Lucinactant for the treatment of respiratory distress syndrome in neonates.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in premature neonates. This syndrome is caused by a lack of endogenous surfactant production in the lungs. Surfactant replacement was established as a safe and effective treatment in the 1990s and has become the standard of care for these infants. Surfactant products are either protein-free synthetic phospholipid compounds or animal-derived lung preparations. Currently, about 90,000 infants a year receive treatment with one of the commercially available animal-derived surfactants. Lucinactant (Surfaxin®) is a new synthetic surfactant with a pulmonary surfactant-associated protein B mimic that recently received FDA approval. The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. This review summarizes the current clinical knowledge about lucinactant.

A pilot, randomized, controlled clinical trial of lucinactant, a peptide-containing synthetic surfactant, in infants with acute hypoxemic respiratory failure.

OBJECTIVE: Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure. We evaluated whether intratracheal lucinactant, a synthetic, peptide-containing surfactant, was safe and well-tolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes. METHODS AND MAIN RESULTS: Infants ≤ 2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, double-blind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12-24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran-Mantel-Haenszel test was used for categorical variables.We enrolled 165 infants (84 lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive end-expiratory pressure and higher tidal volume in placebo subjects. The incidence of transient peri-dosing bradycardia and desaturation was significantly higher in the lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive lucinactant as indicated by fewer second treatments (67% lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was no significant reduction in duration of mechanical ventilation with lucinactant (geometric least square means: 4.0 days lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with lucinactant (least square means: 2.4 days lucinactant vs. 4.3 days placebo; p = .006). CONCLUSIONS: In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that lucinactant might improve lung function in infants with acute hypoxemic respiratory failure.

An open label, pilot study of Aerosurf® combined with nCPAP to prevent RDS in preterm neonates.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) is an accepted mode of respiratory support for preterm infants with respiratory insufficiency. To avoid potential sequelae of endotracheal (ET) intubation and mechanical ventilation, prophylactic aerosolization of surfactant delivered via nCPAP has been attempted with limited success. METHODS: To determine the feasibility and safety of prophylactic aerosolization of a peptide-containing synthetic surfactant, Aerosurf® (lucinactant for inhalation) was delivered by nCPAP to preterm infants at risk for respiratory distress syndrome (RDS). Neonates were enrolled into treatment group 1 (Aerosurf retreatment separated by at least 3 h) or treatment group 2 (Aerosurf retreatment separated by at least 1 h). A vibrating membrane nebulizer Aeroneb Pro® was used to aerosolize 20 mg/mL Aerosurf. All neonates received the initial 3-h treatment, and three retreatments were permitted within 48 h based on clinical response. RESULTS: Seventeen infants were enrolled. Aerosurf was well tolerated, with transient desaturations observed during dosing without bradycardia or hypotension. Variability in output rates of the Aeroneb Pro was observed leading to different average dispensed drug volumes per treatment per patient. All infants survived; 29.4% required subsequent ET surfactant replacement therapy, 23.5% were diagnosed with RDS at 24 h, and 11.8% with bronchopulmonary dysplasia (BPD) at 28 days of life. Mean FiO2 was 0.4 at baseline, and 0.32 at 4 h posttreatment. CONCLUSIONS: Aerosurf can be safely administered via nCPAP in preterm infants at risk for RDS and may provide an alternative to surfactant administration via an ET tube. Further studies are required to evaluate this delivery approach.

Synthetic surfactants: where are we? Evidence from randomized, controlled clinical trials.

The benefits of exogenous synthetic or animal-derived surfactants for prevention or treatment of respiratory distress syndrome (RDS) are well established. Data from head-to-head trials comparing animal-derived surfactants primarily with the synthetic surfactant colfosceril suggest that the major clinical advantages afforded by the presence of surfactant protein (SP)-B and SP-C in animal-derived preparations relate to faster onset of action, a reduction in the incidence of RDS when used prophylactically, and a lower incidence of air leaks and RDS-related deaths. However, no benefits in terms of overall mortality or BPD have been shown in these head-to-head comparisons. Findings from trials of a new-generation synthetic surfactant containing a peptide that mimics SP-B, as well as their follow-up study suggest that its administration improves short-term clinical outcomes compared with colfosceril and results in survival through 1 year of age, which is at least comparable, if not perhaps superior, to that seen with animal-derived surfactants.

Effects of liposomal amphotericin B versus an amphotericin B lipid complex on liver histopathology in patients with hematologic malignancies and invasive fungal infections: a retrospective, nonrandomized autopsy study.

