Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Dec 2014
Propensity-based study of aminoglycoside nephrotoxicity in patients with severe sepsis or septic shock.
To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. ⋯ AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.
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Antimicrob. Agents Chemother. · Nov 2014
Validation of a model to predict the risk of nephrotoxicity in patients receiving colistin.
Despite concerns about its nephrotoxicity, colistin often remains the only effective agent for treating multidrug-resistant Gram-negative infections. Published studies have reported a wide range of nephrotoxicity risk factors. To assess the clinical utility of various models, we compared their performances for predicting the risk of nephrotoxicity. We identified a model demonstrating reasonable overall risk assessment, with an observed/expected ratio of 1.29 (95% confidence interval [CI], 0.68 to 1.90) and a positive predictive value of 87.5% for identifying patients at high risk of developing nephrotoxicity.
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Antimicrob. Agents Chemother. · Nov 2014
In vitro susceptibility of Mycobacterium tuberculosis isolates to an oral carbapenem alone or in combination with β-lactamase inhibitors.
We evaluated the antituberculosis (anti-TB) activity of five β-lactams alone or in combination with β-lactamase inhibitors against 41 clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains. Of those, tebipenem, an oral carbapenem, showed the most potent anti-TB activity against clinical isolates, with a MIC range of 0.125 to 8 μg/ml, which is achievable in the human blood. More importantly, in the presence of clavulanate, MIC values of tebipenem declined to 2 μg/ml or less.
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Antimicrob. Agents Chemother. · Nov 2014
Impact of hypoalbuminemia on voriconazole pharmacokinetics in critically ill adult patients.
Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.9 mg/liter, and 9.0 mg/liter (66 samples from 22 patients). Plasma albumin concentrations ranged from 13.8 to 38.7 g/liter. ⋯ Assuming 50% protein binding on average and an upper limit of 5.5 mg/liter for total voriconazole concentrations, the upper limit for unbound voriconazole concentrations is 2.75 mg/liter. Alterations in voriconazole unbound concentrations caused by hypoalbuminemia and/or elevated bilirubin plasma concentrations cannot be countered immediately, due to the adult saturated hepatic metabolism. Consequently, increased unbound voriconazole concentrations can possibly cause adverse events, even when total voriconazole concentrations are within the reference range.
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Antimicrob. Agents Chemother. · Oct 2014
Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors.
Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. ⋯ CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.