous administration of amphotericin B deoxycholate over 24 hours (24 h-D-AmB) is better tolerated than rapid infusions. However, toxicity and outcome have not been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy between 2007 and 2012 at our institution. We compared a patient group with exposure to 24 h-D-AmB to a patient group without exposure to 24 h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24 h-D-AmB, and 48 (26.5%) did not. Reasons for 24 h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for febrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. Amphotericin B deoxycholate over 24 hours was given for a median 7 days (interquartile range 3-13). Peak creatinine concentration was higher in the 24 h-D-AmB-group (104.5 vs. 76 μmol/L, P < .001) but normalized within 1 month after therapy (65.5 vs. 65 μmol/L, P = .979). In neither of the 2 groups, end-stage renal disease occurred. There was no difference in 60-day survival (90% vs. 90%) and 2-year survival (58% vs. 58%). Invasive fungal disease partial response or better was observed in 68% of the patients. We conclude that antifungal therapy with continuously infused amphotericin B deoxycholate is safe in patients with AML. An antiinfective strategy based on 24 h-D-AmB in first line followed by an oral triazole compound represents an economically attractive treatment option.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Infusion Pumps; Leukemia, Myeloid; Male; Middle Aged; Mycoses; Neutropenia; Retrospective Studies; Survival Analysis; Treatment Outcome

The use of isavuconazole is approved for the management of invasive aspergillosis and mucormycosis, only in adults, as no paediatric pharmacology studies have been reported to date. Very few paediatric cases have been published concerning the use of isavuconazole. Amphotericin B is the only antifungal agent recommended in paediatric mucormycosis, but adverse effects and especially nephrotoxicity, even with the liposomal formulation, could be problematic. In this context, the use of other antifungal molecules active on Mucorales becomes needful.. We describe a case of mucormycosis with rapid onset dissemination in a 3-year-old girl recently diagnosed with acute lymphocytic leukaemia. She was successfully treated with isavuconazole alone and then in combination with liposomal amphotericin B. Isavuconazole therapy was guided by therapeutic drug monitoring.. This case offers new perspectives on the potential use of isavuconazole in children with mucormycosis, as an alternative or adjunct to liposomal amphotericin B.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Child, Preschool; Drug Therapy, Combination; Female; Humans; Leukemia, B-Cell; Mucormycosis; Nitriles; Pyridines; Treatment Outcome; Triazoles

Topics: Acute Disease; Amphotericin B; Animals; Antiprotozoal Agents; Chagas Disease; Chronic Disease; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Mice; Mice, Inbred BALB C; Treatment Failure; Trypanosoma cruzi

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Topics: Acute Disease; Acyclovir; Amphotericin B; Antifungal Agents; Appendicitis; Aspergillosis; Aspergillus; Child; Ciprofloxacin; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Voriconazole

Acute vision loss in the post-partum period can occur due to many reasons. Eclampsia, posterior reversible encephalopathy syndrome (PRES), pituitary apoplexy, and central serous retinopathy are some of the important causes. Cryptococcal meningitis as a cause of acute vision loss in the post-partum period has not been mentioned in literature.. A 25-year-old female presented to us with acute bilateral complete vision loss in the post-partum period. Her serum was tested positive for HIV antibodies. Cerebrospinal fluid (CSF) examination revealed cryptococcal meningitis. She was started on amphotericin B, antiretroviral drugs, and steroids. Though symptoms of meningitis resolved after treatment no significant improvement in vision was observed at 3 months.. Cryptococcal meningitis may be considered as one of the causes of acute vision loss in pregnant/post-partum females with human immunodeficiency virus (HIV) positivity.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Blindness; Female; HIV Antibodies; HIV Seropositivity; Humans; Meningitis, Cryptococcal; Postpartum Period; Pregnancy; Treatment Outcome

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

A 70-year-old man received a course of therapy that consisted of prednisolone, cyclosporine, and etoposide due to hemophagocytic syndrome which had developed during primary myelofibrosis. He also received micafungin (MCFG) as prophylaxis against a potential fungal infection. We diagnosed febrile neutropenia due to the hemophagocytic syndrome therapy and candidemia because Candida species were detected in blood cultures. He received liposomal amphotericin B (L-AMB) for the candidemia but did not respond to this treatment. Oliguria was diagnosed and renal failure progressed rapidly. We suspected that his renal failure had been induced by the antibiotics. We thus changed the antibiotic regimen but he died of progressive renal failure. We performed renal necropsy and diagnosed acute interstitial tubular nephritis, due to a yeast-like fungus that generally invades the renal tubules. The yeast-like fungus was later identified as Trichosporon asahii, rather than candida, by blood cultures. An immunocompromised host receiving MCFG for acute progressive renal failure requires an appropriate antifungal drug considering the possibility of disseminated Trichosporon.

Topics: Acute Disease; Aged; Amphotericin B; Echinocandins; Humans; Kidney Tubules; Lipopeptides; Male; Micafungin; Neutropenia; Primary Myelofibrosis; Trichosporon; Trichosporonosis

Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined.. Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP).. ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment.. ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.

Topics: Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Communication; Cell Cycle Checkpoints; Cell Proliferation; Cells, Cultured; Connexin 43; Female; Fluorescence Recovery After Photobleaching; Gap Junctions; Gene Expression; Humans; Leukemia, Myeloid; Male; Mesenchymal Stem Cells; Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; Tretinoin

We present a case report of young man with Type 1 diabetes who developed acute visual loss after initially presenting with diabetic ketoacidosis. The diagnosis of invasive paranasal sinusoidal aspergillosis was made following CT and biopsy. Although uncommon, visual loss is a recognised complication of disseminated aspergillosis and is more likely in immune-compromised patients and those with diabetes. Early investigation with appropriate sinus imaging and involvement of the Ear Nose and Throat team in recommended when patients with diabetes develop acute visual loss in the context of a non-specific infective illness.

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Biopsy; Blindness; Caspofungin; Diabetes Mellitus, Type 1; Diagnosis, Differential; Echinocandins; Emergency Service, Hospital; Fatal Outcome; Humans; Lipopeptides; Magnetic Resonance Imaging; Male; Meropenem; Middle Aged; Paranasal Sinuses; Thienamycins; Tomography, X-Ray Computed; United Kingdom

Aspergillus pneumonia often is a fatal consequence of prolonged neutropenia in patients with acute leukemia. Despite prompt diagnosis and adequate antifungal therapy, mortality remains high among these patients. Recognizing early signs and symptoms, as well as risk factors, is the key to reducing morbidity and mortality.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Humans; Leukemia; Pneumonia

The efficacy of antifungal prophylaxis for prevention of invasive aspergillosis (IA) may depend on whether IA results from recent inhalation of spores or reactivation of latent colonisation. Compare the efficacy of liposomal amphotericin B (LAmB) for prophylaxis in acute and reactivation models of IA. In the acute model, mice immunosuppressed from day 0 were challenged at day 3 with an aerosol of Aspergillus fumigatus. LAmB (15 mg kg(-1) ) was administered at day 0 or at challenge. In the reactivation model, naïve mice exposed to A. fumigatus remained untreated until clearance of spores from the lungs, then immunosuppressed to induce reactivation. A single LAmB dose was administered at start of immunosuppression. In the acute model, a single administration of LAmB at start of immunosuppression was not effective, but an additional administration resulted in a significant decrease in lung fungal burden (P < 0.05 vs. controls). A significant prophylactic efficacy was observed when LAmB was administered once at challenge (P < 0.01). In the reactivation model, a single LAmB administration at start of immunosuppression significantly reduced both reactivation rate and fungal burden vs. controls (P < 0.01). Our results show that the conditions under which IA develop and timing of administration of LAmB were determinant variables for prophylactic efficacy.

Topics: Acute Disease; Amphotericin B; Animals; Antibiotic Prophylaxis; Antifungal Agents; Aspergillus fumigatus; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lung; Mice; Mice, Inbred BALB C; Neutropenia; Spores, Fungal

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Caspofungin; Combined Modality Therapy; Echinocandins; Humans; Hyphae; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Leukemia, B-Cell; Lipopeptides; Male; Middle Aged; Neutropenia; Spleen; Splenectomy; Splenic Diseases; Triazoles

Blastomycosis is an infection caused by the dimorphic fungus Blastomyces dermatitidis. Infection can disseminate to skin, where characteristic ulcerative and verrucous plaques, sometimes studded with pustules, are typically seen. Herein we report 3 patients, two children and one adult, with pustular blastomycosis. Their cutaneous lesions exhibited a pustular morphology at the onset and throughout the course of their illness, without evolution to more typical verrucous or ulcerative plaques. These patients all resided in Memphis, TN, the site of previous case reports of pustular blastomycosis.

Topics: Acute Disease; Adolescent; Aged; Amphotericin B; Biopsy, Needle; Blastomyces; Blastomycosis; Female; Follow-Up Studies; Humans; Immunohistochemistry; Infusions, Intravenous; Itraconazole; Male; Risk Assessment; Sampling Studies; Severity of Illness Index; Survival Rate

Clinical cases involving paracoccidioidomycosis in children, diagnosed in Mato Grosso State, in the central western region of Brazil, are rare despite the state being classified with a moderate to high incidence. We describe a clinical case of infant acute disseminated Paracoccidioidomycosis in Mato Grosso State, Brazil, highlighting the importance of early differential diagnosis from other severe pathologies, thus contributing to the survival of compromised patients. A 3 year-old male child, weighing 12.8 Kg, originating from Vila Rica, MT, Brazil. The patient presented intermittent 40 masculineC fever evolving over 40 days, dry cough and painless bilateral cervical adenomegaly, showing no signs of inflammation. This was associated with diarrhea, distension and important abdominal pain and weight loss. Diagnosis was achieved by visualization of Paracoccidioides brasiliensis yeasts in a direct mycological exam and posterior fungus isolation in culture medium. The patient evolved presenting good clinical response to antifungal treatment and progressive reduction of abdominal and cervical ganglions. To improve the prognosis of compromised patients it is essential that professionals realize a full clinical-laboratorial evaluation, including differential diagnoses for other severe pathologies, as early as possible. The degree and intensity of paracoccidioidomycosis compromise are determining factors for defining the most efficient treatment.

Topics: Acute Disease; Amphotericin B; Child, Preschool; Humans; Male; Paracoccidioides; Paracoccidioidomycosis; Prednisone

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

We retrospectively analyzed 542 proven/probable mould infections registered, in the course of 2 studies, in 8,633 patients with acute leukemia, focusing on scedosporiosis. We aimed to define scedosporiosis incidence and mortality rate over a 15-year period. Only 5 cases of scedosporiosis were identified, all of them involving patients with acute myeloid leukemia (AML). We also reviewed all cases of Scedosporium spp. infections in acute leukemia reported to date in the international literature. The 52 cases analyzed confirmed that acute myeloid leukemia is the category with the highest risk of scedosporiosis. Clinical features of scedosporiosis were extremely variable and closely related to patient immune status. Infection disseminated to multiple sites in a very high percentage of patients and outcome was confirmed to be very poor. In our surveys all patients died, in spite of Amphotericin B compounds or voriconazole administration. Our review of literature found scedosporiosis attributable mortality rate (AMR) to be 77%. In conclusion, scedosporiosis, although extremely rare, represents a big problem for clinicians because of its aggressive clinical presentation and the lack of an effective therapy. New drugs with in vitro activity against Scedosporium spp (voriconazole, posaconazole) should be considered. However, their clinical activity should be more widely demonstrated.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Child; Child, Preschool; Humans; Leukemia; Male; Middle Aged; Mycetoma; Pyrimidines; Retrospective Studies; Scedosporium; Triazoles; Voriconazole

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Appendicitis; Candidiasis; Female; Fluconazole; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Splenic Diseases

Topics: Acute Disease; Amphotericin B; Antiprotozoal Agents; Drug Therapy, Combination; Hepatitis; Humans; Leishmaniasis, Visceral; Lupus Erythematosus, Systemic; Male; Middle Aged; Treatment Outcome

Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

Topics: Acanthamoeba; Acute Disease; Amebiasis; Amphotericin B; Animals; Antiprotozoal Agents; Chemistry, Pharmaceutical; Female; Humans; Injections, Intravenous; Lipids; Lung Transplantation; Middle Aged; Postoperative Complications; Pyrimidines; Skin Diseases, Parasitic; Treatment Outcome; Triazoles; Voriconazole

We describe 2 patients with hematologic malignancy who developed endophthalmitis due to Trichosporon beigelii during the course of treatment with multiagent chemotherapy. Blood cultures revealed T beigelii for both patients. Although one of the patients was treated with fluconazole (FLCZ) and 5-fluorocytosine, the trichosporonous endophthalmitis was resistant to both drugs. This patient subsequently received amphotericin B (AMPH-B) therapy, and the eyes were treated with vitrectomy. The second patient also received AMPH-B for FLCZ-resistant trichosporonous chorioretinitis. In both patients, systemic treatment with AMPH-B successfully resolved the trichosporonous endophthalmitis that was resistant to multiple antifungal drugs. Endophthalmitis due to trichosporonosis is difficult to treat. The administration of AMPH-B is likely to be more effective in treating endophthalmitis due to trichosporonosis when the disease is at an early stage.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Fungal; Endophthalmitis; Female; Fluconazole; Flucytosine; Humans; Leukemia, Myeloid; Male; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trichosporon

Zygomycosis is an invasive, life threatening fungal infection that usually affects immunocompromised hosts. In the head and neck region, rhino-orbito-cerebral zygomycosis is more common than the cervicofacial variety. We report the first case of otogenic cervicofacial zygomycosis caused by Apophysomyces elegans involving the salivary glands, an uncommon site of infection. The case began after a trivial trauma in a diabetic patient and despite surgical debridement and liposomal amphotericin B therapy, the patient died due to extensive involvement and metabolic/hemodynamic complications.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Diabetes Complications; Facial Paralysis; Fatal Outcome; Humans; Male; Mucorales; Mucormycosis; Otitis; Parotid Gland; Parotitis; Salivary Glands; Sialadenitis

Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Chronic Disease; Female; Humans; Immunocompromised Host; Leukemia, Myeloid; Male; Middle Aged; Myeloproliferative Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sinusitis; Stem Cell Transplantation

Topics: Acute Disease; Aged; Amphotericin B; Aspergillosis; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis

Invasive pulmonary aspergillosis is a serious infectious complication in immunocompromised especially neutropenic patients. Despite improvements in early diagnosis and effective treatment, invasive pulmonary aspergillosis is still a devastating opportunistic infection. These infections also interfere with the anticancer treatment. We report our experience in the diagnosis and therapeutic management of sinopulmonary aspergillosis in 4 children with hematologic malignancy. All patients except the first were neutropenic when sinopulmonary aspergillosis was diagnosed. Clinical signs included fever, cough, respiratory distress, swallowing difficulty, headache, facial pain-edema and hard palate necrosis. Radiodiagnostic methods showed bilateral multiple nodular infiltrations, soft tissue densities filling all the paranasal sinuses, and bronchiectasis. Diagnosis of aspergillosis was established by bronchoalveolar lavage in one case, tissue biopsy, positive sputum and positive cytology, respectively, in the other 3 cases. One patient was treated with liposomal amphotericin B and other 3 cases were treated with liposomal amphotericin B + itraconozole. Outcome was favorable in all cases except the one who died due to respiratory failure. Early diagnosis, appropriate treatment and primary disease status are important factors on prognosis of Aspergillus infections in children with hematological malignancy.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Burkitt Lymphoma; Child; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed

Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as those with haematological malignancies. The sites most frequently involved are the sinuses and the lungs. New diagnostic tools and new antifungal treatments are essential in order to diagnose early and treat efficiently infections due to moulds. We report a case of sinusitis due to Absidia corymbifera occurring during chemotherapy-induced bone marrow aplasia in a patient with acute leukaemia. The sinusitis was successfully treated with AmBisome, and surgical debridement.

Topics: Absidia; Acute Disease; Aerosols; Amphotericin B; Amsacrine; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Debridement; Drug Resistance, Fungal; Drug Resistance, Neoplasm; Etoposide; Fluconazole; Humans; Immunocompromised Host; Leukemia; Liposomes; Middle Aged; Mucormycosis; Sinusitis; Tomography, X-Ray Computed

To report the clinical course of a woman with cryptococcal meningitis and no previous cardiac disease who developed a fatal cardiac arrhythmia after an acute overdose of amphotericin B and to review its toxicity.. A 41-year-old woman with a history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Liposomal amphotericin B was prescribed at the standard dose of 5 mg/kg/day; however, amphotericin B deoxycholate 5 mg/kg was inadvertently administered (usual dose of the deoxycholate formulation is 0.5-0.8 mg/kg/day). The patient developed cardiac arrhythmias, acute renal failure, and anemia. The medication error was noticed after she had received 2 doses of amphotericin B deoxycholate, and it was then discontinued. Despite treatment in the intensive care unit, the woman died on the sixth day after admission.. Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity, with ventricular arrhythmias and bradycardia reported in overdoses in children and in adults with preexisting cardiac disease, even when administered in conventional dosages and infusion rates. Use of the Naranjo probability scale indicated a highly probable relationship between the observed cardiac toxicity and amphotericin B deoxycholate therapy in this patient.. Given the fulminant course of amphotericin B deoxycholate overdosage and lack of effective therapy, stringent safeguards against its improper administration should be in place.

Topics: Acute Disease; Adult; Amphotericin B; Arrhythmias, Cardiac; Chemistry, Pharmaceutical; Deoxycholic Acid; Drug Combinations; Drug Overdose; Fatal Outcome; Female; Humans; Medication Errors; Meningitis, Cryptococcal

Invasive Acremonium infection in humans is rare. We report a patient with leukemia who developed pyomyositis due to Acremonium species. Painful cutaneous nodules and severe myalgia were the first clinical manifestations during the neutropenic stage after chemotherapy. Magnetic resonance image (MRI) revealed multiple nodular lesions scattered along the intramuscular regions of the lower legs. Culture of an aspiration grew Acremonium species. Surgical drainage was performed. Although all antifungal agents tested showed no in vitro inhibitory activity, we successfully treated this patient with amphotericin B, granulocyte colony-stimulating factor (G-CSF), and surgical drainage.

