The use of antibiotics is the single most important driver in antibiotic resistance. Nevertheless, antibiotic overuse remains common. Decline in antibiotic prescribing in the United States coincided with the launch of national educational campaigns in the 1990s and other interventions, including the introduction of routine infant immunizations with the pneumococcal conjugate vaccine (PCV-7); however, it is unknown if these trends have been sustained through recent measurements.

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as “antibiotic adjuvants” to enhance the activity of certain antibiotics.

This study describes a comprehensive programme designed to develop pharmacokinetic–pharmacodynamic (PK–PD) breakpoints for numerous antimicrobial classes against key Gram-negative aerobic bacteria. A 10 000 subject Monte Carlo simulation was constructed for 13 antimicrobials (21 dosing regimens). Published pharmacokinetic data and protein binding were varied according to log-normal and uniform distributions. MICs were fixed at single values from 0.03 to 64 mg/L. The PK–PD susceptible breakpoint was defined as the MIC at which the probability of target attainment was ≥90%. PK–PD, CLSI and European Committee on Antimicrobial Susceptibility Testing breakpoints were applied to MICs from the 2005 worldwide Meropenem Yearly Susceptibility Test Information Collection database to evaluate the impact of breakpoint discrepancies. PK–PD breakpoints were within one dilution of the CLSI and European breakpoints for all antimicrobials tested—with a few exceptions. When discrepancies were noted, the PK–PD breakpoint was lower than the CLSI breakpoint [ceftriaxone (0.5 versus 8 mg/L), ertapenem (0.25 versus 2 mg/L), ciprofloxacin (0.125 versus 1 mg/L) and levofloxacin (0.25–0.5 versus 2 mg/L)] and higher than the European breakpoint [ceftazidime (4–8 versus 1 mg/L), aztreonam (4–8 versus 1 mg/L), although ciprofloxacin was an exception to this pattern (0.125 versus 0.5–1 mg/L)]. For Enterobacteriaceae, breakpoint discrepancies resulted in modest (≤10%) differences in the percentages susceptible. In contrast, large (>15%) discrepancies were noted for Pseudomonas aeruginosa and Acinetobacter baumannii. Breakpoint agreement exists for imipenem, meropenem and the aminoglycosides. In contrast, discrepancies exist for piperacillin/tazobactam, cephalosporins, ertapenem, aztreonam and the fluoroquinolones. These discrepancies are most pronounced for P. aeruginosa and A. baumannii.

Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy.We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model.A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12–2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86–2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82–2.48) in the propensity score analysis.In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy.

Introduction: Antibiotic use is an important risk factor for Clostridium difficile infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed.