amphotericin-b and Renal-Insufficiency

It is not yet established the advantages between amphotericin B lipid complex (ABLC) and liposomal (L-AmB) in patients with invasive fungal infections refractory to usual doses of conventional AmB (d-AmB), previous renal impairment, or unacceptable d-AmB renal toxicity. This systematic review aims to compare ABLC and L-AmB effectiveness and safety outcomes in these subgroups of patients.. The search was performed on Medline, Cochrane Library, EMBASE, and LILACS databases.. treatment comparing L-AmB with ABLC; patients who had (i) refractory infection after being treated with d-AmB, (ii) previous renal impairment, or (iii) unacceptable d-AmB toxicity. Two investigators independently screened the search results, assessed trial quality, and extracted data. A total of 1,054 articles were identified in the literature. Among those, eleven were selected for full-text reading and five met the inclusion criteria.. The five articles included reported on four separate observational studies. Overall, no significant difference was found in clinical relevant outcomes as new-onset dialysis, length of hospital stay, or mortality when comparing both lipid formulations. The studies reported a trend toward lower nephrotoxicity in patients treated with L-AmB. However, the results were imprecise and heterogeneous and the studies presented important methodological biases.. The studies included in this systematic review pointed toward less nephrotoxicity events in the L-AmB group. However, due to low quality of evidence and no statistically significant differences in other clinical relevant outcomes, there is no definitive evidence of overall superiority in effectiveness or safety outcomes regarding one lipid formulation or another in this population subgroup.

Topics: Amphotericin B; Antifungal Agents; Humans; Length of Stay; Mycoses; Observational Studies as Topic; Renal Dialysis; Renal Insufficiency

Fungal granulomas of the central nervous system are rare and have a high rate of mortality and morbidity, irrespective of treatment. The authors report their experience of managing 66 patients during 15 years and discuss the clinical, radiological, surgical, and pathologic findings. This series is among the largest reported.. A retrospective analysis was performed on patients with intracranial fungal granulomas (ICFGs), treated in the authors' institution, between January 1997 and May 2011. Only mass-forming histopathologically proven ICFGs were included in this study.. The age of the patients ranged from 7 years to 67 years (mean = 32.3 years), and most patients were in the third and fourth decades of life. The study population comprised 47 male and 19 female patients. The most common symptom was headache (41 patients), followed by vomiting (16 patients) and blurring of vision (16 patients). Only 3 patients presented with fever. The duration of symptoms was less than 6 months in all cases and less than 3 months in 39 cases. Anterior cranial fossa and frontal lobe was involved in 35 cases (54.5%), followed by middle cranial fossa in 20 cases (30.3%). Three cases had granulomas in the cerebellopontine angle. Three cases had multicompartmental involvement, and 4 had multilobar involvement. Nine patients had predisposing factors for fungal infection Based on clinical and imaging data, preoperative diagnosis of a possible fungal lesion was made in 44 (some had only computed tomography imaging) patients. All the patients were treated surgically, followed by antifungal treatment with amphotericin-B and/fluconazole/itraconazole for a period of 6 weeks. Eight patients had symptomatic recurrence of lesions 3-12 weeks after treatment and underwent reoperation. Six patients were lost to follow-up. Nine patients died in the postoperative period (within 30 days postoperatively). Fifteen patients died during follow-up because of recurrent lesions, repeat surgery, renal failure, and unrelated causes. Overall mortality was 24 (36.3%). Poor neurologic status before surgery, emergency craniotomy, severe brain edema with mass effect, and opening of ventricles during surgery were associated with poor outcome. Aspergillus species were the causative organism in an overwhelming majority of patients (n = 52) followed by Mucor in 7 cases, Cladosporium in 3 cases, eumycetoma in 2 cases, and maduramycosis and blastomycosis in 1 case each.. ICFGs have high rates of morbidity and mortality. Early diagnosis, radical surgery, and antifungal treatment for 6 weeks may improve outcome. Poor neurologic status of patients at the time of presentation, immunocompromised state, contamination of ventricular cerebrospinal during surgery, and renal failure (attributable to amphotericin-B) are associated with poor outcome.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brain; Central Nervous System Fungal Infections; Child; Craniotomy; Drug Therapy, Combination; Emergency Treatment; Female; Fluconazole; Granuloma; Humans; Immunocompromised Host; Itraconazole; Male; Middle Aged; Neuroimaging; Recurrence; Renal Insufficiency; Reoperation; Retrospective Studies; Risk Factors; Survival Rate

To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations.. A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.. Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.

Topics: Amphotericin B; Animals; Anti-Infective Agents; Colloids; Diuretics; Humans; Hypokalemia; Lipids; Liposomes; Pharmaceutical Vehicles; Renal Insufficiency

Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Considerable progress in treating IFDs has been achieved over the last years, through the availability of new, effective drugs. However, many of these newer antifungal agents have some limitations, such as their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions.. This article reviews the literature evaluating the safety profile of the lipid formulations of Amphotericin B, echinocandins, and second-generation triazoles. It also discusses the possible drug-drug interactions with some drugs commonly used in allogeneic HSCT.. Nephrotoxicity is the most frequent side effect of lipid formulations of Amphotericin B, which may cause a reduced clearance of the renally eliminated calcineurin inhibitors used for the control of Graft Versus Host Disease. Second-generation triazoles are characterized by a limited toxicity profile, but also by frequent drug-drug interactions with other drugs metabolized by the hepatic enzymes. The echinocandins are characterized by a very low toxicity profile and negligible interactions with other drugs. Such pharmacological knowledge is crucial in the daily care of allogeneic HSCT patients.