Topics: Acremonium; Acute Disease; Adolescent; Amphotericin B; Drainage; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Mycoses; Neutropenia; Opportunistic Infections

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Bacterial Infections; Humans; Leukemia, Myeloid; Mycoses; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

To understand the presentation and current management of histoplasmosis in a pediatric oncology center. Study design Retrospective review of clinical features of patients with histoplasmosis at a tertiary-care cancer center in an endemic area.. Between 1988 and 2001, 57 patients with cancer had 61 episodes of acute histoplasmosis. Of these, 76% were male, and 64% had acute lymphocytic leukemia (ALL). Most were not neutropenic and had nonspecific febrile illnesses. The most rapid and specific tests for histoplasmosis in patients with cancer were histopathologic examination of lung biopsy specimens in patients with localized pulmonary infection and Histoplasma sp. antigen detection in the urine of patients with disseminated histoplasmosis (DH). The mean times to diagnosis were 20.6+/-15.2 days (pulmonary) and 18.6+/-8.2 days (disseminated) after the onset of symptoms. Most patients were treated with amphotericin B (AmB) followed by azole drugs for a mean of 8.5+/-3.1 weeks (pulmonary) and 10.4+/-7.9 weeks (disseminated). No patient died of histoplasmosis, but cancer therapy often was modified because of the infection. Most received unnecessary antibacterial drugs.. Most readily available diagnostic tests for histoplasmosis lack sensitivity in these patients. Delay in diagnosis of histoplasmosis complicates care. No deaths were attributed to histoplasmosis; outcomes after treatment are good.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Female; Histoplasmosis; Humans; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies

Topics: Acute Disease; Aged; Amphotericin B; Female; Humans; Leukemia, Myeloid; Recurrence; Sweet Syndrome; Treatment Outcome

Topics: Acute Disease; Adolescent; Amphotericin B; Anesthetics, Intravenous; Anti-Bacterial Agents; Humans; Liposomes; Male; Pancreatitis; Propofol

Topics: Acute Disease; Administration, Oral; Aged; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Follow-Up Studies; Histoplasmosis; Humans; Itraconazole; Lung Diseases, Fungal; Male; Prednisone; Radiography, Thoracic; Time Factors; Tomography, Emission-Computed; Tomography, X-Ray Computed

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Dermatomycoses; Fusarium; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukemia; Male; Middle Aged

Pulmonary aspergillosis and other invasive fungal infections (IFIs) commonly complicate the management of patients with acute leukemia. Standard amphotericin-based therapies may be ineffective for many patients and the available salvage agents (itraconazole and caspofungin) are reported to possess only moderate activity against resistant infections. Laboratory evidence suggests a synergistic interaction between amphotericin and caspofungin. The authors treated a group of patients with amphotericin-refractory IFIs with the combination of caspofungin and amphotericin (or liposomal amphotericin).. A retrospective evaluation of patients with amphotericin-resistant IFIs was conducted. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable.. Thirty patients were included in this analysis. Twenty-six patients had acute leukemia. Based on recently published criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4-65 days) and 7.8 mg/kg (range, 4.2-66.1 mg/kg), respectively. The median duration of combination therapy was 24 days (range, 3-74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Mild to moderate nephrotoxicity was noted in 50% of patients, necessitating the substitution of liposomal amphotericin. Mild elevation of alkaline phosphatase levels occurred in 30% of patients. Caspofungin was temporarily withheld from one patient who developed moderate but reversible biochemical hepatotoxicity.. The antifungal combination of caspofungin and amphotericin can be administered safely to high-risk patients with hematologic malignancies. Although an absolute assessment of efficacy is limited by the design of this study, encouraging outcomes were noted for many patients. The authors plan to evaluate this regimen further in a randomized clinical trial.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Humans; Leukemia; Lipopeptides; Lung Diseases, Fungal; Male; Middle Aged; Peptides; Peptides, Cyclic; Pneumonia; Retrospective Studies

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; Child; Enzyme-Linked Immunosorbent Assay; Fatal Outcome; Galactose; Humans; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Mannans; Postoperative Complications

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Cytarabine; Frozen Sections; Humans; Idarubicin; Immunosuppressive Agents; Leukemia, Myeloid; Male; Middle Aged; Mucormycosis; Thoracic Wall

Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent.. Haematology department and bone marrow transplantation unit.. Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis.. Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Drug Evaluation; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid; Lipopeptides; Lipoproteins; Male; Micafungin; Mucormycosis; Multiple Organ Failure; Peptides, Cyclic; Periodontal Abscess; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sinusitis; Splenectomy; Systemic Inflammatory Response Syndrome; Transplantation, Homologous

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida albicans; Candidiasis; Chemoprevention; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Humans; Leukemia; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia

Hepatosplenic microabscesses secondary to invasion by various organisms may result in life-threatening conditions, especially in patients with cancer. Whether these patients should continue ongoing cytotoxic therapy, which might result in neutropenia, with the risk of progressive abscess formation or fungemia, remains a dilemma. We report five cases of pediatric acute leukemia with hepatosplenic microabscesses in children aged 4 years to 18 years. These patients presented with prolonged fever and neutropenia after antineoplastic chemotherapy, followed by abdominal pain, hepatosplenomegaly and hepatic dysfunction. Abdominal ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated multiple small lesions compatible with hepatosplenic candidiasis in all of the patients. Cultures, including blood or stool cultures, were positive in only two cases. Treatment with intravenous antifungal agents, including amphotericin B, liposomal amphotericin B, and/or fluconazole were successful in two cases. These two patients remained event-free and survived for more than 24 months (20 months and 22 months after infection was diagnosed). The duration of systemic antifungal medication administration ranged from 3 months to 22 months. The serial image examinations revealed drastic reductions in small residual lesions in the two patients who survived the longest. The major issues for these patients were how long the antifungal therapy should be administered for, and how to select the optimal drug and dosage to avoid hepatic and renal toxicity. Among our patients, alternative therapy with amphotericin B, liposomal amphotericin B, and fluconazole was used according to the patients' conditions, and the duration of antifungal therapy was determined by clinical manifestations and imaging study changes.

Topics: Abscess; Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Administration Schedule; Humans; Leukemia; Liver Abscess; Male; Splenic Diseases

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Hepatitis; Humans; Leukemia; Lung Diseases, Fungal; Opportunistic Infections; Osteomyelitis; Pyrimidines; Remission Induction; Sacroiliac Joint; Splenic Diseases; Triazoles; Voriconazole

A case of rhinocerebral mucormycosis occurring in a 41-year-old man with insulin-treated diabetes mellitus is reported. Microscopically, biopsy samples obtained from the left ethmoid and middle turbinate sinuses contained fungi that formed mycotic granulomas associated with multinucleate giant cell arteritis. The multinucleate giant cells contained broad, infrequently septate hyphase consistent with mucormycosis. The patient received surgical debridement with extenteration of the left orbit, and intravenous liposome-encapsulated amphotericin B. After 12 months, examination of the patient revealed complete healing. Multinucleate giant cell granulomas and arteritis are only exceptionally associated with rhinocerebral mucormycosis, but these histologic findings may be correlated with a progressive disease with better prognosis.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Biopsy; Debridement; Ethmoid Sinus; Giant Cell Arteritis; Granuloma, Foreign-Body; Humans; Male; Mucorales; Mucormycosis; Orbit; Paranasal Sinus Diseases; Survival Rate; Treatment Outcome; Turbinates

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4-12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0.5 x 109/l after a median of 11.5 d (range 11-13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18-59 d) and are alive and well after a median follow-up of > 390 d (range 336-417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Aortic Aneurysm; Arteriosclerosis; Aspergillosis, Allergic Bronchopulmonary; Bone Marrow Transplantation; Cell Count; Diabetes Complications; Diabetes Mellitus; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Chronic-Phase; Lung Diseases, Fungal; Male; Middle Aged; Neutrophils; Platelet Count; Recurrence; Remission Induction; Tomography, X-Ray Computed; Transplantation, Homologous; Treatment Outcome

Fungal infections can be mainly grouped into four types. The invasive forms are acute sinusitis (fulminant), chronic sinusitis (indolent), whereas the non-invasive forms are mycetoma and allergic fungal sinusitis. From December 1993 to December 1997, 27 cases of fungal sinusitis, 22 of which were noninvasive forms, and 5 of which were invasive forms, were treated and are presented in this study. When we classified the patients with fungal sinusitis, 11 were diagnosed as mycetoma, 9 as allergic fungal sinusitis, 3 as acute fulminant sinusitis and 2 as chronic indolent sinusitis, while 2 patients were not included in our four groups of sinusitis. In all mycetoma cases the active agent was Aspergillus. Patients with non invasive forms of sinusitis were all treated with endoscopic sinus surgery. 2 of the patients with invasive forms of sinusitis underwent maxillectomy and they were given Amphotericin-B. With a mean follow up of 20 months, only 3 recurrences were seen. The infection recurred in 2 patients with allergic fungal sinusitis and 1 patient with chronic invasive sinusitis. However, 2 patients with acute fulminant invasive sinusitis died before they were operated on, and 1 patient died postoperatively.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Biopsy; Chronic Disease; Combined Modality Therapy; Endoscopy; Female; Humans; Incidence; Male; Middle Aged; Mycetoma; Mycoses; Paranasal Sinus Diseases; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome

Acute fulminant fungal sinusitis is characterized by acute symptoms and rapid progress with a mortality rate of 60-80%. A large number of survivors have permanent neurological, visual and cosmetic disabilities. This clearly underscores the need of early recognition of this disease in at risk population in order to start urgent treatment. The at-risk population of diabetics, AIDS and other immunosuppressed is likely to increase, as will the incidence of acute fulminant fungal sinusitis. In the present study we have reviewed nine cases of acute fulminant fungal sinusitis to determine clinical presentation, related radiological picture and optimum treatment. Most common presenting features were fever, headache, facial swelling and proptosis. Many patients presented with blindness, facial paralysis and meningitis. Predisposing causes were uncontrolled diabetes with ketoacidosis in four out of six cases, post renal transplant immunosuppression and leukemia. All patients were treated with amphotericin B or liposomal amphotericin B (AmBisome). Diagnosis was confirmed by biopsy and culture of sinus mucosa, soft tissues of cheek, or orbit. Mucor (Zygomycetes) was identified on culture or histopathology in all cases. Surgical debridement was performed in seven cases. Six out of nine patients survived but morbidity was high: only two patients survived without any permanent disability.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Female; Humans; Male; Middle Aged; Mucor; Mucormycosis; Radiography; Retrospective Studies; Sinusitis

The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post-mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Endophthalmitis; Eye Infections, Fungal; Fatal Outcome; Female; Fluconazole; Fungemia; Humans; Leukemia, Myeloid; Male; Middle Aged; Mycetoma; Neutropenia; Scedosporium

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antimony; Antiprotozoal Agents; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Nephrotic Syndrome; Organometallic Compounds; Pancreatitis

Chronic invasive fungal rhinosinusitis is an increasingly recognized, but inadequately characterized, disease entity which is separate and distinct from acute fulminant invasive fungal sinusitis and allergic fungal sinusitis. Chronic invasive fungal rhinosinusitis is divided into granulomatous and nongranulomatous subtypes based on histopathology, but the clinical distinction between the two subtypes is not clear. Current management includes varying degrees of surgical débridement and a prolonged course of antifungal agents. A protracted clinical course with recurrence after treatment is common.

