We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome.

Objective: To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality. Design and setting: Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web‐based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008. Main outcome measure: 30‐day all‐cause mortality. Results: 1994 episodes of S. aureus bacteraemia were identified, and complete 30‐day follow‐up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%–63.0%). Methicillin‐resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%–25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community‐associated MRSA. All‐cause mortality at 30 days was 20.6% (95% CI, 18.8%–22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non‐β‐lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device‐associated infection with a secondary focus, left‐sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection. Conclusions: S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life‐threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web‐based surveillance of S. aureus bacteraemia and its outcomes is not only important but also easily achievable.

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of >400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of >400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P ‫؍‬ 0.132 and P ‫؍‬ 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P ‫؍‬ 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of >400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Staphylococcal infections are a common and significant clinical problem in medical practice. Most strains of Staphylococcus aureus are now resistant to penicillin, and methicillin-resistant strains of S. aureus (MRSA) are common in hospitals and are emerging in the community. Penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) remain the antibiotics of choice for the management of serious methicillin-susceptible S. aureus (MSSA) infections, but first generation cephalosporins (cefazolin, cephalothin and cephalexin), clindamycin, lincomycin and erythromycin have important therapeutic roles in less serious MSSA infections such as skin and soft tissue infections or in patients with penicillin hypersensitivity, although cephalosporins are contra-indicated in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm or anaphylaxis). All serious MRSA infections should be treated with parenteral vancomycin or, if the patient is vancomycin allergic, teicoplanin. Nosocomial strains of MRSA are typically multi-resistant (mrMRSA), and mrMRSA strains must always be treated with a combination of two oral antimicrobials, typically rifampicin and fusidic acid, because resistance develops rapidly if they are used as single agents. Most community-acquired strains of MRSA in Australia and New Zealand are non multiresistant (nmMRSA), and lincosamides (clindamycin, lincomycin) or cotrimoxazole are the antibiotics of choice for less serious nmMRSA infections such as skin and soft tissue infections. New antibiotics such as linezolid and quinupristin/dalfopristin have good antistaphylococcal activity but are very expensive and should be reserved for patients who fail on or are intolerant of conventional therapy or who have highly resistant strains such as hVISA (heterogenous vancomycin-intermediate S aureus).

Non-multiresistant MRSA infection, relatively frequently observed in Pacific Islanders in south-east Queensland, is now a risk for Caucasians as well, and is usually community acquired. Clinicians should consider taking microbiological specimens for culture and antimicrobial susceptibility testing in patients with suspected staphylococcal infections who are not responding to empirical therapy with beta-lactam antibiotics.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are emerging in southeast Queensland, Australia, but the incidence of carriage of CA-MRSA strains is unknown. The aim of this study was to assess the nasal carriage rate of S. aureus, including CA-MRSA strains, in the general adult population of southeast Queensland. 396 patients presenting to general practices in two Brisbane suburbs and 303 volunteers randomly selected from the electoral rolls in the same suburbs completed a medical questionnaire and had nasal swabs performed for S. aureus. All isolates of S. aureus underwent antibiotic susceptibility testing and single-nucleotide polymorphism (SNP) and binary typing, including determination of Panton-Valentine leukocidin (PVL). The nasal carriage rate of methicillin-susceptible S. aureus (MSSA) was 202/699 (28%), a rate similar to that found in other community-based nasal carriage studies. According to multivariate analysis, nasal carriage of S. aureus was associated with male sex, young adult age group and Caucasian ethnicity. Only two study isolates (one MSSA and one CA-MRSA) carried PVL. The nasal carriage rate of MRSA was low, at 5/699 (0.7%), and only two study participants (0.3%) had CA-MRSA strains. CA-MRSA is an emerging cause of infection in southeast Queensland, but as yet the incidence of carriage of CA-MRSA in the general community is low.

A once-daily regimen of cefazolin (2 g intravenously [iv]) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults. For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively. The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06). The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone. Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048). The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.

Non-multiresistant methicillin-resistant Staphylococcus aureus (nmMRSA) infections are emerging worldwide and are often community-associated. This prospective case-cohort study compares features of 96 nmMRSA clinical isolates with 96 matched multiresistant MRSA (mMRSA) and 192 matched methicillin-susceptible S. aureus (MSSA) clinical isolates. Seventy-four percent of nmMRSA infections were healthcare-associated. nmMRSA infections were much more likely to involve skin and soft tissue (skin and soft tissue infections; SSTIs) and were much less likely to be treated appropriately with antibiotics than MSSA or mMRSA infections. Panton-Valentine leukocidin (PVL) genes were detected in 55% of nmMRSA, 16% of MSSA and 2% of mMRSA isolates. Independent of the methicillin-resistance phenotype, 59% of PVL-positive SSTIs presented as furunculosis compared to only 10% of PVL-negative SSTIs. Patients with PVL-positive infections were much younger than patients with PVL-negative infections. The proportion of PVL-positive infections peaked in the 10-29 years old age group, followed by a linear decline.