amphotericin-b and Kidney-Diseases

Phaeohyphomycosis refers to infections caused by phaeoid fungi that can have an aggressive course in normal hosts. We report a case of left-sided renal phaeohyphomycosis due to Bipolaris spicifera in a 7-year-old immunocompetent male child. He presented with fever, dysuria, nausea, vomiting and flank pain. Examination revealed tenderness at the left costovertebral angle. Histological examination and culture of biopsy from left kidney and blood yielded the fungal pathogen Bipolaris spicifera. His past history revealed that he was diagnosed perinatally with bilateral hydronephrosis due to bilateral pelvic ureteric junction obstruction. He underwent an open dismembered pyeloplasty on the left side followed by the right side pyeloplasty at the age of 6 months and 1.5 years respectively. He was on a regular follow-up for 5 years and had been doing well. Now he was diagnosed as a case of unilateral renal phaeohyphomycosis. The patient was managed successfully with antifungal drugs amphotericin B and itraconazole. A review of previously reported bipolaris cases with their clinical manifestations, treatment and outcome is presented. Renal phaeohyphomycosis remains an unusual disease. Aggressive diagnostic approaches and careful management helped in survival of the patient.

Topics: Amphotericin B; Antifungal Agents; Biopsy; Child; Humans; Immunocompetence; Itraconazole; Kidney; Kidney Diseases; Male; Mitosporic Fungi; Phaeohyphomycosis

Since the introduction of amphotericin B as an antifungal agent, the morbidity and mortality of pediatric patients with mycotic infections have increased, primarily because of the increased immunocompromised patients. Despite the fact that deoxycholate amphotericin B was once the primary drug used for mycotic infections, its administration to children older than neonates is currently controversial because of its nephrotoxic effects. Three lipid-associated formulations have been developed and have reportedly shown similar efficacy and fewer nephrotoxic effects in adults than conventional amphotericin B, but the conclusions from comparative studies in children evaluating the nephrotoxicity risks of the 4 agents are controversial. Nevertheless, guidelines favor liposomal or lipid complex amphotericin B when polyene antifungal therapy is recommended in this age group. However, high acquisition costs often preclude their prescription in economically poor regions. Thus, physicians must consider all of these factors when determining the most cost-effective polyene antifungal treatment for their pediatric patients. This is particularly pertinent in developing countries where resources are scarce. Adjuvant sodium supplementation has been reported to be effective in protecting kidney function in extremely low birth weight infants prescribed deoxycholate amphotericin B. Further pharmacokinetic and pharmacodynamic studies of the drug in children could also provide information for rational dosing regimens designed to decrease nephrotoxicity. Conventional amphotericin B, with appropriate kidney protective measures, still plays a role in the treatment of empiric invasive mycotic infections in most pediatric patients. Liposomal and lipid complex amphotericin B should be reserved for those receiving long-term nephrotoxic agents or with altered renal function or disease. Antifungal susceptibility, renal compromise and the clinical status of the patient should determine treatment for culture-proven infections. Under the current cost limitations, undertaking and evaluating low-cost, kidney-sparing, deoxycholate amphotericin B treatments for children should be a primary concern.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Deoxycholic Acid; Drug Combinations; Humans; Infant; Infant, Newborn; Kidney Diseases; Mycoses

Treatment with Amphotericin B (AmB) deoxycholate, which is still used widely, particularly in low-resource countries, has been challenged due to nephrotoxicity. We sought to study whether continuous infusion of AmB deoxycholate reduces nephrotoxicity retaining, however, the effectiveness of the drug.. PubMed and Scopus databases were systematically searched to identify studies comparing the outcomes of patients receiving 24-h infusion of AmB ("continuous group") and those receiving 2-6-h infusion of AmB ("conventional group"). Nephrotoxicity and all-cause mortality were the primary outcomes of the review, while treatment failure was the secondary outcome.. Five studies met the inclusion criteria; one randomized controlled trial, two prospective cohort studies, and two retrospective cohort studies. The majority of patients were neutropenic with an underlying hematologic malignancy. All 5 studies (392 patients) provided data regarding the development of nephrotoxicity. A non-significant trend towards lower nephrotoxicity was observed for patients receiving continuous infusion of AmB compared with those receiving conventional infusion [RR = 0.61 (95% CI 0.36, 1.02)]. Four studies (365 patients) provided data regarding mortality; no relevant difference was detected between patients receiving continuous and those receiving conventional infusion of AmB [RR = 0.81 (95% CI 0.36, 1.83)]. Data on treatment failure of the two methods of administration was insufficient for meaningful conclusions.. The available evidence from mainly non-randomized studies suggests that continuous infusion of AmB deoxycholate might offer an advantage over the conventional infusion regarding the development of nephrotoxicity, without compromising patient survival. Further randomized studies are needed to investigate this issue.

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Hematologic Neoplasms; Humans; Infusions, Intravenous; Kidney Diseases; Mycoses; Neutropenia; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Treatment Outcome

In this paper, we present a case of cervical spondylitis due to Phaeoacremonium venezuelense, in a fifty-two-year-old male who complained about neck pain and tingles in his right arm. Fungal cervical spondylitis is extremely rare in immunocompetent patients. This case is the first case of spondylitis due to P. venezuelense.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Cervical Vertebrae; Epidural Abscess; Humans; Immunocompetence; Kidney Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Mycoses; Pyrimidines; Species Specificity; Spondylitis; Tomography, X-Ray Computed; Triazoles; Voriconazole

This meta-analysis of 13 studies revealed that amphotericin B delivered as a locally prepared lipid emulsion or in liposomes reduced nephrotoxicity to a similar degree, by 18.4% (relative risk [RR], 0.40 [99% confidence interval, .25-.64]; n = 459) and 18.1% (RR, 0.48 [99% CI, .36-.64]); n = 1233), respectively.

Topics: Amphotericin B; Antifungal Agents; Humans; Incidence; Kidney Diseases

Nephrotoxicity is generally considered as the most clinically significant adverse reaction of amphotericin B, and has been reported in up to 80% of amphotericin B recipients during the first 2 weeks of treatment. Numerous experimental and clinical investigations have been performed over the past 4 decades, to find appropriate interventions for preventing or minimizing the nephrotoxic effects of amphotericin B.. The aim of this literature review was to collect available clinical data regarding interventions to prevent amphotericin B-induced nephrotoxicity in human populations. A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane central register of controlled trials, and Cochrane database systematic reviews. The key words used as search terms were 'amphotericin', 'amphotericin B', 'nephrotoxicity', 'renal failure', 'renal damage', 'renal dysfunction', 'renal impairment', 'prevention', 'preventive measures', and 'preventive interventions'.. Studies in humans have clearly demonstrated that salt loading can prevent or alleviate an amphotericin B-induced rise in serum creatinine, or decrease in glomerular filtration rate, without beneficial effects on tubular toxicity of amphotericin B. Current clinical data regarding the prolongation of amphotericin B duration of infusion in the prevention of nephrotoxicity is controversial and associated with several clinical and practical drawbacks.

Topics: Amphotericin B; Animals; Antifungal Agents; Creatinine; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Function Tests; Sodium Chloride; Time Factors

In 2009 the Infectious Diseases Society of America reviewed the guidelines on the treatment of candidemia in non-neutropenic patients. In this document the preferred treatment was either fluconazole or an echinocandin. Amphotericin-B formulations were considered an alternative. However, careful assessment of published data showed similar efficacy between these drugs.

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Candidemia; Echinocandins; Fluconazole; Fungal Proteins; Humans; Kidney Diseases; Neutropenia; Practice Guidelines as Topic; Treatment Outcome

Amphotericin B lipid complex is a widely used lipid-based formulation of amphotericin B, which has a broad spectrum of activity against a variety of fungal pathogens. It has also been shown to be significantly less nephrotoxic than conventional amphotericin B. However, infusional drug reactions, similar to those seen when using conventional amphotericin B, have been reported in a significant number of patients, so it is important that these are prevented or managed effectively, particularly in light of the changing epidemiology of systemic fungal infections.. This article reviews effective strategies that can be used to reduce the risk of drug delivery reactions associated with amphotericin B lipid complex. Preserving renal function and managing spikes in serum creatinine levels are also discussed.. The aim of this paper is to provide healthcare professionals with clear guidance on the management of adverse events associated with amphotericin B lipid complex. Recommendations are based upon the published evidence and clinical experience from a number of different centres.. Amphotericin B lipid complex represents a valuable therapeutic option in the treatment of fungal infections but improved strategies for the management of infusion-related adverse events are required.

Topics: Amphotericin B; Antifungal Agents; Drug Delivery Systems; Humans; Infusions, Intravenous; Kidney Diseases; Liposomes; Practice Guidelines as Topic

We present two cases of renal zygomycosis caused by Apophysomyces elegans and Mycocladus corymbifer in previously healthy immunocompetent males and an overview of the disease in India. In both cases a percutaneous nephrostomy (PCN) was performed and the etiologic agents were identified by direct microscopy and culture. Amphotericin B was administered and both patients recovered completely. A review of the literature revealed 42 cases of renal zygomycosis in India. The majority of them were from the Postgraduate Institute of Medical Education and Research, Chandigarh, in North India. In contrast to cases from the developed world where transplant recipients and patients with hematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India is uncontrolled diabetes mellitus. However, renal zygomycosis is an exception and the patients in both of our cases had no identifiable underlying disorder and recovered successfully without nephrectomy. It is important to emphasize that treatment of A. elegans must be aggressive and lipid formulations of antifungals are typically favored due to their limited side effects profile and ability of the clinician to use higher doses. A high index of clinical suspicion and knowledge of the varied manifestations in diagnosing this condition cannot be overemphasized.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Humans; India; Kidney Diseases; Male; Mucorales; Mycology; Nephrostomy, Percutaneous; Treatment Outcome; Zygomycosis

Amphotericin B (AmB) is a well known antifungal and antiprotozoal antibiotic used in the clinic for several decades. Clinical applications of AmB, however, are limited by its nephrotoxicity and many other acute side effects which are not acceptable by patients when their life is not threaten. In order to improve the therapeutic index of this drug, lipid formulations have been introduced and many efforts have been made to obtain less toxic AmB derivatives by chemical modifications of the parent drug. This review presents concise knowledge about this fascinating compound and a critical review of the data published within last few years about the mechanism of action of this antibiotic. In particular, in the present work we discuss: i) structure and properties of AmB and its recently synthesized new derivatives; ii) antifungal and antileishmanial activity and toxicity of these compounds; and iii) mode of action of AmB and its derivatives at cellular and molecular levels, with particular attention paid to interactions of AmB and different components of cellular membranes.

Topics: Amphotericin B; Animals; Antifungal Agents; Antiprotozoal Agents; Drug Design; Humans; Kidney Diseases; Leishmaniasis; Mycoses

Amphotericin B (AmB) is a crucial agent in the management of serious systemic fungal infections. In spite of its proven track record, its well-known side effects and toxicity will sometimes require discontinuation of therapy despite a life-threatening systemic fungal infection. The mechanism of action of AmB is based on the binding of the AmB molecule to the fungal cell membrane ergosterol, producing an aggregate that creates a transmembrane channel, allowing the cytoplasmic contents to leak out, leading to cell death. Most of the efforts at improving AmB have been focused on the preparation of AmB with a lipid conjugate. AmB administration is limited by infusion-related toxicity, an effect postulated to result from proinflammatory cytokine production. The principal acute toxicity of AmB deoxycholate includes nausea, vomiting, rigors, fever, hypertension or hypotension, and hypoxia. Its principal chronic adverse effect is nephrotoxicity. AmB probably produces renal injury by a variety of mechanisms. Risk factors for AmB nephrotoxicity include male gender, higher average daily dose of AmB (> or = 35 mg/day), diuretic use, body weight > or = 90 kg, concomitant use of nephrotoxic drugs, and abnormal baseline renal function. Clinical manifestations of AmB nephrotoxicity include renal insufficiency, hypokalemia, hypomagnesemia, metabolic academia, and polyuria due to nephrogenic diabetes insipidus. Human studies show convincingly that sodium loading in excess of the usual dietary intake notably reduces the incidence and severity of AmB-induced nephrotoxicity.

Topics: Amphotericin B; Anemia; Animals; Arrhythmias, Cardiac; Calcium Channel Blockers; Cytokines; Fever; Gastrointestinal Diseases; Humans; Hyperkalemia; Kidney Diseases; Liposomes; Mycoses; Rats; Sodium Chloride

The epidemiology of drug-induced renal disorders is a complex topic. Drug-associated nephrotoxicity accounts for 18 - 27% of all acute kidney injury cases in US hospitals. Medications can affect all aspects of the kidney, and drugs that are associated with renal dysfunction are used commonly in clinical practice. The article reviews six major mechanisms of drug-induced renal dysfunction as well as lists the major medications involved. NSAIDs, aminoglycosides, amphotericin B and calcineurin inhibitors are just some examples of drugs that contribute to renal dysfunction. The medical community must be aware of patient risk factors for nephrotoxicity, as well as the drug's inherent nephrotoxic potential, when prescribing and administering medications.

Topics: Aminoglycosides; Amphotericin B; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcineurin Inhibitors; Drug-Related Side Effects and Adverse Reactions; Humans; Kidney Diseases; Risk Factors; United States

Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Azoles; Candidiasis; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Therapy, Combination; Echinocandins; Fungemia; Hematologic Diseases; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Kidney Diseases; Liver Diseases; Mice; Neutropenia; Risk Factors

Amphotericin B is a low-soluble polyene antibiotic which is able to self-aggregate. The aggregation state can modify its activity and pharmacokinetical characteristics. In spite of its high toxicity it is still widely employed for the treatment of systemic fungal infections and parasitic disease and different formulations are marketed. Some of these formulations, such as liposomal formulations, can be considered as classical examples of drug targeting. The pharmacokinetics, toxicity and activity are clearly dependent on the type of amphotericin B formulation. New drug delivery systems such as liposomes, nanospheres and microspheres can result in higher concentrations of AMB in the liver and spleen, but lower concentrations in kidney and lungs, so decreasing its toxicity. Moreover, the administration of these drug delivery systems can enhance the drug accessibility to organs and tissues (e.g., bone marrow) otherwise inaccessible to the free drug. During the last few years, new AMB formulations (AmBisome, Abelcet, and Amphotec) with an improved efficacy/toxicity ratio have been marketed. This review compares the different formulations of amphotericin B in terms of pharmacokinetics, toxicity and activity and discusses the possible drug targeting effect of some of these new formulations.

Topics: Amphotericin B; Animals; Antifungal Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Kidney Diseases; Liposomes; Solubility

Amphotericin B, a broad spectrum antifungal agent, is widely used despite significant adverse events including nephrotoxicity. Nephrotoxicity occurs frequently in patients receiving amphotericin B. Different definitions for nephrotoxicity are reviewed in the context of outcome in patients with invasive fungal diseases. In most publications, mortality was higher in patients experiencing nephrotoxicity and mean hospital length of stay was prolonged. As a consequence, the use of less nephrotoxic antifungal agents could improve treatment outcomes.

Topics: Amphotericin B; Antifungal Agents; Humans; Immunocompromised Host; Kidney Diseases; Length of Stay; Mycoses; Treatment Outcome

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antiviral Agents; Foscarnet; Humans; Kidney; Kidney Diseases; Peptides

Prior to the 1950s no effective therapy for coccidioidomycosis existed. The advent of amphotericin B ushered in the therapeutic era for coccidioidomycosis. Until this time amphotericin B and its lipid congeners have been regarded as the "gold standard" of therapy for severe pulmonary and disseminated coccidioidomycosis. The availability of azoles and later triazoles for the past three decades have relegated the amphotericins into a rescue mode, used mainly in widely disseminated cases, azole intolerance, or when there are contraindications to Azoles, such as pregnancy. In meningitis the intrathecal use of amphotericin B is still used frequently by some clinicians alone or with a triazole. The newer lipid preparations, while more expensive, have significantly reduced toxicity, particularly nephropathy.

Topics: Amphotericin B; Antifungal Agents; Coccidioides; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Female; Humans; Kidney Diseases; Lipids; Meningitis; Pregnancy; Treatment Outcome; Triazoles

Empirical antifungal therapy has been shown to decrease the number of documented fungal infections in the setting of persistent fever during neutropenia. For decades, amphotericin B deoxycholate has been considered the agent of choice for first-line therapy in this setting. New antifungal agents associated with less toxicity, including the lipid formulations of amphotericin, voriconazole, and caspofungin, are now available and are considered to be suitable alternative first-line agents. In order to ensure appropriate therapy, however, the clinician must consider not only the differences between these antifungals but also patient-specific factors before initiating treatment.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Clinical Trials as Topic; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Echinocandins; Fever; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Liposomes; Liver Diseases; Mycoses; Neutropenia; Pyrimidines; Triazoles; Voriconazole

Primary renal zygomycosis is a rare fungal infection, and only 45 cases have been reported in the literature. The major etiologic agents of the disease were Mucor spp., Rhizomucor spp., Rhizopus spp. and Absidia spp. Here we report a case of primary renal zygomycosis due to Rhizopus oryzae infection. The patient had systemic lupus erythematosus and was treated with corticosteroids. He had frequent micturition, urodynia and passed amorphous and membranous-looking masses through the urethra several times prior to admission. Histopathological examination of the mass showed numerous broad and nonseptate hyphae. Rhizopus oryzae was isolated from the mass. We also reviewed the clinical features of primary renal zygomycosis in the literature.

Topics: Adult; Amphotericin B; Antifungal Agents; Cyclophosphamide; Fatal Outcome; Glucocorticoids; Humans; Hyphae; Immunosuppressive Agents; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Microscopy; Mucormycosis; Prednisone; Pulse Therapy, Drug; Rhizopus

Bilateral fungal obstruction of the renal collecting system is rare in infancy. Treatment options include medical or surgical procedures. Reports of successful medical treatment with liposomal amphotericin B have been published but the duration of treatment is controversial. We report a 3-week-old preterm baby with myelomeningocele who had experienced acute renal failure related to bilateral renal fungus balls, which improved with percutaneous nephrostomy and 12 weeks of liposomal amphotericin B intravenously combined with 5-fluorocytosine orally for 9 weeks.

Topics: Acute Kidney Injury; Amphotericin B; Antifungal Agents; Candidiasis; Female; Flucytosine; Humans; Infant; Kidney Diseases; Liposomes; Time Factors

Amphotericin B is the treatment of choice for severe systemic fungal infections. Nephrotoxicity is the most clinically significant adverse effect, but studies examining nephrotoxicity in children are scarce. Nephrotoxicity includes decreased glomerular filtration rate and distal tubulopathy with urinary loss of potassium and magnesium, renal tubular acidosis, loss of urine concentrating ability, and sometimes Fanconi's syndrome. The mechanisms involved in nephrotoxicity include the use of deoxycholate, the vehicle for amphotericin, reduction in renal blood flow and glomerular filtration rate, increased salt concentrations at the macula densa, interaction of amphotericin with ergosterol in the cell membrane, and apoptosis in proximal tubular cells and medullary interstitial cells. Some risk factors for amphotericin nephrotoxicity have been determined over the years. Cumulative dosage, treatment duration, and dosing schedule as well as the combination of amphotericin with other nephrotoxic drugs, such as diuretics and cyclosporine, are important risk factors. Mechanisms to prevent nephrotoxicity include the use of lipid formulations such as amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B and the concurrent use of volume repletion. Amiloride can be considered in serious potassium loss.

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Child; Humans; Kidney Diseases; Risk Factors

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Carbapenems; Cephalosporins; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Kidney Diseases; Penicillins; Peptides

Candida species are a common cause of urinary tract infection in newborns requiring intensive care. Renal candidiasis is frequently associated with these urinary tract infections and is manifest by "fungus balls" or renal parenchymal infiltration. Candidal urinary tract infections in high-risk newborns are often associated with candidemia, thereby warranting systemic antifungal therapy. Sonography is useful in diagnosing renal candidiasis, obstruction from "fungus balls," and abscesses. The sonographic appearance of "fungus balls" may persist long after clinical resolution of Candida infection in neonates and should not affect duration of antifungal therapy. Amphotericin B is currently the drug of choice for neonates with renal candidiasis and candidal urinary tract infection. Surgical management should be reserved for decompression of obstructive candidiasis and drainage of abscesses.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Drainage; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Kidney Diseases; Urinary Tract Infections

Renal and electrolyte problems are common in patients in the ICU. Several advances that occurred in the recent past have been incorporated in the diagnosis and management of these disorders and were reviewed in this article. Unfortunately, many important questions remain unanswered, especially in the area of ARF, where new therapies are anxiously awaited to make the transition from bench to bedside. Better studies are sorely needed to define the best approach to dialysis in patients who have ARF.

Topics: Acid-Base Imbalance; Acute Kidney Injury; Alkalosis; Amphotericin B; Antifungal Agents; Cardiotonic Agents; Critical Care; Critical Illness; Dopamine; Humans; Kidney Diseases; Renal Dialysis; Sodium Bicarbonate

Amphotericin B is widely used for severe life threatening fungal infections. Its use is limited by a dose-dependent nephrotoxicity manifested by a reduction in glomerular filtration rate and tubular dysfunction. An elevated creatinine associated with amphotericin B is not only a marker for renal dysfunction but is also linked to a substantial risk for the use of hemodialysis and a higher mortality rate; therefore amphotericin B nephrotoxicity is not a benign complication and its prevention is essential. Several manipulations have been proposed to try and minimize amphotericin B induced nephrotoxicity. Systematic hydration is crucial to minimize amphotericin B. Mannitol or intralipids administration were once suggested as protective based on anecdotal observational reports. Small prospective and randomized trials, however did not support a protective effect. Three new formulations have been developed in an attempts to improse both efficacy and tolerability: amphotericin B in lipid complex (ABLC, Abelcet). Colloidal dispersion (ABCD, Amphotec and amphotericin B liposome (Ambisome). Three prospectives randomized studies have clearly shown that Ambisome is less nephrotoxic than amphotericin B. Unfortunately the only randomized trial comparing Abelcet with amphotericin B is an open-label treatment of invasive candidiasis which was presented 5 years ago but never published as a full paper. Furthermore in a recent multicenter double-blind study it has been shown that Ambisome has a better safety profile than Abelcet with less chills/rigors and less nephrotocixity.

Topics: Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Humans; Kidney; Kidney Diseases

Amphotericin B is an effective broad-spectrum antifungal agent, but various side effects, especially nephrotoxicity, have restricted its use. Recently, lipid formulations of amphotericin B have been developed in order to reduce its toxic side effects. Clinical trials, although in the early stages, suggest promising results, and that some of these lipid formulations are potent and less toxic, even at higher doses. We summarize herein the existing information about newer lipid formulations of polyene antifungal drugs, which could attenuate associated nephrotoxicity.

Topics: Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Drug Delivery Systems; Humans; Kidney Diseases; Lipids; Liposomes; Polyenes

Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented life-threatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five open-label clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42 % for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Female; Humans; Kidney Diseases; Male; Middle Aged; Mycoses; Retrospective Studies

We describe the medical management of isolated renal zygomycosis in an adult patient with AIDS during chemotherapy for AIDS-related lymphoma. After initial presentation during the first cycle of chemotherapy, the infection was contained within the kidney following recovery of the neutrophil count without medical or surgical intervention. Since he was not considered to be a candidate for nephrectomy, his infection was treated with amphotericin B lipid complex during subsequent chemotherapy. Neutropenia was minimized by the addition of cytokine support therapy with granulocyte colony-stimulating factor and reduced doses of chemotherapy. Following this strategy, his lymphoma completely resolved, and renal zygomycosis was controlled. At the time of this writing, he had been in complete remission for 18 months without evidence of progressive fungal infection. This report and our literature review indicate that isolated renal zygomycosis can be associated with a favorable prognosis, occurs with greatest frequency in patients with AIDS, is associated with parenteral access, and may be managed by medical therapy alone.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Drug Combinations; Humans; Kidney Diseases; Male; Mucormycosis; Phosphatidylcholines; Phosphatidylglycerols; Radiography; Rhizopus; Tomography Scanners, X-Ray Computed

Renal papillary necrosis (RPN) due to Candida is a rare disease with only 19 cases reported over the past 37 years. But the diagnosis in 17 of the 19 cases was not made until a necropsy was carried out. The 2 cases that were diagnosed antemortem had radiographic sonography. A singapore case with candidal RPN was described in detail. Candidal RPN was associated with underlying diseases in all these cases. The disease may be more frequently encountered in the future with the advent of radiographic tools like sonography which was not described prior to 1980. Indeed, patients with underlying diseases who develop persistent candiduria should have radiographic investigation of the urinary tract to detect candidal RPN to that early remedial measures can be carried out.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Diabetes Mellitus, Type 2; Female; Humans; Kidney; Kidney Diseases; Necrosis; Radiography

Amphotericin B (AmB) has been in clinical use for more than 30 yr but has remained the most effective drug for treatment of serious fungal infections. Its use has increased in recent years, as the result of increases in aggressive intensive care support and increased numbers of immunocompromised patients. Nephrotoxic manifestations are common, and this is the major factor limiting the clinical use of the drug. A number of recent studies have contributed to a better understanding of the mechanism by which AmB exerts its nephrotoxic effect. AmB alters cell membrane permeability and probably as a consequence alters tubular and vascular smooth muscle cell function, leading to various tubular transport defects and vasoconstriction. Decreased RBF appears to play a major role in AmB-induced reduction GFR, and recurrent ischemia may be the basis of permanent structural nephrotoxic effects. Salt loading is the only measure proven by controlled prospective study to ameliorate AmB nephrotoxicity in humans. Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a protective effect based on altering the affinity of AmB for mammalian cell membranes, while preserving high efficacy against fungal cells. However, further studies are needed to evaluate the efficacy and safety of these new AmB formulations.

Topics: Acidosis, Renal Tubular; Amphotericin B; Cell Membrane Permeability; Humans; Hypokalemia; Kidney; Kidney Diseases; Vasoconstriction

We report three cases of zygomycosis (mucormycosis) occurring in three individuals infected with the human immunodeficiency virus (HIV) and review 12 other published cases. We present the only two case reports of disseminated zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone. Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with low CD4+ lymphocyte counts, does not always require the usual predisposing conditions for zygomycosis, and may be the presenting opportunistic infection among HIV-infected persons. Transient episodes of neutropenia occurring within 4 months before presentation may be a risk factor for this disease. Zygomycosis may arise in multiple sites including the basal ganglia, cutaneous tissue, kidney, respiratory tract, and may be disseminated. Occurring more commonly in, but not restricted to, injection drug users, it is significantly associated with sites other than basal ganglia in those patients with advanced HIV disease or AIDS. The presenting symptoms are related to the site of involvement, and the illness may develop insidiously or progress rapidly to a fulminant course. Successful therapy usually consists of surgical debridement and intravenous amphotericin B. Overall mortality in this review is 40%, and is significantly associated with sites of disease inaccessible to surgical debridement.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; CD4 Lymphocyte Count; Female; Fungemia; Humans; Intestinal Diseases; Intestine, Small; Kidney; Kidney Diseases; Male; Middle Aged; Mucorales; Mucormycosis; Neutropenia

Amphotericin B is an effective therapeutic agent for most systemic or invasive mycoses, but its usefulness is limited by the frequent occurrence of nephrotoxicity. Given the high and increasing frequency of serious fungal infections, especially in immunocompromised patients, the importance of the morbidity caused by this toxicity is substantial. Salt loading may prevent and even reverse amphotericin B-induced azotemia by an unknown mechanism. A prospective, randomized, placebo-controlled trial in a relevant patient group would strengthen the support for this simple, safe therapy, but will not likely be carried out because of practical and ethical considerations. Thus, a few prospective and limited controlled human studies may be the only supportive evidence for using this therapy. Supplementing dietary sodium chloride intake with 150 mEq of sodium chloride daily intravenously or orally beginning when or before amphotericin B therapy is initiated will likely prevent much of the observed nephrotoxicity and should be carried out routinely.

