Predictors of Antimicrobial Stewardship Program Recommendation Disagreement.

OBJECTIVETo identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children's hospital.DESIGNRetrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.METHODSThe ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.RESULTSIn total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99-15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08-18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92-19.77), or had been admitted for 31-90 days at the time of the audit (OR, 2.08; 95% CI, 1.36-3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01-1.04).CONCLUSIONSEvaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.Infect Control Hosp Epidemiol 2018;806-813.

Ultrasensitive detection of drug-resistant pandemic 2009 (H1N1) influenza A virus by rare-variant-sensitive high-resolution melting-curve analysis.

Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Although a majority of 2009 (H1N1) influenza A virus remains oseltamivir susceptible, the threat of resistance due to the His275Tyr mutation is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A virus population. In order to better understand the emergence of resistance, we developed a rare-variant-sensitive high-resolution melting-curve analysis method (RVS-HRM) that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultrasensitive detection of influenza A virus N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pretreatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients naive to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.

Real-time PCR testing for mecA reduces vancomycin usage and length of hospitalization for patients infected with methicillin-sensitive staphylococci.

Nucleic acid amplification tests (NAATs) have revolutionized infectious disease diagnosis, allowing for the rapid and sensitive identification of pathogens in clinical specimens. Real-time PCR testing for the mecA gene (mecA PCR), which confers methicillin resistance in staphylococci, has the added potential to reduce antibiotic usage, improve clinical outcomes, lower health care costs, and avoid emergence of drug resistance. A retrospective study was performed to identify patients infected with methicillin-sensitive staphylococcal isolates who were receiving vancomycin treatment when susceptibility results became available. Vancomycin treatment and length of hospitalization were compared in these patients for a 6-month period before and after implementation of mecA PCR. Among 65 and 94 patients identified before and after mecA PCR, respectively, vancomycin usage (measured in days on therapy) declined from a median of 3 days (range, 1 to 44 days) in the pre-PCR period to 1 day (range, 0 to 18 days) in the post-PCR period (P < 0.0001). In total, 38.5% (25/65) of patients were switched to beta-lactam therapy in the pre-PCR period, compared to 61.7% (58/94) in the post-PCR period (P = 0.004). Patient hospitalization days also declined from a median of 8 days (range, 1 to 47 days) in the pre-PCR period to 5 days (range, 0 to 42 days) in the post-PCR period (P = 0.03). Real-time PCR testing for mecA is an effective tool for reducing vancomycin usage and length of stay of hospitalized patients infected with methicillin-sensitive staphylococci. In the face of ever-rising health care expenditures in the United States, these findings have important implications for improving outcomes and decreasing costs.