Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Dec 2019
Improved Antibiotic Prescribing within a Veterans Affairs Primary Care System through a Multifaceted Intervention Centered on Peer Comparison of Overall Antibiotic Prescribing Rates.
Reducing inappropriate outpatient antibiotic use is an important national goal. Limited data exist on targeted education and peer comparison of overall antibiotic prescribing rates as an antimicrobial stewardship strategy. Primary care professionals (PCPs) from all seven clinics within our health care system were offered an education session, followed by monthly e-mails with their antibiotic prescribing rate, peer prescribing rates, and a system target. ⋯ If an antibiotic was indicated, there were no significant differences in prescribing of guideline-discordant agents (21.4% [12/56] versus 19.1% [21/110] [P = 0.8]) or guideline-concordant agents for a guideline-discordant duration (38.6% [17/44] versus 39.3% [35/89] [P = 1]). There were significant reductions in azithromycin and fluoroquinolone prescriptions (50.9% and 59.4% [P values of <0.001], respectively), but most prescriptions for these agents in the intervention period remained inappropriate. Initial education followed by monthly peer comparison of overall antibiotic prescribing rates reduced total and unnecessary antibiotic prescribing in primary care clinics.
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Antimicrob. Agents Chemother. · Nov 2019
Plasmodium falciparum Kelch Propeller Polymorphisms in Clinical Isolates from Ghana from 2007 to 2016.
The continuous surveillance of polymorphisms in the kelch propeller domain of Plasmodium falciparum from Africa is important for the discovery of the actual markers of artemisinin resistance in the region. The information on the markers is crucial for control strategies involving chemotherapy and chemoprophylaxis for residents and nonimmune travelers to the country. Polymorphisms in the kelch propeller domain of Ghanaian malaria parasites from three different ecological zones at several time periods were assessed. ⋯ Three persisting nonsynonymous (NS) mutations, N599Y (0.005%), K607E (0.004%), and V637G (0.004%), were observed in 3 of the 5 time periods nationally. The presence of variants of the validated markers of artemisinin resistance as well as persisting polymorphisms after 14 years of artemisinin-based combination therapy use argues for continuous surveillance of the markers. The molecular markers of artemisinin resistance and the observed variants will be monitored subsequently as part of ongoing surveillance of antimalarial drug efficacy/resistance studies in the country.
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Antimicrob. Agents Chemother. · Oct 2019
Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.
Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). ⋯ The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (bla NDM and bla KPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.
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Antimicrob. Agents Chemother. · Sep 2019
Clinical and Microbiological Outcomes in Obese Patients Receiving Colistin for Carbapenem-Resistant Gram-Negative Bloodstream Infection.
Carbapenem-resistant infections are associated with poor outcomes, and treatment options are limited. Colistin is one of few antibiotics which retain in vitro activity against carbapenem-resistant pathogens. However, despite the availability of international consensus guidelines for the dosing of polymyxins, there are limited data on the effects of dosing on clinical outcomes among obese patients with carbapenem-resistant Gram-negative bacteremia. ⋯ No other secondary outcome differences were observed, though each outcome was numerically worse among obese patients. Obesity was not associated with differences in global cure rates. However, the difference in microbiological clearance warrants further investigation.
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Antimicrob. Agents Chemother. · Sep 2019
In Vivo Pharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models.
The pharmacokinetic (PK) and pharmacodynamic (PD) parameters which correlated with the in vivo efficacy of cefiderocol were evaluated using neutropenic murine thigh and lung infection models in which the infections were caused by a variety of Gram-negative bacilli. The dose fractionation study using the thigh infection model in which the infection was caused by Pseudomonas aeruginosa showed that the cumulative percentage of a 24-h period that the free drug concentration in plasma exceeds the MIC (%fT >MIC) rather than the free peak level divided by the MIC (fC max/MIC) and the area under the free concentration-time curve over 24 h divided by the MIC (fAUC/MIC) was the PK/PD parameter that best correlated with efficacy. ⋯ The mean %fT >MIC for Enterobacteriaceae, P. aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia in the lung infection model were 64.4%, 70.3%, 88.1%, and 53.9%, respectively. These results indicate that cefiderocol has potent efficacy against Gram-negative bacilli, including carbapenem-resistant strains, irrespective of the bacterial species, in neutropenic thigh and lung infection models and that the in vivo efficacy correlated with the in vitro MIC under iron-deficient conditions.