BACKGROUND: Abnormal liver function test (LFT) results are common in patients with hematologic abnormalities, making the assessment of drug-related hepatotoxicity difficult. Studies based on elevated LFT levels have found that use of liposomal amphotericin B (L-AMB) was associated with increased hepatotoxicity compared with amphotericin B (AMB)/deoxycholate or amphotericin B lipid complex (ABLC). Because LFT abnormalities are multifactorial in severely immunocompromised patients, uncertainty remains regarding the clinical significance of these laboratory findings. OBJECTIVE: The aim of this study was to present the hepatic histopathologic findings on autopsy in patients who had hematologic malignancies and fungal infections and had received L-AMB or ABLC. METHODS: This study was conducted at The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Records from 1995 to 2004 of patients who had received L-AMB or ABLC for > or =7 days, within 30 days before death, were reviewed by 1 investigator. Hepatic autopsy slides were independently reviewed by another investigator (pathologist) in a blinded fashion. Histopathologic evidence of amphotericin-related hepatotoxicity was predetermined based on histopathologic abnormalities reported in animal studies (eg, macrophage vacuolation, multifocal hepatocellular necrosis). Based on data from animal studies and in view of the lack of studies in humans, multifocal necrosis, fatty infiltration, macrophage vacuolation, and/or "foamy macrophage" accumulation were all considered histopathologic abnormalities associated with the use of lipid formulations of AMB. RESULTS: Data from 64 patients were included (32 patients per group). The demographic characteristics were comparable between the ABLC and L-AMB groups (median ages, 47.5 and 53.0 years, respectively; male, 44% and 53%; white, 75% and 78%; median weight, 67 and 78 kg; active underlying malignancy, 84% and 78%). There were no significant between-group differences in cumulative dose (6 and 7 g), median daily dose (both, 5 mg/kg), or median duration of treatment (19.5 and 19.0 days). Abnormal results (>5 x from baseline) on LFT were found in 12 (38%) and 10 (31%) patients who received ABLC and L-AMB, respectively, but these findings were thought to be associated with concomitant use of triazoles (4/12 [33%] and 1/10 [10%] patients, respectively), hepatotoxic antibiotics (8/12 [67%] and 5/10 [50%]), and/or other hepatotoxic medications (2/12 [17%] and 1/10 [10%]). Nonspecific abnormalities were observed on histopathology in 94% of patients. There was no evidence of histopathologic abnormalities reported in animal toxicity studies of lipid AMB, such as macrophage vacuolation or multifocal hepatocellular necrosis. CONCLUSIONS: Although abnormal results on LFT and/or histopathologic changes in liver were found in 92% of these debilitated patients with hematologic malignancy, direct histopathologic evidence of toxicity associated with lipid formulations of AMB was not established in our study.

One-year follow-up of very preterm infants who received lucinactant for prevention of respiratory distress syndrome: results from 2 multicenter randomized, controlled trials.

BACKGROUND: The benefits of exogenous surfactants for prevention or treatment of respiratory distress syndrome are well established, but there is a paucity of long-term follow-up data from surfactant-comparison trials. OBJECTIVE: We sought to determine and compare survival and pulmonary and neurodevelopmental outcomes through 1 year corrected age of preterm infants who received lucinactant and other surfactants in the SELECT (Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial) and STAR (Surfaxin Therapy Against Respiratory Distress Syndrome) trials individually and, secondarily, from analysis using combined data from these 2 trials. METHODS: All infants from both trials who were randomly assigned to administration of lucinactant (175 mg/kg), colfosceril palmitate (67.5 mg/kg), beractant (100 mg/kg), or poractant alfa (175 mg/kg) were prospectively followed through 1 year corrected age, at which point masked assessment of outcomes was performed for surviving infants. One-year survival was a key outcome of interest. Other parameters assessed included rates of rehospitalization and respiratory morbidity and gross neurologic status. Data were analyzed by comparing the different surfactants within each trial and, in secondary analysis, combining data from both trials to compare lucinactant versus the animal-derived surfactants (beractant and poractant) used in these trials. Survival rates over time were compared by using the Wilcoxon test for survival through 1 year corrected age and logistic regression for comparison of fixed time points. The latter analyses were performed by using the prespecified approach, where loss to follow-up or withdrawal of consent was imputed as a death, and also using raw data. Other outcomes were analyzed by using the Cochran-Mantel-Haenszel test or logistic regression for categorical data, and analysis of variance on ranks was used for continuous data. RESULTS: Very few cases were lost to follow-up in either trial (29 of 1546 enrolled in both trials [1.9%]). In the primary analysis of the SELECT trial comparing lucinactant to either colfosceril or beractant, there were no significant differences in the proportion of infants who were alive through 1 year corrected age. Fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 28.1% for lucinactant, 31.0% for colfosceril, and 31.0% for beractant. By using raw data without imputing loss to follow-up as a death, mortality estimates at 1 year corrected age were computed to be 26.6%, 29.1%, and 28.3%, respectively. In the primary analysis of the STAR trial, significantly more infants treated with lucinactant were alive through 1 year corrected age compared with those who received poractant alfa. Fixed time estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 19.4% for lucinactant and 24.2% for poractant. These estimates using raw data that did not impute loss to follow-up as a death were 18.6% and 21.9%, respectively. In the combined analysis, survival through 1 year corrected age was higher for infants in the lucinactant group versus that of the infants in the animal-derived surfactants (beractant and poractant) group. The fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death for lucinactant and animal-derived surfactants were 26.0% and 29.4%, respectively. However, the 1-year-corrected-age estimates using combined raw data were 24.6% for the lucinactant group and 26.7% for the animal-derived surfactant group. The incidence of postdischarge rehospitalizations, total number of rehospitalizations, incidence of respiratory illnesses, and total number of respiratory illnesses were generally similar among those in the treatment groups. Neurologic status at 1 year corrected age was essentially similar between infants who received lucinactant and those who received all other surfactants used in these 2 trials. CONCLUSIONS: Findings from this 1-year follow-up of both lucinactant trials indicate that this new peptide-based synthetic surfactant is at least as good, if not superior, to animal-derived surfactants for prevention of respiratory distress syndrome and may be a viable alternative to animal-derived products.