Topics: Amphotericin B; Animals; Humans; Kidney; Kidney Diseases; Sodium Chloride, Dietary

Obstructive uropathy caused by upper urinary tract fungal ball formation is an uncommon but well recognized clinical entity. The clinical course and management of an infant with unilateral fungal ball obstruction is described. Ultrasound and Tc-diaminotetraethylpentacetic acid (DTPA) renal scan contributed significantly to the diagnosis and management of this patient. Complete resolution of the obstruction was achieved by treatment with intravenous amphotericin B and oral 5-fluorocytosine. The clinical course and management of 35 patients described in the literature indicate that prematurity, use of broad spectrum antibiotics, prolonged hospital stay and the use of intravascular catheters are predisposing factors. The mortality rate is 34%. Young age, small size, the presence of candidaemia and withholding antifungal therapy are poor prognostic factors. A rational plan of treatment, extrapolated from the literature, is presented which may help to reduce the mortality rate in this condition.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Flucytosine; Humans; Hydronephrosis; Infant; Infant, Newborn; Kidney Diseases; Kidney Pelvis; Male; Ureteral Obstruction

Topics: Amphotericin B; Animals; Fat Emulsions, Intravenous; Female; Humans; Kidney Diseases; Male; Mycoses; Randomized Controlled Trials as Topic

AmpB remains one of the drugs of choice in the treatment of systemic fungal infection; however, its therapy is limited by the development of renal toxicity. When AmpB was incorporated into negatively charged liposomes composed of DMPC and DMPG (L-AmpB), it was less toxic but as effective as free AmpB. However, the mechanism of L-AmpB's enhanced therapeutic index remains unknown. We have demonstrated that AmpB predominantly associates with HDL when incorporated into positively and negatively charged liposomes. To further understand the therapeutic importance of AmpB predominantly associating with HDL, we next examined the influence of lipoproteins on the antifungal activity and renal cytotoxicity of AmpB. The antifungal activity of AmpB and L-AmpB was not altered in the presence of HDL or LDL. The reduced nephrotoxicity associated with the use of L-AmpB, however, was related to a decreased uptake of AmpB by renal cells when AmpB was associated with HDL, and it may be a result of the low expression of HDL receptors in the LLC PK1 renal cells.

Topics: Amphotericin B; Animals; Cell Line; Kidney Diseases; Lipoproteins, HDL; Lipoproteins, LDL; Liposomes; Rats; Receptors, LDL; Temperature; Tissue Distribution

To report a case of isolated renal mucormycosis in a previously healthy man, and to briefly review the literature relating to this rare condition.. An 18-year-old man presented with a two-month history of fevers followed by two weeks of severe left loin pain. Initial treatment with antibiotics failed and abdominal computed tomography and renal perfusion scans were requested, demonstrating a non-functioning left kidney.. Nephrectomy was performed, the histology of which was consistent with mucormycosis. Amphotericin B was administered for one month. The patient made a complete recovery and no underlying disorder was found.. This man is believed to be the first reported Australian with isolated renal mucormycosis, and only the second person worldwide in whom an identifiable underlying disorder was absent.

Topics: Adolescent; Amphotericin B; Biopsy; Combined Modality Therapy; Humans; Kidney Diseases; Male; Mucormycosis; Nephrectomy; Tomography, X-Ray Computed; Treatment Outcome

Despite the introduction in recent years of novel antifungal agents, the potency and broad spectrum of activity of amphotericin B have ensured that it remains the treatment of choice for most deep-seated mycoses. However, this agent is not without significant toxicity, particularly in patients who are already seriously ill and/or who are receiving other potentially nephrotoxic drugs. We review the various routes by which amphotericin B can be administered, focusing mainly on the intravenous route. The use of more rapid infusion rates, lipid-complexed preparations, sodium supplementation in salt-depleted patients and strategies to reduce the incidence of infusion-related reactions and nephrotoxicity are also considered. Finally, detailed recommendations for the administration of amphotericin B are provided.

Topics: Amphotericin B; Chemistry, Pharmaceutical; Drug Administration Routes; Drug Interactions; Fungi; Humans; Infusions, Intravenous; Kidney Diseases; Mycoses

Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB-PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Daunorubicin; Dimyristoylphosphatidylcholine; Drug Carriers; Female; Follow-Up Studies; Fusarium; Granuloma; Hepatitis; Humans; Immunocompromised Host; Kidney Diseases; Leukemia-Lymphoma, Adult T-Cell; Mycoses; Neutropenia; Phosphatidylglycerols; Prednisone; Recurrence; Splenic Diseases; Vincristine

Drug-induced renal disease is a common problem. Drugs cause several renal syndromes, such as prerenal azotemia, fluid and electrolyte abnormalities, acute tubular necrosis, acute interstitial nephritis, and chronic interstitial nephritis. Acute renal failure due to acute tubular necrosis is the most common syndrome and is most frequently caused by aminoglycoside antibiotics, radiographic contrast agents, and amphotericin B. Avoidance of these drugs in volume-depleted or hypotensive patients with preexisting renal disease or in those receiving multiple nephrotoxic drugs is the most effective way to reduce nephrotoxicity. Acute interstitial nephritis is an immune process that is most commonly caused by penicillins, diuretics, allopurinol, nonsteroidal anti-inflammatory drugs, cimetidine, and sulfonamides. Prompt recognition of the disease and cessation of the responsible drug are usually the only necessary therapy. Chronic interstitial nephritis is most often seen after prolonged use of several different types of analgesic agents, including aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs. These patients develop recurrent papillary necrosis and eventually chronic renal failure. They are also at risk of developing transitional cell carcinomas of the urinary collecting system. Some patients who are receiving cyclosporine also develop chronic renal failure due to interstitial fibrosis.

Topics: Acute Kidney Injury; Amphotericin B; Contrast Media; Humans; Kidney Diseases; Kidney Failure, Chronic; Nephritis, Interstitial

The increased frequency and duration of antifungal treatment with amphotericin B in immunocompromised patients has stimulated a great deal of research into the mechanisms of its nephrotoxic effects and treatment modalities designed to attenuate these effects. A review of amphotericin B-induced nephrotoxicity, the underlying pathophysiologic mechanisms, and the role of salt loading as a means of minimizing renal impairment are described. Both animal and human studies regarding the efficacy of sodium loading are presented as well as a case report describing the use of salt supplementation over a prolonged course of therapy.

Topics: Amphotericin B; Animals; Glomerular Filtration Rate; Humans; Immune Tolerance; Kidney; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Sodium, Dietary

Many clinically popular drugs, such as aminoglycoside antibiotics, amphotericin B, radiographic contrast media, analgesics, platinum-based cancer chemotherapy, and cyclosporine, can cause deterioration of kidney function even when the dose has been adjusted properly for renal insufficiency. The authors review the pathophysiologic mechanisms of nephrotoxicity of these drugs and prevention and treatment strategies.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Carboplatin; Cisplatin; Contrast Media; Cyclosporins; Humans; Kidney; Kidney Diseases; Organoplatinum Compounds

Topics: Amphotericin B; Animals; Fever; Humans; Kidney Diseases; Liposomes; Mycoses

Nephrotoxicity becomes apparent days to months after the institution of amphotericin B therapy. It is characterized by azotemia, decreased renal plasma flow, decreased glomerular filtration rate, tubular defects, nephrocalcinosis, and diffuse, nonspecific histologic changes. Management consists of minimizing exposure to other nephrotoxins and ensuring adequate hydration.

Topics: Amphotericin B; Humans; Kidney Diseases

Amphotericin B is the treatment of choice for most deep-seated mycoses; however, doses may have to be limited because of concern over adverse effects such as nephrotoxicity. Evolving evidence suggests that the extent of amphotericin B-induced renal impairment may be modified via alteration of a normal physiologic feedback response that further contributes to changes due to direct nephrotoxicity. As such, renal impairment has a substantial theoretically preventable and reversible element. In animals exposed to amphotericin B, sodium loading interferes with this response. Mounting clinical evidence also supports the usefulness of sodium supplementation to prevent as well as to reverse amphotericin B-induced nephrotoxicity. At this time, the use of sodium supplementation (eg, intravenous saline and/or ticarcillin disodium, which contains 5.2 mEq of sodium per gram of drug) along with avoiding dehydration appears to be a safe and effective means of reducing the risk of nephrotoxicity associated with amphotericin B administration; however, it is not known whether renal changes can be entirely prevented. These preliminary observations merit confirmation in a prospective, randomized clinical trial.

Topics: Amphotericin B; Animals; Humans; Kidney; Kidney Diseases; Mycoses; Sodium

Topics: Amphotericin B; Animals; Flucytosine; Humans; Kidney; Kidney Diseases; Sodium

Topics: Amphotericin B; Antifungal Agents; Chemical Phenomena; Chemistry; Dermatomycoses; Flucytosine; Griseofulvin; Humans; Imidazoles; Kidney Diseases; Mycoses

The development of the polyene antibiotic, amphotericin B, provided for the first time a drug which was clinically effective in many serious mycotic diseases. Unfortunately, it requires parenteral administration and is often toxic, factors which limit the total cumulative dose which can be given. Efforts to utilise combinations of amphotericin B with other agents were best realised with amphotericin B/flucytosine in cryptococcal meningitis, and to a lesser degree in systemic candidiasis. More recently, the introduction of new imidazoles has extended the range of applications of these drugs to fungal diseases. Two members of this group, miconazole and ketoconazole, are promising agents. Miconazole is a parenterally administered agent for patients acutely ill with candidiasis and other mycotic infections. It may be the drug of choice for Petriellidium boydii infections and it is an attractive alternative to amphotericin B for intrathecal administration to patients with fungal meningitis. Ketoconazole offers much less toxicity, the advantage of oral administration, and the possibility of indefinitely prolonged therapy. However, it does not attain high concentrations in either the urine or cerebrospinal fluid. With the imidazoles, we have entered a new era of antifungal therapy which may produce even better antifungal agents than those currently available.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System; Flucytosine; Humans; Imidazoles; Ketoconazole; Kidney; Kidney Diseases; Kinetics; Miconazole; Mycoses; Piperazines

The recent development of new antifungal antimicrobials that can be administered in combination with amphotericin B or as alternatives to it has expanded the dimensions of treatment for fungal infections of the central nervous system. These disorders have acquired increasing importance as patients with malignant and other illnesses associated with immunosuppression survive longer and as renal transplantation is more widely applied. Amphotericin B has remained the most effective therapeutic preparation for most types of neurological fungal disease, although important roles for 5-fluorocytosine, miconazole, and, more recently, ketoconazole are being recognized.

Topics: Amphotericin B; Antifungal Agents; Central Nervous System Diseases; Chemical Phenomena; Chemistry; Flucytosine; Humans; Kidney Diseases; Miconazole; Mycoses

Topics: Acute Kidney Injury; Amphotericin B; Anti-Bacterial Agents; Cephalosporins; Glomerulonephritis; Humans; Kidney Diseases; Nephritis, Interstitial; Penicillins; Polymyxins; Tetracyclines; Vasculitis

The incidence of genitourinary fungal infections is increasing, and because of their lethal potential, early diagnosis and treatment is mandatory. Candida is the most common urinary fungus and is manifest as renal involvement from systemic candidiasis, primary renal candidiasis, bezoar formation, cystitis, and as asymptomatic candiduria. The clinical status of the patient, serial urine cultures, excretory urogram, and serum candidal titers help to differentiate between the various disease states. Treatment is specific and is based on the clinical manifestation of the disease. Systemic candidiasis is treated with intravenous amphotericin. Fungal bezoars are best treated with oral flucytosine, ureteral and renal irrigation with amphotericin and, occasionally, operation. Cystitis is treated with oral flucytosine or amphoteric bladder irrigations. Asymptomatic candiduria is left untreated. A systematized evaluation and treatment regimen is presented.

Topics: Amphotericin B; Bezoars; Candidiasis; Flucytosine; Humans; Kidney Diseases; Urologic Diseases

Topics: Amphotericin B; Animals; Antifungal Agents; Antitubercular Agents; Crystallization; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Interactions; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Solubility; Sulfonamides

Topics: Amphotericin B; Anti-Bacterial Agents; Cephalosporins; Gentamicins; Humans; Kanamycin; Kidney; Kidney Diseases; Neomycin; Penicillins; Polymyxins; Regional Blood Flow; Streptomycin; Sulfonamides; Tetracycline; Vancomycin

Topics: Amphotericin B; Analgesics; Anesthetics; Anti-Bacterial Agents; Bacitracin; Cephaloridine; Cephalothin; Drug Hypersensitivity; Humans; Kidney Diseases; Penicillins; Polymyxins; Sulfonamides; Tetracycline

Topics: Amphotericin B; Anti-Bacterial Agents; Glycosides; Humans; Iatrogenic Disease; Kidney Diseases; Methoxyflurane; Penicillins; Peptides; Sulfonamides; Tetracycline

Topics: Administration, Oral; Adolescent; Aged; Amphotericin B; Anemia; Anterior Chamber; Blastomycosis; Bronchi; Child; Cryptococcosis; Drug Resistance, Microbial; Fungi; Histoplasmosis; Humans; Injections; Injections, Intravenous; Injections, Spinal; Kidney Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Thrombophlebitis; Water-Electrolyte Balance

Topics: Adult; Amphotericin B; Animals; Anti-Bacterial Agents; Bacitracin; Cats; Cycloserine; Drug Antagonism; Drug Hypersensitivity; Female; Hearing Disorders; Humans; Intestinal Diseases; Kidney Diseases; Liver Diseases; Male; Mental Disorders; Middle Aged; Neomycin; Novobiocin; Polymyxins; Stomach Diseases; Vision Disorders

Amphotericin B deoxycholate (ABD) is the best therapeutic agent available for the treatment of most systemic fungal infections. However, some untoward adverse effects such as nephrotoxicity may limit its appropriate therapeutic use. We conducted a randomized, controlled trial ofthe infusion of fat emulsion (Intralipid) shortly after the infusion of ABD to evaluate its effects on reducing ABD-associated nephrotoxicity. Our patient population was made up of 31 patients who were randomized into two groups: an intervention group (n = 16) and a control group (15 patients). There were no statistically significant differences between the two groups in demographic or clinical variables. All patients received 1mg/kg/day of ABD in dextrose 5%. In addition, the patients in the intervention arm received Intralipid 10%, which was started as soon as possible within 1 hour after the infusion of ABD. ABD-associated nephrotoxicity was defined as a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl. We also measured daily serum creatinine changes during the first 2 weeks of treatment, and we compared some other relevant indices of renal function, as well as ABD-related hypokalemia. We found no statistically significant differences between the two treatments in terms of ABD-associated nephrotoxicity or any of the other indices. We conclude that the administration of Intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity or hypokalemia.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Deoxycholic Acid; Drug Combinations; Fat Emulsions, Intravenous; Female; Head; Humans; Hypokalemia; Invasive Fungal Infections; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Neck; Treatment Outcome; Young Adult

To evaluate the effectiveness of oral N-acetylcysteine (NAC) co-treatment in preventing amphotericin B (AmB)-induced nephrotoxicity (AIN), including creatinine clearance and biomarkers of renal function (cystatin C [Cys C] and kidney injury molecule-1 [KIM-1]).. Either placebo or 600 mg oral NAC was given twice daily during the treatment course of AmB. Renal function test, serum as well as urinary level of Cys C and urinary KIM-1 were determined.. Among the study population (n = 54), 23 (42.59%) patients developed AmB nephrotoxicity during their treatment course. NAC co-treatment was significantly associated with mitigating AmB nephrotoxicity (OR = 0.286, 95% CI: 0.082 - 0.993; p = 0.049). No statistically significant difference regarding accuracy of measured biomarkers including serum creatinine, serum and urine Cys C and urine KIM-1 at days 0 and 7 of treatment in predicting and detecting AmB nephrotoxicity was identified. The changes in mean serum and urine Cys C and urine KIM during AmB treatment within and between treatment groups were not statistically significant.. Co-treatment with 600 mg oral NAC twice a day during AmB treatment, after adjusting for multiple variables, was associated with prevention of AIN. However, significantly higher adverse reactions developed in the patients who were treated with NAC.

Topics: Acetylcysteine; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Cystatin C; Double-Blind Method; Female; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney Diseases; Kidney Function Tests; Male; Membrane Glycoproteins; Middle Aged; Receptors, Virus; Young Adult

BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Canada; Child; Creatinine; Deoxycholic Acid; Double-Blind Method; Drug Combinations; Female; Humans; Kidney Diseases; Male; Meningitis, Cryptococcal; Middle Aged; Treatment Outcome; United States; Young Adult

In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (C(ss,trough)) and plasma creatinine concentrations (C(creat)) were measured in 83 children (age: 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB C(ss,trough) were identified by determining the probability of large (>24%, 75th percentile) increases in C(creat) after 6 days of AmB for a series of C(ss,trough) ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76-1.05 mg/l C(ss,trough) range provided the maximum concentrations that still had a low probability (p < 0.29) of adverse renal effects. 1 mg/kg/day AmB produces C(ss,trough) within this range for children weighing 25-45 kg. Lighter children (10-25 kg) require higher AmB doses (1.25-1.5 mg/kg/day) to achieve target C(ss,trough), while heavier children (45-55 kg) require lower doses (0.75 mg/kg/day). These starting dose guidelines may require individualization and prospective evaluation.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Body Weight; Child; Child, Preschool; Computer Simulation; Creatinine; Cyclosporine; Deoxycholic Acid; Drug Combinations; gamma-Glutamyltransferase; Humans; Immunosuppressive Agents; Infant; Kidney Diseases; Microbial Sensitivity Tests; Models, Biological; Mycoses; Neoplasms; Risk Factors; Urea

Despite improved supportive care, and the introduction of less toxic lipid-formulations of amphotericin B deoxycholate and other new antifungal agents the mortality from invasive fungal infection (IFI) in hematology patients remains high. New management strategies are therefore required to improve outcome.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Kidney Diseases; Liposomes; Male; Middle Aged; Mycoses; Postoperative Complications; Treatment Outcome

Visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in South Asia, Africa, and Brazil. Safe, effective, and affordable new therapies are needed. We conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care in Bihar, India.. In four treatment centers for visceral leishmaniasis, 667 patients between 5 and 55 years of age who were negative for the human immunodeficiency virus and had parasitologically confirmed visceral leishmaniasis were randomly assigned in a 3:1 ratio to receive paromomycin (502 patients) at a dose of 11 mg per kilogram of body weight intramuscularly daily for 21 days or amphotericin B (165 patients) at a dose of 1 mg per kilogram intravenously every other day for 30 days. Final cure was assessed 6 months after the end of treatment; safety assessments included daily clinical evaluations and weekly laboratory and audiometric evaluations. Noninferiority testing was used to compare 6-month cure rates, with a chosen margin of noninferiority of 10 percentage points.. Paromomycin was shown to be noninferior to amphotericin B (final cure rate, 94.6% vs. 98.8%; difference, 4.2 percentage points; upper bound of the 97.5% confidence interval, 6.9; P<0.001). Mortality rates in the two groups were less than 1%. Adverse events, which were more common among patients receiving paromomycin than among those receiving amphotericin B (6% vs. 2%, P=0.02), included transient elevation of aspartate aminotransferase levels (>3 times the upper limit of the normal range); transient reversible ototoxicity (2% vs. 0, P=0.20); and injection-site pain (55% vs. 0, P<0.001); and in patients receiving amphotericin B, as compared with those receiving paromomycin, nephrotoxicity (4% vs. 0, P<0.001), fevers (57% vs. 3%), rigors (24% vs. 0, P<0.001), and vomiting (10% vs. <1%, P<0.001).. Paromomycin was shown to be noninferior to amphotericin B for the treatment of visceral leishmaniasis in India. (ClinicalTrials.gov number, NCT00216346.)

Topics: Adolescent; Adult; Amphotericin B; Animals; Antiprotozoal Agents; Audiometry; Child; Child, Preschool; Disease Reservoirs; Female; Hearing Disorders; Humans; India; Infusions, Intravenous; Injections, Intramuscular; Kidney Diseases; Leishmania donovani; Leishmaniasis, Visceral; Male; Middle Aged; Paromomycin; Prospective Studies; Treatment Outcome

Topics: Aged; Amphotericin B; Antifungal Agents; Drug Carriers; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia

Conventional amphotericin B (c-AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c-AmB is hampered by its safety profile, with frequent infusion-related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c-AmB.. This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c-AmB at 0.6 mg/kg/d for empirical antifungal therapy.. The incidence of renal toxicity was significantly lower in the ABLC group, compared with c-AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c-AmB). The overall response rate was 72% for ABLC compared with 48% for c-AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c-AmB group. The number of emergent fungal infections and overall mortality were similar in both groups.. This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Drug Combinations; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Hypokalemia; Immunocompromised Host; Incidence; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Peripheral Blood Stem Cell Transplantation; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

This study assessed the risk of haematological, renal and hepatic toxicity associated with amphotericin B lipid complex (ABLC; Abelcet) in a multicentre, open-label, non-comparative study of 93 patients from 17 different hospitals who received ABLC because of proven or suspected systemic fungal infection or leishmaniasis. Most (66%) patients had onco-haematological diseases. Optimum treatment with ABLC comprised a slow (2-h) infusion dose of 5 mg/kg/day for a minimum period of 14 days. Biochemical and haematological parameters were measured pre-, during and post-treatment. In the overall patient group, the mean serum creatinine concentration was similar pre- and post-study (1.00 +/- 1.14 mg/dL vs. 1.20 +/- 1.19 mg/dL; p > 0.05). There were no significant changes pre- and post-treatment in concentrations of haemoglobin, potassium, transaminases and bilirubin. There was no significant correlation between the dose administered and the concentrations of serum creatinine (Spearmann 0.22). There was no greater nephrotoxicity in the patients with previous renal failure, or in those who had received amphotericin B previously. There were serious adverse events in five patients, but other alternative causes that could explain these events were present in three of these patients. Fevers or chills were experienced by 23% of the patients during the ABLC infusion, but only in one case did this necessitate the suspension of treatment. It was concluded that ABLC is a drug with low nephrotoxicity, even when administered to patients with pre-existing renal insufficiency. Adverse events were generally slight or moderate, and were managed easily with appropriate pre-medication.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Drug Combinations; Female; Humans; Incidence; Infant; Kidney Diseases; Leishmaniasis, Visceral; Male; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.. In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point.. Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events.. Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Caspofungin; Double-Blind Method; Echinocandins; Female; Fever; Humans; Kidney Diseases; Lipopeptides; Liposomes; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Peptides; Peptides, Cyclic; Survival Rate; Treatment Outcome

To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion.. Randomised, controlled, non-blinded, single centre study.. University hospital providing tertiary clinical care.. 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections.. Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours.. Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis.. Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months' follow up in the rapid infusion than in the continuous infusion group.. Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Prospective Studies; Survival Rate

To determine the usage patterns of the lipid-based amphotericin B formulations at our institution and to compare the observed nephrotoxicity and efficacy of these formulations.. Prospective and retrospective observational study. Urban 350-bed teaching hospital.. Sixty-seven nonhemodialysis patients who were prescribed greater than 3 days of amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB) from 1996-1999.. Forty-six patients received ABLC and 21 received L-AmB. Oncology patients accounted for most prescriptions of both formulations. Amphotericin B lipid complex most frequently was prescribed for treatment of documented fungal infections (50%), followed by treatment of neutropenic fever (33%). Liposomal amphotericin B most frequently was prescribed for treatment of neutropenic fever (62%), followed by treatment of documented fungal infections (29%). Seventy-eight percent of patients treated with ABLC and 90% of those who received L-AmB were started on the lipid-based formulation due to being refractory or intolerant to prior antifungal therapy. Two (4.4%) patients receiving ABLC and four (19%) patients receiving L-AmB experienced nephrotoxicity at the end of therapy (NS). Of the patients with a documented fungal infection, 20 out of 23 (87%) of those treated with ABLC and 4 out of 5 (80%) of those treated with L-AmB had a complete or partial response to therapy (NS). One patient with febrile neutropenia had a breakthrough fungal infection while receiving L-AmB.. No significant differences in nephrotoxicity or efficacy were found between ABLC and L-AmB. Until further studies indicate clinically significant differences in nephrotoxicity between the two liposomal amphotericin B formulations, it is recommended that economics continue to be the major determinant for product selection.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Carriers; Female; Humans; Kidney Diseases; Lipids; Liposomes; Male; Middle Aged; Neutropenia; Prospective Studies; Retrospective Studies

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Bilirubin; Bone Marrow Transplantation; Creatinine; Drug Combinations; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Scandinavian and Nordic Countries

In a randomized, double-blind, comparative, multicenter trial, liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients, using a composite end point, but was more effective in reducing proven emergent fungal infections, infusion-related toxicities, and nephrotoxicity. The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy.. Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial. Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed.. Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ($48,962 v $43,183; P =.022). However, hospital costs were highly sensitive to the cost of study medication ($39,648 v $43,048 when drug costs were not included; P =.416). Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients.. The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Carriers; Drug Costs; Economics, Pharmaceutical; Female; Fever; Hospital Costs; Humans; Kidney Diseases; Liposomes; Male; Middle Aged; Neoplasms; Neutropenia

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 microgram/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (P = 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (P = 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (P = 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Dopamine; Female; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Mycoses; Prospective Studies

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

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

Systemic candidiasis with renal involvement is a rare but well-recognized complication during neonatal intensive care treatment. In addition to intravenous administration of amphotericin B, decompression of the renal pelvis and irrigation of the involved kidney with the same drug through a nephrostomy tube will provide a high concentration of antifungal agent with a flushing effect. This procedure is not always possible due to the small size of the neonatal kidneys. We have conceived a new percutaneous trocar nephrostomy which allows its application directly in an incubator without using X-rays during a single procedure. In 3 cases a bilateral percutaneous nephrostomy was performed directly in the incubator using a one-step ultrasonically guided maneuver under local anesthesia. The funguria was successfully eradicated in all cases. The availability of a nephrostomy trocar of small dimensions leads us to an improved renal approach in newborns.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Combined Modality Therapy; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Kidney Diseases; Nephrostomy, Percutaneous; Therapeutic Irrigation; Ultrasonics

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B. Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15 microg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 microg/mL had peak levels exceeding 40 microg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity. A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of gram-positive bacteremia in cancer patients.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Humans; Kidney Diseases; Neoplasms; Neutropenia; Risk Factors; Slovakia; Vancomycin

Amphotericin B colloidal dispersion (ABCD; Amphocil) was evaluated in a phase I dose-escalation study in 75 marrow transplant patients with invasive fungal infections (primarily Aspergillus or Candida species) to determine the toxicity profile, maximum tolerated dose, and clinical response. Escalating doses of 0.5-8.0 mg/kg in 0.5-mg/kg/patient increments were given up to 6 weeks. No infusion-related toxicities were observed in 32% of the patients; 52% had grade 2 and 5% had grade 3 toxicity. No appreciable renal toxicity was observed at any dose level. The estimated maximum tolerated dose was 7.5 mg/kg, defined by rigors and chills and hypotension in 3 of 5 patients at 8.0 mg/kg. The complete or partial response rate across dose levels and infection types was 52%. For specific types of infections, 53% of patients with fungemia had complete responses, and 52% of patients with pneumonia had complete or partial responses. ABCD was safe at doses to 7.5 mg/kg and had tolerable-infusion-related toxicity and demonstrable antifungal activity.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspartate Aminotransferases; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Chemical and Drug Induced Liver Injury; Cholesterol Esters; Creatinine; Humans; Kidney Diseases; Mycoses

The purpose of this study was to evaluate the pharmacokinetics of amphotericin B colloidal dispersion and its effect on creatinine clearance in bone marrow transplant patients with systemic fungal infections. Seventy-five patients (42 females and 33 males) with a median age of 34.5 years and a median weight of 70.0 kg were enrolled in the study. Patients received 1 of 15 dose levels (range, 0.5 to 8.0 mg/kg of body weight) daily for a mean duration of 28 days and a mean cumulative dose amount of 8 g. Plasma samples for amphotericin B determination (median number, 4; range, 2 to 30) and daily serum creatinine values were obtained for each patient. Iterative two-stage analysis, one of several approaches to population pharmacokinetic and pharmacodynamic modelling, was employed for the pharmacokinetic analysis. The plasma data were available for 51 of 75 patients and were best described by a two-compartment model. Both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Of the covariates studied, only body weight and dose size were significant. Serum creatinine values over the duration of therapy were available for 59 of 75 patients. Overall, there was no net change in renal function over the duration of therapy; 12 patients had > 30% increases in creatinine clearance, whereas 13 had > 30% decreases. No measure of amphotericin B colloidal dispersion exposure, demographic values, or concomitant treatment with other medications was related to changes in the creatinine clearance.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Creatine; Female; Half-Life; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Population

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

The administration of amphotericin B in the conventional prolonged infusion over 4 to 6 hours is complicated by the acute toxicities of fevers and chills in 50% to 90% of patients and the chronic toxicities of increased creatinine levels and hypokalemia in 60% to 80% of patients. To determine the safety and toxicity of rapid infusions, we conducted a prospective, nonrandomized study in patients with clinical indications for antifungal therapy.. Twenty-five granulocytopenic adults with acute leukemia and myelodysplastic syndromes were enrolled in a phase I trial using four sequentially shorter infusion durations: a standard infusion over 4 hours (n = 3) and shortened infusion durations at 3 hours (n = 3), 2 hours (n = 4), and 1 hour (n = 15). Toxicity was assessed by daily examinations of study subjects by one of the study investigators, by documentation of all infusion-related fevers and chills, and by daily monitoring of serum levels of creatinine, potassium, magnesium, and aspartate aminotransferase.. Temperatures greater than 38 degrees C occurred in 16 of 25 (64%) patients, but only two had temperatures exceeding 40 degrees C. Chills were observed in 13 of 25 (56%) patients, but only one had severe symptoms. Serum creatinine increased more than 0.5 mg/dL (44.20 mumol/L) above the pretreatment baseline in 17 of 25 (68%) patients, and the absolute creatinine level was greater than or equal to 2.0 mg/dL (176.8 mumol/L) in 10 of 25 (40%) patients. Serum potassium levels dropped below the normal limit of 3.5 mEq/L (3.5 mmol/L) in all patients, but no patient had potassium levels below 2.5 mEq/L (2.5 mmol/L). Intravenous potassium supplementation was administered to all patients and exceeded 100 mEq/d in 12 of 25 (48%) patients.. Rapid infusions of amphotericin B are safe, are associated with similar toxicity as prolonged infusions, and facilitate inpatient care by decreasing nursing time needed for administration and minimizing scheduling conflicts with other necessary intravenous medications. Shorter infusions also facilitate outpatient and home administration of amphotericin B.