Topics: Amphotericin B; Animals; Antifungal Agents; Drug Interactions; Echinocandins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Mycoses; Opportunistic Infections; Pharmacovigilance; Renal Insufficiency; Stem Cell Transplantation; Triazoles

A systematic review was performed to examine renal function in patients with invasive fungal infections, comparing the nephrotoxicity caused by conventional amphotericin B deoxycholate (c-AmB) with that induced by the use of lipid-based amphotericin B formulations. The analysis considered all comparative studies published in the literature between January 1996 and May 2007. The outcome data reviewed herein focused on renal toxicity as measured by serum creatinine (S-Cr) and the doubling or the mean difference in S-Cr levels from baseline to the end of therapy or the need for dialysis. We found that AmB lipid complex (ABLC), liposomal AmB (L-AmB) and AmB colloidal dispersion (ABCD) were significantly less nephrotoxic than c-AmB in all reported studies. ABLC and L-AmB caused low and comparable nephrotoxicity in nine studies. In one randomized study, L-AmB was significantly less nephrotoxic than ABLC. No studies compared ABCD nephrotoxicity to the other lipid formulations. Based on our review we conclude that lipid formulations of amphotericin B are an important strategy to preserve renal function and improve survival in critically ill patients who require treatment for systemic fungal infections.

Topics: Amphotericin B; Antifungal Agents; Humans; Mycoses; Renal Dialysis; Renal Insufficiency; Treatment Outcome

Amphotericin B (AmB) is considered the drug of choice for the treatment of systemic fungal infections. Nephrotoxicity is a major complication associated with its use, and appears to be related to higher cumulative doses, diuretic use, abnormal serum creatinine at baseline, and the use of concomitant nephrotoxic drugs. The two major hypotheses for the pathogenesis of AmB-related nephrotoxicity are direct effects of the drug on epithelial cell membranes and vasoconstriction. During the last few years, some randomized trials have tested different strategies to reduce AmB-induced renal toxicity. These strategies include sodium supplementation, low-dose dopamine, slower infusion rates, the administration of AmB in lipid emulsions, and in lipid formulations. The results of these trials showed that the lipid formulations of AmB significantly reduce nephrotoxicity. Unfortunately, these agents are costly, restricting their use to patients with a high risk of developing renal failure.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Drug Compounding; Humans; Incidence; Intensive Care Units; Kidney Tubules; Renal Insufficiency; Risk Factors

Post kala-azar dermal leishmaniasis (PKDL) is a skin disorder that usually occurs among patients with a past history of visceral leishmaniasis (VL). Cases are also reported without a history of VL. There is no satisfactory treatment regimen available at present. We aimed to compare the efficacy and safety of amphotericin B in two different doses (0.5mg/kg vs 1mg/kg) in a prospective randomized trial in 50 PKDL patients.. In this open label study 50 patients with PKDL, aged between 5-60 years were randomized in two groups. Group A received amphotericin B in the dose of 0.5 mg/kg in 5% dextrose, daily for 20 infusions for 3 courses at an interval of 15 days between each course and Group B received amphotericin B in the dose of 1mg/kg in 5% dextrose on alternate days, 20 infusions for 3 courses an interval of 15 days between each course and followed up for one year.. A total of 50 patients were enrolled, 25 in each of group A and group B. Two patients lost to follow up and three patients withdrew consent due to adverse events. The initial cure rate was 92% in group A and 88% in group B by intention to treat analysis and final cure rate by per protocol analysis was 95.65% and 95.45% in group A and group B respectively. Two patients each from either group relapsed. Nephrotoxicity was the most common adverse event occurring in both the groups.. The lower dose appears to have fewer adverse events however, nephrotoxicity remains a problem in both regimens. The 0.5mg/kg regimen may be considered instead of the higher dosage however safer treatments remain critical for PKDL treatment.

Topics: Adolescent; Adult; Amphotericin B; Antiprotozoal Agents; Child; Dose-Response Relationship, Drug; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Male; Parasite Load; Renal Insufficiency; Treatment Outcome; Young Adult

The standard therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis of amphotericin B (AmB; 0.7 mg/kg per day) plus flucytosine frequently takes >2 weeks to sterilize the cerebral spinal fluid, and acute mortality remains high. A dosage range for AmB of 0.7-1 mg/kg per day is noted in current guidelines, but there are no data comparing 0.7 mg/kg per day with 1 mg/kg per day.. Sixty-four HIV-seropositive, antiretroviral therapy-naive patients in Cape Town, South Africa, who experienced their first episode of cryptococcal meningitis during the period May 2005-June 2006 were randomized to receive either (1) AmB, 0.7 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 1; 30 patients); or (2) AmB, 1 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 2; 34 patients). Regimens were given for 2 weeks, followed by treatment with oral fluconazole. The primary outcome measure was early fungicidal activity, as determined by results of serial, quantitative cerebral spinal fluid cryptococcal cultures. Secondary outcome measures were safety and mortality. The median duration of follow-up was 1 year.. Early fungicidal activity was significantly greater for group 2 than for group 1 (mean +/- SD, -0.56 +/- 0.24 vs. -0.45 +/- 0.16 log cfu/mL of cerebral spinal fluid per day; P = .02). The incidence of renal impairment did not significantly differ between the 2 groups. Anemia was associated with female sex and, less strongly, with membership in group 2. Renal impairment and anemia reversed after the regimen was switched to fluconazole. Two- and 10-week mortality rates were 6% and 24%, respectively, with no difference between groups.. AmB, 1 mg/kg per day, plus flucytosine is more rapidly fungicidal than is standard-dose AmB plus flucytosine. Because of its size, this study provides limited data on any difference in toxicity between the regimens, but toxicities were manageable and reversible.. ISRCTN68133435 (http://www.controlled-trials.com).

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anemia; Antifungal Agents; Cerebrospinal Fluid; Creatinine; Cryptococcus neoformans; Female; Flucytosine; Follow-Up Studies; Hemoglobins; Humans; Male; Meningitis, Cryptococcal; Renal Insufficiency; Sex Factors; South Africa; Treatment Outcome

Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Chemical and Drug Induced Liver Injury; Confidence Intervals; Female; Fever; Fluconazole; Humans; Male; Middle Aged; Mycoses; Neutropenia; North America; Prospective Studies; Renal Insufficiency; Survival

Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6 weeks. Evaluations included clinical response to treatment and adverse events, with emphasis on changes in serum creatinine levels. ABCD did not appear to have an adverse effect on renal function: mean serum creatinine level tended to decrease slightly with days on therapy, and increases were not dose related. Complete or partial response to treatment was reported for 50% of the 133 intent-to-treat patients and 67% of the 58 evaluable patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Kidney; Male; Middle Aged; Mycoses; Prospective Studies; Renal Insufficiency; Treatment Outcome

To evaluate the differences in efficacy and in clinical and biochemical tolerance to amphotericin B administered in a lipid emulsion compared with amphotericin B administered in 5% dextrose in water in the treatment of Candida albicans infection in intensive care unit (ICU) patients.. Prospective, controlled, randomized study, conducted during a 2.5-yr period, comparing the two treatment protocols.. General ICU of a university-affiliated municipal hospital.. Sixty consecutive critically ill patients with confirmed or suspected Candida infection.. Patients received amphotericin B (1 mg/kg/24 hrs), administered randomly in 5% dextrose in water (group A), or in lipid emulsion (20% intralipid) (group B).. Clinical tolerance (fever, chills, hemodynamics), hepatorenal tolerance, and biological tolerance (serum electrolytes and coagulation profile) were evaluated. Patients receiving amphotericin B in lipid emulsion experienced a lower frequency rate of drug-associated fever (61.4% vs. 5.8%, p < .003) rigors (54% vs. 8.5%, p < .004), hypotension (17% vs. 0%), and nephrotoxicity (increase of serum creatinine concentration 66.7% vs. 20%, p < .0002). Significant (264,500 +/- 71,460 to 163,570 +/- 34,450 mm3, p < .01) thrombocytopenia, not associated with active bleeding, occurred in patients receiving amphotericin B lipid in emulsion but not in patients receiving the drug in dextrose.. Treatment with amphotericin B in a lipid emulsion when given to critically ill patients with Candida sepsis seems to be safer and as effective as the conventional mode of administration.

Topics: Adult; Aged; Amphotericin B; Candidiasis; Critical Illness; Fat Emulsions, Intravenous; Female; Glucose; Humans; Infusions, Intravenous; Intensive Care Units; Liver Function Tests; Male; Middle Aged; Prospective Studies; Renal Insufficiency; Solutions

Topics: Amphotericin B; Critical Illness; Humans; Intraabdominal Infections; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Topics: Amphotericin B; Communicable Diseases; Critical Illness; Humans; Intraabdominal Infections; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity.. To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis.. The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy.. A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (β = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (β = 0.299; 95% CI = -0.38 to 0.98; P = 0.388).. CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Topics: Amphotericin B; Critical Illness; Humans; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

BACKGROUND Visceral leishmaniasis (VL) is an endemic systemic disease in the Mediterranean countries, including Spain. This vector-borne infection can present with several clinical presentations, from asymptomatic to severe forms. Renal impairment is frequently described in VL but is usually mild and related to interstitial nephritis, being that glomerular involvement is rarely found. CASE REPORT We describe a case of a 69-year-old Spanish male presenting with subacute renal failure due to membranoproliferative glomerulonephritis and mixed cryoglobulinemia accompanied by other autoimmune features (hypocomplementemia, antinuclear and antiDNA antibodies). No hepatosplenomegaly was found with abdominal ultrasound. Hepatotropic viruses and human immunodeficiency virus serological markers were negatives. We initially suspect the presence of an autoimmune disease and the patient was treated with steroids without improvement. After an extensive study including renal and bone marrow biopsy, a correct diagnosis of visceral leishmaniasis was made, and treatment with liposomal amphotericin B was initiated, achieving renal function recovery and normalization of immunological manifestations. CONCLUSIONS Renal involvement can be an important feature of VL and it might be associated with increased morbidity and mortality. The association between mixed cryoglobulinemia and renal involvement in VL have rarely been described. VL is frequently associated with diverse autoimmune manifestations and it can be initially misdiagnosed, which could lead to fatal consequences. The role of the immune system in the formation of cryoglobulins are discussed. In our case, an autoimmune disease was initially suspected, and starting treatment with steroids pulses was initiated. However, the presence of mixed cryoglobulinemia in this patient who was hepatitis C serological marker negative and who had poor renal function recovery after immunosuppressive treatment made us suspect other pathologies. The presence of cryoglobulinemia with renal disease in endemic areas of Leishmania should make us exclude this infection before starting immunosuppressive treatment.

Topics: Aged; Amphotericin B; Antiprotozoal Agents; Biopsy; Cryoglobulinemia; Glomerulonephritis, Membranoproliferative; Humans; Leishmania; Leishmaniasis, Visceral; Male; Renal Insufficiency; Urine

Amphotericin-B (d-AmB) has a broader anti-fungal spectrum and is used for neonatal invasive-fungal-infections especially invasive-candidiasis (IC). To prevent d-AmB-induced nephrotoxicity, renal protective effect of fluid and electrolyte management has been established among adults; in this study, the authors determined this effect among neonates.. In this retrospective cohort study, the authors reviewed neonatal medical records, admitted to neonatal intensive care unit and received d-AmB therapy. Patients were divided into, renal-insufficiency-group (RIG) and the non-renal-insufficiency-group (NIG).. A total of 90 cases were analyzed, 41 composed RIG and 49 NIG. Renal insufficiency (RI) was developed on 1.7 (0.84) and 7.8 (1.21) days of d-AmB therapy in 26 (63%) and 15 (37%) cases respectively. Bivariate and multivariate analysis demonstrate that >4 m Eq/kg/d sodium intake across all-time points was significantly (. Adequate hydration before and 48 hours after d-AmB therapy and >4 mEq/kg/day sodium intake before and through d-AmB therapy may protect neonatal RI.

