Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2014
Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis.
Drug efflux is an important resistance mechanism in Mycobacterium tuberculosis. We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of bedaquiline and clofazimine to M. tuberculosis by 8- to 16-fold. This exquisite susceptibility was noted among drug-susceptible and drug-resistant clinical isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and clofazimine, and efflux may emerge as a resistance mechanism to these drugs.
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Antimicrob. Agents Chemother. · Jan 2014
Pharmacokinetics of colistin methanesulfonate and formed colistin in end-stage renal disease patients receiving continuous ambulatory peritoneal dialysis.
Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as last-line therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. ⋯ Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients.
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Antimicrob. Agents Chemother. · Jan 2014
Activity of ceftolozane-tazobactam against a broad spectrum of recent clinical anaerobic isolates.
We evaluated in vitro activity of ceftolozane-tazobactam (TOL-TAZ), formerly CXA-201, against recent clinical anaerobic isolates with emphasis on the Bacteroides fragilis group. Ceftolozane-tazobactam showed good activity against B. fragilis species and intermediate to limited activity against other species of Bacteroides. Ceftolozane-tazobactam showed very good activity against Prevotella spp., Fusobacterium spp., and Propionibacterium spp., varying activities against Gram-positive cocci, and limited activity against Clostridium spp.
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Antimicrob. Agents Chemother. · Jan 2014
Single-dose pharmacokinetics of cidofovir in continuous venovenous hemofiltration.
Dosage recommendations for cidofovir are available for renally competent as well as impaired patients; however, there are no data for patients undergoing continuous renal replacement therapy. We determined the single-dose concentration-versus-time profile of cidofovir in a critically ill patient undergoing continuous venovenous hemofiltration (CVVH). One dose of 450 mg cidofovir (5 mg/kg) was administered intravenously due to a proven cytomegalovirus (CMV) infection and failure of first-line antiviral therapy. ⋯ Total removal of the drug was 30.99% after 24 h. Because of these data, which give us a rough idea of the concentration profile of cidofovir in patients undergoing CVVH, a toxic accumulation of the drug following repeated doses may be expected. Further trials have to be done to determine the right dosage of cidofovir in patients undergoing CVVH to avoid toxic accumulation of the drug.
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Antimicrob. Agents Chemother. · Jan 2014
In vivo efficacy of ceftaroline fosamil in a methicillin-resistant panton-valentine leukocidin-producing Staphylococcus aureus rabbit pneumonia model.
Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with broad-spectrum in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), and common Gram-negative pathogens. This study investigated the in vivo activity of ceftaroline fosamil compared with clindamycin, linezolid, and vancomycin in a severe pneumonia model due to MRSA-producing Panton-Valentine leukocidin (PVL). A USA300 PVL-positive clone was used to induce pneumonia in rabbits. ⋯ Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.