Topics: Aged; Amphotericin B; Bone Marrow; Chemical and Drug Induced Liver Injury; Drug Evaluation; Female; Fever; Humans; Hypokalemia; Infusions, Intravenous; Kidney Diseases; Magnesium; Male; Middle Aged; Pilot Projects; Prospective Studies; Time Factors; Treatment Outcome

Neutropenic patients receiving amphotericin B, frequently in combination with aminoglycosides and vancomycin, were prospectively monitored for the development of nephrotoxicity. Based on previous studies, the authors recommended that these patients receive greater than or equal to 90 meq of sodium/day on each day of amphotericin B administration. Patients who received this amount of sodium on every day of amphotericin B therapy were classified as adequate sodium. The adequate sodium group was further subdivided on the basis of whether or not the adequate sodium was in the form of sodium ticarcillin. Patients not receiving this amount of sodium on every day of amphotericin B therapy were classified as inadequate sodium; overall, these patients received greater than or equal to 90 meq of sodium/day on 74% of days on which they received amphotericin B. The inadequate sodium and adequate sodium groups did not differ significantly with respect to age, gender, diagnoses, or baseline creatinine. The incidence of nephrotoxicity (creatinine greater than or equal to 2.0 mg/dl) was significantly higher, 4 of 14 (29%), in the inadequate sodium group, as compared to the adequate sodium, adequate ticarcillin group, 1 of 35 (3%), or the adequate sodium only group, 1 of 24 (4%), p = .008. To adjust for total amphotericin dose, the risk of nephrotoxicity as a function of time on study was evaluated by the life table method; the risk of nephrotoxicity was significantly greater in the inadequate sodium group, p = .019.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actuarial Analysis; Adult; Amphotericin B; Clinical Trials as Topic; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Kidney Diseases; Male; Prospective Studies; Sodium; Ticarcillin

Previous observations suggest that tubulo-glomerular feedback could be involved in amphotericin B nephrotoxicity. We then investigated the influence of sodium status on the occurrence of renal damage during amphotericin B therapy. A retrospective survey demonstrated that impaired renal function occurred during therapy in 67 per cent of the patients who received amphotericin B alone and in 12 per cent of the patients who received amphotericin B and ticarcillin (parenteral sodium supplement of 100-150 meq per day). Prospective studies were then undertaken both in adults and children. Intravenous sodium supplement was given intravenously as routine prophylaxis with amphotericin B therapy. In all courses amphotericin B was successfully administered without deterioration in renal function. These results support the hypothesis that parenteral sodium supplementation reduces the frequency of developing impaired renal function during amphotericin B therapy.

Topics: Adult; Amphotericin B; Candidiasis; Clinical Trials as Topic; Female; Humans; Infant, Newborn; Kidney; Kidney Diseases; Male; Prospective Studies; Retrospective Studies; Sodium

The role of cyclosporine alone or in combination with amphotericin B in the development of renal toxicity was evaluated in 47 marrow transplant recipients. Cyclosporine alone was given to 21 patients and 10 received cyclosporine plus amphotericin B. These were compared with 16 patients who received methotrexate and amphotericin B. Serum creatinine doubled within 14-30 days in 8 of 21 patients who received only cyclosporine. Of 16 patients given amphotericin B in conjunction with methotrexate, only 3 doubled their serum creatinine within 5 days of starting amphotericin B. In contrast, of 10 patients who received amphotericin B in combination with cyclosporine, 5 doubled and 3 tripled their serum creatinine within 5 days. This increase in creatinine was significantly greater than that seen in patients receiving cyclosporine alone or methotrexate and amphotericin B combined. These results suggest that administration of cyclosporine and amphotericin B simultaneously should be undertaken with caution to avoid severe renal toxicity.

Topics: Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Child; Creatinine; Cyclosporins; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Male; Methotrexate; Random Allocation

Eleven patients with systemic mycotic infections were treated with amphotericin B, 1 mg/kg, on alternate days. Five patients also received mannitol (M), 1 g/kg, in the amphotericin infusion, while six served as controls (C). Renal function studies prior to therapy were repeated at a total cumulative amphotericin B dosage of 25 mg/kg; renal biopsies were obtained from 10 patients. Inulin and creatinine clearances decreased in both the C and M groups, significantly so in the latter. Urinary concentrating ability of five patients (2C, 3M) decreased as did the capacity of three (1C, 2M) to acidify urine after an acid load. Neither the peak and valley levels of amphotericin B in serum nor the urinary excretion thereof differed between the C and M groups. Striking vacuolization of smooth muscle cells, previously unrecognized, was observed in the media of arterioles and arteries in all renal biopsies. Tubular calcification was present in both groups. In summary, M therapy (1 g/kg) did not protect against the nephrotoxicity of amphotericin B. A unique lesion of the renal vasculature secondary to amphotericin B is described.

Topics: Adult; Aged; Amphotericin B; Clinical Trials as Topic; Female; Humans; Infusions, Parenteral; Kidney; Kidney Diseases; Kidney Function Tests; Male; Mannitol; Middle Aged

Topics: Adrenocorticotropic Hormone; Adult; Amphotericin B; Chorioretinitis; Clinical Trials as Topic; Female; Glucocorticoids; Histoplasmosis; Humans; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Male; Sulfonamides; Vision Tests; Visual Perception

Liposomal amphotericin B (L-AMB), a broad-spectrum antifungicidal drug, is often used to treat fungal infections. However, clinical evidence of its use in patients with renal dysfunction, especially those receiving renal replacement therapy (RRT), is limited. Therefore, we evaluated the usage and occurrence of adverse reactions during L-AMB therapy in patients undergoing RRT.. Using claims data and laboratory data, we retrospectively evaluated patients who were administered L-AMB. The presence of comorbidities, mortality rate, treatment with L-AMB and other anti-infective agents, and the incidence of adverse reactions were compared between patients receiving RRT, including continuous renal replacement therapy (CRRT) and maintenance hemodialysis (HD), and those that did not receive RRT.. In total, 900 cases met the eligibility criteria: 24, 19, and 842 cases in the maintenance HD, CRRT, and non-RRT groups, respectively. Of the patients administered L-AMB, mortality at discharge was higher for those undergoing either CRRT (15/19; 79%) or maintenance HD (16/24; 67%) than for those not receiving RRT (353/842; 42%). After propensity score matching, the average daily and cumulative dose, treatment duration, and dosing interval for L-AMB were not significantly different between patients receiving and not receiving RRT. L-AMB was used as the first-line antifungal agent for patients undergoing CRRT in most cases (12/19; 63%). Although the number of subjects was limited, the incidence of adverse events did not markedly differ among the groups.. L-AMB may be used for patients undergoing maintenance HD or CRRT without any dosing, duration, or interval adjustments.

Topics: Amphotericin B; Antifungal Agents; Databases, Factual; Humans; Japan; Kidney Diseases; Mycoses; Renal Replacement Therapy; Retrospective Studies; Time Factors; Treatment Outcome

In this study, we examined patients who received liposomal amphotericin B (L-AMB) to determine the risk factors associated with nephrotoxicity before and during L-AMB treatment. In this retrospective, single-center, observational cohort study, we examined 37 patients who received L-AMB treatment between April 2018 and December 2019. Nephrotoxicity was observed in 11 (29.7%) patients. We focused on the baseline albumin level and body surface area (BSA) before L-AMB treatment. Univariate analysis showed that the BSA and baseline albumin levels in patients with nephrotoxicity were significantly higher than those in patients without nephrotoxicity. Moreover, univariate analysis showed that albumin supplementation was significantly associated with the frequency of nephrotoxicity during L-AMB treatment. Multiple logistic regression analysis revealed the following independent risk factors for nephrotoxicity before or during L-AMB treatment: baseline albumin level (odds ratio [OR] = 16.000; 95% CI 1.480-172.000;

Topics: Adult; Aged; Aged, 80 and over; Albumins; Amphotericin B; Antifungal Agents; Cohort Studies; Female; Humans; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Risk Factors; Young Adult

Liposomal amphotericin B (L-AMB) has the potential to cause two major adverse events, renal dysfunction and serum potassium abnormality; however, appropriate clinical management of these events remains unclear. We retrospectively analyzed data regarding 128 hematology patients who received L-AMB in our institute and examined the association between clinical characteristics and renal dysfunction or serum potassium abnormality. We found that the median weight-normalized dose of L-AMB was 2.69mg/kg and the median administration period was 16days. The overall occurrence rates of renal dysfunction and hypokalemia were 55.7% and 76.6%, respectively. Multivariate analysis revealed that pre-existing renal dysfunction (P=0.017) and concomitant use of nephrotoxic (P<0.0001) or antifungal drugs (P=0.012) were independent risk factors for renal dysfunction. A higher infusion volume did not mitigate the risk of renal dysfunction. Hypokalemia occurred significantly less often in men (P=0.028) and in patients who concomitantly used nephrotoxic drugs (P=0.013). Approximately 40% of the adverse events were improved at 30days after L-AMB termination and there was no significant association between these adverse events improvement and L-AMB dosage or infusion volume. Of note, hyperkalemia was observed in more patients who received allogeneic hematopoietic stem cell transplantation (P=0.0303) and concomitant treatment with nephrotoxic drugs (P=0.0281). These results suggest that imprudent reduction of L-AMB dose or redundant intravenous infusion may have minimal benefit for critical patients with suspected invasive fungal infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Hematologic Diseases; Humans; Hyperkalemia; Hypokalemia; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Retrospective Studies; Risk Factors; Young Adult

Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children.. Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity.. When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Retrospective Studies; Young Adult

Invasive candidiasis is a serious pathogen of late-onset sepsis in very low birth weight infants. Kidney is the most common organ involved, and it causes morbidity and mortality, especially when fungal balls are formed. We report a 34-day-old female infant (born at 28 weeks' gestation, 1152 g) with systemic fungal infection complicated obstructive uropathy. On sonography, the fungal balls filled the entire pelvis without hydronephrosis. Percutaneous nephrostomy was not feasible. In addition to systemic antifungals, we successfully performed cystoscopy-assisted retrograde ureteral catheterization to decompress the pelvis, which also provided a route for local amphotericin B irrigation to achieve therapeutic concentration without nephrotoxicity.

Topics: Amphotericin B; Antifungal Agents; Anuria; Candidiasis; Caspofungin; Female; Flucytosine; Humans; Infant; Infant, Very Low Birth Weight; Kidney Diseases; Therapeutic Irrigation; Ultrasonography; Ureteral Obstruction; Urinary Catheterization

Idiopathic CD4 lymphocytopenia (ICL) is characterised by a low CD4 +lymphocyte count in the absence of HIV or other underlying aetiologies. We report a case of a 17-year-old girl with ICL with autoimmune hepatitis who developed isolated renal mucormycosis, which, to our knowledge, is the first reported case described in literature. Combination therapy with antifungals and surgical resection was done, and the patient improved. This case report illustrates the importance of timely multidisciplinary approach to recognise this highly fatal disease at an early stage.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Kidney; Kidney Diseases; Mucormycosis; T-Lymphocytopenia, Idiopathic CD4-Positive; Triazoles

Amphotericin B (AmpB) nephrotoxicity was used to assess the utility of drug‑induced kidney injury (DIKI) biomarkers in an exploratory study in male cynomolgus monkeys. All animals had quantifiable levels of AmpB in plasma on days 1 and 4. There were no clinical signs of AmpB‑induced toxicity in this study. The gold standard method used to confirm AmpB‑induced DIKI was anatomic pathology which revealed microscopic lesions with varying grades of severity. Immunolocalization of alpha‑1 microglobulin (α‑1M), kidney injury molecule 1 (KIM‑1), osteopontin (OPN) and neutrophil gelatinase‑associated lipocalin (NGAL) proteins was evaluated in formalin‑fixed, paraffin‑embedded monkey kidney tissue sections. AmpB related immunoreactivities were identified in distinct nephron segments of treated monkeys including α‑1M in damaged proximal tubule epithelium, KIM‑1 in damaged medullary tubule epithelium, OPN mostly in the infiltrating cells of cortical tubule interstitium, and NGAL in the granular and cellular cast in dilatated cortical tubules. Variations in α‑1M, KIM‑1, OPN and NGAL immunolocalization appear as promising DIKI protein biomarkers when monitoring for AmpB‑induced corticomedullary tubule injury in male cynomolgus monkeys.

Topics: Alpha-Globulins; Amphotericin B; Animals; Anti-Infective Agents; Biomarkers; Hepatitis A Virus Cellular Receptor 1; Immunohistochemistry; Kidney Diseases; Kidney Tubules; Lipocalin-2; Macaca fascicularis; Male; Osteopontin

Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000-400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region. This is the first report showing such extreme latency of VL in a European traveller. This case is furthermore unusual because it suggests primary treatment failure to liposomal amphotericin B.. An 80-year-old man who was on immunosuppressive treatment due to a non-specific inflammatory disease of the liver and kidney presented to our hospital with recurrent fever, fatigue and bloody diarrhoea. Histopathological analysis from a colon biopsy showed intracellular amastigotes. The diagnosis of VL was confirmed by polymerase-chain-reaction (PCR) of the colon biopsy. PCR was also performed in plasma, a bronchopulmonary lavage, a lymph node, liver and bone marrow biopsy and proved L. donovani as causative species. The disseminated infection was unresponsive to treatment with liposomal amphotericin B as recommended in immunosuppressed individuals despite stopping immunosuppressive treatment.. Imported cases of VL to non-endemic regions are increasing due to extensive international travel and migration. Furthermore, the increase of elderly patients and immunosuppressed individuals, secondary to HIV, post-transplant and chemotherapeutic agents, has resulted in an increase of VL also in endemic regions of Europe. It is thus important for physicians to be able to recognize the infection. This case also demonstrates treatment failure to amphotericin B, which was only a known problem in patients with HIV until now. The knowledge of this as a possible complication is important for specialists treating the disease.

Topics: Aged, 80 and over; Amphotericin B; Antiprotozoal Agents; Azathioprine; Biopsy; Colon; Europe; Humans; Immunocompromised Host; Immunosuppressive Agents; India; Indonesia; Kidney Diseases; Leishmaniasis, Visceral; Liver Diseases; Male; Polymerase Chain Reaction; Positron Emission Tomography Computed Tomography; Severity of Illness Index; Time Factors; Travel; Treatment Failure

Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p < 0.05) improved the bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Biological Availability; Biomarkers; Blood Urea Nitrogen; Candida albicans; Creatinine; Drug Carriers; Drug Compounding; Glycyrrhizic Acid; Hemolysis; Kidney Diseases; Lactic Acid; Microbial Sensitivity Tests; Nanoparticles; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Technology, Pharmaceutical

Primary renal aspergillosis, though a rare entity, is still seen in immune compromised individuals. Renal aspergillosis may lead to formation of focal abscesses, fungal bezoars and may cause ureteric obstruction. Treatment involves stabilization of patient and removal of fungal bezoars along with administration of anti-fungal agents. This report describes the case of localized primary renal aspergillosis with fungal bezoars formation in a 55 years old female, diabetic, hypertensive, who presented with upper urinary tract obstruction and was successfully managed by endoscopic removal of fungal bezoars and intravenous amphotericin followed by oral itraconazole.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bezoars; Female; Humans; Itraconazole; Kidney; Kidney Diseases; Middle Aged; Treatment Outcome; Ultrasonography; Ureteral Obstruction; Ureteroscopy

To date, eight next‑generation urinary protein kidney safety biomarkers have been qualified to enable monitoring for subclinical drug‑induced kidney injury (DIKI) in rat preclinical studies; however, most DIKI biomarker studies have included only male rats. The objective of this study was to assess the utility of novel DIKI biomarkers, including but not limited to urinary total protein, albumin, cystatin C and osteopontin in female Sprague‑Dawley rats (8/group) that received repeated intravenous injections of amphotericin B (AmpB, 3 mg/kg/day) or vehicle for 10 consecutive days. Serial serum/urine samples were collected on study day (D)4, D8, and D11. Surviving animals were necropsied on D11. The AmpB‑induced kidney histopathology findings were characterized by cortical and medullary tubular alterations, interstitial inflammation, intratubular granular and inflammatory cell casts, acute pelvic inflammation and tubular mineralization. Significant elevations in urinary clusterin on D4, D8 and D11 (3.5 fold, 2.2 fold and 3.3 fold respectively) were observed (versus concurrent controls) following repeated injections of AmpB. In addition, significantly elevated (fold changes) in biomarkers, neutrophil gelatinase‑associated lipocalin (14.6 fold), albumin (13.5 fold), cystatin C (13.5 fold), total protein (3.5 fold), kidney injury molecule 1 (3.0 fold) and osteopontin (2.3 fold) were detected in urine as early as D4. These findings demonstrate the value of early elevations in nephron‑specific DIKI biomarkers for detecting subclinical AmpB nephrotoxicity in female Sprague‑Dawley rats. These findings are anticipated to provide the basis for inclusion of female rats on a case‑by‑case basis in preclinical toxicology studies designed to detect DIKI.

Topics: Albuminuria; Amphotericin B; Animals; Biomarkers; Disease Models, Animal; Female; Kidney Diseases; Nephrons; Predictive Value of Tests; Rats, Sprague-Dawley; Time Factors

Amphotericin B (AmB) use is limited by the occurrence of kidney toxicity. Here, we evaluated the incidence and impact of nephrotoxicity in a large series of patients receiving therapy with amphotericin B deoxycholate (d-AmB), liposomal AmB (L-AmB), or AmB lipid complex (ABLC), in a clinical practice scenario. In a retrospective cohort study, patients treated with different AmB formulations between 2003 and 2012 were evaluated. Medical records and laboratory data were reviewed. Nephrotoxicity was determined according to modified RIFLE criteria. Predictors of nephrotoxicity and mortality were determined and treatment groups were compared. About 431 patients were studied (d-AmB, n = 236; L-AmB, n = 105; ABLC, n = 90). Frequency of severe nephrotoxicity (RIFLE 'Failure') was 11.5%, 2.4% and 7.2% for d-AmB, L-AmB and ABLC, respectively (P = 0.046). Use of L-AmB was found to be an independent protective factor (OR: 0.18; 95% CI: 0.03-0.64; P = 0.006) for severe nephrotoxicity, considering d-AmB as a reference. L-AmB was also a protective factor for mortality (OR: 0.56; 95% CI: 0.32-0.99; P = 0.046). In addition, in-hospital overall mortality was associated with cancer, previous dialysis, evolution to dialysis, and stay in the intensive care unit. Patients treated with ABLC showed similar frequency of severe kidney toxicity than those treated with d-AmB. L-AmB was associated with better outcomes than other formulations, including severe nephrotoxicity and overall mortality.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Antifungal Agents; Brazil; Cohort Studies; Deoxycholic Acid; Drug Combinations; Female; Humans; Kidney; Kidney Diseases; Middle Aged; Retrospective Studies

Visceral leishmaniasis is a disease caused by the protozoan Leishmania sp. and is transmitted by Lutzomyia longipalpis (sand fly). In renal transplant recipients, visceral leishmaniasis causes severe damage to the liver, spleen, and hematopoietic system, as well as poor outcomes for patients with transplanted kidneys. This study describes the largest series of cases of visceral leishmaniasis in renal transplant recipients, providing important information about the diagnostic routines and therapeutic strategies in this patient population.. A retrospective, descriptive study was performed to analyze the distribution and evaluate the extent of the epidemiologic, clinical, diagnostic and therapeutic aspects of 30 renal transplant recipients from endemic regions who presented with visceral leishmaniasis in the post-transplantation period.. In this study, visceral leishmaniasis was more frequent in men (80%). The mean age of presentation was 40 ± 10.5 years. The majority of patients worked in urban areas (66.7%), cohabitated with domestic animals (90%), and were from low-income households. In 73.3% of cases, diagnosis was made by direct isolation of Leishmania forms. Patients were treated with liposomal amphotericin, resulting in a high degree of disease remission (80%).. This study describes the largest series of visceral leishmaniasis in renal transplant recipients and expands clinical-epidemiological knowledge for transplantation teams to perform adequate disease management for this specific patient population.

Topics: Adult; Age Distribution; Amphotericin B; Animals; Animals, Domestic; Antiprotozoal Agents; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Leishmania; Leishmaniasis, Visceral; Liver Diseases; Male; Middle Aged; Residence Characteristics; Retrospective Studies; Sex Distribution; Splenic Diseases; Transplant Recipients

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Kidney; Kidney Diseases; Male; Mucormycosis; Pyelonephritis; Tomography, X-Ray Computed

Aspergillus species have angioinvasive properties and can involve extrapulmonary organs by hematogenous spread from the lungs. However, renal involvement by Aspergillus is uncommon and is usually associated with the formation of abscesses. We report an unusual case of invasive renal aspergillosis presenting with extensive renal infarction in a 5-year-old girl with acute lymphoblastic leukemia. This case emphasizes the fact that renal aspergillosis initially presents with only renal infarction, and metastatic-embolism by invasive aspergillosis should be considered in differential diagnosis for any focal lesion of kidney in a patient with leukemia.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Child, Preschool; Female; Humans; Infarction; Kidney; Kidney Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis

The occurrence of nephrotoxicity with vancomycin is approximately 17%, but can increase to 35% when combined with other nephrotoxic agents. Patients with hematologic malignancies may be at greater risk for vancomycin-induced nephrotoxicity due to nephrotoxic chemotherapy and tumor lysis syndrome.. The primary objective of this study was to determine the occurrence of nephrotoxicity in adult patients with leukemia receiving vancomycin.. A retrospective review approved by the Institutional Review Board was conducted on adult patients with leukemia who received at least one dose of vancomycin during hospital admission between 1 January 2009 and 30 April 2009.. Forty patients had an occurrence of nephrotoxicity (16%) while 210 patients did not have an occurrence of nephrotoxicity. In multivariate analysis, variables significantly associated with development of nephrotoxicity included active disease status (odds ratio, 4.38 [95% CI 1.1-29.4], p = 0.0291), concomitant intravenous acyclovir administration (odds ratio, 3.83 [95% CI, 1.6-8.9]; p = 0.0022), and concomitant amphotericin administration (odds ratio, 4.26 [95% CI, 1.9-9.4]; p = 0.0004).. The occurrence of nephrotoxicity in patients with leukemia treated with vancomycin was 16% in our study, similar to previously published reports. Active disease status and concomitant use of intravenous acyclovir and amphotericin were identified as significant risk factors for development of nephrotoxicity. The presence of risk factors for vancomycin nephrotoxicity should be evaluated prior to initiation of therapy to determine appropriateness of use.

Topics: Acyclovir; Administration, Intravenous; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Female; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Vancomycin

Zygomycosis is a rare opportunistic fungal infection in immunocompetent patients. Isolated renal involvement by zygomycosis is extremely rare and diagnosed mainly during postmortem study. We report a case of a 22-year-old man with right upper quadrant pain and fever. The CT of the abdomen revealed renal cell carcinoma and subsequent nephrectomy was performed. The histopathological diagnosis of nephrectomy established zygomycosis. After that patient was given 2 months antifungal therapy and is living well even after her 1 year follow-up.

Topics: Amphotericin B; Antifungal Agents; Diagnosis, Differential; Humans; Immunocompetence; Kidney; Kidney Diseases; Male; Tomography, X-Ray Computed; Young Adult; Zygomycosis

Mucormycosis is a life threatening condition caused by invasion of fungi of the order Mucorales. Gastrointestinal invasion is very rare and often lethal, particularly in disseminated mucormycosis. We present the case of a 26-year-old woman from North Africa with type 2 diabetes who, after a cholecystectomy, developed unexplained septic shock and haematemesis due to gastric necrosis. Computed tomography (CT) revealed a disseminated fungal invasion of the lungs, kidney and paranasal sinuses. A gastrectomy and subsequent amphotericin B treatment resolved her condition. The number of patients with mucormycosis is increasing. Early diagnosis of high risk patients with CT and biopsies from which fungi are directly isolated must be followed by surgery and systemic amphotericin B infusion.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Gastrectomy; Hematemesis; Humans; Kidney Diseases; Lung Diseases, Fungal; Mucormycosis; Necrosis; Paranasal Sinus Diseases; Shock, Septic; Stomach; Stomach Diseases; Tomography, X-Ray Computed

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 μmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 μmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Caffeic Acids; Catalase; Kidney Diseases; Male; Malondialdehyde; Nitric Oxide; Phenylethyl Alcohol; Rats; Superoxide Dismutase

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Humans; Kidney Diseases

Limited data exist regarding echinocandins as antifungal prophylaxis in liver transplant recipients.. The efficacy and safety of targeted prophylaxis with micafungin or amphotericin B lipid complex (ABLC) was assessed in a sequential cohort of high-risk patients (posttransplantation dialysis, retransplantation, or reoperation) and compared with those without high risk who did not receive prophylaxis. Outcomes were assessed at 90 days.. Micafungin versus ABLC recipients were older (P=0.0065) and more likely to have hepatocellular carcinoma (P=0.025). High-risks, that is, dialysis (55.6% vs. 79.2%), retransplantation (5.6% vs. 12.5%), and reoperation (38.9% vs. 20.8%) did not differ between the two groups. Invasive fungal infections developed in 11.1% (2 of 18) of micafungin recipients, 8.3% (2 of 24) of ABLC recipients, and 3% (7 of 234) of patients without high risks (P=0.12). In nondialyzed patients, ABLC versus micafungin recipients had significantly higher serum creatinine on day 14 (P=0.04). However, renal and hepatic function, rejection, graft loss, and mortality did not differ for the two groups on day 90.. Targeted prophylaxis with micafungin or ABLC decreased the risk of mycoses in high-risk recipients compared with that in low-risk recipients. Compared with ABLC, however, micafungin appeared to be associated with lower early-renal dysfunction and no additional risk of hepatic dysfunction.