Topics: Amphotericin B; Antifungal Agents; Cohort Studies; Electrolytes; Female; Fluid Therapy; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Invasive Fungal Infections; Male; Pakistan; Renal Insufficiency; Retrospective Studies; Sodium; Tertiary Healthcare

Liposomal amphotericin B (L-AmB) was developed to reduce nephrotoxicity and maximize the therapeutic utility of amphotericin B in the treatment of invasive fungal infections. However, there is little investigation into the safety of L-AmB in patients with several renal functions. Therefore, we retrospectively evaluated the clinical safety of L-AmB among patients with several renal functions.. We divided patients treated with L-AmB from April 2014 to September 2016 into 4 groups (estimated glomerular filtration rate (eGFR)≥60, 60 > eGFR≥30, eGFR<30 and hemodialysis). The main endpoint was the incidence of nephrotoxicity and the difference in the serum creatinine values at the end of L-AmB treatment as compared with baseline.. The incidence of nephrotoxicity was not significantly different among four groups (eGFR≥60; 27.0%, 60 > eGFR≥30; 30.8%, eGFR<30; 50.0%, hemodialysis; 40.0%, p = 0.56).Only one group of patients with eGFR≥60 admitted the significant increase of serum creatinine value after L-AmB treatment started (p < 0.01). Patients admitted 0.5 mg/dL or more of increase in serum creatinine values until 9 days from the L-AmB therapy started (eGFR≥60; 5.0 days [3.0-8.0 days], 60 > eGFR≥30; 5.0 days [4.0-9.0 days], eGFR<30; 4.5 days [3.0-5.0 days], hemodialysis; 5.5 days [4.0-7.0 days], p = 0.46).. Take previous clinical study results together, our data suggested that L-AmB is safer agent than amphotericin B for the treatment of fungal infections in patients with eGFR<60 and hemodialysis patients at the start of treatment. Also, especially, we should use L-AmB more carefully until 9 days from the treatment started.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Creatinine; Female; Glomerular Filtration Rate; Humans; Invasive Fungal Infections; Male; Middle Aged; Mycoses; Renal Dialysis; Renal Insufficiency; Retrospective Studies

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

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

Invasive aspergillosis (IA) in liver transplant recipients is associated with grave outcomes. We reviewed 116 individual cases reported in the literature from 1985 to 2013. IA was diagnosed after a median of 25 days after transplantation and involved a single organ in 51% of the cases, whereas in the remaining cases, multiple sites were involved. The most common infecting Aspergillus species were Aspergillus fumigatus (73%), Aspergillus flavus (14%), and Aspergillus terreus (8%). Amphotericin B was the drug most frequently used, and it was followed by voriconazole and itraconazole. Combination regimens were used in 51% of the cases. The overall 1-year cumulative survival probability was 35% [95% confidence interval (CI) = 24.6%-49.6%]. Survival was significantly higher for patients reported from the year 2000 and thereafter (P < 0.001), for those diagnosed with IA more than 30 days after transplantation versus those diagnosed earlier (P = 0.019), and for patients without renal failure (P = 0.020). Additionally, the use of voriconazole was significantly associated with a higher probability of survival (P < 0.001). Cox regression analysis showed that subjects with the involvement of multiple sites had a 2.52 times higher risk of a negative outcome (95% CI = 1.08-5.87) than those with the involvement of a single site. Thus, IA causes life-threatening infections in liver transplant recipients. Predictors associated with poor outcomes may help clinicians to optimize the management of this infection.

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Liver Failure; Liver Transplantation; Male; Middle Aged; Probability; Proportional Hazards Models; Renal Insufficiency; Transplant Recipients; Treatment Outcome; Voriconazole

Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

Topics: Acidosis, Lactic; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anemia, Hemolytic; Antifungal Agents; Cryptococcus neoformans; Drug Therapy, Combination; Female; Humans; Male; Meningitis, Cryptococcal; Renal Insufficiency; Thrombocytopenia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The standard treatment of mucosal leishmaniasis (ML) is pentavalent antimonials, agents with serious adverse effects. Alternative agents include amphotericin B deoxycholate and liposomal amphotericin B. We performed a retrospective study including 29 patients treated with liposomal amphotericin B, most of whom had comorbidities, history of previous treatment of ML, and contraindications to the use of antimonial pentavalent or amphotericin B deoxycholate. We observed a cure rate of 93.1%. Kidney failure was the most important side effect, reported in five patients (17.2%). This study showed a good efficacy and safety profile of liposomal amphotericin B in patients with ML and contraindications to the use of other agents.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antiprotozoal Agents; Brazil; Female; Humans; Leishmania; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Renal Insufficiency; Retrospective Studies; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Critical Illness; Cross Infection; Deoxycholic Acid; Drug Combinations; Fluconazole; Humans; Intensive Care Units; Practice Patterns, Physicians'; Renal Insufficiency

Nephrotoxicity evaluations between liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) have provided mixed results. This retrospective study used an electronic medical record database of hospitalized patients with invasive fungal infections treated with either L-AMB or ABLC. Patients had renal insufficiency, clinical condition suggesting intolerance to amphotericin B deoxycholate (CAB), or recent CAB exposure. Baseline SCr, exposure to other nephrotoxic agents, and total amphotericin B exposure were similar between the groups. In 105 patients administered L-AMB, 10.6% had nephrotoxicity versus 22.6% of 222 patients administered ABLC (P = 0.020). A logistic regression model found ABLC patients had 3.48 higher odds (95% CI 1.05-11.52) than L-AMB of developing nephrotoxicity. Infusion reactions were more prevalent with ABLC (23.9% versus 9.5%, P = 0.002) as was hypomagnesemia (44.3% versus 28.1%, P = 0.033). This study demonstrated that L-AMB is associated with less nephrotoxicity, infusion reactions and hypomagnesemia than ABLC in patients at increased risk of nephrotoxicity.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Hypokalemia; Length of Stay; Male; Middle Aged; Multivariate Analysis; Mycoses; Renal Insufficiency; Retrospective Studies

Literature provides much evidence regarding liposomal amphotericin B treatment for fungal infections in neonates and infants. Relevant data regarding critically ill paediatric patients of older age are scarce. We aimed to present our experience regarding liposomal amphotericin B use in critically ill paediatric patients from a tertiary-care paediatric hospital in Athens, Greece.. We prospectively identified all paediatric patients who received treatment with liposomal amphotericin B in the intensive care unit of a tertiary-care paediatric hospital during a 3-year period (2005-2008). Data were retrieved from the evaluation of the available medical records.. Twenty-three (nine females, mean age: 26·4 months, range: 5-39 months) critically ill paediatric patients were included; 12 had malignancy. In 16 of the 23 included children, liposomal amphotericin B was administered for the treatment of confirmed fungal infections (all but one were invasive), whereas in seven patients, it was used as pre-emptive treatment. One patient received voriconazole concomitantly. Eleven of the 16 children with documented infections were cured; five improved. Six of the seven children who received pre-emptive treatment also showed clinical improvement. Nine deaths were noted, all attributed to underlying diseases. Two cases of hepatotoxicity and one case of nephrotoxicity (all leading to drug-discontinuation) occurred. Seven and five cases of mild reversible hypokalaemia and hyponatraemia, respectively, were also noted.. According to the findings of our small case series, liposomal amphotericin B may provide a useful treatment option for fungal infections of vulnerable critically ill paediatric patients with considerable comorbidity.

