Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2014
Multicenter StudyClinical experience of colistin-glycopeptide combination in critically ill patients infected with Gram-negative bacteria.
A colistin-glycopeptide combination (CGC) has been shown in vitro to be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especially Acinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for ≥48 h. ⋯ Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for ≥5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P = 0.001) and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P = 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for ≥5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for ≥5 days.
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Antimicrob. Agents Chemother. · Jan 2014
Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis.
Little is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-cocultured Mycobacterium tuberculosis versus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. ⋯ The mean TDAs were 2.52 ± 0.76 in subjects converting to negative in ≤2 months and 1.88 ± 0.57 in subjects converting to negative in >2 months (P = 0.08). In Tanzania, MDR-TB drug concentrations were frequently low, and a wide concentration/MIC range was observed that affected plasma drug activity ex vivo. An opportunity exists for pharmacokinetic optimization in current MDR-TB regimens, which may improve treatment response.
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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
Daptomycin dosing based on ideal body weight versus actual body weight: comparison of clinical outcomes.
Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. ⋯ After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.
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Antimicrob. Agents Chemother. · Jan 2014
Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia.
Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor outcomes and frequently merits empirical antibiotic consideration despite its relatively low incidence. Nasal colonization with MRSA is associated with clinical MRSA infection and can be reliably detected using the nasal swab PCR assay. In this study, we evaluated the performance of the nasal swab MRSA PCR in predicting MRSA pneumonia. ⋯ The MRSA PCR assay demonstrated 88.0% sensitivity and 90.1% specificity, with a positive predictive value of 35.4% and a negative predictive value of 99.2%. In patients with pneumonia, the MRSA PCR nasal swab has a poor positive predictive value but an excellent negative predictive value for MRSA pneumonia in populations with low MRSA pneumonia incidence. In cases of culture-negative pneumonia where initial empirical antibiotics include an MRSA-active agent, a negative MRSA PCR swab can be reasonably used to guide antibiotic de-escalation.