Topics: Acute Disease; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Chronic Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Rhinitis; Sinusitis; Tomography, X-Ray Computed

The development of a rash in response to trimethoprim-sulfamethoxazole (TMP-SMX) administration is a frequent adverse reaction in people with the acquired immunodeficiency syndrome (AIDS). In contrast, there are no published reports in the English language literature describing TMP-SMX induced delirium in an AIDS patient. This report describes the development of frank delirium in a person with AIDS receiving TMP-SMX. The episode resolved completely within 72 h of withdrawal of the drug.

Topics: Acute Disease; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents; Delirium; Drug Therapy, Combination; Histoplasmosis; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Amphotericin B; Anemia, Macrocytic; Bone Marrow; Child; Choroiditis; Female; Fever; Histoplasmosis; Humans; Treatment Outcome

Blastoschizomyces capitatus (BC), a filamentous fungus of genus Trichosporum, is as an important opportunistic pathogen in the compromised host. Within the past 10 years, 47 cases of BC infection have been published. Most of the patients had acute leukemia (AL) or related disorders and had received chemotherapy treatment. Due to BC's resistance to currently used antifungal agents, this infection represents a therapeutic challenge and serious complication in the treatment of hematology malignancies. Here we report our experience with BC infection in four patients with acute leukemia or related disorders.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Female; Humans; Immunosuppression Therapy; Leukemia; Male; Middle Aged; Mycoses; Neutropenia; Trichosporon

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.

Topics: Acute Disease; Amines; Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis, Vulvovaginal; Disease Models, Animal; Dose-Response Relationship, Drug; Echinocandins; Female; Fungal Proteins; Mice; Microbial Sensitivity Tests; Peptides; Peptides, Cyclic; Proline; Solubility; Structure-Activity Relationship; Yeasts

Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5.75 d (range 0-14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Candidiasis; Female; Fever of Unknown Origin; Genes, Fungal; Hematopoietic Stem Cell Transplantation; Humans; In Situ Hybridization; Leukemia, Myeloid; Liver Diseases; Lung Diseases, Fungal; Male; Middle Aged; Monitoring, Physiologic; Neutropenia; Polymerase Chain Reaction; Sensitivity and Specificity

Candida kruzei-related systemic infections are increasing in frequency, particularly in patients receiving prophylaxis with antifungal triazoles. A Caucasian male with newly diagnosed acute myeloid leukaemia (AML M1) developed severe and persistent fever associated with a micropustular eruption scattered over the trunk and limbs during induction chemotherapy. Blood cultures grew Candida kruzei, and biopsies of the skin lesions revealed a candida vasculitis. He responded to high doses of liposomal amphotericin B and was discharged well from hospital.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Candidiasis; Drug Carriers; Humans; Leukemia, Myeloid; Liposomes; Male; Middle Aged; Triazoles; Vasculitis

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Esophageal Diseases; HIV Seropositivity; HIV-1; Humans; Male; Pancreatitis; Substance Abuse, Intravenous

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis; Chemical and Drug Induced Liver Injury; Esophageal Diseases; HIV-1; Humans; Male

The objectives of this study were to analyze the changes in the incidence of cryptococcal disease in the last 10 years (1987-1997) and to assess the factors of poor prognosis in HIV-1 infected patients.. Clinical records of HIV-1 infected patients diagnosed with cryptococcal infection from June 1987 to December 1997 at Hospital Clinic i Provincial in Barcelona, Spain, were examined. An univariate and multivariate analysis of the predictors of poor outcome was performed.. Sixty clinical records were analyzed. The number of cases per 100 exposed patients per year decreased from 1991 to 1993 and, afterwards, decreased again from 1996. Fifty patients had a resolution of clinical symptoms, 17 out of this 50 patients (34%) had a relapse. Factors associated with a higher risk of relapse were a positive blood culture and cryptococcal antigen title in cerebrospinal fluid above 1/1.024.. The decrease in the number of cases of cryptococcal infection coincides with the broad use of triazole antifungal drugs for oral candidiasis (1990-1991) and, afterwards, with the initiation of highly active antiretroviral therapy (1996). The best predictors of relapse are a positive blood cryptococcal culture and a high titter of cryptococcal antigen.

Topics: Acute Disease; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Analysis of Variance; Antifungal Agents; Cohort Studies; Cryptococcosis; Data Interpretation, Statistical; Female; Fluconazole; Flucytosine; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Recurrence; Spain; Treatment Outcome

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Dermatomycoses; Fusarium; Humans; Leukemia, Myeloid; Male; Ulcer

A retrospective study of 23 patients with acute leukaemia and hepatosplenic candidiasis (HSC) was conducted to evaluate clinical treatment characteristics in terms of amount and duration of antifungal agents and to assess treatment outcome. Patients were admitted to two major tertiary care centres between 1990 and 1998. The diagnosis of HSC was based on clinical, blood cultures, histologic and imaging studies. Patients were treated with amphotericin B without interruption of the planned chemotherapy regimens. Serial magnetic resonance imaging (MRI) studies were the main tool for following patients' response and activity of the fungal lesions in conjunction with clinical and laboratory parameters. Treatment with amphotericin B was continued until resolution of all clinical symptoms and signs attributable to HSC, obtaining negative blood cultures and the appearance of at least healed lesions on MRI. Amphotericin B was discontinued in four patients because of severe nephrotoxicity (two patients), or continuous fever and persistent fungal lesions on MRI (two patients). Amphotericin B lipid complex (ABELCET) was successfully used as salvage therapy for these refractory patients. Four patients died with evidence of HSC despite treatment and supportive measures. The response rate for treatment of HSC was 82%. The mean total dose of amphotericin B including empirical treatment was 4 g and the median duration of treatment for responding patients was 112 d. The median number of days of anti- fungal treatment before the disappearance of fever was 19 d. Our results confirmed the need for protracted courses of antifungal agents for the successful eradication of HSC. Chemotherapy for the underlying disorder should not be interrupted or delayed in order to treat HSC.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Female; Fever; Humans; Leukemia, Myeloid; Liver Diseases; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Splenic Diseases

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candidiasis; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Humans; Leukemia, Myeloid; Liver Diseases; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Splenic Diseases

Topics: Acute Disease; Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Cholangitis; Female; Humans; Leukemia

Pancreatic infection by Candida is an infrequent entity. We report two cases and review literature. A 67 year-old woman who was admitted for severe acute pancreatitis of biliary origin developed high fever during fourth week of stay; it was secondary to a pancreatic abscess due to Candida. On the other hand, a 67 year-old man with severe acute biliary pancreatitis and renal insufficiency showed an abscess of similar characteristics that was identified during fourth week of evolution. Both of them recovered completely after surgical drainage and antifungical parenteral treatment. The use of broad spectrum antibiotics recently recommended for prophylaxis of pancreatic infection in patients with necrotizing acute pancreatitis, can favour opportunistic infection by several agents. Pancreatic abscesses by Candida often occurs in patients receiving broad spectrum antibiotics, although it isn't an essential condition. The fact that Candida could be only a contaminant may delay diagnosis and early treatment, and then it can determine a poor outcome. Adequate treatment is urgent surgical drainage associated with antifungical parenteral therapy. Usefulness of antifungic drugs in patients undergoing long term antibiotic prophylaxis for secondary infection must be evaluated.

Topics: Abscess; Acute Disease; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Drainage; Female; Humans; Imipenem; Male; Pancreatic Diseases; Pancreatitis; Radiography; Thienamycins

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Cefuroxime; Cephalosporins; Humans; Infusions, Intravenous; Male; Parotitis; Streptococcal Infections; Streptococcus pyogenes

In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values, P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.

Topics: Acute Disease; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Female; Leishmaniasis, Visceral; Male; Mice; Mice, Inbred BALB C; Surface-Active Agents

Topics: Acute Disease; Adult; Amphotericin B; Ethmoid Sinusitis; Eye Infections, Fungal; Female; Follow-Up Studies; Fundus Oculi; Humans; Mucormycosis; Orbital Diseases; Retinal Diseases

Plasma and tissue concentrations of amphotericin B were determined in a patient treated with liposomal amphotericin B during liver transplant failure. A cumulative rise in amphotericin B plasma concentrations was observed accompanied by an enhanced pulmonary deposition of the drug. Failure of the liver as a major component of the reticuloendothelial system may cause elevated plasma concentrations of liposomal amphotericin B and may consequently enhance deposition of liposomes in the lungs as a substitutive clearing organ.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Fatal Outcome; Humans; Kidney; Liposomes; Liver Failure; Liver Transplantation; Lung; Male; Middle Aged

Compared to non-invasive aspergillosis, invasive aspergillosis in the region of the mouth, jaw and face has rarely been reported. It occurs particularly often in the presence of haematological oncological illness. The case of a patient suffering from acute myeloid leukemia is described; he contracted invasive aspergillosis of the lungs and the alveolar processes in the course of chemotherapeutic treatment. All the alveolar processes in the region of the premolars and molars were demarcated and had to be removed by sequestrectomy. The therapy of invasive aspergillosis should be carried out within the framework of intensive interdisciplinary treatment. In addition to systemic and local antimycotic therapy, the debridement of necrotic hard and soft tissue was necessary.