Topics: Amphotericin B; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child, Preschool; Comorbidity; Drug Monitoring; Female; Greece; Hospitals, Pediatric; Humans; Hypokalemia; Hyponatremia; Infant; Intensive Care Units, Pediatric; Liposomes; Male; Mycoses; Neoplasms; Prospective Studies; Renal Insufficiency

Lysis syndrome is a constellation of metabolic disorders usually seen after the initiation of chemotherapy for rapidly proliferating malignancies (tumor lysis syndrome). Reported herein is a tumor lysis-like syndrome after the initiation of anti-infective therapy for visceral leishmaniasis.. Ten consecutive patients with visceral leishmaniasis were administered liposomal amphotericin B. Levels of serum uric acid, phosphate, creatinine, blood urea nitrogen, potassium, calcium, and magnesium were evaluated prior to as well as 4 and 30 days following the initiation of treatment.. During the 4th post-treatment day significant increases in the levels of serum uric acid, phosphate, creatinine, and blood urea nitrogen were seen, while the levels of calcium, potassium, and magnesium were not significantly altered. Patients were treated by hydration, urine alkalization, and administration of allopurinol as needed. A recovery of metabolic abnormalities was recorded 1 month later, although some patients had evidence of residual injury.. A lysis syndrome may complicate the treatment of visceral leishmaniasis. Awareness of this complication can lead to the initiation of prophylactic treatment as well as to early recognition and management of this syndrome in susceptible patients.

Topics: Adult; Aged; Amphotericin B; Antiprotozoal Agents; Female; Humans; Hyperphosphatemia; Hyperuricemia; Leishmaniasis, Visceral; Male; Middle Aged; Renal Insufficiency; Statistics as Topic; Tumor Lysis Syndrome; Young Adult

Hepatic and renal functions are important considerations when selecting antifungal therapy. This investigation of liposomal amphotericin B (L-AMB) was conducted to determine the incidence and factors associated with the development of hepatotoxicity and nephrotoxicity. A retrospective chart review was conducted of 100 consecutive patients receiving L-AMB at doses of 1, 3, and 5 mg/kg. Hepatotoxicity was defined as an increase of bilirubin greater than 1.5 mg/dl or AST and ALT greater than three times the normal range. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or an increase of 50% from baseline. Patients were included if they were 18 years of age or older. Patients were excluded if they had developed hepatic or renal dysfunction prior to L-AMB administration. Seventy-five patients were included based upon the predefined inclusion/exclusion criteria. Twenty-one percent (16/75) developed hepatotoxicity based upon the predefined criteria. There were no additive correlates for this adverse effect. Overall, 56% (42/75) of patients developed nephrotoxicity. Seventy-four percent (31/42) were exposed to IV contrast, and 90% (38/42) were receiving nephrotoxins concurrently. Age, cumulative dose, concomitant nephrotoxins, and IV contrast exposure were associated with increased nephrotoxicity (p<0.001). The development of hepatotoxicity was observed; however, no correlates (age, dose escalation, or cumulative dose) were significantly associated with its occurrence. Overall nephrotoxicity with L-AMB was common and often multifactorial. Lipid amphotericin B products are associated with lower rates of nephrotoxicity than conventional amphotericin; however, in this analysis, L-AMB was associated with a high incidence of nephrotoxicity.

Topics: Adult; Age Factors; Aged; Amphotericin B; Antifungal Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Contrast Media; Creatinine; Dose-Response Relationship, Drug; Drug Carriers; Humans; Incidence; Liposomes; Middle Aged; Renal Insufficiency; Retrospective Studies

Fungal infection of the kidneys is a rare condition that has been reported in premature babies and in diabetic or immunocompromised adult patients. Candida spp. is the most frequent micro-organism involved. This paper reports a case of an immunocompetent newborn with a bladder exstrophy who suffered from an acute renal failure caused by bilateral renal aspergilloma (Aspergillus flavus). The newborn was treated with amphotericin B urinary tract irrigation through bilateral nephrostomy catheters, combined with liposomal amphotericin B and voriconazole therapy, which improved his renal function. However, due to persistent fungal colonization, a long antifungal treatment and permanent ureterostomies were necessary to deal with new episodes of ureterorenal obstruction. As of November 2009, despite the renal injuries, renal function had been conserved. The management of the mechanical obstruction and the choice of antifungal drugs are discussed in this unusual case.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Bladder Exstrophy; Humans; Infant, Newborn; Male; Nephrostomy, Percutaneous; Pyrimidines; Renal Insufficiency; Treatment Outcome; Triazoles; Ureterostomy; Voriconazole

The optimal treatment of cutaneous leishmaniasis is controversial. We report our experience managing Old World cutaneous leishmaniasis in a pediatric refugee clinic. Conventional amphotericin B therapy caused reversible renal failure in 2 of 3 children treated. The choice of treatment for cutaneous leishmaniasis needs to balance the risks of treatment against the likely cosmetic benefits of therapy.

Topics: Amphotericin B; Animals; Antifungal Agents; Australia; Child; Female; Fluconazole; Humans; Infant; Leishmaniasis, Cutaneous; Liposomes; Male; Refugees; Renal Insufficiency; Treatment Outcome

We describe the first reported case of renal zygomycosis presenting as an isolated fungus ball (bezoar) without renal parenchymal invasion. Since all previous descriptions of renal involvement have discussed tissue invasion, our case is unique in that the infection was confined solely in the renal pelvis and extended to the distal ureter without signs of contiguous renal infection. Our patient later developed renal insufficiency while receiving amphotericin B Lipid Complex (ABLC). The therapy was changed to posaconazole with subsequent clinical, mycologic, and radiographic improvement and the patient has remained free of recurrence 5 years after diagnosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Kidney Diseases; Kidney Pelvis; Male; Mucormycosis; Renal Insufficiency; Rhizopus; Triazoles; Ureter

This case report adds pharmacokinetic knowledge regarding amphotericin B. Amphotericin B is highly protein bound. Plasma exchange removes 50-75% of a substance in plasma within 1-2 h, corresponding to an elimination half-life of 30-40 min. Amphotericin B reduction ratio by plasma exchange was 40% in this patient who had both liver and renal failure.

