International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Aug 2011
Randomized Controlled TrialHigher than recommended amikacin loading doses achieve pharmacokinetic targets without associated toxicity.
Antibiotic therapy improves the outcome of severe sepsis and septic shock, however pharmacokinetic properties are altered in this scenario. Amikacin (AMK) is an option to treat community or nosocomial infections, although standard doses might be insufficient in critically ill patients. The aim of this study was to evaluate two AMK dosage regimens in comparison with standard therapy with regard to efficacy in achieving adequate plasma levels as well as safety. ⋯ A C(max)>60 μg/mL was reached by 39%, 76% and 0% of patients in Groups 1, 2 and 3, respectively (P<0.001) and creatinine clearance at Day 28 was 95.6±47.4, 89.7±26.6 and 56.4±18.4 mL/min, respectively. In conclusion, a 30 mg/kg daily dose of AMK presents significantly higher C(max) compared with the other groups, with 76% of patients reaching recommended peak plasma levels with no association with higher nephrotoxicity. Standard doses are insufficient in critically ill patients to reach the recommended C(max).
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Int. J. Antimicrob. Agents · Aug 2011
Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.
The objective of this study was to determine the pharmacokinetics and dosing recommendations of vancomycin in critically ill patients receiving continuous venovenous haemofiltration (CVVH). A prospective study was conducted in the Intensive Care Unit of a university hospital. Seven patients receiving CVVH with a triacetate hollow-fibre dialyser were enrolled. ⋯ In conclusion, elimination of vancomycin by CVVH contributed to ca. 50% of the total elimination in critically ill patients. The maintenance dose of vancomycin, calculated from parameters from patients in this study, would be 500-750 mg every 12 h to provide a steady-state trough concentration of 15-20 mg/L. Owing to alterations in clinical conditions, serum vancomycin concentrations must be closely monitored in critically ill patients.
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Int. J. Antimicrob. Agents · Jul 2011
Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008-2009).
Minimum inhibitory concentration (MIC) data from the SENTRY Antimicrobial Surveillance Program generated by reference methods were analysed to compare the antifungal resistance profiles and species distribution of Candida bloodstream infection (BSI) isolates obtained from patients in the Intensive Care Unit (ICU) and those from non-ICU locations. Results from 79 medical centres between 2008 and 2009 were tabulated. MIC values were obtained for anidulafungin, caspofungin, micafungin, fluconazole, posaconazole and voriconazole. ⋯ Candida glabrata was the only species in which resistance to azoles and echinocandins was noted, and this multidrug-resistant phenotype was found in both settings. In conclusion, the findings from this global survey indicate that invasive candidiasis can no longer be considered to be just an ICU-related infection, and efforts to design preventive and diagnostic strategies must be expanded to include other at-risk populations and hospital environments. Concern regarding C. glabrata must now include resistance to echinocandins as well as azole antifungal agents.
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Int. J. Antimicrob. Agents · Jun 2011
ReviewClinical implications of β-lactam-aminoglycoside synergism: systematic review of randomised trials.
β-Lactam-aminoglycoside combinations are commonly used despite lack of evidence of a clinical benefit. In this study, all randomised controlled trials (RCTs) assessing directly the clinical implications of synergism by comparing a β-lactam with the same β-lactam in combination with an aminoglycoside as empirical or definitive therapy for any type of infection and clinical scenario were compiled. A systematic search was undertaken to identify all trials regardless of language, date or publication status. ⋯ Combination therapy resulted in a significantly higher incidence of adverse events, mainly nephrotoxicity. Overall, no clinical benefit was found for the use of a β-lactam with an aminoglycoside compared with a β-lactam alone. Treatment with β-lactams as monotherapy entailed more antibiotic regimen modifications in open trials.