Topics: Amphotericin B; Antifungal Agents; Chi-Square Distribution; Drug Administration Schedule; Echinocandins; Female; Graft Rejection; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Liver Transplantation; Male; Micafungin; Middle Aged; Mycoses; Premedication; Renal Dialysis; Reoperation; Risk Factors; Time Factors; Treatment Outcome

To evaluate the characteristics of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients, and their effect as a prophylactic regimen on severity and outcome.. This study included 204 allogeneic hematopoietic stem cell transplants performed on 187 children whose data retrospectively described the risk factors, prophylaxis, and treatment modalities of veno-occlusive disease. A prophylactic regimen composed of enoxaparin versus ursodeoxycholic acid and vitamin E was given to 167 of 204 patients.. Veno-occlusive disease developed in 22 patients (10.8%). Nineteen patients experienced veno-occlusive disease despite this prophylactic regimen. The prophylaxis seemed ineffective in preventing veno-occlusive disease (P = .657). Regarding risk factors, oral busulphan use, liposomal amphotericin B vancomycin treatment, and total parenteral nutrition were associated with an increased risk of veno-occlusive disease. Conversely, renal impairment also was associated with increased mortality in patients with veno-occlusive disease. The mortality rate in the first 100 days after a hematopoietic stem cell transplant was higher in the patients with veno-occlusive disease than it was in those without the disease.. Our prophylactic regimen may have played a role in the fairly low incidence of veno-occlusive disease in a pediatric population with high-risk features.

Topics: Administration, Oral; Adolescent; Age Factors; Amphotericin B; Anticoagulants; Antifungal Agents; Busulfan; Child; Child, Preschool; Drug Therapy, Combination; Enoxaparin; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Incidence; Infant; Kaplan-Meier Estimate; Kidney Diseases; Male; Parenteral Nutrition, Total; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Turkey; Ursodeoxycholic Acid; Vitamin E; Young Adult

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney Diseases

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney Diseases

This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT).. Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated.. A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%.. Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; APACHE; Bacterial Infections; Cohort Studies; Critical Illness; Female; Hemodynamics; Hospital Mortality; Humans; Kidney Diseases; Length of Stay; Male; Middle Aged; Prospective Studies; Renal Replacement Therapy; Spain; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Humans; Infant, Premature, Diseases; Kidney Diseases; Mycoses

Topics: Amphotericin B; Antifungal Agents; Humans; Infant, Premature, Diseases; Kidney Diseases; Mycoses

Systemic Candidia infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic Candida infection. We report a very rare case of candidiasis caused by Candida kefyr in a term neonate.. Renal agenesis on the left side was diagnosed antenatally and anal atresia postnatally. Moreover, a vesico-ureteral-reflux (VUR) grade V was detected by cystography. The first surgical procedure, creating a protective colostoma, was uneventful. Afterwards our patient developed urosepsis caused by Enterococcus faecalis and was treated with piperacillin. The child improved initially, but deteriorated again. A further urine analysis revealed Candida kefyr in a significant number. As antibiotic resistance data about this non-albicans Candida species are limited, we started liposomal amphotericin B (AMB), but later changed to fluconazole after receiving the antibiogram. Candiduria persisted and abdominal imaging showed a Candida pyelonephritis. Since high grade reflux was prevalent we instilled AMB into the child's bladder as a therapeutic approach. While undergoing surgery (creating a neo-rectum) a recto-vesical fistula could be shown and subsequently was resected. The child recovered completely under systemic fluconazole therapy over 3 months.. Candidiasis is still of major concern in neonates with accompanying risk factors. As clinicians are confronted with an increasing number of non-albicans Candida species, knowledge about these pathogens and their sensitivities is of major importance.

Topics: Amphotericin B; Antifungal Agents; Anus, Imperforate; Candida; Candidiasis; Congenital Abnormalities; Enterococcus faecalis; Fluconazole; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Kidney; Kidney Diseases; Sepsis; Treatment Outcome; Urinary Tract Infections; Urine; Vesico-Ureteral Reflux

Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited.. A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded.. A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible.. AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

Topics: Adolescent; Amphotericin B; Analysis of Variance; Antifungal Agents; Candidemia; Child; Child, Preschool; Female; Humans; Hypokalemia; Infant; Kidney Diseases; Male; Retrospective Studies; Risk Factors

Liposomal amphotericin B (LAMB) is frequently administered in NICU to preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal infections (SFI). Concerns exist on safety and tolerability of such drug in patients who are at risk for renal function impairment due to their prematurity.. To assess the occurrence of renal function impairment related to LAMB in a 10-year cohort of VLBW neonates treated with this drug.. Through database search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in the years 1998-2007 and undergoing treatment with LAMB were identified. The occurrence of LAMB-attributable renal toxicity was investigated; infants withdrawn from treatment for development of adverse effects or toxicity were identified.. In the study period, 71 of 792 admitted VLBW neonates (8.9%) underwent antifungal treatment with LAMB administered at the recommended dosages (3-to-5 mg/kg/day). Mean duration of treatment was 14 (±9) days, mean cumulative dose given was 58 (±25) mg/kg per infant. Renal compromise, defined as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine output, occurred in 2 of 71 (2.8%) treated patients, by 5 (±3) mean days after treatment initiation. In both patients LAMB was withdrawn; renal function impairment was only mild and transient, and normal renal function was restored at discharge. No other significant adverse effects were recorded in any treated neonate.. LAMB is generally safe and well tolerated in VLBW neonates. The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and transient.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Cohort Studies; Creatinine; Fluconazole; Humans; Hypokalemia; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney; Kidney Diseases; Kidney Function Tests; Mycoses; Premature Birth; Retrospective Studies; Sepsis

To assess the tolerability of liposomal amphotericin B (L-AmB) in critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5 mg/dL) at starting L-AmB therapy.. Retrospective, multicenter, comparative study of two cohorts of critically ill patients treated with L-AmB during 3 or more days, the difference between them was the level of Cr at the beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established. Patients undergoing extrarenal depuration procedures before or 48 hours after starting L-AmB were excluded. The primary endpoint was the difference between Cr values at the end of treatment as compared with Cr at starting L-AmB. Secondary endpoints were treatment-related withdrawals, need of extrarenal depuration techniques, and treatment-related severe adverse events. Demographic data, underlying illness, indication of L-AmB therapy, concomitant risk factors of nephrotoxicity, and vital status at ICU and hospital discharge were recorded.. A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106 with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both groups were the broad spectrum of the drug and the presence of hemodynamic instability. L-AmB was administered as first-line treatment in 68.8% of patients with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU admission was 25 in patients with elevated Cr and 17 in those with normal Cr values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in patients with elevate and normal Cr values, respectively, with a mean dose of 3.5 vs 3.9 mg/kg/day. The use of concomitant nephrotoxic drugs, mortality rate, and ICU and hospital length of stay were similar in both cohorts. In patients with renal function impairment at the initiation of L-AmB treatment, an absolute decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels to normal limits was observed in 50% of the patients; in 37.5% of patients there was a decrease but normal levels were not achieved, whereas a Cr increased occurred in only one (6.25%) patient. None of the patients required withdrawal of L-AmB or use of extrarenal depuration procedures. Treatment-related severe adverse events were not reported.. In critically ill patients with impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB can be used for the treatment of fungal infections in critically ill patients independently of renal function at the initiation of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Cohort Studies; Creatinine; Critical Illness; Female; Humans; Infant; Kidney; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Retrospective Studies; Young Adult

Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has been shown to have a better safety profile than both the deoxycholate and lipid complex forms of amphotericin B; however, the frequency of major side effects is still unclear. Thus, the aim of the present study was to assess retrospectively the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia as well as the relationship between daily dose of L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre-treatment) and anaemia were observed in 7 and 10 of 21 adult patients, respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of L-AmB that are estimated to cause side effects of a low RBC count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day, respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of total bilirubin, γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7, 8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9 patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not caused in a dose-dependent manner. In conclusion, the present analyses showed that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult patients. It is important to pay attention to causing anaemia and thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and >3.0mg/kg/day, respectively.

Topics: Aged; Amphotericin B; Anemia; Antifungal Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Thrombocytopenia

Amphotericin B deoxycholate is associated with infusion-related toxicity and renal toxicity.. To evaluate medical indications of this compound in a tertiary care center, analyze adverse reactions, infusion protocols and outcome of treated patients.. Retrospective analysis of 39 treatments indicated in 33 patients during 2007, exploring indications, infusion protocols and renal protective measures, infusion-related adverse reactions, nephrotoxicity, hypokalemia and outcomes.. On average, therapy lasted 12 days (2 to 39) and reached 600 mg of accumulated dose (100 to 1950) respectively. 24-hours infusions were applied in 63.2% of prescriptions and 35.9% received a 4-6 hour infusion schedule. In addition, 36.8% received daily a saline infusion before amphotericin. Adverse reactions were observed in 40% of treatments, predominating fever (25%). Nonetheless, nephrotoxicity was infrequent (9.4%), of low magnitude, only affecting patients without previous renal disease, and not requiring dialysis. Hypokalemia developed in 21.6% of treatments. More than half of medical indications were empirical (59%), for presumed infections by either filamentous fungi or yeasts. In the subgroup with microbiological information, main indications were invasive aspergillosis (15.4% of total), systemic candidiasis (12.8%) or meningeal cryptococcosis (10.3%). A favorable response was registered in 41%, and only 48.5% of patients survived. In a multivariate analysis, only age > 60 years remained as an independent factor for developing infusion-related adverse reactions. In the same manner, a SOFA score > 3 and corticosteroids administration at the same time than amphotericin B, were independently associated to a fatal outcome.. infusion-related adverse reactions are frequent during amphotericin B deoxycholate therapy, but renal toxicity is occasionally observed. Amphotercin B was used mainly as empirical therapy in this study.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Chile; Deoxycholic Acid; Drug Combinations; Female; Hospitals, University; Humans; Kidney Diseases; Male; Middle Aged; Mycoses; Retrospective Studies; Time Factors; Young Adult

The aim of this study was to investigate the factors associated with acute kidney injury (AKI) in patients with visceral leishmaniasis (VL). The study patients had a diagnosis of VL and were admitted to a tertiary hospital. A multivariate analysis was performed to analyze the risk factors for AKI. A total of 224 patients were included. The mean age was 36 +/- 15 years. AKI was observed in 33.9% of cases. Risk factors associated with AKI were male gender (odds ratio [OR] = 2.2; P = 0.03), advanced age (OR = 1.05; P < 0.001), and jaundice (OR = 2.9; P = 0.002). There was an association between amphotericin B use and AKI (OR = 18.4; P < 0.0001), whereas glucantime use was associated with lower incidence of AKI compared with amphotericin B use (OR = 0.05; P < 0.0001). Mortality was 13.3%, and it was higher in AKI patients (30.2%). Therefore, factors associated with AKI were male gender, advanced age, and jaundice. Amphotericin B was an important cause of AKI in VL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Kidney Diseases; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Risk Factors; Young Adult

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

Topics: Amphotericin B; Antifungal Agents; Creatinine; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Mycoses; Retrospective Studies

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Male; Sarcoidosis; Sarcoidosis, Pulmonary; Treatment Outcome

The aim of this retrospective, case-control study was to determine the effect of the amphotericin B lipid complex (ABLC) on serum creatinine (SCr), blood urea nitrogen (BUN), sodium (Na), and potassium (K) in very low birth weight (VLBW) infants. Medical records of all VLBW infants who were admitted to our Neonatal Intensive Care Unit between May 1998 and May 2006 and had received ABLC for at least 2 weeks were reviewed for patient demographics, use of medications (ABLC, diuretics, xanthines, indomethacin, vancomycin, gentamicin, pressors, and inotropes), fluid intake, urinary output, and serum electrolytes. Thirty-five patients who received ABLC were identified and matched by gestational age (GA) to 35 patients who served as controls. Infants who received ABLC had an average GA of 25.7 +/- 2.1 weeks and a birth weight of 764 +/- 196 g. Between day 1 and 14 of ABLC treatment, the BUN decreased from 17.5 +/- 11.5 to 10.5 +/- 6.8 mg/dl (p = 0.01), the SCr varied between 0.78 +/- 0.32 and 0.69 +/- 0.32 mg/dl, Na varied between 136.6 +/- 5.8 and 137.8 +/- 3.6 mEq/l, and K varied between 4.8 +/- 0.9 and 4.9 +/- 0.6 mEq/l, respectively. Based on these results, we conclude that treatment with ABLC for 2 weeks did not increase BUN or SCr, nor decrease Na or K in VLBW infants.

Topics: Amphotericin B; Antifungal Agents; Blood Urea Nitrogen; Case-Control Studies; Creatinine; Female; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Kidney; Kidney Diseases; Male; Potassium; Retrospective Studies; Risk Factors; Sodium

This study was conducted to characterize blood and urinary biochemistry, and renal morphology, after single or 1-week repeated dosing of mice with the polyene macrolide antibiotic, amphotericin B (AMB). AMB was intravenously administered to mice at 2 or 4 mg/kg for the single-dose experiment or once daily at 1 or 2 mg/kg for 1 week for the repeated-dose experiment. The most prominent histopathological findings included necrosis of the tubular epithelial cells in the thick ascending limb of Henle's loop in the renal outer medulla at a single dose of 2 or 4 mg/kg, and the severity of the lesion was dose-dependent. Blood chemistry and urinalysis revealed several changes suggestive of renal dysfunction such as reduction of plasma filtration ability (increases in plasma creatinine and blood urea nitrogen, a decrease in creatinine clearance) and polyuria accompanied with dehydration (decrease in renal water reabsorption, increases in plasma total protein and albumin) at a dose of 4 mg/kg in the single-dose experiment. Among the parameters analyzed, urinary lactate dehydrogenase was the most sensitive and reliable parameter for the prediction of AMB-induced nephrotoxicity in mice. These data provided comprehensive information on the nephrotoxicity of AMB and indicate useful markers for the sensitive detection of AMB-induced renal injury in mice.

Topics: Amphotericin B; Animals; Antifungal Agents; Blood Chemical Analysis; Body Weight; Creatinine; Dose-Response Relationship, Drug; Eating; Kidney; Kidney Diseases; Kidney Function Tests; Male; Mice; Mice, Inbred ICR; Organ Size; ROC Curve; Urinalysis

Isolated renal infections with fungal organisms of the class Zygomycetes are rare, but these infections are most frequently seen in patients who are immunocompromised. We report the case of a 45-year-old African American man who presented with symptoms of right-sided pyelonephritis, including fever, dysuria, and flank pain. The patient's history was significant only for sickle cell trait, and no evidence of immunosuppression was identified. Renal ultrasound imaging revealed a hypoechoic lesion in the superior pole of the right kidney, and the radiologic differential diagnoses included neoplasm, abscess, and infarct. Urine cultures were negative, but urinalysis showed white blood cells, which were too numerous to count. A computed tomography scan of the abdomen and pelvis performed 2 weeks after the initial presentation showed a slight increase in the renal mass, despite antimicrobial therapy, and a right nephrectomy was subsequently performed. On gross sectioning, an 8.5-cm well-circumscribed lesion was identified in the upper pole of the kidney. Microscopic sections showed extensive necrosis of the renal parenchyma, and, in areas of both infarcted and viable renal tissue, large, broad, aseptate fungal hyphae with irregular branching. Angioinvasion with associated thrombosis was seen in the renal tissue. The morphologic features of the organism were most compatible with that of a zygomycete. No evidence of disseminated fungal disease was identified on imaging studies. This case represents a successful outcome of a rarely reported isolated renal zygomycosis in a patient with no known underlying risk factors for the infection and illustrates the wide range of clinical presentations with which zygomycotic infections may present.

Topics: Adrenalectomy; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Humans; Immunocompetence; Kidney Diseases; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Pyrimidines; Tomography, X-Ray Computed; Triazoles; Voriconazole; Zygomycosis

The prevalence of nephrotoxicity in neonates receiving amphotericin B deoxycholate (amphoB) is not well-defined. While some studies report a lack of toxicity, others claim a frequency as high as 85%.. We reviewed medical records of all infants < or = 90 days of age in the neonatal intensive care unit who received at least 3 doses of amphoB between January 1990 and December 2004. A standardized form was used to collect demographic, therapeutic, microbiologic, and laboratory data for each patient. Nephrotoxicity was defined as a rise in serum creatinine (SCr) of at least 0.4 mg/dL any time during amphoB therapy.. A total of 92 infants met entry criteria. Median gestational age was 26 (range: 23-41) weeks and median birth weight was 863 (range: 546-4000) grams. Overall, 15 (16%) infants experienced nephrotoxicity, and 16 (17%) developed hypokalemia (<3.0 mmol/L). There were no differences between infants who did or did not develop nephrotoxicity in terms of gestational age, birth weight, gender, underlying medical conditions, or use of other potentially nephrotoxic medications. AmphoB exposure and duration of therapy were similar between infants who developed nephrotoxicity and those who did not, with a mean cumulative dose of 13.5 +/- 9.6 mg/kg and duration of 16.3 +/- 10.4 days. With the exception of 1 infant, the elevated SCr values resolved in all infants by the end of amphoB therapy.. AmphoB administration does not appear to be associated with lasting measurable nephrotoxicity in neonates. Because of changes in serum creatinine and potassium, renal function and potassium levels should be monitored closely in infants receiving amphoB.

Topics: Amphotericin B; Candidiasis; Creatinine; Deoxycholic Acid; Drug Combinations; Humans; Infant, Newborn; Kidney; Kidney Diseases; Retrospective Studies; Statistics, Nonparametric

To describe the incidence of renal dysfunction, hypokalaemia and hypomagnesaemia in AIDS patients with cryptococcal meningitis and on amphotericin B treatment. Secondary objective was to determine all-cause mortality in the same group.. Prospective, observational study.. Kenyatta National Hospital (KNH), Nairobi, Kenya.. Seventy consecutive patients with AIDS and cryptococcal meningitis on amphotericin B.. About 58.6% of the patients had at least 100% rise in the creatinine level. Thirty eight point six per cent of patients experienced a rise in serum creatinine of at least 50%. Ninty three per cent of the patients developed hypokalaemia and 80% had hypomagnesaemia at trough magnesium level. Only 54.3% of patients completed the intended 14-day treatment. Thirty point five per cent of patients died within the two week follow-up period.. The incidences of amphotericin B associated nephrotoxicity, hypokalemia and hypomagnesaemia were high in this studied population.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Creatinine; Female; Humans; Kenya; Kidney Diseases; Male; Meningitis, Cryptococcal; Middle Aged; Prospective Studies

The therapeutic efficacy of a composition of amphotericin B and dialdehyde dextran was much higher than that of amphotericin B in the therapy for systemic candidiasis. This conclusion was derived from the earlier and progressive decrease in the number and size of candidal granulomas in the kidneys. The composition of amphotericin B and dialdehyde dextran was more potent than amphotericin B in decreasing the nephrotoxic effect of C. albicans. The opposite strains of CBA and C57Bl/6 mice differed in morphological signs of granulomatosis in the kidneys, but not in the nephrotoxic effect of C. albicans metabolites.

Topics: Amphotericin B; Animals; Anticoagulants; Antifungal Agents; Candidiasis; Dextrans; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Child; Child, Preschool; Echinocandins; Fatal Outcome; Female; Humans; Kidney; Kidney Diseases; Leukemia, Myeloid, Acute; Lipopeptides; Lung; Lung Diseases, Fungal; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tomography, X-Ray Computed

Our aim in the present investigation was to develop a nanoparticulate carrier of amphotericin B (AmB) for controlled delivery as well as reduced toxicity. Nanoparticles of different gelatins (GNPs) (type A or B) were prepared by two-step desolvation method and optimized for temperature, pH, amount of cross-linker, and theoretical drug loading. AmB-loaded GNPs were characterized for size, polydispersity index (PI), shape, morphology, surface charge, drug release, and hemolysis. The developed GNPs (GNP(A300)) were found to be of nanometric size (213 +/- 10 nm), having low PI (0.092 +/- 0.015) and good entrapment efficiency (49.0 +/- 2.9%). All GNPs showed biphasic release characterized by an initial burst followed by controlled release. The in vivo hematological toxicity results suggest nonsignificant reduction (P > .05) in hemoglobin concentration and hematocrit. Nephrotoxicity results showed that there was a nonsignificant (P > .05) increase in blood urea nitrogen and serum creatinine levels. The results confirm that developed GNPs could optimize AmB delivery in terms of cost and safety, and type A gelatin with bloom number 300 was found suitable for such preparation.

Topics: Amidohydrolases; Amphotericin B; Animals; Antifungal Agents; Blood Urea Nitrogen; Drug Carriers; Gelatin; Hematocrit; Hemoglobins; Humans; In Vitro Techniques; Kidney Diseases; Kinetics; Male; Mice; Nanoparticles

Topics: Amphotericin B; Child; Cyclosporine; Humans; Ifosfamide; Kidney Diseases; Kidney Function Tests; Time Factors

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Creatinine; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Retrospective Studies; Risk Factors

Amphotericin B-induced nephrotoxicity is frequent, severe and associated with an increased risk of death. Patients with underlying renal disease are considered to be at high risk for amphotericin B nephrotoxicity. Amphotericin B is a molecule that is highly protein bound over a wide range of protein and drug concentrations, including those seen in patients with >or= 3 + proteinuria. We hypothesized that amphotericin B treatment in patients with proteinuria will be associated with less hypokalaemia than patients with non-proteinuric renal disease.. Thirty-six subjects who received amphotericin B deoxycholate were studied retrospectively. Twenty-five patients with proteinuria < 3 g/L and 11 with proteinuria >or= 3 g/L were compared.. Hypokalaemia (K+ < 3.5 mmol/L) developed in 47.2% (17/36) of our cohort of patients. There was a 64% (16/25) incidence of hypokalaemia in the group with < 3 g/L of proteinuria in contrast to an incidence of 9.1% (1/11) in the other group.. In our study, heavy proteinuria appears to protect the tubular luminal membrane by decreasing the luminal concentration of free drug available to bind with the membrane. Our findings redefine the patient population deemed to be at risk of developing amphotericin B nephrotoxicity. This ensures the benefit of this important antifungal treatment option to patients with heavy proteinuria who might otherwise not be administered this drug due to the presence of pre-existing kidney disease.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Mycoses; Proteinuria; Retrospective Studies; Risk

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

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

We describe a case of primary cutaneous Absidia corymbifera infection in an AIDS patient with renal complications. The Sensititre YeastOne panel was adopted to determine antifungal susceptibility and liposomial amphotericin B was used which initially produced a significant clinical response.

Topics: Absidia; Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Female; Humans; Injections, Intravenous; Kidney Diseases; Leg Injuries; Mucormycosis; Soft Tissue Infections

Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene-block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure homogenizer. Nephrotoxicity of the nanoparticle was investigated along with antifungal activity and self-aggregation status of the drug in the nanoparticle. Nephrotoxicity was markedly reduced when AmB was intravenously administered to rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission electron microscopy of tubular cells and creatinine clearance. Antifungal activity of AmB was not altered when the drug was in the form of mixed micellar nanoparticle compared to both conventional formulation and AmB micelle treated by same procedure without PS-block-PEO. Self-aggregation status of AmB molecules revealed monomeric in the mixed micellar nanoparticle with PS-block-PEO up to the therapeutic level of the drug (1-3 mM). The reduced nephrotoxicity of AmB in mixed micellar nanoparticle may be associated with the existence of the drug as monomeric form in the nanoparticle. Based on our result, formulation of AmB as mixed micellar nanoparticle with PS-block-PEO may be a promising alternative for the treatment of fungal diseases in patients who are at risk of renal dysfunction.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Male; Micelles; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Polyethylene Glycols; Polystyrenes; Rats; Rats, Sprague-Dawley; Surface Properties

The objective of this study was to determine if total plasma and lipoprotein cholesterol (C) and triglyceride (TG) concentrations could predict the degree of nephrotoxicity caused by the antifungal agent amphotericin B (AmpB); and to use the average amount of potassium supplementation received daily as a indicator of nephrotoxicity in pediatric oncology patients.. Plasma samples from 18 patients (ages < 17 years) who were receiving AmpB due to suspected or confirmed fungal infection at British Columbia Children's Hospital were analyzed for lipid concentrations. The high density lipoprotein (HDL) fractions were separated by precipitation; total (TOT) plasma and fraction C and TG concentrations were measured by enzymatic colorimetric assays; and low density lipoprotein (LDL) C levels were determined by Friedewald's formula. Changes in serum creatinine levels from baseline and amounts of potassium supplementation were used as indicators of nephrotoxicity; both were obtained from patients' medical charts. Pearson correlation coefficients (r) were determined and considered significant if P < 0.05.. The total cumulative AmpB dose, adjusted for weight, does not seem to predict AmpB-induced nephrotoxicity. Positive but relatively weak correlations were found between total potassium supplementation and LDL C (r = 0.489, P < 0.02); and TOT C (r = 0.551, P < 0.01). In addition, a positive but relatively weak correlation between the average amount of potassium supplementation per day above baseline and HDL C (r = 0.407; P < 0.02) was observed.. Differences in total plasma and LDL cholesterol concentrations may be used as predictors of AmpB-induced nephrotoxicity in pediatric oncology patients.

Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Cholesterol; Creatinine; Female; Humans; Infant; Kidney Diseases; Kidney Function Tests; Male; Mycoses; Neoplasms; Prognosis; Triglycerides

Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy.

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Hospitalization; Humans; Kidney Diseases; Male; Medical Records; Middle Aged; Mycoses; Retrospective Studies

We describe a 9-yr-old boy who received the highest cumulative dose so far reported of liposomal amphotericin B. The patient underwent an allogeneic bone marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin, cyclosporin and prednisone were used as prophylaxis against graft vs. host disease (GVHD). Post-transplant Epstein-Bar-virus-related lymphoma was diagnosed on day +68 and was treated with donor-derived lymphocytes. The patient developed a severe form of GVHD, and a progressive worsening of his neurological status because of progression of his underlying disease. Death from septic shock occurred 23 months after BMT. During prolonged hospitalization, 19,750 mg of liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or empirical therapeutic purposes without significant nephrotoxicity. This case suggests that liposomal amphotericin B is safe and well-tolerated even if is administered for long periods and a cumulative dose fivefold greater than the nephrotoxic threshold of amphotericin B deoxycholate is achieved.