Topics: Acute Disease; Adult; Alveolar Process; Alveolectomy; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Humans; Jaw Diseases; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Osteonecrosis

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Child; Combined Modality Therapy; Debridement; Humans; Leukemia; Male; Mucormycosis; Muscular Diseases

We report on seven adult leukemic patients who were autografted in spite of a prior history of invasive pulmonary aspergillosis (IPA). Their median age was 41 years (range: 19-61); six patients were male and one female. All seven had acute myeloblastic leukemia (AML) and underwent an autologous marrow transplantation (ABMT) with a marrow purged in vitro by mafosfamide. IPA was suspected prior to ABMT on clinical and radiological features. CT scan confirmed nodular infiltrates and cavitations in six cases. Microbiological documentation consisted of: identification of the fungus from bronchoalveolar lavage: one case, positive antigenemia: one case, positive antibodies: two cases. Prior ABMT patients received amphotericin B for a median total dose of 1915 mg (range: 970-3300). No patient underwent surgery. The median time from diagnosis of IPA to ABMT was 7.3 months (range: 3-10). During ABMT all patients received prophylactic amphotericin B and itraconazole. No patient died from toxicity and no IPA reactivation was observed in any patients. Post-graft, itraconazole was kept on for a median of 3 months (range: 3-5). This study demonstrates that IPA occurring during the management of AML patients is not necessarily a contraindication to subsequent ABMT.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Purging; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; Cause of Death; Combined Modality Therapy; Cyclophosphamide; Feasibility Studies; Female; Humans; Itraconazole; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Middle Aged; Premedication; Tomography, X-Ray Computed; Transplantation Conditioning; Transplantation, Autologous

We undertook a retrospective review of all patients with hematologic malignancies in whom candidemia developed during chemotherapy-induced neutropenia in 1989 and 1990. Candidemia developed in 11 patients; five were receiving therapeutic doses of amphotericin B at the time of infection. Disseminated infection occurred in 2 of 5 patients with breakthrough infection and 3 of 6 patients with candidemia before receipt of amphotericin B. Among patients with breakthrough candidemia there was a trend toward more-prolonged neutropenia prior to infection (P = .069), but otherwise they were indistinguishable from other candidemic patients with regard to risk factors for candidemia. Amphotericin B-susceptible Candida albicans was isolated from two patients and Candida krusei from three patients with breakthrough infection. All patients were treated with amphotericin B; all breakthrough infections responded to treatment. Neutropenic patients with breakthrough candidemia were clinically similar to those whose candidemia preceded amphotericin B therapy, and there was no increase in morbidity and mortality among individuals with breakthrough infection.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Candida; Candida albicans; Candidiasis; Fatal Outcome; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Treatment Failure

To describe the MR appearance of necrotizing fungal granulomas occurring in the liver of leukemic patients with hepatosplenic fungal disease and transfusional hemosiderosis on antifungal antibiotics.. Four patients with acute myelogenous leukemia (n = 2) or acute lymphocytic leukemia (n = 2) who developed hepatosplenic fungal disease, and were treated with antifungal medication, underwent MRI examination on a 1.5 T MR imager. MR images were prospectively evaluated and correlated with liver biopsy (three patients), and clinical picture (one patient).. Multiple liver lesions measuring approximately 1 cm in diameter were identified in all patients. Lesions possessed a distinctive MR appearance: central mild hyperintensity with a peripheral ring of very low signal intensity on precontrast T1- and T2-weighted images. The central region of the lesions enhanced following gadolinium administration with the peripheral ring remaining low in signal intensity.. Necrotizing fungal granulomas in the liver of patients with transfusional hemosiderosis on treatment with antifungal antibiotics have a distinctive appearance of moderate high signal intensity center on T1- and T2-weighted and postgadolinium MR images with a peripheral rim of low signal intensity. This appearance reflects the presence of iron-laden macrophages in the periphery of granulomas and may be expected in processes that initiate an immune response involving aggregation of macrophages in the liver of patients with transfusional iron overload.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Candidiasis; Child; Female; Granuloma; Hemosiderosis; Humans; Itraconazole; Leukemia; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Opportunistic Infections; Transfusion Reaction

A 52-year-old male diagnosed with acute myeloid leukemia (AML) developed an invasive middle-ear mucormycosis during the neutropenic period after consolidation chemotherapy which resolved successfully with surgery and antifungal therapy. The patient underwent autologous peripheral blood stem cell transplantation (APBSCT) in first complete remission with antifungal prophylaxis with liposomal amphotericin B (AmB). There was no clinical, radiological or microbiological data of mycotic reactivation. This is the first reported stem cell transplantation (SCT) in a patient with prior invasive mucormycosis.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Facial Paralysis; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Leukemia, Myeloid; Male; Mastoid; Middle Aged; Mitoxantrone; Mucormycosis; Myringoplasty; Neutropenia; Otitis Media, Suppurative; Remission Induction; Transplantation Conditioning; Transplantation, Autologous

The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis.. Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon.. Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney.. The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics.. Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.

Topics: Acute Disease; Administration, Oral; Amphotericin B; Animals; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Cecal Diseases; Cefotaxime; Colistin; Disease Models, Animal; Drug Therapy, Combination; Imipenem; Injections, Intravenous; Kidney Diseases; Male; Necrosis; Pancreas; Pancreatic Diseases; Pancreatitis; Rats; Rats, Sprague-Dawley; Survival Rate; Tobramycin

Pulmonary toxicity with acute dyspnea occurred during infusion of a liposomal amphotericin B preparation (AmBisome) in two adult leukemic patients. The preparation was administered as a one hour infusion at a dose of 3 mg/kg body weight. Within 15 min after starting the infusion, both patients experienced sudden onset of dyspnea and chest tightness. Physical examination showed the patients to be anxious and restless with tachycardia and orthopnea but without other cardiopulmonary findings. No elevation of body temperature, rigors or chills were recorded. Symptoms disappeared within minutes after discontinuing the infusion. At present, the pathophysiologic mechanisms underlying these side effects are unknown.

Topics: Acute Disease; Amphotericin B; Drug Carriers; Dyspnea; Humans; Infusions, Intravenous; Leukemia, Myeloid, Acute; Liposomes; Male; Middle Aged; Respiratory System

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

A 44-year-old man was admitted with symptoms compatible with Addison crisis. Abdominal computer tomography revealed extensive bilateral adrenal abscesses. Histoplasma capsulatum was cultured from a needle aspirate. The patient was HIV-seronegative and had no underlying malignancy. He may have acquired the infection during several stays in endemic areas in the United States, South America and Asia. The case was also remarkable for moderate brain atrophy, thrombosis of the portal and splenic veins and liver cirrhosis caused by alpha-1-antitrypsin deficiency (phenotype MZ). The patient recovered fully under substitution of adrenal hormones and antifungal treatment. He received intravenous amphotericin B (75 mg q24h) for 10 days, followed subsequently by oral treatment with itraconazole (400 mg q24h) over several months. Radiologic follow-up 9 and 18 months later showed a pronounced decrease of the inflammatory adrenal lesions.

Topics: Abscess; Acute Disease; Addison Disease; Adrenal Gland Diseases; Adult; alpha 1-Antitrypsin Deficiency; Amphotericin B; Histoplasmosis; Humans; Itraconazole; Liver Cirrhosis; Male; Tomography, X-Ray Computed

This is a retrospective study comparing the methods of preventing fungal infection in a total of 420 episodes of chemotherapy-induced neutropenia of more than 10 days' duration between 1986 and 1992 in 104 patients with acute leukemia and 62 patients who underwent bone marrow transplantation. The episodes were divided into five groups according to the prophylactic regimens (group 1, oral amphotericin B (OA) only; 2, OA and nebulization of amphotericin B (NA); 3, OA and NA with a laminar air flow system (LAF); 4, oral fluconazole (OF) and NA; 5, OF, NA, and LAF. The total numbers of neutropenic episodes were 115, 141, 95, 37, and 32, respectively. A total of 15 episode of invasive fungal infections were documented. Aspergillosis was seen on two occasions each in groups 1 and 2, while none was seen in the patients who were under the LAF system. Nebulization of amphotericin B did not have a significant preventive effect in this study and it needs to be evaluated further by a randomized study.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Fluconazole; Humans; Leukemia; Middle Aged; Neutropenia; Retrospective Studies

Postoperative fungal endophthalmitis typically manifests as an indolent uveitis, weeks to months after surgery. In our patient, Torulopsis magnoliae endophthalmitis appeared as an acute, purulent postoperative endophthalmitis on the third day following extracapsular cataract extraction with implantation of a posterior chamber intraocular lens (IOL). The patient required three separate vitrectomy operations with instillation of intravitreal Amphotericin B; the last operation also included complete removal of the posterior capsule and IOL. This case, which is to our knowledge the first reported case of T. magnoliae endophthalmitis, is unusual in that it manifested as an acute, fulminant infection in the early postoperative period and was recalcitrant to standard endophthalmitis therapy.