Amphotericin B-associated hyperbilirubinemia: case report and review of the literature.

A 53-year-old woman with an intraabdominal infection secondary to Candida albicans experienced hyperbilirubinemia after receiving amphotericin B in two different formulations--amphotericin B deoxycholate and amphotericin B lipid complex. Only a few case reports of amphotericin B-induced hyperbilirubinemia have been documented in the literature, each with different patterns of corresponding abnormalities in liver function tests. The unpredictable nature of this adverse effect warrants monitoring of bilirubin levels and liver function at baseline and potentially during therapy with amphotericin B, regardless of formulation, dosage, or duration of therapy.

What is the current and future status of conventional amphotericin B?

Amphotericin B deoxycholate has been the 'gold standard' treatment for invasive fungal infections for over 40 years. Driven to improve on the renal toxicity of amphotericin B deoxycholate, extensive pharmaceutical research has led to the development of several new antifungals including lipid formulations of amphotericin B, broad-spectrum azoles and echinocandins. Compared with amphotericin B deoxycholate, the lipid formulations of amphotericin B (amphotericin B lipid complex, amphotericin B colloidal dispersion and liposomal amphotericin B) share distinct advantages in improved drug safety, in particular reduced incidence and severity of amphotericin B deoxycholate-related nephrotoxicity. However, the lipid formulations of amphotericin B are significantly more expensive than amphotericin B deoxycholate and, as for many of these new antifungals, there are as yet insufficient published studies to guide clinicians. This paper examines aspects of safety, efficacy, and health economic data for the lipid formulations of amphotericin B in particular, in order to provide a rationale to justify substituting amphotericin B deoxycholate with the lipid formulations of amphotericin B.

Antifungal combination treatment: a future perspective.

The use of antifungal combination therapy is a new clinical approach for combating fungal infections. Although few conclusive clinical studies have been performed to date, data exist that strongly suggest that combination therapy would benefit specific patient subgroups (e.g. stem-cell transplant recipients). This paper examines the evidence available from in vitro, experimental, and clinical studies, and seeks to discover viable clinical strategies for this promising new therapeutic approach.

Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased risk for invasive fungal infections (IFIs) over prolonged periods of time. Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung transplant recipients as a convenient means of delivering protective drug to the upper airways avoiding systemic toxicities. The safety and tolerability of aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively investigated in an open-labeled, non-comparative study. Subjects received aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks; fluconazole was administered daily as standard of care through post-transplant day 100. Pulmonary mechanics were measured before and after each dose of inhaled ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough, nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC administrations; 5.2% of inhaled ABLC administrations were associated with >or=20% decrease in pulmonary function measurements (forced expiratory volume in 1 second or forced vital capacity) and none required treatment with bronchodilators or withdrawal from study. Four mild AEs were considered possibly or probably related to study treatment; no deaths or withdrawals from treatment were attributed to study drug. Of 3 proven IFIs occurring during the study period, only 1, a catheter-related case of disseminated fusariosis, occurred while the subject was receiving study medication. Aerosolized ABLC was well tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing IFI while receiving treatment, the combination of fluconazole and inhaled ABLC warrants further study as antifungal prophylaxis following allogeneic HSCT.

Effectiveness of amphotericin B lipid complex (ABLC) treatment in allogeneic hematopoietic cell transplant (HCT) recipients with invasive aspergillosis (IA).

