No abstract

These data confirm the potent in vitro activity of fidaxomicin against C. difficile. Moreover, this study provides an important baseline for ongoing long-term surveillance of antimicrobial resistance and prospective tracking of prominent and emerging strain types.

The best screening method for detecting heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) remains unclear. Using population analysis profiling utilizing the area under the concentration-time curve (PAP-AUC) as the gold standard, we screened 458 consecutive methicillin-resistant S. aureus (MRSA) bloodstream isolates to determine the most accurate and cost-effective testing strategy to detect the presence of heteroresistance. All isolates were also tested using the macromethod Etest (MET) and glycopeptide resistance detection (GRD) Etest. The MIC was determined by several methods, including standard vancomycin Etest, vancomycin broth microdilution (BMD), and Vitek2 testing. Fifty-five (12%) hVISA and 4 (1%) VISA isolates were detected by PAP-AUC. Compared to PAP-AUC, the sensitivities and specificities of MET, GRD Etest, BMD (using a MIC cutoff of >2 mg/liter), and standard vancomycin Etest (using a MIC cutoff of >2 mg/liter) were 89 and 55%, 71 and 94%, 82 and 97%, and 71 and 94%, respectively. Combination testing increased the overall testing accuracy by reducing the number of false-positive results. Cost was determined predominately by the number of PAP-AUC runs required following a screening assay. The most cost-effective strategy was BMD (using a MIC cutoff of >2 g/ml) as a standalone assay or in combination with PAP-AUC, provided that BMD testing was batched. GRD Etest remained an alternative, with 71% of hVISA isolates detected. Prevalence influenced both cost and test accuracy, with results remaining unchanged for hVISA prevalences of up to 25%. Implementation of any testing strategy would therefore be dependent on balancing cost with accuracy in a given population and clinical context.

Differences between the features of invasive community-onset methicillin-resistant Staphylococcus aureus (cMRSA) and methicillin-susceptible S. aureus (cMSSA) infections are incompletely understood. Fifty-seven patients with invasive cMRSA infection were prospectively identified at two teaching hospitals; for each cMRSA case, two cases of invasive cMSSA infection acted as controls. The primary outcome was 30-day all-cause mortality. Patients with invasive cMRSA infection were more likely to be Aboriginal (25% vs. 14%, age-adjusted odds ratio [OR] 2.5, p = 0.037), reside in a long-term care facility and/or have been hospitalised in the previous year (51% vs. 34%, p = 0.04) and less likely to have endocarditis (2% vs. 12%, p = 0.02) or require admission to an intensive care unit or high-dependency area (7% vs. 21%, p = 0.02). All-cause mortality at 30 days was similar in the cMRSA and cMSSA groups (9% vs. 7%, p = 0.68). Panton-Valentine leukocidin (PVL) genes were detected in a similar proportion of cMRSA and cMSSA isolates (32% vs. 27%, p = 0.49) and the presence of PVL genes was associated with younger age (35 years vs. 55 years, p < 0.001), Aboriginal ethnicity (38% vs. 10%, p < 0.001), skin and soft-tissue infection (54% vs. 19%, p < 0.001), lower illness severity at presentation (SAPS II score 9 vs. 21, p = 0.001) and shorter hospitalisation (9 days vs. 24 days, p < 0.001). Patients with "PVL-positive" and "PVL-negative" S. aureus infection had similar 30-day all-cause mortality (4% vs. 9%, p = 0.28). Few clinical features differentiated patients with invasive cMRSA infection from those with infection caused by cMSSA. Invasive "PVL-positive" S. aureus infection was associated with less morbidity but similar mortality to "PVL-negative" infection.