Topics: Adult; Amphotericin B; Antifungal Agents; Half-Life; Humans; Injections, Intravenous; Liver Failure; Male; Plasma Exchange; Protein Binding; Purpura, Thrombotic Thrombocytopenic; Renal Dialysis; Renal Insufficiency

The impact of current transplantation practices on the characteristics of cryptococcosis in solid-organ transplant recipients is not well defined. The incidence of cryptococcal disease among solid-organ transplant recipients has remained unchanged; however, patients are less likely to present with central nervous system or disseminated disease and are more likely to have cryptococcosis limited to the lungs. Additionally, lipid formulations of amphotericin B are now used more frequently, whereas their use in combination with flucytosine has decreased. The overall mortality of cryptococcosis has significantly improved in the current era. Renal failure remains associated with poor outcome, whereas use of lipid formulations of amphotericin B is associated with a higher survival rate. Despite rare infectious complication, certain peculiar attributes of cryptococcal disease in hematopoietic stem cell recipients and tissue transplant recipients warrant recognition.

Topics: Amphotericin B; Antifungal Agents; Cryptococcosis; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Organ Transplantation; Renal Insufficiency; Tissue Transplantation

AmBisome, a liposomal formulation of amphotericin B (CAS 1397-89-3, L-AMB), shows different pharmacokinetics from the conventional formulation, amphotericin B deoxycholate (D-AMB). To characterize the clearance process of L-AMB, the form in which it exists in rat plasma, pharmacokinetics in hepatic or renal failure rats, cellular distribution in rat liver, and placental and milk transfer in rat were investigated. Furthermore, to predict the drug-drug interaction, in vitro metabolism of amphotericin B (AMB) by rat, dog and human liver S9 fraction, and effects of L-AMB on drug-metabolizing enzyme systems were investigated. L-AMB was found to exist stably as a liposomal form in rat plasma without any notable transfer to milk or fetus in rats. After administration to hepatic failure rats, the CLtot of AMB decreased to 1/4 and the Vdss decreased to 1/8 compared with the control rat case. In contrast, after administration to renal failure rats, plasma AUC of AMB did not significantly change compared with sham-operated rats. These data suggest that hepatic clearance is the main determinant of the CLtot for L-AMB. In rat liver, L-AMB was distributed mainly to non-parenchymal cells. In the in vitro metabolism study using liver S9 fraction, no metabolite peaks were observed. After repeated administration of L-AMB to rats, there was no change in parameters related to the drug-metabolising enzyme system in liver microsomes. These data demonstrate that clinically significant metabolism-based drug interaction with L-AMB should be less likely.

Topics: Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Dogs; Drug Carriers; Drug Interactions; Female; Half-Life; Humans; In Vitro Techniques; Liposomes; Liver; Liver Failure; Male; Microsomes, Liver; Milk; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Renal Insufficiency

We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.

Topics: Adolescent; Amphotericin B; Child; Drug Combinations; Female; Humans; Hyperphosphatemia; Male; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Renal Insufficiency

A 76 year-old woman was admitted to our hospital because of pyrexia and fatigue. One year earlier, she was diagnosed as nephrotic syndrome(NS) caused by focal segmental glomerulosclerosis and immunosuppressive therapy was started with marked amelioration of proteinuria. Thereafter, her renal function worsened, but only supportive treatment was continued. After admission, a cerebrospinal fluid (CSF) examination revealed Cryptococcus neoformans (C. neoformans) by india ink staining and a subsequent CSF culture confirmed C. neoformans infection. Accordingly, we made the diagnosis of cryptococcal meningitis and immediately started multiple anti fungal drugs with dosage modification according to her impaired renal function. Immunosuppressive therapy for NS was temporarily terminated. The inflammatory signs and symptoms soon were markedly improved, but the anti cryptococcal antibody titer in the serum and CSF remained high. Immunosuppressive therapy was started again at a low dosage because urinary protein had increased again. One hundred and eight days from admission, she was discharged with a regimen of multiple anti fungal drugs. Proteinuria and renal insufficiency was almost stable during hospitalization. Most fungal infection develops in patients in an immunosuppressive state induced by immunosuppressive drugs, HIV infection and so on. Patients with NS are frequently in an immunosuppressive state because of urinary loss of immunoglobulins and the use of immunosuppressive drugs. Therefore, it should be remembered that patients with NS are at a high risk of suffering from fungal infection.

Topics: Aged; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Cyclosporine; Drug Administration Schedule; Female; Fluconazole; Humans; Immunosuppressive Agents; Meningitis, Cryptococcal; Nephrotic Syndrome; Prednisolone; Renal Insufficiency

An analysis was conducted that evaluated and compared the cost differences between caspofungin and liposomal amphotericin B when the medications were used as empirical antifungal therapy for persistent fever during neutropenia.. Rates of drug use and impaired renal function (IRF) were based on data from published studies. IRF was defined as a doubling of the serum creatinine level or, if the creatinine level was elevated at enrollment, an increase of at least 1 mg/dL. The estimates of the costs for drug acquisition and treating IRF were derived using published data and applied to compare caspofungin with liposomal amphotericin B. Sensitivity analyses were performed by varying the IRF and relative acquisition costs to assess the effect of these factors on the cost differences.. The acquisition costs per patient were 6942 dollars for liposomal amphotericin B and 3996 dollars for caspofungin. The estimated cost per patient from IRF was 3173 dollars for liposomal amphotericin B and 793 dollars for caspofungin. Combining drug acquisition and IRF costs, the overall treatment cost per patient for caspofungin was 5326 dollars less than for liposomal amphotericin B. In sensitivity analyses of drug costs, the price of liposomal amphotericin B would have to be 23.95 dollars per vial for the overall treatment costs to be equal.. Comparison of cost estimates derived from published data revealed that a combined estimate of acquisition costs and costs related to the treatment of IRF was lower for caspofungin than for liposomal amphotericin B for empirically treating patients with neutropenic fever.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Cost-Benefit Analysis; Drug Costs; Echinocandins; Fever; Humans; Kidney Function Tests; Lipopeptides; Liposomes; Neutropenia; Peptides, Cyclic; Renal Insufficiency; Retrospective Studies; Sensitivity and Specificity