Topics: Adrenoleukodystrophy; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candidiasis; Child; Creatinine; Disease Progression; Epstein-Barr Virus Infections; Fatal Outcome; Graft vs Host Disease; Humans; Kidney; Kidney Diseases; Liposomes; Lymphoma; Male; Pseudomonas Infections; Shock, Septic; T-Lymphocytes, Cytotoxic; Transplantation Conditioning

Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity.. The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe.. Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection.. This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Europe; Female; Humans; Immunocompromised Host; Kidney Diseases; Length of Stay; Male; Middle Aged; Mycoses; Polyenes; Prospective Studies

Systemic fungal infections have significantly increased. The mainstay of treatment is amphotericin B deoxycholate. A limitation of using amphotericin B includes infusion-related reactions and nephrotoxicity. A continuous infusion of amphotericin B was found to reduce nephrotoxicity and infusion-related reactions.. To implement clinical practice policy on the continuous intravenous administration of amphotericin B in the patients hospitalized in general medical wards at Siriraj Hospital.. A one-page evidence-based clinical practice policy on continuous intravenous administration of amphotericin B was prepared and disseminated to all general medical wards in Siriraj Hospital. The information on the patients who received amphotericin B treatment between March 2004 and March 2006 was collected. The data were analyzed using descriptive statistics, univariate analysis and multivariate analysis as appropriate. A p-value of < 0. 05 was considered statistically significant.. Of 166 courses of amphotericin B treatment in 148 patients, 102 courses (61.4%) were given continuous intravenous administration of amphotericin B (CI group) and 64 courses (38.6%) were given conventional 4-to 6-hour intravenous administration (RI group). The mean age of the patients in the CI group was significantly greater than that in the RI group. The CI group had more patients with neutropenia with persistent fever whereas the RI group had more patients with HIV/AIDS and cryptococcal meningitis. The incidence of amphotericin B-related nephrotoxicity was 27.5% in the CI group compared with 39.1% in the RI group (p = 0.164). Chills were observed in 6.9% of the patients in the CI group compared with 26.6% in the RI group (p = 0. 001). Overall mortality at the end of therapy was significantly higher in the CI group. However, most of the deaths in the CI group were unrelated to fungal infections or amphotericin administration.. Continuous infusion of amphotericin B was associated with a decrease in infusion-related reactions and tended to have less nephrotoxicity than those in the 4-to 6-hour infusion group.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Mycoses; Organizational Policy; Prognosis; Program Development; Prospective Studies; Risk Factors

Amphotericin B may cause acute reduction in renal function. N-acetylcysteine (NAC) has a renoprotective activity in several nephrotoxic renal insults, but its effect on amphotericin-induced renal failure has not been investigated yet.. Acute renal failure was induced in 30 Sprague-Dawley rats by a single intraperitoneal injection of amphotericin B (50 mg/kg). NAC (10 mg/kg) in isotonic saline or isotonic saline alone were administered daily for 4 days, starting 1 day before the amphotericin B injection. Glomerular filtration rate (GFR) was assessed using 99m-technetium diethylene triaminepentaacetic acid. Before and following amphotericin B administration, a 24-hour urine collection was performed for sodium, potassium and magnesium determination. The kidneys were preserved for pathologic examination.. Amphotericin B induced a significant decrease of GFR in both groups. Four days after amphotericin injection the GFR in the NAC-treated group was significantly higher than in the control group (0.62 +/- 0.20 vs. 0.46 +/- 0.14 ml/min, p = 0.042). Histologic signs of acute tubular necrosis were attenuated in the NAC-treated group. There were no significant differences between the groups in sodium, potassium and magnesium urine excretion after amphotericin injection.. NAC treatment exerted a renoprotective effect on deterioration of GFR in a rat model of amphotericin-induced renal failure. No functional protection on tubular function, as obviated by similar polyuria and urine losses of potassium and magnesium in both groups, was observed.

Topics: Amphotericin B; Animals; Disease Models, Animal; Glomerular Filtration Rate; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Treatment Outcome

The safety and efficacy of amphotericin B lipid complex injection (ABELCET; Enzon Pharmaceuticals, Piscataway, NJ) was assessed in 548 children and adolescents 0-20 years of age who were enrolled in the Collaborative Exchange of Antifungal Research (CLEAR) registry. To our knowledge, this is the largest series of pediatric patients treated for invasive mycoses with a single agent. All patients had cancer or had received a bone marrow, cord blood or solid organ transplant and were treated with amphotericin B lipid complex for documented or suspected fungal infection.. The CLEAR database was queried for all patients 0-20 years of age from 1996 to 2000. Data gathered included demographic variables, underlying disease type, reasons for the use of amphotericin B lipid complex injection, dosing information, clinical response and renal effects.. Most patients were either intolerant of or refractory to conventional antifungal therapy, and almost one-half were neutropenic at treatment onset. Of the 548 patients, 300 (54.7%) were transplant recipients and 393 (71.7%) had received one or more concomitant nephrotoxins. Candida and Aspergillus were the most commonly isolated species in patients with proven or probable infections. Response data were evaluable for 255 of the 285 patients with documented single or multiple pathogens. A complete (cured) or partial (improved) response was achieved in 54.9% of patients, with an additional 16.9% of patients having a stable outcome. Among patients with proven Aspergillus infection, the response rates (cured + improved) were 40.5 and 37.5% in transplant and nontransplant patients, respectively. When stable responses were added, the response rates were 48.6 and 71.9%, respectively. There were few clinically significant deleterious effects on renal function. There was no significant difference between the rates of new hemodialysis versus baseline hemodialysis. Elevations in serum creatinine of >1.5 x baseline and >2.5 x baseline values were seen in 24.8 and 8.8% of all patients, respectively.. The safety and efficacy data from this large pediatric population support the use of amphotericin B lipid complex injection for treatment of invasive fungal infections in immunocompromised children and adolescents, including the high risk subgroup of transplant recipients. The overall response rate and safety profile in pediatric patients who were largely intolerant of or refractory to conventional antifungal therapy were consistent with earlier reported findings of smaller trials.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Drug Combinations; Drug Interactions; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Mycoses; Organ Transplantation; Phosphatidylcholines; Phosphatidylglycerols; Registries; Retrospective Studies

To investigate the renal safety of amphotericin B lipid complex (ABLC), records from 3514 ABLC-treated patients with fungal infections were reviewed. The median change in predicted creatinine clearance (CCr) from baseline to the end of therapy was -3 mL/min (range, -119 to 118 mL/min); doubling of serum creatinine (S-Cr) level occurred in 13% of patients, and new dialysis was needed for 3% of patients. Patients with underlying renal disease who had received prior antifungal therapy demonstrated a median CCr of 0.5 mL/min (range, -107 to 52 mL/min). Despite increased risk for renal impairment in allogeneic hematopoietic stem-cell transplant recipients, only 17% of patients demonstrated end-of-therapy doubling of S-Cr levels, and the median change in CCr was -10 mL/min (range, -107 to 108 mL/min). In ABLC-treated patients, concomitant treatment with potentially nephrotoxic agents and a baseline S-Cr level of <2 mg/dL were factors predisposing for the development of nephrotoxicity. These data provide evidence that ABLC may be used safely to treat patients who are at increased risk for renal impairment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Drug Combinations; Female; Humans; Infant; Kidney Diseases; Male; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Registries; Risk

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney Diseases; Middle Aged; Mycoses

Topics: Acute Kidney Injury; Adult; Amphotericin B; Aspergillosis; Aspergillus niger; Female; Follow-Up Studies; Fungemia; Humans; Injections, Intralesional; Kidney Diseases; Kidney Tubules, Collecting; Radiography; Risk Assessment; Treatment Outcome; Ureter

The current study assessed renal function based on medical records in adult hematopoietic stem cell transplant (HSCT) recipients with proven or probable invasive fungal infection (IFI) transplanted between 1995 and 2000. We confirm that amphotericin B deoxycholate (AmB-d) is nephrotoxic in a large percentage of HSCT recipients. Due to nephrotoxicity, defined as serum creatinine (SCr) >2.5 mg/dl or a 100% increase in SCr from baseline, 88% of patients treated with AmB-d were switched to a lipid formulation of amphotericin B (LFAB). In total, 53% of patients initiated on AmB-d were switched within the first week of therapy. Significantly more patients (70.6%) treated with AmB-d experienced a 100% increase in SCr from baseline compared to patients treated with either AmBisome (44.4%) or Abelcet (41.2%). A Cox Proportional Hazards Model revealed that, compared to patients initiated on AmBisome or Abelcet, the risk of nephrotoxicity (RR=1.5 vs AmBisome; RR=1.7 vs Abelcet), dialysis (RR=2.4 vs AmBisome; RR=1.4 vs Abelcet), and death (RR=2.0 vs AmBisome; RR=1.1 vs Abelcet) were all increased for patients initiated on AmB-d. Study results suggest that renal function improves and mortality declines when an LFAB is given to HSCT patients as initial therapy rather than as second-line therapy, the current practice.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Kidney Diseases; Liposomes; Male; Middle Aged; Mycoses; Proportional Hazards Models; Retrospective Studies

Greater use of invasive procedures and aggressive antimicrobial therapy predispose extremely low birth weight (ELBW) infants to systemic fungal sepsis. Despite its adverse effects (including renal and electrolyte disturbances), amphotericin B (amphoB) remains the preferred drug for fungal therapy. Multiple studies have indicated that sodium loading may prevent renal toxicity among animals and human adults. The effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants have not been evaluated extensively. The purpose of this study was to examine the effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants.. The medical records were reviewed for all ELBW infants (birth weights of < or =1250 g) who developed systemic fungal sepsis, requiring amphoB therapy, between January 1992 and December 2000. Demographic, clinical, and laboratory data were collected from the medical records for each patient.. Fungal sepsis requiring amphoB treatment developed for 4.4% of ELBW infants (25 of 573 infants), with a gestational age of 25 +/- 1 weeks and a birth weight of 738 +/- 37 g, at a postnatal age of 16 +/- 2 days. Renal compromise, as manifested by low urine output and high creatinine levels, occurred for 44% of those infants (11 of 25 infants). There was no difference between the infants who developed renal compromise (renal compromise group [RCG], n = 11) and those who did not (no-renal-compromise group [NCG], n = 14) with respect to birth weight, gestational age, and risk factors predisposing the infants to fungal sepsis. The RCG demonstrated a decrease in urine output by 3.4 +/- 2 days and an increase in serum creatinine levels by 3.9 +/- 2 days after the initiation of amphoB therapy. Infants in the RCG had a significantly higher incidence of hyponatremia, compared with infants in the NCG (7 of 11 infants vs 0 of 14 infants), with no significant difference in the incidences of hypokalemia (2 of 11 infants vs 0 of 14 infants). Infants in the RCG, compared with infants in the NCG, had significantly lower mean daily sodium intakes in the 4 days before the initiation of amphoB therapy (2.6-2.9 mEq/kg per day vs 4.2-4.7 mEq/kg per day) and in the first 4 days of amphoB treatment (2.7-3.1 mEq/kg per day vs 4.5-5.6 mEq/kg per day). Mean daily sodium intakes were not statistically significantly different between the 2 groups between day 5 and day 10 of amphoB therapy. Infants in the RCG tended to have lower mean daily potassium intakes in the 4 days before the initiation of amphoB therapy and during the first 4 days of amphoB therapy. Subsequently, the mean daily potassium intakes remained not statistically significantly different between the groups. Mean daily fluid intakes were not different between the groups.. Conventional amphoB combined with adequate hydration and higher sodium intakes of >4 mEq/kg per day may provide effective protection against amphoB-induced nephrotoxicity among ELBW infants. Our data confirm the published results of animal and human adult studies and suggest that higher sodium intakes may prevent renal compromise during amphoB therapy among ELBW infants.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Creatinine; Female; Fluid Therapy; Fungemia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney Diseases; Male; Potassium; Retrospective Studies; Risk Factors; Sodium; Water-Electrolyte Balance

Hydrophilic albumin microspheres are proposed as a new delivery system for amphotericin B (AMB; AMB microspheres). The acute toxicity of AMB microspheres was lower than that of the AMB-deoxycholate (AMB-Doc) reference formulation in hamsters. Lethal doses in healthy and infected animals were improved at least eight times. Intravenous bolus administration of doses of AMB microspheres up to 40 mg/kg of body weight did not produce acute symptoms of toxicity. The efficacy of this new formulation was tested against Leishmania infantum-infected hamsters at doses of 2, 10, 20, and 40 mg/kg. With the 2-mg/kg dose, the activity of AMB, as assessed through the parasite load reductions in the liver and spleen and the evolution of antibody levels, was also improved (P < 0.05) by use of the AMB microsphere system. At the higher doses of 10, 20, and 40 mg/kg, reductions in parasite levels of more than 99% were achieved in the liver and spleen after the administration of AMB microspheres. A pharmacokinetic study was performed to study the serum, liver, and spleen AMB concentrations after administration of AMB microspheres and the reference formulation. Interestingly, a significant accumulation of AMB in the spleen and liver was observed after AMB microsphere administration. Our results suggest that this new formulation is a promising alternative to the conventional AMB-Doc formulation for the treatment of visceral leishmaniasis.

Topics: Amphotericin B; Animals; Antigens, Protozoan; Antiprotozoal Agents; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Cricetinae; Drug Delivery Systems; Injections, Intravenous; Kidney Diseases; Leishmania infantum; Leishmaniasis, Visceral; Liver; Male; Mesocricetus; Microspheres; Particle Size; Serum Albumin; Spleen

The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus.. Infected rats were administered FZ and HFZ at a dosing regimen of 1 mg/kg i.v. once daily for 4 consecutive days. Following administration the number of colony forming units (CFUs) of Aspergillus fumigatus in different organs and serum creatinine concentrations were determined.. FZ and HFZ had similar overall effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to controls. Except for the serum creatinine concentrations reported in the nontreated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine.. Taken together, these findings suggest that HFZ at 1 mg/kg once daily x 4 days appears to be as effective as FZ as an antifungal agent without renal toxicity.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Evaluation, Preclinical; Drug Stability; Hot Temperature; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley

An in vivo study has been performed in order to determine the influence of amphotericin B (AMB) molecular organization on the toxicity and activity of this drug in the treatment of experimental visceral leishmaniasis. Three formulations with similar composition but different drug molecular self-association in aqueous media were prepared. Acute toxicity was evaluated by injecting them in healthy hamsters. Sub-acute toxicity and efficacy were studied administering them to animals previously infected with Leishmania infantum. The preparation with drug molecules completely dissolved into monomers (formulation "C") and produced the highest acute toxicity. The formulation whose AMB molecules were disposed as non-water-soluble multi-aggregates (formulation "B") proved to provide the lowest acute toxicity. This formula also showed an improved activity, mainly in the liver, if compared with the third tested formulation containing AMB molecules disposed as smaller dimerical "water-soluble" aggregates (formulation "A"). As a conclusion, molecular aggregation in biological media should be an important factor to consider when researching or optimizing medicines containing AMB. The liberation of molecules as large dispersed non-water-soluble multi-aggregates seems to improve the narrow therapeutic margin attached to the use of this drug.

Topics: Amphotericin B; Animals; Antibody Formation; Antiprotozoal Agents; Chemistry, Pharmaceutical; Cricetinae; Immunoglobulin G; Kidney Diseases; Leishmania infantum; Leishmaniasis, Visceral; Liver; Male; Mesocricetus; Spectrophotometry, Ultraviolet; Spleen

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Kidney Diseases; Kidney Tubules; Leukemia, Monocytic, Acute; Liposomes; Male; Sodium; Vasopressins

Amphotericin B (AmB) has been a most effective systemic antifungal agent, but its use is circumscribed by the dose-limiting toxicity of the conventional micellar dispersion formulation Fungizone (D-AmB). To lower AmB-associated toxicity, AmB may be integrated into oil-in-water lecithin-based microemulsions. The present study compares the pharmacokinetic characteristics of D-AmB with the alternative formulation of AmB in microemulsion (M-AmB), which has proved effective in a murine candidiasis model. Both formulations were given by intravenous bolus: D-AmB 1 mg/kg, and M-AmB 0.5, 1 or 2 mg/kg. The pharmacokinetics of D-AmB and M-AmB have several differences, specifically with regard to the respective Cmax and AUC0- infinity values. Elimination of AmB from serum was biphasic for both M-AmB and D-AmB. Single-dose D-AmB (1 mg/kg) achieved a Cmax of 3.89 +/- 0.48 mg/L and an AUC0- infinity of 32.28 +/- 7.31 mg.h/L, whereas single-dose M-AmB (1 mg/kg) by comparison achieved a lower Cmax (2.92 +/- 0.54 mg/L) and a lower AUC0- infinity (21.89 +/- 5.17 mg.h/L). To evaluate the safety of M-AmB, a multiple-dose toxicity study was performed in groups of 10 mice, each receiving D-AmB 1 mg/kg, or M-AmB 1, 1.5, 2 or 3 mg/kg. The findings suggest that, in comparison with D-AmB, M-AmB produces no histologically demonstrable renal lesions, or changes in clinical chemistry.

Topics: Amphotericin B; Animals; Area Under Curve; Creatinine; Deoxycholic Acid; Drug Combinations; Emulsions; Freeze Drying; Hemoglobins; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Male; Mice; Oils; Rabbits; Water

Primary renal aspergillosis is a very rare complication of AIDS which usually have fatal outcome (53% of mortality). The immune status of the patient and the early and correct therapeutic approach are the main factors that predict disease advancement. The new antiretroviral therapies improve the CD4 cell count and permit to treat these patients as immuno-competent. The local approach with antifungal drugs instillations, percutaneous drainage combined with systemic antifungal therapy can increase the number of patients that may benefit from a conservative treatment. We report a case of a 44-year-old homosexual patient with AIDS since 1991 in stage IVc (CDC--Centers for Disease Control and Prevention) in antiretroviral treatment. In September 1999 he came because of left low back pain. Laboratory data showed leucocytosis. Urinalysis revealed the presence of white and red blood cells and a negative urine culture. The abdominal ultrasound examination, the intravenous pyelogram and finally the computerized tomography confirm the presence of solid material that occupied the renal pelvis and the middle and superior caliceal group of the left kidney associated with lymph nodes enlargement. An echo-guided needle aspiration allowed us to identify Aspergillus fumigatus. Local instillations with amfotericina B through a nephrostomy and systemic antifungal drugs resolved the urinary infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Humans; Injections; Kidney; Kidney Diseases; Male; Ultrasonography

The purpose of this study was to determine the effects of various lipid and mixed-micelle formulations on the oral absorption and renal toxicity of amphotericin B (AMB) in rats. The maximum concentration of AMB in plasma and the area under the concentration-time curve for 0 to 24 h for AMB were elevated in rats administered triglyceride (TG)-rich AMB formulations in comparison to those in rats given (i) AMB preformulated as a micelle containing sodium deoxycholate with sodium phosphate as a buffer (DOC-AMB), (ii) an AMB-lipid complex suspension, or (iii) AMB solubilized in methanol. Furthermore, our findings suggest that AMB incorporated into TG-based oral formulations has less renal toxicity than DOC-AMB.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Creatinine; Deoxycholic Acid; Drug Delivery Systems; Kidney Diseases; Lipids; Male; Micelles; Phosphates; Rats; Rats, Sprague-Dawley; Tissue Distribution; Triglycerides

Amphotericin B (AmB)-treated rats develop severe polyuria, polydypsia, impairment of renal concentrating ability, and morphologic signs of tubular damage. However, renal insufficiency develops quickly only in animals in which water intake is restricted to the median volume drunk by rats of the control group. Therefore, vigorous hydration seems crucial for prevention of AmB-induced nephrotoxicity. In a clinical study, 61 patients with hematologic malignancies receiving AmB therapy were massively hydrated to ensure urine output of > or =4000 mL/day. Urine sodium, potassium, and magnesium were also measured, and all losses were supplemented (potassium as a 7.45% solution via central venous catheter). AmB-treated patients developed signs of renal tubular damage (increased fractional excretion of sodium and potassium) and required large amounts of ion supplementation. The serum ion concentration and creatinine clearance remained stable. No clinically significant renal damage developed to force premature cessation of AmB treatment.

Topics: Acetylglucosaminidase; Amphotericin B; Animals; Antifungal Agents; Creatinine; Humans; Kidney Diseases; Magnesium; Male; Microscopy, Electron, Scanning; Mycoses; Potassium; Rats; Rats, Wistar; Sodium; Specific Pathogen-Free Organisms; Statistics, Nonparametric; Ultrasonography; Water-Electrolyte Balance

To characterize amphotericin B-associated nephrotoxicity and to determine the variables associated with it that can be used to identify, a priori, at-risk patients.. Retrospective analysis.. University hospital.. A homogeneous population of 69 recipients of a bone marrow (BMT) or peripheral blood stem cell transplant (PBSCT) with multiple myeloma and who received at least two doses of amphotericin B deoxycholate from January 1, 1992-January 1, 1995.. Data on demographics, prior and concomitant nephrotoxic drug therapy, daily laboratory values, and amphotericin B dosing were collected serially from medical and pharmacy records.. Forward stepwise logistic regression analysis was performed on the data from the first day of therapy to characterize and determine variables related to amphotericin B-associated nephrotoxicity. Nephrotoxicity occurred in 30 patients (43%) and developed rapidly Patients who developed nephrotoxicity were similar to those who did not in many aspects associated with their treatment. However, baseline estimated creatinine clearance, cyclosporine therapy, nephrotoxic drug therapy within 30 days of starting amphotericin B, and the number of concomitant nephrotoxic drugs were significant predictors of amphotericin B-associated nephrotoxicity.. Recipients of a BMT or PBSCT who have multiple myeloma and are receiving cyclosporine or multiple nephrotoxic drugs at the start of amphotericin B therapy should be considered at high risk for developing amphotericin B-associated nephrotoxicity. Also, because amphotericin B-associated nephrotoxicity develops rapidly, clinicians should be aware of the rapid changes in serum creatinine and electrolyte levels that can occur.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Creatinine; Female; Hospitals, University; Humans; Kidney Diseases; Length of Stay; Male; Middle Aged; Multiple Myeloma; Mycoses; Peripheral Blood Stem Cell Transplantation; Retrospective Studies

Nephrotoxicity is an important side effect of amphothericin B deoxycholate (ampho B) and cyclosporine A (CsA). The combined administration of these drugs is frequent in patients with haematological diseases undergoing allogeneic stem cell transplantation.. To assess the additional renal toxicity of ampho B given as a continuous infusion in addition to CsA.. In a retrospective study renal function was investigated in patients receiving CsA alone or in combination with ampho B (24-hour infusion) after allogeneic stem cell transplantation between January 1998 and April 2001.. Of a total of 84 patients, 22 were treated with ampho B. There was a statistically significant decline in renal function in comparison to the 62 patients receiving CsA alone. However, renal insufficiency in all patients remained in a clinically acceptable range and was reversible. The residual renal dysfunction at the end of the hospitalisation was mainly due to continuing therapy with CsA.. Amphotericin B deoxycholate in addition to CsA leads to a statistically significant but clinically tolerable worsening of renal function. Using a 24-hour infusion and strict salt repletion, amphotericin B can be administered safely as deoxycholate in bone marrow transplant patients in conjunction with CsA for proven or suspected fungal infections.

Topics: Adult; Amphotericin B; Cyclosporine; Deoxycholic Acid; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Female; Humans; Infusion Pumps; Kidney Diseases; Male; Stem Cell Transplantation

Lipid-based formulations of amphotericin B (AMB) have been shown to significantly lessen the occurrence of nephrotoxicity associated with the conventional form of AMB. A MEDLINE search of literature published from 1983 to 2002, using the search terms amphotericin B and nephrotoxicity, identified only 1 large, randomized, prospective trial that has tried to compare the nephrotoxicity rates among lipid-based AMB formulations. Using the nephrotoxicity surrogate marker of doubling of serum creatinine (SCr) level, the investigators reported a high rate of AMB lipid complex (ABLC)-associated nephrotoxicity (42.3%). However, enrollment in that study was limited to only febrile neutropenic patients.. This retrospective study estimated the rate of ABLC-associated nephrotoxicity in various clinical settings at a university hospital and compared that rate with previously reported rates of nephrotoxicity.. Data from adult neutropenic and nonneutropenic patients receiving ABLC were collected and the degree of nephrotoxicity was determined using 2 definitions: (1) doubling of baseline SCr level using the peak value within the first 7 days, and (2) end-of-therapy doubling of baseline SCr level using the end-of-therapy value.. Data from 33 patients (20 men, 13 women; mean age, 48.6 years) were collected. Using these definitions of ABLC-associated nephrotoxicity, only 2 cases (6.1%) were observed. This rate was significantly below the 42.3% rate reported in the only large published study (95% CI, 1.7-19.6; P < 0.001). The median change in SCr level was 0.1 mg/dL (range, -1.1 to 4.3 mg/dL). Rates of change were higher in patients who died during hospitalization, but the difference was not significant. Use of concomitant nephrotoxic agents did not account for significant changes in SCr level.. Data from this study suggest that ABLC infrequently causes clinically significant nephrotoxicity. Therefore, when formulary decisions are made in the selection of a drug for use in various clinical settings, earlier data derived from a single study in febrile neutropenic patients that suggested a significantly higher rate of nephrotoxicity should be interpreted cautiously. Larger trials with more diverse patient populations are needed to better characterize institutional rates of ABLC-associated nephrotoxicity and to aid formulary decision makers.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Combinations; Female; Hospitals, University; Humans; Kidney Diseases; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies

Topics: Amphotericin B; Anti-Infective Agents; Humans; Kidney Diseases

The mechanisms responsible for amphotericin B nephrotoxicity remain incompletely understood, but clearly involve reduction in renal blood flow and glomerular filtration rate. Both direct effects of amphotericin B on contractile vascular cells, and indirect effects, due to humoural mediators, have been proposed. This study examines the role of nitric oxide, endothelin and angiotensin II in the acute nephrotoxic effects of amphotericin B in rats, and compares the anti-fungal and nephrotoxic effects of liposomal amphotericin B and amphotericin B-deoxycholate. Anaesthetized rats were given infusions of amphotericin B-deoxycholate in the presence or absence of N-nitro-L-arginine, PD 145065, a non-specific endothelin receptor antagonist, and L-158809, an angiotensin II type I receptor antagonist, or increasing doses of liposomal amphotericin B. Amphotericin B-deoxycholate (0.03 mg/kg/min intravenously) caused a significant 44% reduction in glomerular filtration rate and 65% maximal fall in renal blood flow. N-Nitro-L-arginine-treated rats had a lower renal blood flow and glomerular filtration rate at baseline, but sustained similar reduction of 53% and 75% in these parameters, respectively. PD145065 and L-158809 did not modify these effects either. Increasing doses of liposomal amphotericin B (from 0.01 up to 0.50 mg/kg/min.) induced no change in either glomerular filtration rate or renal blood flow. In vitro susceptibility tests revealed similar potency for liposomal amphotericin B and amphotericin B-deoxycholate in their fungistatic effects and slightly higher potency for amphotericin B-deoxycholate in their fungicidal effect. These results suggest that endogenous endothelin, angiotensin II or nitric oxide systems are not involved in the nephrotoxic effects of amphotericin B. The liposomal amphotericin B results suggest that amphotericin B nephrotoxicity is due to a direct interaction of amphotericin B with renal cells that is prevented by its encapsulation in liposomes.

Topics: Amphotericin B; Angiotensin II; Animals; Antifungal Agents; Arginine; Candida albicans; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Endothelins; Glomerular Filtration Rate; Imidazoles; In Vitro Techniques; Injections, Intravenous; Kidney Diseases; Liposomes; Male; Nitric Oxide; Nitroso Compounds; Oligopeptides; Rats; Rats, Sprague-Dawley; Renal Circulation; Tetrazoles

We report a case of Candida glabrata perinephric abscess in a patient with diabetes mellitus who recently underwent ureteropelvic surgery for lithiasic urinary tract obstruction. Surgical drainage and amphotericin B treatment led to resolution of the infection. C. glabrata urinary infection has become more prevalent over the last decade in immunocompromised patients. Drainage is indicated for development of a fungal abscess in the perinephric area. Most authors recommend administration of an antifungal adjuvant treatment.

Topics: Abscess; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drainage; Escherichia coli Infections; Female; Humans; Hypertension; Immunocompromised Host; Kidney Diseases; Postoperative Complications; Risk Factors; Serotyping; Urinary Calculi; Urinary Tract Infections

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Epididymitis; Humans; Hydronephrosis; Infant; Kidney; Kidney Diseases; Male; Risk Factors; Treatment Outcome; Ultrasonography

Topics: Aminoglycosides; Amphotericin B; Contrast Media; Cyclooxygenase Inhibitors; Cyclosporine; Humans; Intensive Care Units; Kidney Diseases

Topics: Amphotericin B; Animals; Antifungal Agents; Chemistry, Pharmaceutical; Colloids; Kidney Diseases; Mycoses

NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B.

