A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia
ABSTRACT The goal of this investigation was to determine whether more aggressive vancomycin dosing is associated with greater risk for renal toxicity in patients with health care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA).
This was a retrospective, single-center, observational cohort study. The following information was obtained for all study patients from automated hospital, microbiology, and pharmacy databases: age, sex, weight, serial serum creatinine (SCr), age- and sex-adjusted creatinine clearance (CrCl) during receipt of vancomycin, vancomycin serum trough concentrations, duration of vancomycin therapy, and Acute Physiology and Chronic Health Evaluation II scores. Renal toxicity was defined as either a 0.5-mg/dL increase from baseline in SCr or a >or=50% increase in SCr based on serial SCr measurements. Data for patients who met the definition of renal toxicity were compared with data for those who did not.
Ninety-four patients (mean [SD]age, 59.0 [15.6] years; 59 [62.8%] men; 73 (77.7%) white; mean baseline CrCl, 70.3 [23.0] mL/min) were identified as having MRSA HCAP. Forty (42.6%) patients developed renal toxicity. Patients who developed renal toxicity were significantly more likely than patients who did not develop renal toxicity to have greater mean vancomycin serum trough concentrations (20.8 [9.9] g/mL vs 14.3 [6.7] g/mL, respectively; P < 0.001), vancomycin serum trough concentrations >or=15 g/mL (67.5% vs 40.7%; P = 0.01), and a prolonged duration (>or=14 days) of vancomycin treatment (45.0% vs 20.4%; P = 0.011). Logistic regression analysis identified a maximum vancomycin serum trough concentration of >or=15 g/mL as being independently associated with renal toxicity (adjusted odds ratio = 2.82; 95% CI, 1.02-7.74; P = 0.045). The overall mean change in CrCl for the study population was -13.5 (-16.0) mL/min (range, 0.0 to -62.6 mL/min). Patients with maximum measured vancomycin serum trough concentrations >or=15 g/mL (n = 49) had significantly greater absolute changes in CrCl compared with patients with maximum measured vancomycin serum trough concentrations <15 g/mL (n = 45) (-18.9 [-17.0] vs -7.6 [-12.5] mL/min, respectively; P < 0.001).
The results suggest that aggressive vancomycin dosing and prolonged vancomycin administration may be associated with greater risk for renal toxicity in patients with MRSA HCAP. However, this retrospective study cannot establish causation, and a prospective, randomized, double-blind trial is needed.
Article: Reply to TarchiniClinical Infectious Diseases 05/2011; 52(11):1391-1392. DOI:10.1093/cid/cir193 · 9.42 Impact Factor
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ABSTRACT: This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged.International Journal of Nanomedicine 01/2015; 10:885-91. DOI:10.2147/IJN.S78675 · 4.20 Impact Factor
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ABSTRACT: Clinical management of community-acquired pneumonia (CAP) is increasingly complicated by antibiotic resistance. CAP due to pathogens resistant to guideline-recommended drugs (CAP-DRP) has increased. 2005 ATS/IDSA guidelines introduced a new category, healthcare-associated pneumonia (HCAP), and recommend extended-spectrum antibiotic treatment for patients meeting HCAP criteria. However, the predictive value of the HCAP model is limited and data suggest that outcomes are not improved using HCAP guideline-concordant therapy. Better methods to predict risk of CAP-DRP are needed. We reviewed currently published literature on the performance status of HCAP as a predictive tool and studies describing additional risk factors for CAP-DRP. We also summarize the performance characteristics of the currently published alternative clinical prediction scores and compare them to that of the HCAP model. In addition to the five risk factors incorporated in HCAP, at least 13 other factors have been identified. The independent predictive value of any single factor is low, but accumulating factors results in increased risk of CAP-DRP. The performance characteristics of 9 clinical prediction scores are reviewed. Nearly all of the scores outperformed HCAP in their study populations. However, no single model has yet demonstrated adequate specificity to minimize unnecessary antibiotic use, while retaining sufficient sensitivity to prevent inadequate initial empiric antibiotic therapy when validated across a wide range of CAP-DRP prevalence. Additional development and validation of prediction scores based upon more refined risk factors for CAP-DRP is needed. Once an accurate, adequately validated prediction score is available, an interventional trial will be needed to determine clinical impact. Copyright © 2014 Elsevier Ltd. All rights reserved.Respiratory Medicine 11/2014; 109(1). DOI:10.1016/j.rmed.2014.10.017 · 2.92 Impact Factor