In a randomized, comparative, clinical trial, caspofungin was found to be as effective as amphotericin B deoxycholate (ampho B) for treating candidemia (favorable outcomes in 71.7% and 62.8% of patients, respectively) and exhibited a generally better safety profile, particularly with respect to impaired renal function (IRF) (P = 0.02).. The goal of this study was to examine whether cost savings generated from the reduced rates of IRF observed in the clinical trial would be enough to offset the higher acquisition cost of caspofungin relative to ampho B.. We developed an economic model in which 100 hypothetical patients with candidemia were treated with caspofungin or ampho B. Rates of IRF and duration of drug therapy were taken from the clinical trial. Information on the cost of treating IRF was obtained through a search of MEDLINE using the terms amphotericin and cost, amphotericin and resource, amphotericin and hospital, and amphotericin and toxicity; and the medical subject headings kidney failure, acute/drug therapy; kidney failure, acute/epidemiology; kidney failure, acute/etiology; kidney/drug effects; cost of illness; costs and cost analysis; kidney failure, acute, and economics; and kidney failure, acute/economics. In addition, the Web site was searched for relevant references, and the Merck publication alert system was used. Antifungal drug costs were estimated using data from IMS Health. Costs were reported in year-2003 US dollars.. In the base case, the model projected that using caspofungin instead of ampho B would result in substantially lower treatment costs for IRF, which would more than offset the higher drug acquisition cost (cost-offset percentage, 122%), leading to a net mean savings of 758.60 US dollars per patient. These results were not very sensitive to the difference in daily drug cost, but were sensitive to the mean cost attributable to treating IRF. As that varied, the cost-offset percentage varied from 61% (substantial cost offset) to 183% (cost savings).. The results of this economic model suggest that, based only on differences in drug acquisition cost and renal toxicity, the use of caspofungin instead of ampho B in patients with candidemia may be a cost-saving strategy from the perspective of a hospital.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Cost-Benefit Analysis; Echinocandins; Economics, Pharmaceutical; Female; Humans; Lipopeptides; Male; Middle Aged; Models, Economic; Peptides, Cyclic; Randomized Controlled Trials as Topic; Renal Insufficiency

Invasive aspergillosis is an important factor in the morbidity and mortality of patients suffering from hematologic disorders treated with chemotherapy. Treatment with amphotericin B is often limited because of toxicity, particularly nephrotoxicity. We describe a case of invasive pulmonary Aspergillus fumigatus infection in acute myeloid leukemia with renal failure due to amphotericin B therapy, which responded to treatment with a new antifungal agent, micafungin. Micafungin appears to be an effective and safe therapy for Aspergillus infections with renal failure due to amphotericin B.

Topics: Amphotericin B; Aspergillosis; Echinocandins; Humans; Leukemia, Monocytic, Acute; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Middle Aged; Peptides, Cyclic; Renal Insufficiency; Treatment Outcome

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bone Marrow Transplantation; Caspofungin; Cyclosporine; Echinocandins; Humans; Lipopeptides; Mycoses; Peptides; Peptides, Cyclic; Pyrimidines; Renal Insufficiency; Triazoles; Voriconazole

A retrospective 9-year cohort study was conducted to identify the hospitalization costs, length of hospital stay, and mortality associated with nephrotoxicity (NT) among 494 inpatients who were treated with conventional amphotericin B (CAB). Survival regression methods were used to model the effect of NT. The rate of NT was 12%; the overall in-hospital mortality rate was 22%. After adjustment for confounding, NT was associated with a 2.7-fold higher risk of death (P<.001). Although the unadjusted effects of NT on length of hospital stay and hospitalization costs after the initiation of CAB were consistent with small increases, such effects were not significant in multivariate models (time ratio, 1.2 [P=.2]; cost ratio, 1.1 [P=.8]). The greater the number of days before the onset of NT that were included in the analysis, the greater the apparent effect of NT on costs. CAB-associated NT was associated with increased mortality, but it did not impact the costs and length of hospital stay.

Topics: Amphotericin B; Antifungal Agents; Cohort Studies; Female; Health Care Costs; Humans; Kidney; Length of Stay; Male; Middle Aged; Mortality; Renal Insufficiency; Retrospective Studies

Although nephrotoxicity is a common and well-recognized side effect of amphotericin B, hepatotoxicity is rare. We report on a 9-year-old girl with cystic fibrosis who developed fulminant renal and hepatic dysfunction following a short course of intravenous amphotericin B for a suspected aspergillus infection, although she did not have clinical evidence of invasive aspergillosis. The toxicity became apparent after changing to liposomal amphotericin. This association of renal and hepatotoxicity with liposomal amphotericin B has not previously been reported in children.

Topics: Amebicides; Amphotericin B; Aspergillosis; Child; Cystic Fibrosis; Female; Humans; Liver Failure; Renal Insufficiency

Topics: Amphotericin B; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Child; Humans; Renal Insufficiency

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

Mucormycosis is an opportunistic fungal infection usually observed in diabetic or neutropenic patients. Prognosis is serious with a high rate of mortality. Intravenous amphotericin B is the gold standard treatment. The main side effect is renal failure. Liposomal amphotericin B (AmBisome(R)) is not nephrotoxic and can be proposed as an alternative treatment although its cost is high. We report a case of mucormycosis in a diabetic woman who developed renal failure after intravenous amphotericin B treatment. AmBisome(R) could not be used for long-term treatment due to its high case. The patient was given nebulized amphotericin B and achieved recovery. This kind of treatment may provide a useful alternative to intravenous amphotericin B.