Topics: Alanine Transaminase; Amphotericin B; Animals; Antifungal Agents; Aspartate Aminotransferases; Blood Urea Nitrogen; Cells, Cultured; Creatinine; Drug Carriers; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Tubules, Proximal; Microspheres; Rats

In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride-rich emulsion (AB-emulsion). The present paper compares the severity of the histopathological alterations as determined by morphometry produced in the target tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the conventional formulation AB-deoxycholate (DOC) following subacute AB treatment. No morphological alterations were seen in the spleen and heart following both AB-DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and lungs are basically the same for both formulations, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compared to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration. These three treatment regimens consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive days. Thus, these regimens consisted of total doses varying from 8-12 mg/kg of body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition, acute interstitial inflammation was observed in the lungs prior to interstitial and alveolar edema. The intensity of the histopathological damage increase with the dose and with the reduction in the time interval between AB administrations. Abnormal serum biochemical parameters were observed for serum urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decreased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effects induced by in vitro and in vivo tests with AB-emulsion treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Chemical and Drug Induced Liver Injury; Deoxycholic Acid; Fat Emulsions, Intravenous; Kidney; Kidney Diseases; Liver; Liver Diseases; Lung; Lung Diseases; Male; Myocardium; Rats; Rats, Wistar; Triglycerides

At the age of 8 weeks, an extremely low birth weight infant (gestational age 26 0/7 weeks, birth weight 740 g) had non-obstructing bilateral renal fungal balls. Urine cultures had repeatedly grown Candida albicans. Combination therapy with liposomal amphotericin B intravenously and fluconazole orally was administered for 6 weeks. Monotherapy with fluconazole was then continued until complete resolution of the renal fungal balls.. Combination therapy with liposomal amphotericin B and fluconazole was successful in eliminating non-obstructing bilateral renal fungal balls and obviated the need for surgical intervention.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Fluconazole; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Kidney Diseases; Remission Induction

Fungal infections are an important cause of morbidity and mortality in patients with malignancies. Therefore, the use of amphotericin B (AmB) is essential for these patients. Results from the literature to date show that renal toxicity is the most serious adverse effect of AmB. Renal impairment manifests as a decrease in glomerular filtration and damage to tubular function. Currently, there is no reliable method of preventing nephrotoxicity. We have observed that sodium supplementation alone may not prevent nephrotoxicity. We noted that a large decrease in serum potassium and magnesium was followed by a significant reduction in creatinine clearance and an increase in both serum urea and creatinine. Therefore, we surmised that potassium and magnesium supplements corresponding to the amounts lost by the kidneys, as well as sufficient hydration, are necessary to prevent renal function damage. We decided to test our hypothesis in 32 cancer patients. During AmB therapy, serum electrolyte concentrations and biochemical parameters of renal function and fluid balance were monitored frequently. The daily ion supplementation corresponded to the amount lost through the kidneys. The total duration of administration ranged from 4 to 39 days, with a mean of 13.7 days (median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88 mg/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The daily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesium was 9.0 mmol. The frequency of infusion-related side-effects was only 10.0%. These reactions were treated with hydrocortisone. We observed a significant increase in potassium and magnesium lost through the kidneys, and a significant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinine and ion imbalances. Interestingly, the average creatinine clearance did not decrease, but actually increased slightly, though to a statistically insignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use. Sufficient hydration of patients and ion supplementation corresponding to the amount lost by the kidneys is an effective prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use of AmB. The frequency of

Topics: Adult; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Creatinine; Diuresis; Female; Fluid Therapy; Glomerular Filtration Rate; Humans; Hydrocortisone; Infusions, Intravenous; Kidney; Kidney Diseases; Kidney Tubules; Magnesium; Male; Middle Aged; Mycoses; Neoplasms; Potassium; Sodium; Urea; Water-Electrolyte Balance

Evidence for temporal variation in the nephrotoxicity of amphotericin B was recently reported in experimental animals. The role of food in these variations was determined by studying the effect of a short fasting period on the temporal variation in the renal toxicity of amphotericin B. Twenty-eight normally fed and 28 fasted female Sprague-Dawley rats were used. Food was available ad libitum to the fed rats, while the fasted animals were fasted 12 h before and 24 h after amphotericin B injection to minimize stress for the animals. Water was available ad libitum to both groups of rats, which were maintained on a 14-h light, 10-h dark regimen (light on at 0600 h). Renal toxicity was determined by comparing the levels of excretion of renal enzyme and the serum creatinine and blood urea nitrogen (BUN) levels at the time of the maximal (0700 h) or the minimal (1900 h) nephrotoxicity after the intraperitoneal administration of a single dose of dextrose (5%; control group) or amphotericin B (50 mg/kg of body weight; treated group) to the rats. The nephrotoxicities obtained after amphotericin B administration at both times of day were compared to the nephrotoxicities observed for time-matched controls. In fed animals, the 24-h urinary excretion of N-acetyl-beta-D-glucosaminidase and beta-galactosidase was significantly higher when amphotericin B was injected at 0700 and 1900 h. The excretion of these two enzymes was reduced significantly (P < 0.05) in fasting rats, and this effect was larger at 0700 h (P < 0.05) than at 1900 h. The serum creatinine level was also significantly higher (P < 0.05) in fed animals treated at 0700 h than in fed animals treated at 1900 h. Fasting reduced significantly (P < 0.05) the increase in the serum creatinine level, and this effect was larger in the animals treated at 0700 h. Similar data were obtained for BUN levels. Amphotericin B accumulation was significantly higher (P < 0.05) in the renal cortexes of fed rats than in those of fasted animals, but there was no difference according to the time of injection. These results demonstrated that fasting reduces the nephrotoxicity of amphotericin B and that food availability is of crucial importance in the temporal variation in the renal toxicity of amphotericin B in rats.

Topics: Acetylglucosaminidase; Amphotericin B; Animals; Antifungal Agents; beta-Galactosidase; Blood Urea Nitrogen; Cholesterol, HDL; Creatinine; Fasting; Female; Kidney Cortex; Kidney Diseases; Kidney Function Tests; Rats; Rats, Sprague-Dawley; Time Factors; Triglycerides

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney Diseases; Sodium Chloride

Invasive zygomycosis (mucormycosis) occurs predominantly in immunocompromised patients in whom it carries a grave prognosis. While renal involvement is not so uncommon in disseminated infection, isolated renal zygomycosis is rare.. Forty-five patients with systemic zygomycosis were seen over a 12-year period from January 1986 to December 1997. Among these, 18 had renal involvement, nine with disseminated disease and nine with isolated renal zygomycosis. No underlying predisposing disease was identified in the majority of patients (72%). Renal involvement was confirmed at autopsy in 13 and by ante-mortem renal biopsy in five patients. The infection involved one kidney in five patients and was bilateral in the remaining. The manifestations included fever, flank pain, haematuria and pyuria with evidence of enlarged non-functioning kidneys on computerised tomography (CT). Of those with bilateral disease, 12 (92.3%) had anuric acute renal failure. Anti-fungal therapy was given to six patients (amphotericin B in mean total dose of 1.1 g) and of these only two with unilateral disease who also underwent nephrectomy survived while all the other 16 died.. This study shows that renal zygomycosis has emerged as a cause of acute renal failure in the last decade since no patient with renal involvement was identified at our centre prior to 1986 even though autopsies have been done regularly in patients dying of unknown causes. Bilateral renal zygomycosis should be suspected in any patient who presents with haematuria, flank pain and otherwise unexplained anuric renal failure. Characteristic CT findings and an early renal biopsy can confirm the diagnosis and help in effective management of this serious disease.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Female; Humans; Image Enhancement; Kidney Diseases; Male; Middle Aged; Tomography, X-Ray Computed; Zygomycosis

The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Creatinine; Drug Evaluation; Female; Humans; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Organ Transplantation; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Survival Rate; Time Factors

Very-low-birth-weight premature infants are at high risk for invasive candidiasis. The most commonly involved organ is the kidney. Renal candidiasis may present as fungus-ball obstructive uropathy. We describe unilateral renal obstruction secondary to fungus-ball in a premature infant. Noninvasive, systemic antibiotic treatment, including amphotericin B and fluconazole, resulted in disappearance of the finding.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Kidney Diseases; Male; Ultrasonography

The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL-very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC

Topics: Amphotericin B; Animals; Antifungal Agents; Blood Proteins; Cholesterol, Dietary; Cholesterol, LDL; Drug Combinations; Female; Hypercholesterolemia; Kidney Diseases; Kidney Function Tests; Phosphatidylcholines; Phosphatidylglycerols; Protein Binding; Rabbits

Topics: Amphotericin B; Anorexia; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Fluconazole; Flucytosine; Gynecomastia; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney Diseases; Liposomes; Male; Mixed Function Oxygenases; Mucormycosis; Nausea; Paracoccidioidomycosis; Sporotrichosis; Teratogens

The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1 mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted epithelial cells, was examined. Repeated administration of cyclosporin A (45 and 56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted epithelial cells. The degree of excretion of epithelial cells after administration of both drugs was compared with the urinary excretion of alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, which indicated nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than the increase in the excretion of epithelial cells. In the experiment with cyclosporin A, urinary excretion of epithelial cells was further correlated with renal functional tests (clearance of polyfructosan and hippurate.

Topics: Acetylglucosaminidase; Amphotericin B; Animals; Anti-Bacterial Agents; CD13 Antigens; Cyclosporine; Dose-Response Relationship, Drug; Epithelial Cells; Epithelium; Glomerular Filtration Rate; Hippurates; Immunosuppressive Agents; Iodine Radioisotopes; Kidney Diseases; Kidney Tubules; Male; Rats; Rats, Wistar; Toxicology; Urine; Xenobiotics

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

The pharmacokinetic profiles of amphotericin B (AmB) after administration of Amphocil, an AmB/cholesteryl sulfate colloidal dispersion (ABCD) and the micellar AmB/deoxycholate (Fungizone) were compared after repeated dosing in rats. After administration of ABCD and Fungizone at an equal AmB dose (1 mg/kg), AmB concentrations in plasma and most tissues were lower for the ABCD dose, especially in the kidneys where reduced drug concentration correlated with reduced nephrotoxicity. In contrast, AmB concentrations in the liver were substantially higher when ABCD was administered; however, without an accompanying increase in hepatotoxicity. Daily administration of ABCD for 14 days did not lead to AmB accumulation in plasma; while a slight accumulation was observed after multiple administration of Fungizone. AmB was eliminated more slowly from the plasma and various tissues and urinary and fecal recoveries of AmB were reduced after ABCD administration. These results suggest that ABCD may be stored in tissues in a form that is less toxic and is eliminated from the systemic circulation by a different mechanism than the free and protein-bound AmB in plasma. AmB accumulation in the spleen was observed when higher, doses of ABCD (5 mg/kg) were administered, which could be due to saturation of hepatic uptake of AmB. Comparison of spleen concentrations of AmB between ABCD and Fungizone at 5 mg/kg AmB doses was not possible because of Fungizone's toxicity in rats. In all other organs, AmB concentrations reached or approached a steady state within two weeks of dosing with ABCD. Urinary and fecal clearences of AmB were not different between ABCD and Fungizone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Animals; Colloids; Feces; Injections, Intravenous; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Tissue Distribution

The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer.. The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed.. Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis.. A radiographic syndrome resembling hepatic, splenic, or renal candidiasis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Breast Neoplasms; Candidiasis; Combined Modality Therapy; Female; Fluconazole; Fungemia; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Kidney Diseases; Liver Diseases; Middle Aged; Neutropenia; Retrospective Studies; Splenic Diseases; Syndrome; Tomography, X-Ray Computed; Transplantation, Autologous

Although the importance of Aspergillus in AIDS is now increasing, extra-pulmonary disease is still an unusual event, especially when a single localization occurs. A case of isolated renal aspergilloma in an AIDS patient is described. At onset, no recognized risk factors were present in our patient. An early surgical approach combined with antifungal chemotherapy (amphotericin B, Itraconazole) led to a good control of the disease, with no evidence of recrudescence at 8 months' follow-up.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Humans; Itraconazole; Kidney Diseases; Male

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Emulsions; Female; Humans; Kidney Diseases; Lipids; Male; Middle Aged; Mycoses

We describe three severe clinic cases due to fungus balls of Candida albicans in hospitalized risky patients which presented a quickly clinical evolution. Because of their different local presentations medical and surgical management was needed. In the first case a intestinal fungus ball was found whereas in the other two cases were localized in the urinary tract. Here we present their clinical findings rather than their evolution after a medical and surgical management.

Topics: Adolescent; Amphotericin B; Candidiasis; Fluconazole; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Jejunal Diseases; Kidney Diseases; Male; Ultrasonography; Ureteral Obstruction

Topics: Amphotericin B; Candidiasis; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Kidney Diseases; Male; Ultrasonography

We describe the clinical course and successful treatment of a previously healthy man who, after experiencing trauma, presented with severe cutaneous mucormycosis due to Apophysomyces elegans and subsequently developed secondary renal infection. A multidisciplinary approach employing aggressive surgical debridement and therapy with hyperbaric oxygen, liposomal amphotericin B, and interferon-gamma was successful in controlling his infection, obviating the need for nephrectomy.

Topics: Adult; Amphotericin B; Humans; Hyperbaric Oxygenation; Interferon-gamma; Kidney Diseases; Liposomes; Male; Mucorales; Mucormycosis; Soft Tissue Infections; Soft Tissue Injuries; Tomography, X-Ray Computed

A unilamellar liposomal formulation of amphotericin B (LAmB) known as AmBisome was safely administered intravenously to 20 rabbits at 0.5, 1.0, 2.5, 5, or 10 mg/kg of body weight, whereas of 12 rabbits given desoxycholate amphotericin B (DAmB) intravenously at 0.5, 1.0, or 1.5 mg/kg, 2 died of acute cardiac toxicity when DAmB was administered at the highest dose. Single-dose LAmB (1 mg/kg) achieved a maximum concentration in serum (Cmax) of 26 +/- 2.4 micrograms/ml and an area under the curve to infinity (AUC0-infinity) of 60 +/- 16 micrograms.h/ml, while single-dose DAmB (1.0 mg/kg), by comparison, achieved a lower Cmax (4.7 +/- 0.2 micrograms/ml; P = 0.001) and a lower AUC0-infinity (30.6 +/- 2.2 micrograms.h/ml; P = 0.07). Following administration of a single dose of LAmB (10 mg/kg), a disproportionately higher Cmax (287 +/- 14 micrograms/ml) and AUC0-infinity (2,223 +/- 246 micrograms.h/ml) occurred, indicating saturable elimination. After chronic dosing (n = 4) with LAmB at 5.0 mg/kg/day for 28 days or DAmB at 1.0 mg/kg/day for 28 days, LAmB achieved daily peak levels of 122.8 +/- 5.8 micrograms/ml and trough levels of 34.9 +/- 1.8 micrograms/ml, while DAmB reached a peak of only 1.76 +/- 0.11 microgram/ml and a trough of 0.46 +/- 0.04 microgram/ml (P < or = 0.001). Significant accumulations of amphotericin B into reticuloendothelial organs were observed, with 239 +/- 39 micrograms/g found in the liver after chronic LAmB dosing (5 mg/kg/day), which was seven times higher than the 33 +/- 6 micrograms/g after DAmB dosing (1 mg/kg/day) (P = 0.002). Accumulation in kidneys, however, remained 14-fold lower (P =0.04) following LAmB dosing (0.87 +/- 0.61 microgram/g) than after DAmB dosing (12.7 +/- 4.6 microgram/g). Nephrotoxicity occurred in only one of four LAmB treated animals, while it occurred in all four chronically DAmB-treated animals: mild hepatozicity with transaminase elevations was seen in one LAmB-treated rabbit. We conclude that LAmB safely achieved higher Cmax(s) and AUC0-infinity(s) and demonstrated saturable, nonlinear elimination from plasma via reticuloendothelial organ uptake. Take reduced nephrotoxicity of LAmB correlated with diminished levels of amphotericin B in the kidneys.

Topics: Amphotericin B; Animals; Antifungal Agents; Chromatography, High Pressure Liquid; Deoxycholic Acid; Drug Carriers; Drug Combinations; Female; Kidney Diseases; Liposomes; Rabbits; Spectrophotometry, Ultraviolet; Tissue Distribution

Various formulations have been developed in an effort to reduce the toxicity of amphotericin B. We report a case of cryptococcal meningitis in a 31-year-old HIV-positive man which was successfully treated with amphotericin B lipid emulsion.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Drug Resistance, Microbial; Fat Emulsions, Intravenous; Flucytosine; HIV Seropositivity; Humans; Itraconazole; Kidney Diseases; Male; Meningitis, Cryptococcal

A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. D-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, D-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits.

Topics: Agranulocytosis; Amphotericin B; Animals; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Biomarkers; Bronchoalveolar Lavage Fluid; Ergosterol; Galactose; Kidney Diseases; Life Tables; Liposomes; Lung Diseases; Mannans; Mannitol; Opportunistic Infections; Rabbits; Survival Analysis

Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy.. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests.. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy.. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy.

Topics: Amphotericin B; Animals; Bone Marrow Transplantation; Busulfan; Cyclosporine; Gentamicins; Kidney; Kidney Diseases; Male; Rats; Whole-Body Irradiation

We compared the experimental toxicities and activities of deoxycholate amphotericin B (d-AmB) dissolved in glucose (Dd-AmB) or mixed with 20% Intralipid (ILd-AmB). In vitro, ILd-AmB against renal tubular cells in primary culture. In vivo, the toxicities and activities of Dd-AmB and ILd-AmB were studied in DBA2 mice with cryptococcosis. The maximum tolerated dose of intravenously administered d-AmB, i.e., the dose that induced less than 15% mortality because of toxicity, was 1.7 to 2.5 times higher when it was administered as ILd-AmB than when it was administered as Dd-AmB. Both treatments given intravenously at the same dose were equivalent for improving the survival of mice and reducing CFU counts in infected tissue, but at maximum tolerated doses, ILd-AmB (2 mg/kg of body weight) was more effective than Dd-AmB (0.8 to 1.2 mg/kg). AmB concentrations in spleen, liver, lung, and kidney were measured by high-pressure liquid chromatography 4 and 24 h after a single injection of 1.2 mg of Dd-AmB per kg, 1.2 mg of ILd-AmB per kg, or 2 mg of ILd-AmB per kg. In a given organ, AmB levels were similar after administration of 1.2 mg of Dd-AmB or ILd-AmB per kg but were significantly higher after administration of 2 mg of ILd-AmB per kg. The lower level of toxicity of ILd-AmB might be explained by circular dichroism experiments, showing that ILd-AmB contained 10-fold less soluble oligomeric AmB, which is believed to be the toxic form of the drug, than Dd-AmB. We conclude that ILd-AmB is as efficient as Dd-AmB and is better tolerated than Dd-AmB in mice with experimental cryptococcosis. By allowing higher doses of AmB to be infused, Intralipid enhances AmB concentrations in infected sites, and thus the therapeutic activity of the drug.

Topics: Amphotericin B; Animals; Cells, Cultured; Colony Count, Microbial; Cryptococcosis; Dose-Response Relationship, Drug; Drug Carriers; Fat Emulsions, Intravenous; Kidney Diseases; Kidney Tubules; Male; Mice; Mice, Inbred DBA; Rabbits

We examined the influence of high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs) on the toxicity of amphotericin B (AmpB) to fungal and renal cells. Candida albicans was incubated for 18 h at 37 degrees C with AmpB and deoxycholate (Fungizone) or liposomal AmpB (L-AmpB) (0.1 to 2.0 micrograms of AmpB per ml) in the presence or absence of HDLs or LDLs (0.5 mg of protein per ml). The MICs of AmpB and L-AmpB, whether or not HDLs or LDLs were present, were similar. LLC PK1 renal cells, derived from primary cultures of pig proximal tubular cells, were incubated for 18 h at 37 degrees C in serum-free medium that contained AmpB and deoxycholate or L-AmpB at 20 micrograms of AmpB per ml, HDLs or LDLs at 0.5 mg of protein per ml, mixtures of AmpB with HDLs or LDLs, and mixtures of L-AmpB with HDLs or LDLs. HDL-associated AmpB was less toxic than AmB to LLC PK1 cells (53.0% +/- 2.5% versus 81.3% +/- 3.6% cytotoxicity; P = 0.01), while LDL-associated AmpB was as toxic as AmpB. L-AmpB, HDL-associated L-AmpB, and LDL-associated L-AmpB were less toxic to LLC PK1 cells than was AmpB (48.3% +/- 1.5%, 25.5% +/- 2.2%, and 52.2% +/- 2.5% versus 81.3% +/- 3.6% cytotoxicity; P = 0.02). To further understand why HDL-associated AmpB reduced renal cytotoxic effects, the LLC PK1 cells were examined for the presence of HDL and LDL receptors. LLC PK1 cells expressed high-affinity (K(d) = 0.0538 nanograms/ml; 96,000 sites per cell) and low-affinity (K(d) = 222.22 nanograms/ml; 77 sites per cell) LDL receptors but only a low-affinity HDL receptor (K(d) = 71.43 nanograms/ml; 2 sites per cell). HDL-associated AmpB and LDL-associated AmpB were less toxic than AmpB to trypsinized LLC PK1 cells (46.6% +/- 10.9% and 16.8% +/- 15.98% versus 74.7% +/- 7.7% cytotoxicity; P = 0.02). HDL-associated AmB and LDL-associated L-AmpB were also less toxic than AmpB to the cells (20.4% +/- 6.2% and 13.5% +/- 8.6% versus 74.7% cytotoxicity; P = 0.01). The antifungal activities of AmpB and L-AmpB were not altered in the presence of HDLs or LDLs. We conclude that the reduced nephrotoxicity associated with the use of L-AmpB is related to a decreased uptake of AmpB by renal cells when AmpB is associated with HDLs because of the low level of expression of HDL receptors in these cells.

Topics: Amphotericin B; Animals; Candida albicans; Cell Line; Dose-Response Relationship, Drug; Drug Carriers; Kidney; Kidney Diseases; Lipoproteins, HDL; Lipoproteins, LDL; Liposomes; Receptors, LDL; Receptors, Lipoprotein; Swine

We investigated the safety and efficacy of amphotericin B colloidal dispersion (ABCD) for the treatment of invasive pulmonary aspergillosis in persistently granulocytopenic rabbits. Treatment groups included ABCD in dosages of 1, 5, and 10 mg/kg/day intravenously or conventional desoxycholate amphotericin B (DAmB) at 1 mg/kg/day intravenously. Antifungal activity was directly related to increasing dosage of ABCD as determined by the concentration of Aspergillus fumigatus organisms in lungs and the frequency of hemorrhagic pulmonary lesions. At 5 and 10 mg/kg/day, there was a significant reduction in the tissue burden of A. fumigatus as measured by percent culture-positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day measured by percent culture-positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day the tissue burden of A. fumigatus was not significantly different from that in untreated controls. Microbiological clearance was significantly greater at 1 mg of DAmB per kg per day than at 1 mg of ABCD per kg per day (P < or = 0.001). There was no difference in microbiological clearance of bronchoalveolar lavage fluid among the treatment groups as measured by CFU per milliliter. As determined by survival, ABCD at 5.0 mg/kg/day was more effective than DAmB at 1.0 mg/kg/day and ABCD at 10 mg/kg/day. ABCD at 10 mg/kg/day was more nephrotoxic than the lower dosages of ABCD and resulted in higher mortality. Impairment of glomerular filtration developed as a direct function increasing the ABCD dosage (r = 0.77; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Agranulocytosis; Amphotericin B; Animals; Aspergillosis; Bronchoalveolar Lavage Fluid; Colloids; Creatinine; Dose-Response Relationship, Drug; Female; Heart; Hemorrhage; Immunosuppression Therapy; Kidney Diseases; Kidney Function Tests; Lung; Lung Diseases, Fungal; Rabbits

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Humans; Itraconazole; Ketoconazole; Kidney Diseases

The two major hypotheses for the pathogenesis of amphotericin nephrotoxicity are direct interaction with epithelial cell membranes and vasoconstriction. Studies indicating the special vulnerability of the medullary ray and medulla to hypoxia led to a reexamination of amphotericin nephrotoxicity. Twenty-four rats were divided into four groups: amphotericin injection (5 mg/kg daily for 3 wk), amphotericin plus salt depletion, vehicle, and salt depletion and vehicle. The amphotericin group had polyuria (P < 0.01) but normal serum creatinine. In contrast, amphotericin plus salt depletion rats exhibited renal failure (creatinine of 1.49 +/- 0.05 versus amphotericin alone 0.98 +/- 0.01; P < 0.01). Semiquantitative histologic analysis of cortical and medullary injury correlated with functional impairment. Cortical changes in the amphotericin group were largely restricted to the medullary ray, where focal rupture and calcification of thick ascending limbs were noted. The S2/S3 tubules in the medullary rays showed focally diminished cell complexity with histiocytic/lymphocytic infiltration. However, calcification was also seen in the area of the macula densa. Morphometry revealed that the thick ascending limbs in the medulla were hypertrophied (1,420 +/- 63 versus 1,195 +/- 48 microns 2 for vehicle; P < 0.05). In contrast, in the amphotericin and salt depletion group, the changes in the medullary ray extended to the labyrinth and the thick ascending limbs in the inner stripe showed atrophic changes (772 +/- 23 microns 2; P < 0.01 versus vehicle). Thus, changes as a result of amphotericin toxicity take place both in areas known to be most vulnerable to hypoxia (medullary ray and medulla), and in areas rich in oxygen (adjacent to glomerulus). Salt depletion potentiates the cortical changes and converts medullary hypertrophy to atrophy. These findings support a dual pathogenesis for amphotericin nephropathy (direct toxicity and vasoconstriction).

Topics: Amphotericin B; Animals; Cell Hypoxia; Chronic Disease; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Microscopy, Electron; Rats; Rats, Sprague-Dawley

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Cisplatin; Humans; Japan; Kidney Diseases; Penicillamine; Prognosis

The effect of the selective dopamine DA1 receptor agonist fenoldopam (1 microgram/kg/min i.v.) on the acute nephrotoxic response to amphotericin B (2 mg/kg i.v.) has been studied in the anesthetized dog. Animals were prepared for the measurement of blood pressure, renal blood flow, urine flow, glomerular filtration rate and sodium and potassium excretion. Amphotericin B was given over 20 min and the animals were followed for an additional 160 min. The fenoldopam infusion was started 20 min before amphotericin B and was continued for the duration of the experiment. In control animals, amphotericin B markedly increased renal vascular resistance without affecting blood pressure and thus produced a significant reduction in renal blood flow. The renal vasoconstrictor response to amphotericin B was not attenuated by fenoldopam. Concomitant with the renal vasoconstriction produced by amphotericin B was a marked reduction in glomerular filtration rate, sodium excretion and urine flow rate, which lasted for at least 160 min after amphotericin B treatment. Fenoldopam did not have any effect on the initial reductions in glomerular filtration rate, sodium excretion and urine flow rate but did produce a significant return of these parameters toward control levels by 160 min, despite the continued renal vasoconstriction. The effect of fenoldopam (0.5 microgram/kg/min) given continuously by i.v. infusion on the subacute nephrotoxic response produced by amphotericin B given every other day for 8 days was also investigated. One day after the start of the fenoldopam infusion, venous samples were drawn for the analysis of serum creatinine and blood urea nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amphotericin B; Animals; Creatinine; Dogs; Dopamine Agents; Female; Fenoldopam; Kidney Diseases; Male; Receptors, Dopamine; Renal Circulation

The combination of intravenous flucytosine (FC) in 0.9% saline (NaCl) and amphotericin B (AmB) provides synergistic antifungal activity and is associated with a lower incidence of nephrotoxicity than with AmB treatment alone. This study was conducted to examine whether flucytosine can influence renal function and whether it can modify the acute and chronic renal responses to AmB in the rat. In the in situ perfused rat kidney, FC at a concentration of 10 mg/kg/min for 15 min had a vasodilator effect, increasing renal blood flow by 2.5 +/- 0.7 ml/min, an effect not observed with vehicle. After the infusion of FC was stopped for 15 min, AmB induced a decrease in renal blood flow similar to that with both FC and vehicle. In a second series of studies, AmB (5 mg/kg/day intraperitoneally) was administered to four groups of rats for 7 days. In addition, the following groups received the intravenous daily interventions indicated: group 1, 5% dextrose in water (15 ml/kg/12 h); group 2, FC (150 mg/kg/12 h) in 0.9% saline (15 ml/kg/12 h); group 3, 0.9% saline (15 ml/kg/12 h); and group 4, FC (150 mg/kg/12 h) in 5% dextrose in water. Group 1 sustained a 77% decrease in creatinine clearance over the 7 days and a threefold increase in serum creatinine concentration (P of < 0.05). Groups 2, 3, and 4 sustained significantly less nephrotoxicity, with no change in serum creatinine concentration and only 38, 41, and 53% decreases in creatinine clearance, respectively (P of < 0.05), compared with that for group 1. AmB levels in renal tissue varied inversely to creatinine clearance (r of 0.57, P of < or = 0.005). However, no significant differences were found in levels in tissue between groups (P of 0.06). The results of this study suggest that FC has a small but significant effect in reducing chronic AmB-induced nephrotoxicity. This amelioration of renal injury is independent of saline administration. There was evidence that the extent of renal uptake of AmB related to the efficiency of renal function at the end of the experiment.

