Treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin-susceptible Staphylococcus aureus bloodstream infections.

Clinical preference for a semisynthetic penicillin (oxacillin or nafcillin) over cefazolin for deep-seated methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) perseveres despite limited data to support this approach. A retrospective cohort study of patients treated for MSSA BSI with either oxacillin or cefazolin was performed across two medical centers in Chicago, IL. The outcome measures included documented in-hospital treatment failure, all-cause in-hospital mortality, duration of MSSA BSI, and incidence of documented adverse events. Of 161 patients with MSSA BSI, 103 (64%) received cefazolin, and 58 (36%) received oxacillin. The identified sources of BSI were central line (37.9%), osteoarticular (18%), and skin and soft tissue (17.4%). Patients with endocarditis (29/52 [44.2%]) and other deep-seated infections (23/52 [55.8%]) were classified under the subset of deep-seated infections (52/161 [32.3%]). Multivariate models found deep-seated infection (adjusted odds ratio [aOR], 4.52; 95% confidence interval [CI], 1.23 to 16.6; P = 0.023), metastatic disease (aOR, 4.21; 95% CI, 1.13 to 15.7; P = 0.033), and intensive care unit (ICU) onset of infection (aOR, 4.80; 95% CI, 1.26 to 18.4; P = 0.022) to be independent risk factors for in-hospital treatment failure. Treatment group was not an independent predictor of failure (aOR, 3.76; 95% CI, 0.98 to 14.4; P = 0.053). The rates of treatment failure were similar among cefazolin-treated (5/32 [15.6%]) and oxacillin-treated (4/20 [20.0%]) patients (P = 0.72) in the subset of deep-seated infections. Mortality was observed in 1 (1%) and 3 (5.2%) cases of cefazolin- and oxacillin-treated patients, respectively (P = 0.13). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI.

Multicenter study of high-dose daptomycin for treatment of enterococcal infections.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis.

OBJECTIVES: Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥ 8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE. METHODS: This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥ 8 mg/kg/day (based on total body weight) for ≥ 72 h were included. RESULTS: Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations. CONCLUSIONS: Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.

Evaluation of a low, weight-based dose of rasburicase in adult patients for the treatment or prophylaxis of tumor lysis syndrome.

PURPOSE: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS. PATIENTS/METHODS: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS. RESULTS: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer's dosing recommendation. CONCLUSIONS: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.

BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

The effect of time to antifungal therapy on mortality in Candidemia associated septic shock.

The timely administration of appropriate antifungal therapy for Candida bloodstream infections (CBSI) improves clinical outcomes. However, little data exist on the effect of antifungal therapy in patients with septic shock and candidemia. We describe antifungal treatment of patients with septic shock due to CBSI and its impact on in-hospital mortality. We retrospectively reviewed medical records of hospitalized patients identified with at least one positive blood culture for Candida between January 2003 and June 2007. All septic shock patients received vasopressor therapy and had candidemia within 72 hours of refractory shock. Data collected included demographics, comorbidities, antibiotic exposure, in-hospital mortality, and intensive care-related factors. Acute Physiology and Chronic Health Evaluation II scores were calculated. Time to antifungal therapy was defined as the interval between time of collection of the first positive Candida blood culture and the time when appropriate antifungal therapy was initiated. Univariate and multivariate analyses were performed to identify variables associated with in-patient mortality. Classification and regression tree analysis was used to identify the mortality breakpoint between early and late antifungal therapy. Septic shock developed in 23% (31 of 135) patients with CBSI. In-hospital mortality was 68%. Nonalbicans Candida spp. accounted for 48% of blood isolates. Appropriate antifungal therapy was administered to 24 patients; 15 (63%) of these patients died. Classification and regression tree analysis revealed that patients who received appropriate antifungal therapy within 15 hours of collecting the first positive Candida blood culture had improved survival (P = 0.03). Early, appropriate antifungal therapy improves survival among patients with septic shock due to CBSI.

Faropenem medoxomil.

OBJECTIVE: To review the literature concerning the in vitro activity, pharmacokinetic properties, in vivo efficacy, and adverse events associated with a new penem antibiotic, faropenem medoxomil. DATA SOURCES: We conducted a search of MEDLINE/PubMed and International Pharmaceutical Abstracts databases for articles or abstracts using the terms faropenem, faropenem daloxate, faropenem medoxomil, SUN5555, SY5555, WY49605, RU67655, ALP201, BLA 857, and YM 044 and published through July 2007. Information on poster presentations was obtained from the drug's manufacturer. Additional articles were identified from citations in the bibliographies of review articles. Articles written in languages other than English were excluded. STUDY SELECTION AND DATA EXTRACTION: All published reports that evaluated faropenem (or its chemical synonyms) and faropenem medoxomil were used in this review. Abstracts subsequently published as full reports were excluded, and only the resulting reports were included. Abstracts without subsequently published reports were included. DATA SYNTHESIS: The in vitro activity of faropenem has been evaluated extensively against respiratory pathogens and less extensively against aerobic gram-positive, gram-negative, and anaerobic organisms. Prospective, randomized, multicenter clinical trials have demonstrated noninferiority of faropenem to comparators for the treatment of acute bacterial sinusitis, community-acquired pneumonia, acute exacerbation of chronic bronchitis, and uncomplicated skin and skin structure infections. Adverse events associated with faropenem appear to be minimal and include nausea, vomiting, and diarrhea. CONCLUSIONS: Faropenem has demonstrated excellent in vitro activity against common respiratory pathogens, many aerobic gram-positive organisms, and anaerobes. Activity against gram-negative organisms is more reserved. In vivo data suggest that faropenem is efficacious in treating community-acquired infections including uncomplicated skin and skin structure infections; however, more data may help to characterize faropenem's place in antimicrobial therapy. Replidyne, Inc., the manufacturer of faropenem, is conducting studies to address the Food and Drug Administration's concerns that resulted in a nonapprovable letter in October 2006.

