A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia

Division of Pulmonary and Critical Care, Washington University in St. Louis, San Luis, Missouri, United States
Clinical Therapeutics (Impact Factor: 2.73). 06/2007; 29(6):1107-15. DOI: 10.1016/j.clinthera.2007.06.014
Source: PubMed


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.

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    • "One major difficulty of antibiotic therapy is not only induction but also termination of therapy, especially in patients with renal insufficiency. Prolonged nephrotoxic therapy is one determinant of progressive renal impairment as was demonstrated for vancomycin [31], gentamicin [32], and tobramycin [33]. Comparing different percentages of SOP adherence by the Wilcoxon Mann-Whitney test, there was a significant change in impact on incidence of AKI, duration of treatment with the antibiotics, duration of mechanical ventilation, and length of first stay in the ICU. Figure 2 shows the dependence between duration of treatment of the first pneumonia episode, duration on ventilation, length of stay in the ICU, and percentage of SOP adherence. "
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    ABSTRACT: IntroductionAcute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI.MethodsThis study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charité – Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05).ResultsLAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039).ConclusionLow adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI.Trial registrationCurrent Controlled Trials ISRCTN54598675. Registered 17 August 2007.
    Critical care (London, England) 06/2014; 18(3):R120. DOI:10.1186/cc13918 · 4.48 Impact Factor
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    • "In terms of safety, several investigations indicate that vancomycin serum levels > 15 μg/mL [5,7], and particularly > 20 μg/mL [8], can result in significant nephrotoxicity. Using Monte Carlo simulation and a pharmacokinetic/pharmacodynamic model derived from patient data, Patel et al. [9] suggested that for infections due to S. aureus with MIC values ≥ 1 μg/mL, vancomycin doses with an acceptable probability of AUC/MIC target attainment would result in unacceptable levels of nephrotoxicity. "
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    ABSTRACT: Existing data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving target trough levels are used. A retrospective, post hoc, subgroup analysis of prospectively collected data from the Phase 3 ATTAIN trials of telavancin versus vancomycin for treatment of nosocomial pneumonia was conducted to further investigate the relationship between vancomycin serum trough levels and patient outcome. Study patients were enrolled in 274 study sites across 38 countries. A total of 98 patients had Staphylococcus aureus nosocomial pneumonia and vancomycin serum trough levels available. These patients were grouped according to their median vancomycin trough level; < 10 mug/mL, 10 mug/mL to < 15 mug/mL, and >= 15 mug/mL. Clinical cure rates in the < 10 mug/mL, 10 mug/mL to < 15 mug/mL, and >= 15 mug/mL vancomycin trough level groups were 70% (21/30), 55% (18/33), and 49% (17/35), respectively (p = 0.09), and the frequencies of patient death were 10% (3/30), 15% (5/33), and 20% (7/35), respectively (p = 0.31). Renal adverse events were more frequent in the >= 15 mug/mL (17% [6/35]) than the < 10 mug/mL (0%) and 10 mug/mL to < 15 mug/mL (3% [1/33]) trough level groups (p < 0.01). When patients with acute renal failure or vancomycin exposure within 7 days prior to study medication were excluded, clinical cure rates in the < 10 mug/mL, 10 mug/mL to < 15 mug/mL, and >= 15 mug/mL vancomycin trough level groups (71% [12/17], 60% [9/15], and 27% [3/11], respectively; p = 0.04) and the number of deaths (12% [2/17], 20% [3/15], and 45% [5/11], respectively; p = 0.07) demonstrated a trend towards worse outcomes in the higher vancomycin trough level groups. The findings of our study suggest that higher vancomycin trough levels do not result in improved clinical response but likely increase the incidence of nephrotoxicity.Trial registration: NCT00107952 and NCT00124020.
    BMC Infectious Diseases 04/2014; 14(1):183. DOI:10.1186/1471-2334-14-183 · 2.61 Impact Factor
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    • "Vancomycin has long been the workhorse agent for management of infections due to methicillin-resistant Staphylococcus aureus (MRSA); however, its clinical use is limited by nephrotoxicity [1–10]. While older data suggested that nephrotoxicity was initially associated with impurities in original formulations [1, 11], newer data suggest that nephrotoxicity is associated with risk factors, including patient-specific risk factors [8, 9], concurrent nephrotoxins [5–7, 10] and greater vancomycin exposures [2, 3]. Risk factor identification has greatly improved the ability of clinicians to determine which patients are at high risk for nephrotoxicity. "
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    ABSTRACT: Introduction: Little is known regarding age-related risk of nephrotoxicity during vancomycin therapy after the publication of the 2009 vancomycin consensus guidelines for therapeutic drug monitoring. We sought to evaluate incidence and risk factors for acute kidney injury in three age groups. Methods: Matched cohort study of patients receiving vancomycin, grouped by age: young adults (18-64 years), older adults (65-79 years) and very elderly (≥80 years), matched on previously published risk factors for nephrotoxicity. Outcomes included traditional vancomycin nephrotoxicity and Acute Kidney Injury Network-modified definition of nephrotoxicity. Results: The incidence of acute kidney injury was 34.1% vs. 34.1% vs. 31.8% in the young, older adults and very elderly groups, respectively (p = 0.97). In the logistic regression model, after adjusting for baseline risk factors, age was not a significant predictor of acute kidney injury. Lower respiratory tract infection (adjusted odds ratio [aOR] 5.18; 95% confidence interval [CI] 2.15-12.41) and duration of treatment (aOR 1.12; 95% CI 1.03-1.22) were found to be independently associated with outcome. Conclusion: No differences in risk of acute kidney injury were identified between young, older, and very elderly adults when adjusting for other risk factors. Further research is required to identify strategies to optimize the safety of vancomycin in the aging population.
    12/2013; 2(2):201-8. DOI:10.1007/s40121-013-0022-6
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