Topics: Amphotericin B; Animals; Disease Models, Animal; Drug Combinations; Drug Interactions; Flucytosine; Kidney Diseases; Kidney Function Tests; Male; Rats; Rats, Sprague-Dawley; Renal Circulation

The in vitro and in vivo toxicities and activities of MS-8209, a new hydrosoluble amphotericin B (deoxycholate-amphotericin B [D-AmB]; Fungizone) derivative, were studied. In vitro, MS-8209 was less toxic than AmB against renal tubular cells in primary culture and less active against Candida albicans and Cryptococcus neoformans. However, at 10-fold the AmB concentration, MS-8209 in vitro antifungal activity paralleled that of AmB. Fifty-percent lethal doses of MS-8209 and D-AmB in OF1 noninfected mice were 26 and 2.3 mg/kg, respectively. Therapeutic efficacy of MS-8209 was assessed in murine candidiasis, cryptococcosis, and aspergillosis. In each model of infection, we determined the maximum tolerated dosages of MS-8209 and D-AmB, i.e., the dosage inducing less than 15% mortality due to toxicity; the efficacies of MS-8209 and D-AmB at their respective maximum tolerated dosages were compared. In candidiasis, MS-8209 (15 mg/kg) significantly increased the survival time compared with D-AmB (0.5 mg/kg). Both compounds were equally effective at reducing CFU counts in the kidney. MS-8209 was the most effective agent for increasing the survival time in cryptococcal meningoencephalitis and for reducing CFU counts in spleen, brain, and lung during both cryptococcal pneumonia and meningoencephalitis. In aspergillosis, MS-8209 and D-AmB similarly prolonged the survival of treated mice compared with controls. These results show that when MS-8209 and D-AmB were used at the maximum tolerated dosage, MS-8209 was as effective as or more effective than D-AmB for the treatment of systemic mycoses. These findings warrant further experiments to study the pharmacokinetic properties and toxicity of MS-8209 under conditions of chronic administration.

Topics: Amphotericin B; Animals; Aspergillosis; Cells, Cultured; Cryptococcosis; Kidney Diseases; Kidney Tubules, Proximal; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mycoses; Rabbits

Renal candidal bezoar is uncommonly encountered in neonatal intensive care. An affected neonate who improved only after surgical removal of obstructive fungus from the renal pelvis and local irrigation with amphotericin B is described. The need for early consideration of surgical intervention is stressed.

Topics: Amphotericin B; Candidiasis; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Kidney; Kidney Diseases; Male; Ultrasonography

Topics: Amphotericin B; Humans; Kidney; Kidney Diseases; Sodium; Vasoconstriction

Topics: Alcohols; Amphotericin B; Animals; Diabetes Mellitus, Experimental; Escherichia coli; Humans; Infant, Newborn; Kidney Diseases; Male; Membrane Fluidity; Neutrophils; Phagocytosis; Rats; Rats, Inbred Strains; Superoxides; Tetradecanoylphorbol Acetate

The effect of Myrj 59 (a polyoxyethyleneglycol derivative of stearic acid) on amphotericin B (Am B) solubility, toxicity and activity has been investigated. We showed that Myrj 59 could solubilize the antibiotic. Moreover, it also decreased and abolished the haemolytic activity of the drug by increasing the resistance of the red blood cells and impairing the interaction of Am B with the cellular membrane cholesterol, but it did not modify the in-vitro antifungal activity of the drug. On the other hand, Myrj 59 did not decrease the acute in-vivo toxicity of the drug (LD50 and nephrotoxicity). In a previous study we have shown that a polyoxyethleneglycol derivative of cholesterol could solubilize Am B and was able to decrease the in-vitro and in-vivo toxicity of the antibiotic without altering its in-vitro antifungal activity. The results of the present study suggest that the cholesterol moiety of the surfactant is not necessary to decrease the in-vitro lytic activity of the drug but could play a role in the reduction of the in-vivo toxicity.

Topics: Amphotericin B; Animals; Chemistry, Pharmaceutical; Excipients; Fungi; Hemolysis; In Vitro Techniques; Kidney Diseases; Lethal Dose 50; Male; Mice; Polyethylene Glycols; Rats; Rats, Inbred Strains; Solubility

In anesthetized rats we tested the hypothesis that amphotericin B (AmB) reduces glomerular filtration rate (GFR) by activating the tubuloglomerular feedback (TGF) mechanism. Infusion of 1 mg/kg AmB over 50 min was followed by a reduction in kidney GFR (from 0.47 +/- 0.03 to 0.39 +/- 0.02 ml/min per 100 g body wt during the second hour after infusion; P less than 0.05) and by an increase in urine flow and urinary chloride excretion. Single-nephron GFR (SNGFR) measured in proximal (TGF interrupted) or distal tubules (TGF intact) decreased to a similar degree from 33.4 +/- 1.8 and 30.6 +/- 1.2 nl/min in the control period to 19.7 +/- 1.9 and 21.2 +/- 1.6 nl/min during the second hour after AmB infusion (P less than 0.05). Distal chloride concentrations and TGF responses to changes in loop of Henle flow rate were not significantly altered by AmB. AmB at 10(-5) M reduced the diameter of isolated perfused afferent arterioles from rabbit kidneys. In isometrically contracting rings of rabbit aorta and renal artery in vitro AmB produced endothelium-independent constriction, with half-maximal contraction (EC50) being achieved by 1.8 x 10(-6) and 2.6 x 10(-6) M in intact vessels and 1.3 x 10(-6) and 1.7 x 10(-6) M in endothelium-denuded vessels respectively. Tension development did not occur in Ca-free media or in the presence of Ca channel blockers. Pretreatment with ouabain or Bay K 8644 potentiated the effect of AmB. The vasoconstrictive effect of AmB was counteracted by aminophylline and atrial natriuretic peptide. We conclude that the AmB-induced reduction in GFR is not caused by TGF activation and that AmB has a direct vasoconstrictor effect that is probably initiated by depolarization-induced opening of Ca channels. This effect may be an important component of the nephrotoxic actions of AmB.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Amphotericin B; Animals; Aorta; Arterioles; Atrial Natriuretic Factor; Calcium; Calcium Channels; Glomerular Filtration Rate; In Vitro Techniques; Inulin; Kidney Diseases; Male; Metabolic Clearance Rate; Muscle, Smooth, Vascular; Ouabain; Phentolamine; Rats; Rats, Inbred Strains; Renal Artery; Sodium Chloride; Theophylline; Vasoconstriction

Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens.

Topics: Acetylglucosamine; Amphotericin B; Animals; Body Weight; Diuresis; Enzymes; Kidney Diseases; Kidney Tubules; Liposomes; Male; Osmolar Concentration; Phosphates; Rats; Rats, Inbred Strains

Invasive Aspergillus infections cause significant morbidity and mortality in marrow transplant patients. In this study, we examined whether administration of intravenous low-dose prophylactic amphotericin B could reduce the incidence and mortality associate with invasive aspergillosis in patients undergoing allogenic marrow transplantation.. The subjects of this analysis were 186 consecutive patients undergoing allogeneic marrow transplantation in an adult bone marrow transplant unit between July 1, 1985, and September 30, 1990, utilizing consistent disease-specific chemoirradiation and graft-versus-host disease protocols. The incidence, morbidity, and case fatality of invasive aspergillosis in the study group receiving amphotericin chemoprophylaxis were compared with that in two historic cohorts managed without prophylactic amphotericin B. Univariate and multivariate statistical analyses were performed to examine whether an apparent protective effect could be attributed to differences in patient and treatment variables among the cohorts and to determine potential toxicities of the chemoprophylaxis regimen.. There was a significant reduction in both the incidence (p = 0.003) and mortality (p = 0.03) of invasive aspergillosis in patients receiving amphotericin B chemoprophylaxis as compared with those not receiving chemoprophylaxis. The prophylactic amphotericin B schedule, as employed here, was not associated with increased renal or hepatic toxicity as compared with that in historically managed patients.. These data suggest that the risks of invasive aspergillosis in allogeneic marrow transplant recipients can be reduced by administration of prophylactic amphotericin B during the pretransplant and peritransplant periods.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Chemical and Drug Induced Liver Injury; Cohort Studies; Female; Humans; Kidney Diseases; Male; Middle Aged; Premedication; Retrospective Studies; Statistics as Topic; Transplantation, Homologous; Treatment Outcome

Topics: Administration, Oral; Adult; Amphotericin B; Bone Marrow Transplantation; Cyclosporins; Humans; Kidney Diseases; Pentoxifylline; Pilot Projects; Prospective Studies; Transplantation, Homologous

Between 1975 and 1988, 92 pediatric patients have undergone bone marrow transplantation (BMT) at our institution for malignant or immune deficiency disease. We evaluated in a retrospective fashion 64 of these patients who survived beyond the first 60 days post-BMT. The clinical course was divided into: less than 60 days post-BMT (early) and greater than 60 days post-BMT (late). The presence or absence of renal insufficiency was noted as well as all known potential factors predisposing to insufficiency. Step-wise regression analysis was then performed to determine which of the factors were most significantly associated with renal dysfunction during the two periods. The follow-up period was 2 months to 11 years (mean 17.5 months). The mean age of the patients was 7.6 years (1 month-18 years). Fifty percent of the patients had renal insufficiency during the early period and 28% of the patients had insufficiency after the initial 60 days. Three major predictors of renal insufficiency were discovered. Cyclosporin A or amphotericin B early or late post-BMT was independently predictive of developing insufficiency during the same period. Conditioning with total body irradiation was a predictor for insufficiency in both periods. Early insufficiency was not predictive of late insufficiency. Hypertension was present in 31% of patients during the early period and in 16% during the late period. Hypertension was strongly associated with cyclosporin use and renal insufficiency. Renal insufficiency is a frequent sequela in children following BMT and likely results from a combination of radiation injury and drug toxicity.

Topics: Adolescent; Amphotericin B; Bone Marrow Transplantation; Child; Child, Preschool; Cyclosporins; Follow-Up Studies; Graft Rejection; Humans; Hypertension; Infant; Kidney Diseases; Regression Analysis; Retrospective Studies

The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model. CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5) Candida albicans yeast cells. Intraperitoneal LY or amphotericin B (AmB) therapy was begun 4 days after infection and was continued daily for 2 weeks. LY and AmB were compared at 62.5, 6.25, and 0.625 mg/kg per day, with the LY dose split into two treatments per day. Mice were observed for 30 days postinfection, and survivors were necropsied. AmB at 62.5 mg/kg per day was lethal in the absence of infection. Cumulative mortality for infected controls was 94% (17 of 18). Survival of mice treated with the control diluent for LY was the same as survival with no treatment. Survival after 0.625 mg of LY per kg per day was the same as that of the controls, and 6.25 or 62.5 mg of LY per kg per day was significantly superior. AmB treatment at 0.625 or 6.25 mg/kg per day was protective and superior to the same LY doses. Atrophied kidneys were common in AmB-treated mice, and mice treated with 6.25 mg of AmB per kg per day appeared ill during therapy. The number of CFU recovered from kidneys and spleens of surviving mice reflected the same relationships between drugs and doses as those described for mortality. C. albicans was not cleared from the kidneys of mice in any group, and only in the 6.25-mg/kg-per-day AmB treatment group was not detectable C. albicans found in the spleens. These data indicate that LY or AmB suppresses candida infection but neither is curative in this model.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Echinocandins; Half-Life; Kidney Diseases; Male; Mice; Microbial Sensitivity Tests; Peptides; Peptides, Cyclic; Spleen

Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Culture Media; Kidney Cortex; Kidney Diseases; Kidney Glomerulus; Mice; Triazoles

Perirenal candidial abscesses are rare, with few well-documented cases in the literature. We describe a case of a perinephric abscess treated with amphotericin B and nephrectomy.

Topics: Abscess; Aged; Amphotericin B; Candidiasis; Drainage; Humans; Kidney Diseases; Male; Nephrectomy

We report a case of anuria in a premature neonate secondary to bilateral ureteropelvic junction obstructions related to Candida bezoars. Percutaneous decompression and drainage of both kidneys contributed significantly to the successful management of renal candidiasis in this patient. A review of the literature is presented.

Topics: Amphotericin B; Anuria; Bezoars; Candidiasis; Drainage; Flucytosine; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Nephrostomy, Percutaneous

Two very low birth weight infants who developed renal candidiasis with pelvicalyceal fungal concretions were treated medically with Amphotericin B and 5 Fluorocytosine. Two months following cessation of therapy, the fungal concretions decreased in size, became sterile and developed calcification in residual debris. The calcifications was still present at demise in one patient and at 18 months follow up in the other. These calcifications occurred in the absence of simultaneous furosemide therapy.

Topics: Amphotericin B; Candidiasis; Female; Flucytosine; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Kidney Calculi; Kidney Diseases

The mechanism of acute nephrotoxicity following the administration of amphotericin B (AmpB) remains unclear despite a number of studies describing hypermagnesuria, hyperkaluria, and hemodynamic changes. The present experiments attempted to elucidate the mechanism by using a novel hemorheologic probe, pentoxifylline (PTX). Acute studies were performed with rats given single intravenous doses of AmpB (1 mg/kg of body weight) with or without intraperitoneal PTX (45 mg/kg). Renal function, assessed by inulin clearance (CLIN) and electrolyte handling, and morphology were compared with those of controls given sterile water and PTX. A significant decrease in CLIN not observed in rats given AmpB and PTX or in the controls was found in rats given AmpB. Electrolyte handling was not different among groups. Whereas pronounced (3 and 4+ on a scale of mild to significant [1+ to 4+]) vascular congestion was found in rats given AmpB, rats coadministered PTX had mild (1 and 2+) medullary and glomerular vascular congestion. In chronic studies, intravenous AmpB (1 mg/kg per day) or sterile water was coadministered with intraperitoneal PTX (45 mg/kg every 12 h) or saline for 10 days. Mean CLIN of rats coadministered AmpB and PTX was not significantly different from that of PTX control rats (1.61 +/- 0.19 versus 1.31 +/- 0.29 ml/min per g of kidney weight). A 46% decline in CLIN was found in rats treated with AmpB and saline (P less than 0.05). Renal sodium and potassium excretions were increased in both AmpB-treated groups compared with controls. Coupled with histologic evidence of the acute studies, these data suggest that the benefit of PTX in the prevention of AmpB-induced nephrotoxicity is, in part, due to vascular decongestion.

Topics: Amphotericin B; Animals; Kidney; Kidney Diseases; Male; Pentoxifylline; Rats; Renal Circulation; Theobromine; Time Factors; Vascular Diseases

The clinical usage of amphotericin B in treating systemic fungal infections is limited by its nephrotoxicity, which is caused by reductions in renal blood flow and alterations in renal tubular function. Aminophylline, an adenosine receptor antagonist, attenuates amphotericin B-induced reductions in renal blood flow in both dogs and rats, which suggests that endogenous adenosine may participate in this response. However, aminophylline per se is a vasodilator and also changes intracellular levels of cyclic nucleotides and calcium. In this study, we re-examined the hypothesis that adenosine participates in amphotericin B-induced renal vasoconstriction by employing a novel adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl)xanthine (DPSPX). This antagonist because of its negative charge at physiological pH, has limited access to the intracellular space. In a group of male Sprague-Dawley rats, an extracorporeal shunt was established between the carotid artery and left renal artery, via an aortic pouch, such that flow through the shunt was equivalent to renal blood flow. Also, a catheter was inserted into the left ureter for collection of urine and measurement of creatinine and electrolyte excretion. Amphotericin B-induced changes in renal blood flow and renal excretory function were measured in both control rats and rats pretreated with DPSPX at a dosage that abolishes the renovascular effects of exogenous adenosine in this model. In both control rats and rats pretreated with DPSPX, amphotericin B caused a marked decrease in renal blood flow, creatinine excretion, and potassium excretion; however, these effects of amphotericin B were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Animals; Creatinine; Kidney Diseases; Male; Potassium; Rats; Rats, Inbred Strains; Receptors, Purinergic; Renal Circulation; Sodium; Xanthines

Although amphotericin B remains the mainstay of therapy for serious fungal infections, numerous acute and chronic toxicities make clinical usage difficult. Nevertheless, utilization of amphotericin B has increased dramatically in recent years. Accordingly, a study to reassess toxicity associated with the use of amphotericin in the modern era and to determine the aggregate impact toxicities have on the overall therapeutic course of patients was undertaken.. The charts of 50 patients at our institution who had received amphotericin B were retrospectively reviewed for the occurrence of drug-related acute and chronic toxicities and their impact on therapy. Patients evaluated were at least 21 years of age, had received at least 100 mg of amphotericin B, and were treated for at least 3 days. An analysis to investigate associations between drug administration variables and toxicities was also undertaken.. The mean age of study subjects were 54 years, the average duration of therapy was 19 days, and the mean cumulative dose of amphotericin B was 582 mg. Acute toxicities accompanying infusion occurred in 66% of all patients. Fever was experienced by 34% of study subjects and chills by 56%, with rates of 2.6 and 3.5 mean episodes per patient per treatment course, respectively. Other acute toxicities including hypotension were rare, and no patients exhibited bronchospasm or anaphylaxis. Nephrotoxicity occurred in 30 patients (60%). Baseline creatinine values in these patients rose by a mean of 1.55 mg/dL (137 mumol/L), with increases in creatinine ranging from 0.2 to 5.2 mg/dL (18 to 460 mumol/L). Analysis of six drug administration parameters by stepwise multiple linear regression failed to reveal any significant associations with nephrotoxicity. The mean nadir potassium value was 3.1 mEq/L (3.1 mmol/L) (range: 2.3 to 4.8 mEq/L [2.3 mmol/L]), with 45 of 50 patients (90%) receiving potassium supplementation (average daily supplement = 69 mEq). Only increasing amphotericin B concentration was correlated with an increased requirement for potassium supplementation (p less than 0.01, stepwise multiple linear regression).. Although clinically important toxicities continue to occur with usage of amphotericin B despite current methods of infusion and premedication, these are usually manageable and rarely limit the course of therapy.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Female; Fever; Humans; Incidence; Kidney Diseases; Length of Stay; Male; Middle Aged; Potassium; Retrospective Studies

The effect of ureteral obstruction on the course of renal candidiasis in a rat model was studied, using both normal and diabetic Sprague-Dawley rats, and a clinical isolate of Candida albicans. Diabetes was induced by streptozotocin injection 1 week prior to inoculation and transabdominal ligation of the left ureter. On day 9 post inoculation, mean titers of Candida were similar in right and left kidneys of obstructed rats. Mean left renal titers for obstructed and control rats were similar (log10 2.68 CFU/g +/- 0.73 (SE) vs. log10 2.21 +/- 0.09, P greater than 0.01). Diabetes produced higher renal titers of Candida, regardless of the presence of ureteral obstruction (log10 5.74 CFU/g +/- 0.57 (SE) vs. log10 2.21 +/- 0.09, P less than 0.01). Animals treated for one week with amphotericin B showed a marked difference in Candida titers between obstructed and control animals (log10 4.14 CFU/g +/- 0.45 (SE) vs. 1.57 +/- 0.38) for both kidneys, and between obstructed and nonobstructed kidneys in the same animals.

Topics: Amphotericin B; Animals; Candidiasis; Diabetes Mellitus, Experimental; Kidney Diseases; Male; Rats; Rats, Inbred Strains; Ureteral Obstruction

To evaluate the role of amphotericin B (AmB) in the biochemical modulation of antineoplastic agents, AmB was administered as a continuous infusion over a period of 52 to 120 h to 14 patients (26 courses) with advanced carcinomas. Continuous infusion amphotericin B (CI-AmB) was delivered at a rate of 0.5 to 0.8 mg/kg/d (19-31 mg/m2/d). The AmB plateau levels assayed by HPLC ranged from 0.7 to 1.9 micrograms/mL and were directly related to the infusion rate. The AmB plasma disposition was biphasic, with mean half-lives of 17 h for the first phase and 11 d for the terminal phase, and a mean residence time of 12 d. Biochemical modulation of antineoplastic agents (lomustine, doxorubicin, cyclophosphamide) by CI-AmB was not demonstrated clinically. Acute toxicities of fever and chills were noted in only 3 of the 26 courses. Reversible renal toxicity was observed in 23 courses. Therapeutic antifungal plasma levels were rapidly reached and maintained for the duration of infusion, with a reduction of acute toxicities associated with shorter infusions. These observations provide impetus for further clinical investigation of CI-AmB.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Neoplasms

Amphotericin B nephrotoxicity limits its therapeutic use. The mechanisms involved in the deleterious effect on the kidney include a preglomerular vasoconstriction. Nifedipine, a calcium antagonist which acts also on the afferent arteriolar tone, did not, however, prevent renal impairment in the rats of our study. This could be due either to a negligible role of the hemodynamic changes in the development of renal failure or to a lack of efficacy of nifedipine on the vasoconstrictor mechanism induced by amphotericin B.

Topics: Amphotericin B; Animals; Glomerular Filtration Rate; Hemodynamics; Kidney Diseases; Nifedipine; Rats

To investigate the protective effect of liposomes on acute amphotericin B (AMB) renal toxicity, we compared in rabbits the acute toxicity of 4 mg/kg of free-AMB and 4 or 10 mg/kg of liposomal AMB (L-AMB) during 90 min after antibiotic infusion. Free-AMB exhibited immediate nephrotoxicity with a 44% decrease of the glomerular filtration rate and alteration of tubular cell membrane permeability expressed as increases in urinary pH (6.5 vs. 4.7), potassium fractional excretion (95% vs. 30%) and sodium fractional excretion (26% vs. 4%). Urinary excretion of the lysosomal enzyme N-acetylglucosaminidase was unchanged by free-AMB. Incorporation of AMB into liposomes prevented the toxic effects of free-AMB on glomerular filtration and tubular cells membrane, but significantly increased N-acetylglucosaminidase urinary excretion (380 and 180% in animals receiving 4 and 10 mg/kg of L-AMB, respectively). Absolute AMB urinary excretion during the experiment was unchanged by liposomes and was always less than 1% of the total dose administered. Liposomes alone exhibited no toxicity. These results suggest that liposomes could increase the interaction between AMB and lysosomes leading to an additional mechanism of cellular injury. They admonish close monitoring of renal function and enzymuria in clinical situations in which L-AMB is being used.

Topics: Amphotericin B; Animals; Drug Carriers; Glomerular Filtration Rate; Kidney Diseases; Kidney Tubules; Liposomes; Male; Rabbits

The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.

Topics: Amphotericin B; Animals; Creatinine; Glomerular Filtration Rate; Injections, Intraperitoneal; Kidney Diseases; Male; Potassium; Rats; Rats, Inbred Strains; Sodium; Time Factors

A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity.. Thirty-five patients receiving intravenous amphotericin B for treatment of proven or suspected fungal infection who developed nephrotoxicity (greater than 100% increase in baseline serum creatinine to a level above the normal range) were compared with 60 control patients receiving amphotericin B who did not develop nephrotoxicity. Amphotericin B dosing variables and other potential risk factors were analyzed in a logistic regression model.. Cases of nephrotoxicity received a significantly higher average daily dose of amphotericin B (0.49 +/- 0.18 mg/kg/day) than did controls (0.34 +/- 0.17 mg/kg/day). In a multivariate model, the risk of nephrotoxicity increased 3.7-fold for each 50-mg increase in total dose for a fixed duration of therapy and patient weight. Risk decreased by a factor of 0.4 for each extra day of therapy for a fixed total dose and weight. An increase in weight was also protective when the two other dosage variables were held constant. Each 0.10 mg/kg/day dose increment was associated with a 1.8-fold (95% confidence interval, 1.2 to 2.7) increase in the risk of nephrotoxicity. Other significant risk factors included diuretic use during amphotericin B therapy (12.5, 1.7 to 94.7), for which a linear dose-response relationship was demonstrated, and an abnormal baseline serum creatinine level (15.4, 1.4 to 173.2).. Risk factors for amphotericin B-associated nephrotoxicity include higher average daily doses (approximately a doubling for each 0.10 mg/kg/day increment), diuretic use, and abnormal baseline renal function. These data suggest possible protective interventions and will aid clinicians in assessing the risk-benefit ratio of amphotericin B therapy for deep fungal infection.

Topics: Adult; Aged; Amphotericin B; Case-Control Studies; Creatinine; Diuretics; Dose-Response Relationship, Drug; Humans; Kidney Diseases; Middle Aged; Pennsylvania; Risk Factors

Twelve leukemic patients (19%) receiving amphotericin B and aminoglycosides had nephrotoxicity (creatinine value greater than 2.0 mg/dl). Patients with nephrotoxicity tended to be older than patients without nephrotoxicity; gender and total amphotericin B dose were not related to nephrotoxicity. Sodium administration has previously been shown to reverse amphotericin B nephrotoxicity. In this series, among patients receiving ticarcillin at greater than or equal to 18 gm/day (93.6 mEq of sodium per day) the incidence of nephrotoxicity was significantly decreased (1/30, or 3.3%). A multivariate analysis showed that this protective effect of ticarcillin was not dependent on the fact that patients receiving ticarcillin were less likely to receive vancomycin. There were insufficient patients receiving sodium in the absence of ticarcillin to study the effect of sodium alone. However, our observations are consistent with the hypothesis that sodium can prevent renal dysfunction in this clinical situation.

Topics: Adult; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Kidney Diseases; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Sodium; Statistics as Topic; Ticarcillin; Vancomycin

Topics: Amphotericin B; Humans; Kidney Diseases; Mannitol

The second documented case of renal aspergilloma due to Aspergillus flavus is presented. The merits of the medical therapy that failed are discussed. Pathological examination showed a nidus of aspergillus around suture material persisting from a pyelolithotomy operation 2 years before in India. We argue that this was the reason for the failure of the medical therapy. This is the first case of its kind reported.