A total of 85 allogeneic hematopoietic cell transplant (HCT) recipients with invasive aspergillosis treated with amphotericin B lipid complex (ABLC) were identified from the Collaborative Exchange of Antifungal Research (CLEAR) database. Of these patients, 78% (66/85) presented with pulmonary aspergillosis. Graft-versus-host disease (GVHD) was present in 24 of 85 patients. The response rate to ABLC was 31% (26/85) overall and 21% (5/24) in patients with GVHD. The overall response rate to first-line ABLC treatment was 41% (11/27). Four of nine (44%) patients with GVHD responded to first-line treatment with ABLC, while only one of 13 (8%) responded to ABLC as second-line therapy. Five of 18 (28%) and four of 14 (29%) patients, respectively, responded to sequential or concurrent treatment with ABLC and itraconazole. None of seven patients responded who continued receiving itraconazole after the start of ABLC therapy. At the end of ABLC therapy, serum creatinine had doubled in 12% of patients (10/85), and 2% (2/85) had developed a requirement for dialysis. These data suggest that ABLC, especially when administered as first-line therapy, can result in clinical response even in the most immunocompromised patients, that is, HCT recipients with GVHD, with minimal effects on renal function.

The hepatotoxicity of antifungal medications in bone marrow transplant recipients.

BACKGROUND: Systemic antifungal medications can be lifesaving but can also have important toxicities. With a number of new antifungal drugs being introduced, there is a compelling need to define the toxicities associated with existing therapies. METHODS: We identified cases of hepatotoxicity among patients who underwent bone marrow transplantation and selected matched control subjects from the same population. Multivariable logistic regression modeling was used to control for patient characteristics in evaluating the relationship between hepatotoxicity and exposure to antifungal medications. Follow-up analyses were performed for patients who continued receiving antifungal medications after developing hepatotoxicity. RESULTS: The unadjusted incidence of hepatotoxicity was 0.78 cases per 100 patient-days of exposure to amphotericin deoxycholate, 0.98 for fluconazole, and 1.50 for liposomal amphotericin B. Case-control analyses found that liposomal amphotericin B was associated with a substantial increase in the risk of hepatotoxicity in these patients (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.61-6.88); a smaller increase in risk was found for fluconazole (OR, 1.99; 95% CI, 1.21-3.26). There was no statistically significant association between amphotericin B deoxycholate and the development of hepatotoxicity. Patients had greater elevations of serum transaminase values associated with exposure to larger cumulative doses of liposomal amphotericin B. In the follow-up analysis of patients who developed hepatotoxicity and who continued receiving antifungal medication, one-third of those receiving liposomal amphotericin B had marked increases in bilirubin levels, as opposed to 8% of patients treated with fluconazole. CONCLUSIONS: In these bone marrow transplant recipients, liposomal amphotericin B and fluconazole were both associated with increased risk of hepatotoxicity, independent of other treatments received or patient characteristics; the magnitude of the risk was larger for liposomal amphotericin B. Patients who develop hepatotoxicity appear to tolerate continued therapy with fluconazole, but a large fraction of those who received liposomal amphotericin B have worsening conditions with continued treatment.

Treatment of non-Aspergillus moulds in immunocompromised patients, with amphotericin B lipid complex.

An assessment was made of the efficacy and renal safety of amphotericin B lipid complex (ABLC) in the treatment of patients with invasive fungal infections caused by moulds other than Aspergillus species, on the basis of a retrospective analysis of data from the Collaborative Exchange of Antifungal Research (CLEAR) database. Data from CLEAR for 64 patients with zygomycosis were published previously. The database was further queried and yielded results for 28 patients with fusariosis and 84 patients infected with other non-Aspergillus moulds. Of 26 patients with fusariosis whose results could be evaluated, 46% (n = 12) were cured or improved, and an additional 12% (n = 3) were stable. Of 79 patients infected with other non-Aspergillus moulds whose results could be evaluated, 61% (n = 48) were cured or improved, and an additional 15% (n = 12) were stable. In an area with little guidance for therapy, the CLEAR data indicate that ABLC can be an effective broad-spectrum treatment choice for several invasive and refractory non-Aspergillus mould infections.

Study of renal safety in amphotericin B lipid complex-treated patients.

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.

Efficacy and safety of amphotericin B lipid complex in 548 children and adolescents with invasive fungal infections.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Fatal fat embolism following amphotericin B lipid complex injection.

A case of amphotericin B lipid complex induced fatal fat embolism is described. A 41-year-old Caucasian man with AIDS was undergoing treatment for cryptococcal meningitis with amphotericin B. His course was complicated by renal failure necessitating a change in therapy to amphotericin B lipid complex (Abelcet). At approximately 48 h, the patient developed tachycardia, tachypnea, respiratory failure, decline in hematocrit, thrombocytopenia, and alteration in mental status. Autopsy findings included fat emboli involving heart, lungs, kidney, and brain. To our knowledge, this is the first case report of a fatal fat embolism caused by intravenous liposome drug delivery.

Assessment of nephrotoxicity in patients receiving amphotericin B lipid complex: a pharmacosurveillance study in Spain.

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.