Topics: Acute Disease; Aged; Aged, 80 and over; Amphotericin B; Candidiasis; Cataract Extraction; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Lenses, Intraocular

The study objective was to identify prognostic factors associated with survival in patients treated for acute leukemias who developed invasive aspergillosis (IA) during induction therapy. This retrospective analysis involved 21 patients treated in two hematologic centers over a six-year period. All were treated in protective isolated rooms with high-dose amphotericin B as soon as fungal infection was suspected. Ten (45%) of the twenty-one patients died. There was no statistical difference between the patients who survived and those who died in relation to the mean time of onset of IA or the total and mean daily dose of amphotericin B. On the other hand a favourable outcome correlated strongly with complete leukemic remission (p < 0.0001): all but one of the patients with objective residual leukemia died of IA, whereas all those who achieved complete hematological remission survived. In conclusion, it seems that the main vital prognostic factor in these leukemic patients with IA was the achievement of complete remission. We were unable to control IA in 10 of 11 patients with refractory leukemia, regardless of neutropenic status, despite early administration of high-dose amphotericin B. All the patients who achieved complete remission were successfully treated with amphotericin B.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Humans; Leukemia; Lung Diseases, Fungal; Middle Aged; Neutropenia; Patient Isolation; Prognosis; Remission Induction; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome

Reports of the concurrent isolation of more than one non-albicans species of Candida from blood cultures of immunocompromised patients with disseminated candidiasis are extremely infrequent. We report on the isolation of Candida krusei and Candida tropicalis from 17 blood cultures that were taken from a 67-year-old white man with a diagnosis of acute biphenotypic leukemia during a 2-week period of hospitalization for induction chemotherapy. Despite receiving high-dose amphotericin B throughout this period, the status of the patient worsened, and he experienced pancytopenia, hypernatremia, azotemia, and disseminated intravascular coagulation, which led to his death. Candida krusei and C tropicalis were isolated concurrently from 10 of the 17 blood cultures, while C krusei was the single isolate in three cultures and C tropicalis was isolated alone in four cultures. Each species manifested markedly different colonial morphological features. This case report serves to emphasize to microbiologists that they must exercise extreme suspicion when non-albicans species of Candida are isolated singly or concurrently from blood cultures in neutropenic patients, given the increasing clinical significance of these yeasts.

Topics: Acute Disease; Aged; Amphotericin B; Candida; Candidiasis; Dose-Response Relationship, Drug; Humans; Leukemia; Male

Between 1984 and 1986 six patients with acute respiratory failure (requiring ventilation for at least 3 days) complicating acute pancreatitis were managed on the intensive care unit (median ventilation period 6 days; range 3-41 days). Between 1987 and 1989 nine similar patients were managed (median ventilation period 35 days, range 4-69 days), and a regimen of enteral tobramycin, polymyxin and amphotericin to selectively decontaminate the digestive tract (SDD) was introduced. Five of six patients treated before 1987 had serious infections (three Gram-negative, one fungal), compared with only one of nine patients treated with SDD (P < 0.05). Clinical signs of sepsis were evident for 62% of the pre-SDD period, compared with 39% of the period during SDD therapy (P < 0.001). Systemic antibiotic prescribing was reduced in the SDD group; however, mortality remained unaffected with only two patients surviving pre-SDD and three during SDD treatment. SDD reduces infection rates and sepsis in patients with acute pancreatitis and may help to improve the prognosis of this life-threatening condition.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Bacteremia; Bacterial Infections; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pancreatitis; Polymyxins; Tobramycin

Low-dose methotrexate sodium therapy used for nonmalignant disease has been associated with a variety of opportunistic infections with pathogens occurring in patients with defective cellular immunity. This article describes the unusual development of disseminated histoplasmosis as a probable complication of immunosuppression resulting from use of methotrexate.. We report the cases of three patients in whom disseminated histoplasmosis developed while receiving low-dose methotrexate therapy for psoriasis. Disease manifestations were unusually severe in two of the three patients. All three cases were disseminated, and two cases resulted in illnesses requiring intensive medical treatment. Each patient responded appropriately to antifungal treatment, although one patient has required long-term suppressive treatment because of persistent Histoplasma antigenuria. These cases illustrate the risk for opportunistic fungal infections in patients receiving low-dose methotrexate therapy for nonmalignant diseases.. Histoplasma should be added to the list of pathogens to be suspected in patients receiving such therapy.

Topics: Acute Disease; Adult; Amphotericin B; Female; Histoplasmosis; Humans; Immunity, Cellular; Male; Methotrexate; Opportunistic Infections; Psoriasis; Time Factors

The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects.

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Drug Carriers; Humans; Leukemia; Liposomes; Liver Diseases; Male; Opportunistic Infections; Splenic Diseases

To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment.. Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole.. All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis.. Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Candidiasis; Child; Child, Preschool; Fluconazole; Flucytosine; Humans; Leukemia; Liver Diseases; Remission Induction; Splenic Diseases; Tomography, X-Ray Computed

To investigate the potential use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, its in vivo antifungal activity was studied in three models of disseminated candidiasis in persistently granulocytopenic rabbits: acute, subacute, and chronic disseminated candidiasis. Fluconazole was compared with the combination of amphotericin B and flucytosine for preventive, early, and late treatment of disseminated candidiasis, depending on the model. Fluconazole was most effective when used for preventive or early treatment of acute and subacute disseminated candidiasis. When compared with the combination of amphotericin B plus flucytosine, fluconazole was similarly effective in early treatment of acute and subacute disseminated candidiasis. When treatment was delayed 6 days after established infection, fluconazole was less active in clearing tissues in comparison with its activity in preventive and early treatment. The combination of amphotericin B plus flucytosine, however, was significantly more active than fluconazole in treatment of chronic disseminated candidiasis in all tissues. In summary, fluconazole was most effective against disseminated candidiasis in persistently granulocytopenic rabbits when used for prevention or early treatment.

Topics: Acute Disease; Agranulocytosis; Amphotericin B; Animals; Candidiasis; Chronic Disease; Disease Models, Animal; Female; Fluconazole; Flucytosine; Kidney; Liver; Rabbits; Specific Pathogen-Free Organisms

Topics: Acute Disease; Adult; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Ciprofloxacin; Combined Modality Therapy; Drug Evaluation; Drug Therapy, Combination; Humans; Leukemia; Roxithromycin; Sepsis; Streptococcal Infections

Over a 2-year period, all surgical patients from whom Candida was isolated from intra-abdominal specimens were evaluated. All but 1 of the 49 evaluable patients had either a spontaneous perforation (57%) or a surgical opening of the gastrointestinal tract (41%). Candida caused infection in 19 patients (39%), of whom 7 had an intra-abdominal abscess and 12 peritonitis. In the other 30 patients (61%), there were no signs of infection and specific surgical or medical treatment was not required. Candida was more likely to cause infection when isolated in patients having surgery for acute pancreatitis than in those with either gastrointestinal perforations or other surgical conditions. The development of a clinical infection was significantly associated with a high initial or increasing amount of Candida in the semiquantitative culture. Surgery alone failed in 16 of 19 patients (84%), of whom 7 died and 9 recovered after combined antifungal and surgical treatment. The overall mortality and the mortality related to infections were significantly higher in the patients with intraabdominal candidal infections than in those without such infections.

Topics: Abscess; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Candida; Candidiasis; Child; Child, Preschool; Combined Modality Therapy; Drainage; Female; Humans; Infant; Intestinal Perforation; Male; Middle Aged; Pancreatitis; Peritoneum; Peritonitis; Postoperative Complications; Prospective Studies; Retrospective Studies; Time Factors

We report here on an eight-year-old boy who first developed acute intravascular hemolysis following therapy with amphotericin B (AmB) and subsequently a delayed hemolytic transfusion reaction due to alloantibodies. Although there is as yet no evidence for metabolism of AmB in vivo, the hemolysis appeared to be the result of sensitization against a degradation product of the drug. The patient's serum contained a hemagglutinating IgM antibody that reacted with all red blood cells (RBC) tested in the presence of plasma obtained from patients receiving AmB (ex vivo antigen), but not in the presence of their urine, AmB itself, or with AmB-pretreated RBC. These findings indicate that the antibody was directed against a degradation product of AmB, presumably a trace metabolite, that has not yet been identified.

Topics: Acute Disease; Amphotericin B; Anemia, Hemolytic, Autoimmune; Biotransformation; Child; Hemagglutination Tests; Hemoglobins; Humans; Isoantibodies; Male

Using serial examination and oral cytology, 50 adult patients undergoing induction therapy for acute leukemia were studied for oral colonization with candida species. Ninety percent of patients were found to be colonized with Candida, with most of these colonizations present by day 14. The 30 patients exhibiting colonization with pseudohyphae received ketoconazole 400 mg daily by mouth. Of 20 patients in this group treated for 5 or more days, Candida organisms were eradicated in nine. Sixteen patients from the above group with persistent colonization on ketoconazole were treated by independent clinical decision for sustained fever and neutropenia with Amphotericin B, but only one responded by elimination of colonization. Seven of the 15 patients who did not initially receive ketoconazole developed Candida dissemination in contrast to two of 30 who received ketoconazole initially (P = 0.003, Fisher's exact test). No patient who initially had or acquired a negative cytology developed oral or disseminated candidiasis. Clinical oral candidiasis occurred in three patients, all of whom were receiving amphotericin B. Approximately 90% of these patients have or develop oral colonization with Candida organisms as identified by oral cytology. Those with colonization, both with and without pseudohyphae present, are at risk for dissemination. Amphotericin B does not eliminate colonization remaining after treatment with 400 mg of ketoconazole daily. More effective diagnostic and therapeutic strategies are needed to identify and eliminate Candida organisms and to prevent disseminated candidiasis in this population of patients.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Candida; Candidiasis, Oral; Female; Humans; Ketoconazole; Leukemia; Male; Middle Aged

The authors report the case of 5 1/2 year-old boy with insulin-dependent diabetes mellitus revealed during the induction therapy of an acute leukemia of the mixed type, and who presented with an unusual type of pulmonary fungal infection: mucormycosis. It had a favourable outcome with surgical excision preceded and followed by amphotericin B treatment.