Efficacy of ertapenem for consolidation therapy of extended-spectrum beta-lactamase-producing gram-negative infections: a case series report.

BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms are becoming increasingly common and present significant challenges in terms of treatment. Carbapenems is the antibiotic class of choice for treatment of these types of infections. Ertapenem is the newest carbapenem, capable of being dosed once daily, and has some in vitro but little in vivo evidence supporting its use for the treatment of these resistant infections. OBJECTIVE: To examine the clinical and microbiologic outcomes associated with ertapenem therapy of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis infections. METHODS: This was a retrospective case series that examined the clinical and microbiologic outcomes of 22 patients who received ertapenem for treatment of an ESBL infection at Rush University Medical Center in Chicago, IL, during 2003-2005. RESULTS: The majority (16/22) of patients received ertapenem for consolidation rather than initial therapy. Different antibiotics most commonly used were other carbapenems, piperacillin/tazobactam, and aminoglycosides. The most common infections treated were lower urinary tract infections and osteomyelitis. Clinical efficacy was determined in all 22 patients, with 20 (91%) patients having a positive outcome, defined as either clinical improvement or clinical cure. The best clinical cure rate was seen with wound infections, where all 3 patients examined were found to be clinically cured. Microbiologic efficacy was determined in 7 patients, with 6 (85.7%) defined as microbiologic cure. One patient was found to be both a clinical and microbiologic failure and was also found to have developed an ertapenem-resistant strain of E. coli. CONCLUSIONS: These results demonstrate potential microbiologic and clinical efficacy of ertapenem for treatment of ESBL-producing infections and the need for a prospective, randomized study examining its efficacy versus that of other carbapenems.

Antibiotic therapy of methicillin-resistant Staphylococcus aureus in critical care.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the critically ill patient is challenging. Data for treatment of critically ill patients are often lacking because many such patients are excluded from industry-sponsored prospective randomized clinical trials. Infections due to MRSA are common in the critical care setting. Up to 24% of patients in intensive care units are colonized with MRSA, and 20% of all nosocomial bloodstream infections are due to MRSA. It is also one of the leading bacterial causes of ventilator- and hospital-acquired pneumonia. Vancomycin has been the drug of choice for treatment of MRSA in the critical care setting. Recent data showing vancomycin resistance, increasing numbers of MRSA isolates with higher vancomycin minumum inhibitory concentrations, and an apparent increase in vancomycin clinical failures have brought vancomycin's utility into question. A variety of treatment options for MRSA are available. Quinupristin-dalfopristin was the first alternative to vancomycin. However, its safety profile and potential for drug interactions limit its use. Linezolid has been shown to be effective in the treatment of pneumonia and skin and skin-structure infections due to MRSA. The drug's potential to cause bone marrow suppression limits its use, especially in treatment durations extending beyond 14 days. Daptomycin has been shown to be effective for the treatment of MRSA bloodstream and of MRSA skin and skin-structure infections. Tigecycline is the newest available drug with MRSA activity. It has demonstrated noninferiority to vancomycin in skin and skin-structure infections. However, its role in the treatment of ventilator- and hospital-acquired pneumonia is still unclear.

Daptomycin for the treatment of gram-positive bacteremia and infective endocarditis: a retrospective case series of 31 patients.

STUDY OBJECTIVE: To evaluate the outcomes in patients with bacteremia and/or infective endocarditis who were treated with daptomycin. DESIGN: Retrospective chart review. SETTING: A university-affiliated medical center in Chicago, Illinois, and a regional hospital in Fountain Valley, California. PATIENTS: Thirty-one inpatients treated with daptomycin for bacteremia and/or infective endocarditis. MEASUREMENTS AND MAIN RESULTS: Patients were given daptomycin 4-6 mg/kg intravenously every 24-48 hours based on the practitioner's discretion and depending on the patient's clinical condition and presence of comorbidities. Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin-resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin-resistant entercocci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin-sensitive S. aureus infection and 1 patient had coagulasenegative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22-43 days) than that for bacteremia only (< or = 14 days), and no patients discontinued daptomycin because of adverse events. CONCLUSION: In these patients, daptomycin was safe and well tolerated even for extended durations of treatment. Daptomycin may provide an effective option for treating drug-resistant gram-positive bloodstream infections and endocarditis.

Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years.