Topics: Administration, Inhalation; Aerosols; Aged; Amphotericin B; Antifungal Agents; Diabetes Complications; Female; Humans; Infusions, Intravenous; Lung Diseases, Fungal; Mucormycosis; Nebulizers and Vaporizers; Renal Insufficiency

The first case of a cutaneous cryptococcosis associated with systemic erythematous lupus (SLE) diagnosed in our Mycology Reference Centre is presented: a 24-year-old female patient diagnosed with SLE, nephrotic syndrome, arterial hypertension, renal insufficiency due to glomerulonephritis type IV and cellulitis in the right thigh and gluteus. Cryptococcus neoformans was isolated by cutaneous biopsy and haemoculture. Cryptococcal antigen was detected in serum by the latex agglutination test. As the patient did not respond to fluconazol intravenous treatment, amphotericin B administration was performed. She died of acute renal insufficiency.

Topics: Adult; Agglutination Tests; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cellulitis; Cryptococcosis; Cryptococcus neoformans; Dermatomycoses; Fatal Outcome; Female; Fluconazole; Fungemia; Humans; Injections, Intravenous; Lupus Erythematosus, Systemic; Renal Insufficiency

Topics: Acid-Base Imbalance; Amphotericin B; Humans; Immunosuppressive Agents; Renal Dialysis; Renal Insufficiency

Although renal function is generally unaffected by liposome formulations of amphotericin B-deoxycholate, there is nevertheless a risk.. Two patients immunodepressed patients treated for candidosis involving the mouth and esophagus unresponsive to local care and flucanazol developed renal failure when given the liposome formulation of amphotericin B-deoxycholate (AmBisome). In one with normal renal function prior to treatment, moderate impairment was observed after initiating AmBisome. In the second patient, impaired renal function worsened after initiating treatment with amphotericin B-deoxycholate then progressed to very severe renal failure after switching to AmBisome.. The indication for AmBisome (amphotericin B-deoxycholate treatment in patients with active renal impairment) must not overshadow the risk of worsening renal function under treatment.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Female; Humans; Immunocompromised Host; Male; Renal Insufficiency; Risk Factors

The association of amphotericin B with nephrotoxicity is well known, but risk factors for this complication are not well characterized. One hundred and seventy-eight patients who received > 3 days of intravenous amphotericin B and a minimal total cumulative dose > 100 mg were reviewed retrospectively. The mean age, average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22 years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of patients received amphotericin B for empirical therapy of febrile neutropenia. Various definitions of nephrotoxicity were used; these were as follows (the incidence of nephrotoxicity as determined by the given definition is given in parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3, a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a change in creatinine of > 92 mumol/L (49%); definition 5, an increase in creatinine to > 230 mumol/L (8%). Multivariate analysis showed that nephrotoxicity was associated with a greater cumulative dose of amphotericin B and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In those patients who experienced severe nephrotoxicity (creatinine increased to > 230 mumol/L), cyclosporin therapy was the most significant risk factor (odds ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple concomitant risk factors for renal dysfunction were present. No patient experienced irreversible nephrotoxicity. These findings allow for stratification of patients at risk for amphotericin B-induced nephrotoxicity and rational use of alternative agents.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Creatinine; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Renal Insufficiency; Risk Factors

Topics: Amphotericin B; Humans; Lipids; Renal Insufficiency

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

Topics: AIDS-Related Opportunistic Infections; Allopurinol; Amebicides; Amphotericin B; Analysis of Variance; Anti-HIV Agents; Antimetabolites; Antimony; Antiprotozoal Agents; Blood; Bone Marrow; CD4-Positive T-Lymphocytes; Cerebrospinal Fluid; Didanosine; Digestive System; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatic Encephalopathy; HIV; Humans; Intestinal Mucosa; Leishmaniasis, Visceral; Lymphocyte Count; Male; Myocarditis; Neutrophils; Pancreatitis; Pentamidine; Renal Insufficiency; Spain; Zidovudine

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiviral Agents; Candidiasis; Contraindications; Cytomegalovirus Retinitis; Drug Therapy, Combination; Foscarnet; Humans; Male; Renal Insufficiency

Four patients undergoing allogeneic bone marrow transplantation were treated with liposomal (3 patients) and conventional (one patient) amphotericin-B for disseminated candidosis. Candida krusei was isolated from 3, and C. glabrata from 1 patient. The patients were treated with liposomal amphotericin-B in doses from 3 to 5 mg/kg. The fourth patient received conventional amphotericin-B in a reduced dose due to renal impairment. The patients died from multiorgan failure due to disseminated fungal infection. In 1 case, the switch to the conventional drug resulted in clearance before death. The 3 fungus isolates, together with the fourth strain obtained from patient no. 4 without any exposition to liposomal amphotericin-B were tested for their susceptibility to conventional, liposomal and discoidal amphotericin-B. All strains showed good sensitivity to the conventional and discoidal drug. The minimal inhibitory concentrations (MIC) of liposomal amphotericin-B were 1 to 3 titre steps higher indicating a reduced sensitivity of the tested strains to this preparation. We conclude that the use of liposomal amphotericin-B is recommended mainly on the base of the low incidence of side-effects. Intensive microbial resistance tests, pharmacokinetic investigations and randomized studies are necessary before the conventional drug is replaced as the gold standard for systemic antimycotic therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candidiasis; Drug Carriers; Drug Resistance, Microbial; Female; Humans; Liposomes; Male; Microbial Sensitivity Tests; Renal Insufficiency; Transplantation, Homologous

Mucormycosis is a rare fungal disease commonly affecting individuals with diabetes mellitus, hematological malignancy, and immune deficiency. Isolated pulmonary mucormycosis is extremely rare. This article reports a case of isolated pulmonary mucormycosis that presented as a solitary cavity infiltrate in a patient with no underlying risk factors.

Topics: Aged; Amphotericin B; Fatal Outcome; Fungemia; Humans; Lung Diseases, Fungal; Male; Mucormycosis; Radiography; Renal Insufficiency; Shock, Septic

Topics: Acute Kidney Injury; Amphotericin B; Bronchopneumonia; Burns; Candida; Candidiasis; Child; Drug Therapy; Erythroblastosis, Fetal; Female; Geriatrics; Heart Failure; Humans; Hyperbilirubinemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Postgastrectomy Syndromes; Renal Insufficiency; Sepsis; Toxicology; Uterine Cervical Neoplasms; Wounds, Gunshot

Topics: Acute Kidney Injury; Amphotericin B; Coccidioidomycosis; Humans; Kidney Transplantation; Pathology; Renal Insufficiency; Toxicology