Topics: Acute Disease; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Diabetes Mellitus, Type 1; Humans; Leukemia; Male; Mucormycosis; Postoperative Care; Remission Induction

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Humans; Immune Tolerance; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mitosporic Fungi; Mycoses; Opportunistic Infections; Remission Induction

Topics: Acute Disease; Administration, Oral; Adult; Aged; Amphotericin B; Female; Fungi; Humans; Leukemia; Male; Middle Aged; Mycoses

Over 80 percent of patients with invasive pulmonary aspergillosis (IPA) undergoing intensive antileukemic chemotherapy in a recent two-year period survived the pulmonary infection as a result of early diagnosis and aggressive therapy with high-dose amphotericin B and 5-fluorocytosine. CT played an important role in establishing the early diagnosis of IPA and affected management. Since our original communication describing the CT findings of IPA, we have added ten new cases, each subsequently substantiated by lung biopsy (two), autopsy (two), and/or positive cultures of sputum or extrapulmonary sites (seven). The CT halo sign, or zone of lower attenuation surrounding a pulmonary mass, was present in eight of nine patients with early CT scans obtained during bone marrow aplasia. Characteristic CT progression from multiple fluffy masses to cavitation or air crescent formation suggested IPA in five of seven patients with serial CT scans. CT directly affected patient management in seven of ten cases. Scan findings were one criterion for increasing to high-dose amphotericin B or for adding 5-fluorocytosine. CT characteristics of healing IPA lesions were similar to resolving pulmonary infarcts and were used to monitor disease activity in patients on long-term amphotericin B and prior to retreatment chemotherapy.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Aspergillosis; Female; Flucytosine; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adult; Amphotericin B; Cryptococcosis; Flucytosine; Humans; Male

Serum total iron-binding capacity (TIBC) was measured serially on 70 patients with acute leukemia throughout the period of chemotherapy-induced granulocytopenia. Fungal infections were documented in 13 of these patients (18.6%), while 41 patients (58.6%) had clinically suspected fungal infections and 16 (22.9%) had no evidence of fungal infections during the granulocytopenia. Documented fungal infection occurred in patients with the greatest reduction in TIBC (P less than .015). Early reduction in TIBC also correlated with a greater risk for occurrence of fungal infection, and the earliest institution of amphotericin B (Amp-B) (P less than .004). Effective antifungal therapy was further associated with a return of TIBC levels toward normal. These data demonstrate that altered iron metabolism during granulocytopenia is associated with the development of fungal infections in compromised patients. Serial monitoring of TIBC, along with other clinical and mycologic findings, may prove useful in developing strategies for predicting patients at risk for developing a fungal infection and directing the appropriate use of empiric therapy with Amp-B.

Topics: Acute Disease; Adult; Aged; Agranulocytosis; Amphotericin B; Blood Transfusion; Disease Susceptibility; Erythrocyte Transfusion; Humans; Iron; Leukemia; Middle Aged; Mycoses; Platelet Transfusion; Protein Binding; Risk; Transferrin

Identification of the cause and subsequent specific therapy are indicated for those prolonged or relapsing fevers that follow abdominal surgery. On rare occasions, these fevers can be attributed to potentially life-threatening occult infections, including maxillary sinusitis, acute cholecystitis, antibiotic-related pseudomembranous colitis, toxic shock syndrome, systemic candidiasis, and transfusion-related cytomegalovirus disease, malaria, and babesiosis. Early recognition and appropriate treatment of these infections relieve anxiety, reduce hospital costs, and increase patient survival rates.

Topics: Abdomen; Acute Disease; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cholecystitis; Clostridium Infections; Colitis; Fever; Foreign Bodies; Humans; Intubation, Gastrointestinal; Intubation, Intratracheal; Maxillary Sinus; Postoperative Complications; Shock, Septic; Sinusitis; Staphylococcal Infections; Transfusion Reaction

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Digestive System; Drug Combinations; Humans; Leukemia; Leukocyte Count; Neomycin; Polymyxin B; Polymyxins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We have reported the first case of successful treatment of disseminated histoplasmosis in a renal allograft recipient using a short course (14 days) of amphotericin B in combination with prolonged therapy (161 days) with ketoconazole. This regimen should decrease the risk of antibiotic induced nephrotoxicity, but it requires further study. Five days of treatment with ketoconazole alone was ineffective in our patient's infection. Our protocol might not be as efficacious in patients who are more profoundly immunocompromised, eg, bone marrow allograft recipients. Because relapse of histoplasmosis may occur as long as nine years after treatment, immunocompromised patients being treated with ketoconazole must have close long-term clinical follow-up.

Topics: Acute Disease; Adult; Amphotericin B; Drug Combinations; Follow-Up Studies; Histoplasmosis; Humans; Immunosuppression Therapy; Ketoconazole; Kidney Transplantation; Male; Postoperative Complications

A 32-year-old man with diabetes had rapid development of acute respiratory failure and severe hypoxemia. Radiologic and hemodynamic evaluation confirmed the clinical diagnosis of adult respiratory distress syndrome, and open-lung biopsy disclosed blastomycosis as the etiologic agent. The survival of this patient, after amphotericin therapy, to our knowledge is the first reported recovery from substantiated adult respiratory distress syndrome secondary to blastomycosis.

Topics: Acute Disease; Adult; Amphotericin B; Blastomycosis; Humans; Lung; Lung Diseases, Fungal; Male; Radiography; Respiratory Distress Syndrome

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.

Topics: Acute Disease; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Diagnosis, Differential; Diagnostic Errors; Humans; Leukemia; Lung Diseases, Fungal

Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period. One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein. The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution. Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common. Blood cultures were positive in only 35 percent of patients with disseminated candidiasis. Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered. Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients. Only six (4.5 percent) of 133 patients with proved deep organ infections recovered. Respiratory failure was the clinical cause of death in 62 percent of patients. Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Bacteriological Techniques; Candida; Candidiasis; Cytomegalovirus Infections; Humans; Ketoconazole; Leukemia; Lymphoma; Miconazole; Mycoses; Neoplasms; Neutropenia

Topics: Acute Disease; Amphotericin B; Humans; Ketoconazole; Leukemia; Mycoses

Topics: Acute Disease; Adolescent; Adult; Aged; Alabama; Amphotericin B; Bone Diseases; Chronic Disease; Histoplasmosis; Humans; Imidazoles; Ketoconazole; Lung Diseases, Fungal; Male; Mediastinal Diseases; Middle Aged; Pericarditis; Piperazines

The use of granulocyte transfusions in profoundly neutropenic patients has increased markedly in recent years. Whenever a pulmonary infiltrate develops during the course of these transfusions, the question arises as to what role the transfusions are playing and whether the transfusions should be discontinued to prevent pulmonary deterioration. We have analyzed our recent experience of 593 granulocyte transfusions in 93 patients. 18 patients (19%) developed respiratory compromise or pulmonary infiltrates at some time during the course of granulocyte transfusion. 6 of the 18 cases were reactions to the granulocytes while the remainder were due to fluid overload or other causes. The risk of pulmonary complications did not correlate with the development of cytotoxic leukocyte antibodies, length of transfusion, or concomitant use of Amphotericin. They appeared to be more common in patients with active sepsis. Acute life-threatening pulmonary reactions were rare. Patients receiving granulocyte transfusions should be monitored carefully for pulmonary infiltrates, but other cases should be sought before the transfusions are discontinued.

Topics: Acute Disease; Agglutination; Amphotericin B; Bacterial Infections; Bronchopulmonary Sequestration; Child; Child, Preschool; Granulocytes; Humans; Infant; Lung Diseases; Respiratory Distress Syndrome; Transfusion Reaction

We reviewed the records of 32 patients with acute leukemia and proved invasive fungal infections to determine the clinical and pathologic characteristics of systemic mycosis in patients undergoing intensive induction chemotherapy. The incidence of invasive fungal infections among our patients was at least 27 percent, and Candida and Aspergillus accounted for the majority of these infections. Patients with systemic candidiasis generally had prolonged severe neutropenia, fever refractory to antibiotics, and evidence of mucosal colonization by fungi. At autopsy, Candida was always widely disseminated. Patients with aspergillosis generally had neutropenia, fever, and pulmonary infiltrates at the time of admission to the hospital and, at autopsy, their infections were primarily confined to the lungs. Patients infected with both Candida and Aspergillus had clinical and pathologic findings that were a combination of the features of each type of infection. A diagnosis of invasive fungal infection was established before death in only nine of the patients, all of whom had systemic candidiasis. Four of these patients were successfully treated and survived their hospitalization. The reasons for frequently misdiagnosing and unsuccessfully treating systemic mycosis in patients with acute leukemia are examined, and suggestions are made for improved management of patients at high risk for these infections. These suggestions are based upon recognition of the clinical settings in which fungal infections occur, the aggressive use of invasive diagnostic procedures, and the early empiric use of amphotericin B.