BACKGROUND: Extremely low birth weight (ELBW) infants are exposed to many painful procedures while in the neonatal intensive care unit (NICU), such as catheter insertion and endotracheal intubation. Exposure of ELBW infants to repetitive pain and stress in the NICU can lead to cardiovascular instability and may alter neuronal and synaptic organization. Opioid analgesics are administered to reduce pain, stress and to potentially reduce poor neurologic outcomes. They may also be utilized as sedation for mechanically ventilated ELBW infants. There is limited data in regards to neurodevelopmental outcomes of preterm infants exposed to opioids, and available studies have conflicting results. OBJECTIVE: To examine the relationship between cumulative opioid dose in ELBW infants in the NICU and neurodevelopmental outcomes at 20 months corrected age (CA). STUDY DESIGN: 100 ELBW infants who had complete neurodevelopmental assessments at 20 months CA were categorized by cumulative opioid exposure during the NICU stay (high vs. low/no opioid). Outcome measures included cognitive, motor and language scores from the Bayley Scales of Infant and Toddler Development-III (BSITD-III). Multiple regression analyses adjusted for the impact of social and neonatal risk factors on outcome. RESULTS: There were 60 patients with high and 40 with low/no opioid exposure. Infants in the high dose group had a higher number of median ventilator days (53.5 vs. 45.6 days, p=0.046) and a higher incidence of necrotizing enterocolitis (5% vs. 21.7%, p=0.022). There were no significant differences in BSITD-III scores between the two opiate groups. In multivariate analysis cumulative opioid dose was associated with lower cognitive scores on the BSITD-III even after adjusting for social and neonatal risk factors (ß=-0.247, p=0.012). CONCLUSION: Cumulative opioid dose is associated with worse cognitive scores at 20 months CA even after adjusting for social and neonatal risk factors.

Use of daptomycin to treat drug-resistant Gram-positive bone and joint infections.

OBJECTIVE: Drug-resistant, Gram-positive bacteria are a growing concern in treating bone and joint infections, including osteomyelitis. This report describes the experience in a series of cases of the use of a novel antibiotic, daptomycin, for the treatment of bone and joint infections. RESEARCH DESIGN AND METHODS: This retrospective analysis included patients from two medical centers diagnosed with Gram-positive bone and joint infections and treated with daptomycin. RESULTS: A total of 10 patients were included in this report, of which nine received previous antibiotic therapy, including vancomycin, linezolid, and quinupristin/dalfopristin. Methicillin-resistant Staphylococcus aureus was isolated from eight patients while the remaining patients were infected with enterococci or streptococci. All patients initially resolved the infection while undergoing daptomycin treatment and were discharged from the hospital. One patient was switched to ampicillin (after receiving daptomycin for 4 days) once the infection was identified due to vancomycin-susceptible enterococcus. However, one patient was readmitted after 18 days due to a clinical relapse, possibly caused by under-dosing of daptomycin. CONCLUSION: Eight out of nine patients who received daptomycin for at least 8 days were successfully treated with the agent for Gram-positive bone and joint infections. Daptomycin was found to be well tolerated, even up to 44 days of treatment.

Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management.

Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

Effectiveness and feasibility of pharmacist-led admission medication reconciliation for geriatric patients.

PURPOSE: Pharmacists have been shown to improve medication reconciliation at hospital admission. Limited resources may obligate pharmacy departments to target resources for medication reconciliation rather than extend services to the entire hospital. We conducted a prospective, randomized, nonblinded assessment of the effectiveness and feasibility of pharmacist-led admission medication reconciliation for geriatric patients. METHODS: Eighty-one geriatric patients were randomized 1:1 to receive medication reconciliation per current hospital practice or to pharmacist-led medication reconciliation at admission. The primary end point was medication profile appropriateness by pharmacist review at 48 hours postadmission. Secondary end points involved in determining the impact and feasibility of this program. RESULTS: Pharmacist-led medication was superior to standard hospital practice, with 48% of controls and 71% of intervention patients having appropriate medication profiles at 48 hours postadmission (P = .033). Pharmacists identified 116 discrepancies among 81 patients including predominantly omissions (41%) and a composite of wrong dose, route, or frequency (35%). Pharmacists spent a median 15 minutes per patient. CONCLUSION: Pharmacists improved admission medication reconciliation for geriatric patients. Pharmacists identified a significant number of discrepancies, including predominantly omissions and wrong dose, dosage form, or frequency. Pharmacists' contributions to medication reconciliation could yield substantial benefit to patient care.

Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems? A review of the evidence.

The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram-negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem, a group 1 carbapenem, was introduced, questions were raised about the potential for ertapenem to select for imipenem- and meropenem-resistant Pseudomonas. Results from ten clinical studies evaluating the effect of ertapenem use on the susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem use does not result in decreased Pseudomonas susceptibility to these antipseudomonal carbapenems. Here we review these studies evaluating the evidence of how ertapenem use affects P. aeruginosa as well as provide considerations for ertapenem use in the context of institutional stewardship initiatives.

An evaluation of hepatotoxicity and nephrotoxicity of liposomal amphotericin B (L-AMB).

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