Estimating creatinine clearance: a meta-analysis.

Pharmacotherapy. 2011 Jul;31(7):658-64

Authors: Wilhelm SM, Kale-Pradhan PB

Abstract
STUDY OBJECTIVES: To determine which body weight descriptor most accurately predicts measured creatinine clearance (Cl(cr)) and whether rounding serum creatinine concentration (S(cr)) to 1 mg/dl when it is less than 1 mg/dl accurately predicts measured Cl(cr).
DESIGN: Meta-analysis of 13 English-language trials comparing 24-hour measured Cl(cr) with Cockcroft-Gault estimated Cl(cr) by using various body weights or rounded S(cr) values.
PATIENTS: A total of 1197 patients (mean age 53.3 yrs, 48.7% male) were included in the meta-analysis.
MEASUREMENTS AND MAIN RESULTS: A thorough literature search of the PubMed, MEDLINE, and the Cochrane Library databases was performed (1976-June 2010) to identify relevant clinical trials. Patient population, number of subjects, age, and 24-hour measured and estimated Cl(cr) were extracted independently by two investigators by using standardized data collection forms. Mean difference (MD) between estimated and measured Cl(cr) was assessed. Thirteen studies met all selection criteria. A random-effects model was applied secondary to a high level of heterogeneity among the studies (I(2)>50%). Total body weight in the Cockcroft-Gault equation overestimated measured Cl(cr) (MD 15.91 ml/min, 95% confidence interval [CI] 7.17-24.65 ml/min). Ideal body weight underestimated Cl(cr) (MD-5.15 ml/min, 95% CI -9.92 to -0.38 ml/min). No body weight (i.e., assumes body weight is 72 kg, thus removing the factor of 72 from the denominator of the equation) closely estimated Cl(cr) (MD 0.43 ml/min, 95% CI -5.42-6.27 ml/min). Adjusted body weight with correction factors of 0.3 or 0.4 also closely estimated Cl(cr) (MD 4.55 ml/min, 95% CI -11.41-20.50 ml/min, and MD 19.94 ml/min, 95% CI -9.6-49.49 ml/min, respectively). Total body weight with a rounded S(cr) value closely estimated measured Cl(cr) (MD 3.51 ml/min, 95% CI -17.18-24.20 ml/min). Ideal body weight with a rounded S(cr) value underestimated Cl(cr) (MD -29.45 ml/min, 95% CI -48.46 to -10.43).
CONCLUSION: Using the Cockcroft-Gault equation with no body weight and actual S(cr) value most closely estimated measured Cl(cr). In obese patients, it may be reasonable to use actual body weight with a correction factor of 0.3 or 0.4 and actual S(cr) value in the Cockcroft-Gault equation. Based on this analysis, the use of total body weight, ideal body weight, and a rounded S(cr) value cannot be recommended.

PMID: 21923452 [PubMed - indexed for MEDLINE]

Safety of daptomycin in patients receiving hemodialysis.

Pharmacotherapy. 2011 Jul;31(7):665-72

Authors: Mueller BA, Crompton JA, Donovan BJ, Yankalev S, Lamp KC

Abstract
STUDY OBJECTIVE: To determine the safety of daptomycin administered using a variety of doses and dosing frequencies in patients receiving intermittent hemodialysis who had probable or confirmed gram-positive infections.
DESIGN: Analysis of data from the Cubicin Outcomes Registry and Experience (CORE), a multicenter, retrospective, observational registry.
SETTING: Fifty-four study sites, mostly (46%) large teaching hospitals.
PATIENTS: Three hundred ninety-three adults in the CORE registry who received intermittent hemodialysis between 2005 and 2008.
MEASUREMENTS AND MAIN RESULTS: The CORE registry is noninterventional and collects standard-of-care data on daptomycin treatment from health care institutions. Of the 393 patients, 370 (94%) could be categorized by daptomycin dosing frequency: every 48 hours (251 patients [64%]), 3 times/week (87 [22%]), and every 24 hours (32 [8%]); the remaining 23 (6%) had unreported dosing frequencies or received a single dose of daptomycin. Three hundred eighty-four patients (98%) received part of their daptomycin therapy as an inpatient and 129 patients (33%) received part of their daptomycin therapy in an intensive care setting. The primary infection type was bacteremia (224 patients [57%]), and the most common pathogen was Staphylococcus aureus (155 patients [39%]). Thirty-eight adverse events possibly related to daptomycin occurred in 28 patients (7%); increased blood creatine kinase level (7 patients [1.8%]) was the most common adverse event. Adverse-event rates were similar across all dosing regimens.
CONCLUSION: In these patients undergoing hemodialysis, daptomycin was a well-tolerated treatment for gram-positive infections across several doses and dosing frequencies. Further study in prospective trials is warranted.

PMID: 21923453 [PubMed - indexed for MEDLINE]

Empiric antifungal therapy in patients with febrile neutropenia.

Pharmacotherapy. 2011 Apr;31(4):369-85

Authors: Ferrara JJ, Macdougall C, Gallagher JC

Abstract Invasive fungal infections, most commonly candidiasis or aspergillosis, are a major cause of morbidity and mortality among patients with neutropenia. Difficulty in diagnosing invasive fungal infections in these patients complicates decisions regarding pharmacotherapy. Because of the difficult diagnosis and the significant morbidity and mortality of fungal infections in patients with neutropenia, systemic antifungal agents are used as empiric antifungal therapy in patients with febrile neutropenia who are not responding to antibacterial therapy. The pharmacotherapy of invasive fungal infections has evolved rapidly within the past several years as numerous antifungal agents-different formulations of amphotericin B, azoles, and echinocandins-have become available for use as empiric antifungal therapy in patients with febrile neutropenia. Various levels of evidence support the use of these agents for this indication. Their use is limited, however, by drug intolerance, drug interactions, adverse-event profiles, and limited activity with some mold species. Thus, considerations for selecting an antifungal drug for empiric use in patients with febrile neutropenia should include the epidemiology of fungal infections in the individual patient's institution and the specific clinical circumstances of the patient.

PMID: 21449626 [PubMed - in process]