Topics: Acute Disease; Amphotericin B; Aspergillosis; Candidiasis; Humans; Leukemia; Lung; Lung Diseases, Fungal; Nausea; Retrospective Studies; Vomiting

Two patients with acute leukemia were found to have candidal splenic abscesses. Both patients were in remission and had normal granulocyte counts at the time the abscesses became evident. Both patients were treated with splenectomy and antifungal therapy with a definite response. The incidence and treatment of fungal splenic abscesses in leukemia patients is discussed with emphasis on the role of splenectomy.

Topics: Abscess; Acute Disease; Amphotericin B; Candidiasis; Humans; Infant; Leukemia; Leukemia, Lymphoid; Male; Splenectomy; Splenic Diseases

Lymphadenitis caused by Candida developed in a patient with acute leukemia but there was no other evidence of disseminated infection. He was successfully treated intravenously with only 800 mg of amphotericin B. The presentation of disseminated candidiasis in immunocompromised hosts is discussed. The unusual finding in this case of Candida infection apparently confined to a lymph node was interpreted as a stage of fungal invasion more limited than the widely disseminated disease. The concept of a locally invasive but nondisseminated Candida infection was the basis for giving this patient a low dose of amphotericin B.

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Humans; Leukemia; Lymph Nodes; Lymphadenitis; Male; Neck

Topics: Acute Disease; Administration, Oral; Adult; Amphotericin B; Female; Hematologic Diseases; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma; Mycoses

Between January 1974 and July 1976, three adult patients with leukemia, therapy-associated granulocytopenia and febrile courses unresponsive to broad spectrum antibiotic therapy were operated upon for a preoperative diagnosis of candidal abscess of the spleen. The diagnosis was based upon a high index of suspicion of invasive candidiasis in this immunosuppressed group of patients; the failure of the patients to respond to the empiric administration of broad spectrum antibiotics, salicylates and steroids, and the presence of discrete scintiscan defects on liver-spleen scan with both 99Tc sulfur colloid and 67Ga citrate. Multiple splenic abscesses containing candidal organisms were confirmed in all three patients, and two of the three also had multiple small abscesses of the liver. The fourth patient, whose liver-spleen scintiscans were abnormal only in showing splenomegaly and whose febrile course responded to aspirin, did not have a candidal abscess of the spleen at the time of celiotomy which was undertaken for fever of unknown cause. The antemortem diagnosis and treatment of candidal splenic abscess in patients with leukemia is dependent upon a high index of suspicion and appropriate clinical correlation with diagnostic tests. Although the prophylactic oral administration of mycostatin to patients at high risk may prevent this once fatal complication, only prompt and aggressive treatment can cure it.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Candidiasis; Female; Humans; Leukemia; Male; Middle Aged; Splenic Diseases

The diagnosis of rhinocerebral mucormycosis is most often made at autopsy. We report a series of nine patients in whom the diagnosis was established premortem. Six of the patients had underlying diabetes mellitus and three had acute leukemia. Facial or ocular pain was the complaint found in all patients, and frequently was the initial symptom. The diagnosis was established by examination and culture of infected tissue obtained by biopsy. In seven patients, identification of hyphal elements in smears of biopsy material allowed the immediate institution of amphotericin B therapy. Four of the seven patients treated with amphotericin B survived. All surviving patients had underlying diabetes mellitus and had undergone surgical debridement. Early diagnosis leading to immediate institution of appropriate therapy is most important for survival of patients with mucormycosis.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Diabetes Complications; Female; Humans; Leukemia; Male; Middle Aged; Mucormycosis; Nose Diseases

Topics: Acute Disease; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia; Middle Aged; Rifampin

A patient with coccidioidal meningitis was treated with intrathecally administered amphotericin B, and an acute toxic delirium with EEG abnormalities developed. Clinical recovery followed discontinuation of therapy and paralleled EEG resolution. This complication was dose related and argues for caution when initiating intrathecal therapy with amphotericin B at doses greater than 0.025 mg.

Topics: Acute Disease; Adult; Amphotericin B; Coccidioidomycosis; Electroencephalography; Humans; Injections, Spinal; Male; Meningitis; Psychoses, Substance-Induced

A patient wtih acute epidemic pulmonary histoplasmosis was treated with 500 mg of amphotericin B. Traditionally, such patients have not been treated, since the illness is usually self-limited; however, fatalities have been reported, and some authorities have recommended therapy with small doses of amphotericin B. Patients with acute pulmonary histoplasmosis who are acutely ill should be considered for low-dose treatment with amphotericin B, inasmuch as they are likely candidates for early dissemination. Cures have been reported with as little as 105 mg of amphotericin B administered intravenously.

Topics: Acute Disease; Adult; Amphotericin B; Drug Evaluation; Histoplasmosis; Humans; Lung Diseases, Fungal; Male

Topics: Acute Disease; Amphotericin B; Child; Female; Histoplasmosis; Humans; Lung Diseases, Fungal; Radiography

An Aspergillus fumigatus immunodiffusion test was performed biweekly for one year on 80 hospitalized patients with acute leukemia to determine if serologic conversion accompanied clinical aspergillosis. A micro-ouchterlony technique with agarose was used. The antigens were prepared from concentrated A. fumigatus culture filtrates and the sera were concentrated 3-fold before testing. Of 80 patients, 10 were proved at autopsy, lung biopsy, or closed space culture to have invasive aspergillosis. Six of 10 patients converted from a negative to a positive immunodiffusion test, whereas a seventh patient's weakly positive test became strongly positive. Three patients with documented aspergillosis did not develop a positive immunodiffusion test. Four of the patients who converted from a negative to a positive test were treated early and successfully with amphotericin B. A fifth patient developed immunodiffusion test antibody late in the course and died despite therapy. A sixth patient died of concomitant mucormycosis despite early therapy. Six additional patients who converted from a negative to a positive immunodiffusion test could not be evaluated because of inadequate documentation of aspergillosis. In severely immunosuppressed patients, our immunodiffusion test proved to be a specific but not always a sensitive test for aspergillosis. In 4 patients, biweekly tests showed conversion associated with invasive aspergillosis, which was diagnosed early and treated successfully.

Topics: Acute Disease; Amphotericin B; Antibodies, Fungal; Humans; Immunodiffusion; Immunosuppression Therapy; Leukemia; Lung Diseases, Fungal

The diagnosis and successful control of systemic Aspergillus niger infection in 2 adult patients with acute leukemia is reported. During induction therapy, the first patient developed pulmonary infiltrates, skin lesions and abnormal liver function tests. Aspergillus niger was found on skin and liver biopsy. This patient was successfully treated with Amphotericin B and granulocyte transfusions and he remains in remission. The second patient developed a pneumonitis and adynamic ileus with positive sputum and stool cultures for Aspergillus niger. The infection only responded to Amphotericin B and granulocyte transfusions and the leukemia to cytoreductive chemotherapy. The patient later relapsed and died after a febrile illness. Fungi morpholocially consistent with Aspergillus were found in the liver at autopsy. Infection with A. niger is rare even in this patient population; however fungal infections have become an increasing problem. The need for a high index of suspicion, especially when an infection is unresponsive to antibacterial antibiotics, the various diagnostic tools, and the need for aggressive therapy are stressed. Amphotericin B is the chemotherapy of choice but may be insufficient in a severely neutropenic host where the simultaneous use of granulocyte transfusions might be lifesaving.

Topics: Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Aspergillosis; Aspergillus; Aspergillus niger; Blood Transfusion; Female; Granulocytes; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Myeloid, Acute; Leukocytes; Male; Sputum

Topics: Acute Disease; Adult; Aged; Amphotericin B; Antibodies, Fungal; Antigens, Fungal; Arthrodermataceae; Candidiasis; Cell Adhesion; Cell Count; Chronic Disease; Dermatomycoses; Female; Hand Dermatoses; Humans; Immune Adherence Reaction; Immunity, Cellular; Inguinal Canal; Leukocytes; Male; Middle Aged; Onychomycosis; Prednisone; Scrotum; Tinea; Tinea Pedis

Topics: Acute Disease; Amphotericin B; Arthritis, Infectious; Biopsy; Candida albicans; Candidiasis; Humans; Knee; Male; Middle Aged; Synovial Membrane

Topics: Acute Disease; Adult; Aged; Amphotericin B; Arthritis, Infectious; Blastomyces; Blastomycosis; Dermatomycoses; Humans; Lung Diseases, Fungal; Male; Radiography; Sputum; Stilbamidines; Synovial Fluid

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Autopsy; Biopsy; Candidiasis; Candidiasis, Oral; Child, Preschool; Female; Fever of Unknown Origin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Mucor; Mycoses; Retrospective Studies

Topics: Acute Disease; Amphotericin B; Drug Hypersensitivity; Histoplasmosis; Humans; Lung Diseases, Fungal

Topics: Acute Disease; Amphotericin B; Candidiasis, Vulvovaginal; Chronic Disease; Female; Humans; Vaginal Smears

Topics: Acute Disease; Adult; Amphotericin B; Blood Cell Count; Blood Platelets; Candida; Candidiasis; Cytarabine; Feces; Fever; Humans; Hypersplenism; Leukemia; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Nose; Pharynx; Prednisone; Skin; Spleen

Topics: Acute Disease; Adult; Amphotericin B; Arachnoiditis; Cryptococcosis; Humans; Laminectomy; Male; Myelography; Spinal Cord Diseases; Subarachnoid Space

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Cryptococcosis; Cryptococcus neoformans; Hodgkin Disease; Humans; Male; Pericarditis; Young Adult

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Fungicides, Industrial; Histoplasmosis