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Nephrotoxicity ..

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Various recent case series and an international prospective observational cohort study have shown that Staphylococcus aureus is now more commonly found as the causative organism in infective endocarditis (IE) than viridans group streptococci.1 This change has been linked to inferior outcomes in the treatment of IE.2 Standard therapy for IE caused by S. aureus includes either an antistaphylococcal penicillin or vancomycin with the option of adding low-dose gentamicin for the first 3 to 5 days of treatment.2 Early and effective antimicrobial therapy is necessary to improve the clinical course, however, controversy surrounds whether the use of gentamicin along with the standard treatment options recommended by the guidelines is helpful or harmful for the patient.

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A recent prospective cohort study by Cosgrove et al found the use of gentamicin combination therapy for S. aureus bacteremia and native valve IE to be nephrotoxic and discouraged its use for this indication.3 The authors analyzed data obtained from an open-label, randomized trial evaluating the effectiveness of daptomycin versus standard treatment.4 One study arm received standard therapy with most receiving initial low-dose gentamicin (n = 116) and the other treatment arm received daptomycin monotherapy (n = 120). This particular trial found that daptomycin was non-inferior to standard therapy for the treatment of IE. Daptomycin recipients had significantly higher rates of creatine kinase elevations and peripheral nervous system adverse events. The study revealed higher rates of renal impairment in the standard therapy group versus the daptomycin group; with a similar incidence between those receiving vancomycin plus gentamicin and patients on a penicillin plus gentamicin.4 The two groups of patients from the original study were evaluated. The cohorts were then rearranged to combine those patients that had received gentamicin as a study treatment with any patient that had received gentamicin ≤2 days before the study began. Two analyses were conducted. The first compared the incidence of renal function changes between both original treatment arms. The second analyzed the same changes in the rearranged cohort that included all patients in the trial that had been exposed to initial low-dose gentamicin. Outcomes measured included a decrease in creatinine clearance (CLCR) and the time to that decrease, and the number of patients with a sustained decrease in CLCR of 25% or 50%. The study also looked at the relationship between the gentamicin dosage regimen and renal impairment, as well as any risk factors for the development of decreased CLCR observed in this population.3

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Results in the original treatment arms displayed clinically significant decreases in CLCR for patients receiving standard therapy compared to patients receiving daptomycin (24% vs 8%, P = 0.002). As for the rearranged cohorts, patients in the gentamicin group had higher rates of clinically significant decreases in CLCR compared to those who had not received the aminoglycoside (22% vs 8%, P = 0.005). A sustained decrease in CLCR of 25% or 50% was significantly higher in the gentamicin ...

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