Topics: Amphotericin B; Aspergillosis; Female; Flucytosine; Humans; Ketoconazole; Kidney Diseases; Middle Aged; Nephrectomy

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Topics: Amphotericin B; Blood Urea Nitrogen; Creatinine; Drug Therapy, Combination; Humans; Infusions, Intravenous; Kidney Diseases; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Middle Aged; Mycoses; Penicillins; Risk; Sodium; Ticarcillin

The role of cyclosporine (CSA) alone or in combination with various chemotherapeutics in the development of renal toxicity was evaluated in rats. Administration of 20 mg/kg/day CSA for 4 weeks caused renal functional and structural changes similar to those reported in man. The combined administration of CSA and various chemotherapeutic drugs with a nephrotoxic potential, such as gentamicin (at therapeutic doses), amphothericin B and ketoconazole, which are frequently used in immunosuppressed patients, did not aggravate the CSA induced toxicity in the rat model. Gentamicin at toxic doses, however, increased CSA nephrotoxicity. Thus, the nephrotoxicity induced by CSA has a different pathogenetic mechanism.

Topics: Amphotericin B; Animals; Anti-Infective Agents; Cyclosporins; Drug Interactions; Gentamicins; Ketoconazole; Kidney; Kidney Diseases; Male; Rats; Rats, Inbred Strains; Risk

Systemic candidiasis with renal involvement is a well recognised complication of intensive care in premature newborns. However, the development of reversible obstructive oliguric acute renal failure has not been well documented. We report a premature infant who developed anuria associated with bilateral candidal bezoar formation in the renal collecting system. The sonographic appearance of the renal fungus balls is described. Treatment by surgical removal of the bezoars, open placement of nephrostomy tubes and intravenous antifungal therapy resulted in apparent complete recovery.

Topics: Amphotericin B; Anuria; Bezoars; Candidiasis; Female; Flucytosine; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Injections, Intravenous; Kidney Diseases; Radiography; Time Factors; Ureteral Diseases

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Female; Flucytosine; Itraconazole; Ketoconazole; Kidney Diseases; Mice; Mice, Inbred Strains; Miconazole; Triazoles

The hospital records of 45 infants and children with one or more blood cultures positive for Candida species were studied retrospectively in an attempt to define the risk of Candida-related complications. Death of eight of the patients (18%) was related to Candida infection, and five additional patients (11%) had metastatic foci of infection but survived. No characteristics were identified that would predict patients who were at high risk for complications of candidemia. Eleven patients were treated with amphotericin B for longer than a week and were examined for evidence of nephrotoxicity. None had persistent abnormalities of blood urea nitrogen or serum creatinine concentrations develop during treatment; two patients had hypokalemia.

Topics: Adolescent; Amphotericin B; Blood; Blood Urea Nitrogen; Candidiasis; Child; Child, Preschool; Creatinine; Drug Therapy, Combination; Female; Flucytosine; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Retrospective Studies

A well controlled diabetic presented with recurrent attacks of renal colic and passage of soft masses per urethra, which were identified as aspergillus fungus balls; he was treated with amphotericin B, subsequent to which he was free of renal colic and urine cultures were negative for aspergillus.

Topics: Amphotericin B; Aspergillosis; Colic; Diabetes Complications; Humans; Kidney Diseases; Male; Middle Aged

Topics: Acetaminophen; Age Factors; Amphotericin B; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Hemolysis; Humans; Isoniazid; Kidney Diseases; Methotrexate; Pharmaceutical Preparations; Probability; Time Factors

The kidneys of newborn rats, which are both morphologically and physiologically immature, have been shown to be relatively insensitive to the nephrotoxic effects of several chemicals. To examine the specificity of these age-related differences, pups received sc injections of either 20 mg/kg of amphotericin B or 250 mg/kg folic acid, two known nephrotoxins in adult animals, on postnatal Day 1, 8, or 15. Renal function was examined by a basal clearance test and a hydropenia challenge at 1, 2, or 5 (6 in the case of amphotericin B) days after treatment. We observed no difference in degree of renal toxicity with age, but repair of renal damage tended to proceed slower at the youngest age. Amphotericin treatment produced uremia, increased fractional excretion of water and sodium, a decreased fractional excretion of urea, and a diminished hydropenia response but no change in creatinine clearance and no renal pathology. The observed pattern of renal toxicity may be attributed to an inability to maintain urea gradients in the distal segment of the nephron. Folic acid treatment resulted in greatly increased kidney weights with marked pathology, uremia with decreased creatinine clearance, increased fractional excretion of water, and a decreased hydropenia response. Unlike the renal toxicity observed following amphotericin treatment, renal toxicity from folic acid appears to be a nonspecific response to cell injury within the renal tubules. The data indicate that, in general, neonates do not possess a relative insensitivity to nephrotoxins and that renal physiological measurements which can be performed in neonatal rats are useful in evaluating and interpreting alterations in renal function.

Topics: Aging; Amphotericin B; Animals; Animals, Newborn; Body Weight; Creatinine; Female; Folic Acid; Injections, Subcutaneous; Kidney; Kidney Diseases; Kidney Function Tests; Male; Organ Size; Rats; Uremia

The treatment of 62 dogs with blastomycosis was reviewed to identify prognostic factors and response to various treatment regimens. Severity of lung involvement, as determined by radiography, and the number of nonsegmented neutrophils were useful prognostic factors. Females survived treatment better than did males, but females were more prone to relapse. Ketoconazole treatment at a dose of 10 mg/kg daily for 60 days was not as effective as amphotericin B. The most notable adverse effect of amphotericin B treatment was nephrotoxicosis . Treatment with amphotericin B followed by ketoconazole was as effective as amphotericin B alone and resulted in less nephrotoxicosis . Most dogs that had relapses were retreated effectively with amphotericin B and/or ketoconazole. Canine blastomycosis was shown to be a treatable disease, with a cure rate of approximately 75%.

Topics: Amphotericin B; Animals; Blastomycosis; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Ketoconazole; Kidney Diseases; Lung Diseases, Fungal; Male; Mannitol; Prognosis

The widely accepted practice of empirically administering amphotericin B to immunocompromised patients with fever unresponsive to antibiotics poses a hazard to transplant recipients receiving immunosuppression with cyclosporine. Improved methods of Candida detection and less toxic antifungals are urgently needed, but in the interim, treatment regimens should require a greater index of suspicion before initiating amphotericin therapy in patients receiving cyclosporine.

Topics: Amphotericin B; Bacterial Infections; Blood Transfusion; Bone Marrow Transplantation; Candidiasis; Cyclosporins; Graft Rejection; Granulocytes; Humans; Kidney Diseases; Potassium; Transplantation Immunology; Washington

Primary renal candidiasis and hydronephrosis were diagnosed in two premature neonates in whom systemic hypertension developed. The clinical course in these patients and in 16 patients with renal candidiasis described in the literature indicated that prematurity, use of broad-spectrum antibiotics, and use of intravenous (IV) catheters are predisposing factors. Anuria and flank mass were the initial manifestations in the reviewed cases. Only four of the 16 patients survived following either antifungal therapy or nephrectomy. Both of our patients survived after antifungal therapy with amphotericin B and flucytosine for systemic effect as well as topical instillation of amphotericin B solution via a nephrostomy. We believe that a high index of suspicion in infants at risk and early institution of antifungal therapy for systemic as well as topical effect can improve the outcome in infants with renal candidiasis.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Hydronephrosis; Hypertension; Infant; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Kidney Pelvis; Male

A sixteen day old infant developed candiduria after surgery on a single functioning, hydronephrotic kidney with ureteropelvic junction stenosis. Masses of candida albicans caused obstruction of the ureter with acute anuria. Endoscopic relief of the obstruction together with aggressive antifungal therapy led to irradication of the fungal infection. This case history emphasizes the fact that candida infection in early childhood should be evaluated carefully. Unfortunately no guidelines are yet available for the indications and the preferred mode of treatment, and length of therapy of infantile renal candidiasis.

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Infant, Newborn; Kidney; Kidney Diseases; Male; Ureteral Obstruction

The authors described a 6 years old boy suffering from acute lymphoblastic leukemia and treated by the B.F.M. protocol who presented during intensive chemotherapy period a aspergillus renal abscess apparently unique. During the postoperative period the evolution was progressively favorable under prolonged anti-fungal treatment. The different clinical features, the non facilities of diagnosis and the mean possibility of treatment in aspergillus infection in immunodeficient patients are reviewed.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Child; Humans; Kidney; Kidney Diseases; Leukemia, Lymphoid; Male; Neutropenia

The polyene antibiotic, amphotericin B, causes an acute reduction in renal blood flow and glomerular filtration rate. The purpose of this study was to evaluate the hypothesis that the renal vascular response to amphotericin B can be blocked by aminophylline. Toward this end, the effect of aminophylline on the renal response to amphotericin B in sodium-depleted dogs was examined. In dogs not treated with aminophylline, amphotericin B (0.5 mg/kg infused i.v. over 20 min) significantly reduced renal blood flow and glomerular filtration by 49.9 +/- 12.6 ml/min (mean +/- S.E.M.) and 23.4 +/- 2.4 ml/min, respectively at 140 min after the amphotericin B infusion. In dogs treated with an intrarenal aminophylline infusion (5 mg/min), the renal blood flow and glomerular filtration rate response to amphotericin B did not differ from that of amphotericin B vehicle. We conclude that aminophylline inhibits the renal response to amphotericin B. The possible clinical relevance of these observations are discussed.

Topics: Aminophylline; Amphotericin B; Animals; Dogs; Feedback; Glomerular Filtration Rate; Kidney; Kidney Diseases; Kidney Tubules, Distal; Receptors, Cell Surface; Receptors, Purinergic; Reflex; Renal Circulation

In a diabetic renal transplant recipient a nephrocutaneous fistula developed after percutaneous renal graft biopsy, and ureteral obstruction due to Candida albicans fungus balls was demonstrated. Local irrigation with amphotericin B, systemic antifungal therapy, and rigid blood sugar control led to rapid clearing of the fungal infections. This cause of renal transplant insufficiency should be considered prior to renal biopsy in diabetic patients with yeast forms in the urine.

Topics: Adult; Amphotericin B; Blood Glucose; Candidiasis; Diabetic Nephropathies; Female; Fistula; Graft Rejection; Humans; Kidney Diseases; Kidney Transplantation; Skin Diseases; Ureteral Diseases; Ureteral Obstruction; Urography

A major limitation in the use of amphotericin B is its potential to cause nephrotoxicity. In animals, increased dietary sodium reduces renal toxicity. Experience with five patients in whom impaired renal function developed early during amphotericin B therapy is reported. In four of the patients, there was evidence of sodium depletion due to low sodium intake, diuretic administration, or vomiting. In all five patients, sodium loading was associated with improved renal function, which permitted amphotericin B therapy to be continued in fully effective doses to the completion of elective courses of treatment without evidence of residual impaired renal function. These observations are consistent with the hypothesis that intrarenal regulatory mechanisms contribute to changes in renal function due to amphotericin B therapy.

Topics: Aged; Amphotericin B; Creatinine; Diet; Female; Humans; Kidney Diseases; Male; Middle Aged; Sodium; Sodium Chloride; Urea

The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in seven patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal renal function. Total plasma clearance of amphotericin B ranged from 16.7 to 39.9 ml/min, correlated directly with the plasma creatinine concentration, and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 +/- 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 +/- 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. This suggests that plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are not affected by renal impairment, and that dosage requirements will be overestimated if based on measurements of total drug plasma concentration.

Topics: Adult; Aged; Amphotericin B; Female; Humans; Kidney Diseases; Male; Middle Aged

Topics: Adult; Amphotericin B; Diet, Sodium-Restricted; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Sodium

Topics: Amphotericin B; Animals; Dog Diseases; Dogs; Kidney Diseases; Mycoses

This study was undertaken to examine the value of mannitol as protection against the acute nephrotoxicity of amphotericin B under controlled conditions in a reproducible model of toxicity in the dog. Eleven dogs received amphotericin B, 2.5 mg x kg-1 b. wt. by i.v. infusion over a 4-h period. Six dogs were treated with mannitol, 6.25 g, i.v. every hour and five served as controls. Urinary volume (V), inulin clearance (CIn), p-aminohippurate clearance (CPAH), and Na excretion (UNaV) were measured every hour throughout the experiment. Although a higher urinary output was maintained in mannitol-treated dogs, a progressive decline in renal function was observed in treated and in control dogs. During the 4th h, mannitol-treated dogs showed higher CIn (37.4 vs. 19.7 ml x min-1 and CPAH (95 vs. 54 ml x min-1 than controls. However, statistically the differences were barely significant. The results fail to show that mannitol offers a definite protection against amphotericin B nephrotoxicity.

Topics: Amphotericin B; Animals; Disease Models, Animal; Dogs; Female; Infusions, Parenteral; Kidney Diseases; Kidney Function Tests; Mannitol

The influence of sodium balance and furosemide administration on acute amphotericin B-induced nephrotoxicity has been investigated in the anesthetized dog. In sodium-depleted dogs, amphotericin B (1 mg/kg i.v.) reduced renal blood flow by 32% and glomerular filtration rate by 90% 40 min after the infusion and 32 and 65%, respectively, 140 min after infusion. Although filtration fraction was reduced, fractional sodium excretion increased 13-fold. Renal renin secretion rate decreased by 64%. Prior sodium loading abolished the acute response to amphotericin B. Pretreatment of sodium-depleted dogs with furosemide (5 mg/kg bolus followed by 260 micrograms/kg/min i.v.) attenuated the reduction in renal blood flow and glomerular filtration rate produced by amphotericin B. The data indicate that acute reductions in renal blood flow and glomerular filtration rate in response to amphotericin B infusion are not direct but related to sodium status. The changes do not seem to be mediated by the renin-angiotensin system and can be inhibited by sodium loading and attenuated by concurrent furosemide administration. These observations are consistent with the hypothesis that the acute response is mediated by tubulo-glomerular feedback.

Topics: Amphotericin B; Animals; Dogs; Female; Furosemide; Glomerular Filtration Rate; Kidney; Kidney Diseases; Male; Regional Blood Flow; Sodium

Topics: Acid-Base Imbalance; Ammonium Chloride; Amphotericin B; Animals; Bicarbonates; Carbon Dioxide; Hydrogen-Ion Concentration; Infusions, Parenteral; Kidney Diseases; Male; Rats

A diabetic patient presenting with bilateral enlarged kidneys and acute renal failure was found to have renal parenchymal candidiasis without obstruction. Treatment with amphotericin B resulted in return of renal function and decrease in renal size.

Topics: Acute Kidney Injury; Amphotericin B; Candidiasis; Female; Humans; Kidney Diseases; Middle Aged

Polyuria and polydipsia developed in two cases during amphotericin B therapy for deep mycoses. Neither patient could concentrate his urine in response to water deprivation or exogenous vasopressin. Other causes of vasopressin-resistant nephrogenic diabetes insipidus were not present. Three months after amphotericin B therapy had been discontinued, concentrating ability improved toward normal. A third patient was further observed and demonstrated normal diluting capacity but impaired free-water reabsorption, suggesting a distal tubular defect consistent with nephrogenic diabetes insipidus. Four months after discontinuing therapy, renal concentrating ability was normal. Amphotericin B can induce a reversible form of nephrogenic diabetes insipidus.

Topics: Amphotericin B; Diabetes Insipidus; Humans; Kidney Concentrating Ability; Kidney Diseases; Male; Middle Aged; Osmolar Concentration; Urine; Vasopressins; Water Deprivation

Topics: Amphotericin B; Clotrimazole; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Meningitis; Miconazole; Mycoses; Rifampin; Thrombophlebitis

Topics: Amphotericin B; Animals; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Mice; Mycoses

Renal transplant recipients are susceptible to a number of fungal infections amenable to therapy with amphotericin B, but azotaemia is an almost invariable sequel to the use of this agent. As intravenous mannitol has been shown to minimize nephrotoxicity induced by amphotericin B in dogs we treated four kidney transplant recipients who had systemic fungal infections with mannitol and amphotericin B. None showed significant reduction in renal function though a mild metabolic acidosis did develop.

Topics: Acidosis; Adult; Amphotericin B; Candidiasis; Cryptococcosis; Histoplasmosis; Humans; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Male; Mannitol; Middle Aged; Postoperative Complications; Transplantation, Homologous; Uremia

The recent increased use of steriods, immunosuppressive agents and cytotoxic drugs has been associated with a rise in the incidence of significant fungal disease. The first case of bilateral renal aspergillosis without disseminated involvement is reported. A multitherapeutic approach, including surgical evacuation of masses of hyphae, parenteral antimycotic chemotherapy and topical instillations of amphotericin B, were necessary to clear the kidneys. Newer systemic agents such as 5-fluorocytosine and rifampicin were also used. Treatment of fungal infections of the urinary tract is discussed.

Topics: Adult; Amphotericin B; Aspergillosis; Drug Synergism; Flucytosine; Humans; Kidney Diseases; Male; Rifampin; Therapeutic Irrigation

In a retrospective study of 51 cases of systemic North American blastomycosis 11 patients were found to have genitourinary tract involvement, the prostate and epididymis being most commonly affected. Diagnosis was made by culture of the fungus from urine, abscess or prostate secretions, morphologic identification of the characteristic organism in urine or secretions, or histologic examination of tissue specimens. Treatment with amphotericin B reduced the mortality rate of 90 per cent to as low as 10 per cent. Long-term followup is necessary because of a relapse rate of 10 to 15 per cent.

Topics: Adult; Aged; Amphotericin B; Blastomycosis; Epididymitis; Genital Diseases, Male; Humans; Kidney Diseases; Male; Middle Aged; Penile Diseases; Potassium Iodide; Prostatic Diseases; Stilbamidines; Testicular Diseases

Topics: Agranulocytosis; Amphotericin B; Anemia, Aplastic; Anemia, Hemolytic; Anti-Bacterial Agents; Ataxia; Bacitracin; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Chloramphenicol; Deafness; Gastrointestinal Diseases; Gentamicins; Humans; Kanamycin; Kidney Diseases; Leukopenia; Lung Diseases; Neomycin; Neuromuscular Diseases; Nitrofurantoin; Optic Neuritis; Peripheral Nervous System Diseases; Skin Diseases; Streptomycin; Sulfonamides; Tetracycline; Thrombocytopenia; Vertigo

Topics: Administration, Oral; Amphotericin B; Arrhythmias, Cardiac; Brain Diseases; Cytosine; Flucytosine; Gastrointestinal Diseases; Humans; Hypokalemia; Injections, Intravenous; Injections, Spinal; Intestinal Perforation; Kidney Diseases; Meningitis; Mycoses; Paralysis; Radiculopathy; Vision Disorders

Topics: Adult; Aged; Amphotericin B; Anterior Chamber; Aspergillosis; Aspergillus fumigatus; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Cytosine; Drug Resistance, Microbial; Female; Flucytosine; Humans; Keratitis; Kidney Diseases; Kidney Transplantation; Male; Meningitis; Middle Aged; Mycoses; Transplantation, Homologous

Topics: Amphotericin B; Humans; Kidney Diseases; Mycoses

Topics: Adult; Amphotericin B; Antibody Formation; Antifungal Agents; Fungi; Humans; Hypersensitivity, Delayed; Imidazoles; Immunity; Immunity, Cellular; Kidney; Kidney Diseases; Male; Mycoses; Nephrectomy; Radiography; Trityl Compounds

Topics: Amphotericin B; Candida albicans; Candidiasis; Cystitis; Female; Flucytosine; Humans; Kidney Diseases; Male; Prostatitis; Urinary Catheterization; Urinary Tract Infections

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Blood Vessels; Brain Diseases; Fungi; Heroin Dependence; Humans; Kidney Diseases; Male; Mucormycosis; Necrosis; Urography

Topics: Acute Kidney Injury; Aged; Amphotericin B; Autopsy; Biopsy; Fungi; Humans; Kidney Diseases; Male; Mycoses; Renal Dialysis

Five cases are described in which fear of the possibly hazardous effects of giving amphotericin to patients with kidney disease resulted in death from progressive infection by an amphotericin-sensitive fungus (Cryptococcus neoformans in three cases, Blastomyces dermatitidis in one case, and Histoplasma capsulatum in one case).

Topics: Adrenal Insufficiency; Adult; Amphotericin B; Attitude of Health Personnel; Blastomycosis; Cryptococcosis; Decerebrate State; Drug Prescriptions; Female; Histoplasmosis; Hodgkin Disease; Humans; Kidney Diseases; Lung Diseases, Fungal; Male; Medication Errors; Meningitis; Meningoencephalitis; Mycoses; Phobic Disorders; Sarcoidosis; Spinal Diseases

Topics: Adolescent; Adult; Amphotericin B; Candidiasis; Diabetes Complications; Female; Humans; Kidney Diseases; Kidney Pelvis; Male; Middle Aged; Radiography; Ureter; Urinary Bladder Diseases

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Amphotericin B; Blastomycosis; Carbon Dioxide; Glomerular Filtration Rate; Histoplasmosis; Humans; Hydrogen-Ion Concentration; Hypokalemia; Kidney Diseases; Kidney Tubules; Mycoses; Partial Pressure; Potassium; Uric Acid

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Amphotericin B; Blastomycosis; Carbon Dioxide; Glomerular Filtration Rate; Histoplasmosis; Humans; Hydrogen-Ion Concentration; Hypokalemia; Kidney Diseases; Kidney Tubules; Mycoses; Partial Pressure; Potassium; Uric Acid

Topics: Adolescent; Adrenal Gland Diseases; Adult; Aged; Amphotericin B; Chemical and Drug Induced Liver Injury; Child; Dose-Response Relationship, Drug; Drug Tolerance; Female; Hematopoiesis; Humans; Kidney Diseases; Male; Middle Aged; Mycoses

Topics: Adult; Amphotericin B; Azathioprine; Creatinine; Cryptococcosis; Cryptococcus; Cytosine; Female; Fluorine; Humans; Kidney Diseases; Kidney Transplantation; Male; Metabolic Clearance Rate; Postoperative Complications; Transplantation, Homologous

Topics: Aged; Amphotericin B; Ampicillin; Anti-Bacterial Agents; Cephalothin; Chloramphenicol; Humans; Kanamycin; Kidney Diseases; Male; Methicillin; Middle Aged; Streptomycin; Urinary Tract Infections; Urography

Topics: Acidosis, Renal Tubular; Ammonium Chloride; Amphotericin B; Animals; Bicarbonates; Bile Acids and Salts; Body Weight; Carbon Dioxide; Creatinine; Disease Models, Animal; Hydrogen-Ion Concentration; Injections, Intraperitoneal; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Male; Polyuria; Potassium; Quaternary Ammonium Compounds; Rats; Sodium

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Humans; Kidney Diseases; Meningitis

Topics: Aged; Amphotericin B; Aspergillosis; Female; Humans; Kidney Diseases

Topics: Adolescent; Aged; Amphotericin B; Anemia; Blastomycosis; Chemical Phenomena; Chemistry; Humans; Hypokalemia; Kidney Diseases; Male; Microbial Sensitivity Tests

Topics: Adult; Amphotericin B; Anuria; Candida; Candidiasis; Humans; Kidney Diseases; Male; Urinary Catheterization; Urine; Urography

Topics: Adolescent; Adult; Aged; Amphotericin B; Candida; Candidiasis; Drug Tolerance; Female; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Perfusion

Topics: Amphotericin B; Anti-Bacterial Agents; Cephalosporins; Humans; Kidney Diseases; Kidney Function Tests; Penicillins; Polymyxins; Tetracycline

Topics: Adolescent; Aged; Amphotericin B; Female; Humans; Injections, Intravenous; Injections, Spinal; Kidney; Kidney Diseases; Male; Mycoses

Topics: Adult; Amphotericin B; Blastomyces; Blastomycosis; Bone Diseases; Bronchial Diseases; Fluorescent Antibody Technique; France; Humans; Immunodiffusion; Kidney Diseases; Lung Diseases; Male; Tunisia

Topics: Abscess; Adolescent; Adult; Amphotericin B; Candida; Candidiasis; Diabetes Mellitus, Type 1; Female; Humans; Kidney Diseases; Male; Middle Aged; Perinephritis; Urine; Urography

Topics: Acetazolamide; Adolescent; Amphotericin B; Candidiasis; Humans; Infectious Mononucleosis; Kidney Diseases; Leukemia; Male; Mercaptopurine; Methotrexate; Nystatin; Penicillins; Peripheral Nervous System Diseases; Prednisone; Rolitetracycline; Sepsis; Uric Acid

Topics: Aged; Amphotericin B; Cryptococcosis; Diabetes Complications; Female; Humans; Kidney Diseases

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antifungal Agents; Brain Diseases; Candida; Candidiasis; Kidney Diseases; Lung Diseases; Lung Diseases, Fungal; Mice; Nystatin; Pharmacology; Research; Spleen; Virulence

Topics: Administration, Intravenous; Amphotericin B; Animals; Dog Diseases; Dogs; Dosage Forms; Heart Diseases; Injections; Injections, Intravenous; Kidney Diseases; Mycoses; Pharmacology; Toxicology

Topics: Amphotericin B; Blood; Coccidioidomycosis; Humans; Hypokalemia; Kidney Diseases; Muscular Diseases; Paralysis; Pathology; Potassium; Statistics as Topic; Toxicology; Urine

Topics: Amphotericin B; Blood; Blood Chemical Analysis; Blood Urea Nitrogen; Creatine; Creatinine; Cryptococcosis; Drug Therapy; Hematocrit; Histoplasmosis; Kidney Calculi; Kidney Diseases; Pathology; Phenolphthaleins; Potassium; Sodium; Sodium, Dietary; Toxicology; Urea; Urine

Topics: Amphotericin B; Blood Urea Nitrogen; Calcium; Carbonates; Dogs; Drug Therapy; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Pathology; Pharmacology; Phosphates; Research; Toxicology

Topics: Amphotericin B; Anaphylaxis; Anemia; Anuria; Blushing; Feeding and Eating Disorders; Fever; Headache; Heart Failure; Humans; Hypokalemia; Kidney Diseases; Liver Diseases; Meningitis; Nausea; Pain; Paralysis; Paresthesia; Phlebitis; Seizures; Thrombocytopenia; Toxicology; Ventricular Fibrillation; Vertigo; Vomiting

Topics: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antitubercular; Candidiasis; Child; Humans; Infant; Kidney; Kidney Diseases; Mycoses; Toxicology

Topics: Alopecia; Amphotericin B; Candida tropicalis; Candidiasis; Child; Haemophilus; Humans; Kidney Diseases; Liver Diseases; Meningitis; Meningitis, Haemophilus; Sepsis

Topics: Amphotericin B; Calcinosis; Calcium; Dogs; Kidney Diseases; Kidney Tubules; Research; Toxicology

Topics: Amphotericin B; Anuria; Coccidioidomycosis; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Toxicology; Uremia

Topics: Amphotericin B; Dogs; Dosage Forms; Kidney Diseases; Research; Toxicology; Uremia

Topics: Amphotericin B; Coccidioidomycosis; Humans; Kidney Diseases; Kidney Function Tests; Toxicology

Case reports of three residents of Ontario with clinical histoplasmic chorioretinitis are presented. The diagnosis was made on the basis of the clinical appearance, the presence of calcified lesions in the chest, a negative skin test to tuberculin, and a positive skin test to toxoplasmin. All patients were treated with intravenous amphotericin B. Except for transitory elevation of blood urea nitrogen, there were no serious complications from the drug and in all cases the lesions in the eyes were improved. Histologic or cultural proof of the presence of fungus in the eye is not available, but clinical and laboratory findings can combine to point to the diagnosis of histoplasmosis. In such cases, since vision is at stake, treatment with amphotericin B should be considered.

Topics: Amphotericin B; Blood Chemical Analysis; Blood Urea Nitrogen; Canada; Chorioretinitis; Histoplasmin; Histoplasmosis; Humans; Hydrocortisone; Kidney Diseases; Leukocyte Count; Nitrogen; Ontario; Prednisone; Toxicology; Tuberculin Test; Urea

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney; Kidney Diseases; Male

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney; Kidney Diseases; Medical Records; Mucormycosis; Mycoses; Nephrectomy