Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago.

The efficacy of cefazolin with high-inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred as being due to an inoculum effect (InE). This study investigated the local prevalence of a cefazolin InE (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, IL, contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 h by the broth microdilution method using a standard inoculum (SI; 5 × 105 CFU/ml) and a high inoculum (HI; 5 × 107 CFU/ml). The CInE was defined as (i) a ≥4-fold increase in C-MIC between SI and HI and/or (ii) a pronounced CInE, i.e., a nonsusceptible C-MIC of ≥16 µg/ml at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate were susceptible to cefazolin at SI, and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ positive, with the blaZ types led by gene type C (40%). CInE was seen in 45 blaZ-positive isolates (23%), with 44 (22%) presenting a ≥4-fold increase in C-MIC (SI to HI) and 5 (3%) a pronounced CInE. Four of the five met both definitions of CInE, two of which expressed the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

Empirical therapy in Methicillin-resistant Staphylococcus Aureus infections: An Up-To-Date approach.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be an important pathogen worldwide, with high prevalence of infection in both community and hospital settings. Timely and appropriate choice of empirical therapy in the setting of MRSA infection is imperative due to the high rate of associated morbidity and mortality with MRSA infections. Initial choices should be made based on the site and severity of the infection, most notably moderate skin and soft tissue infections which may be treated with oral antibiotics (trimethoprim-sulfamethoxazole, clindamycin, doxycycline/minocycline, linezolid) in the outpatient setting, versus choice of parenteral therapy in the inpatient setting of more invasive or severe disease. Though the current recommendations continue to strongly rely on vancomycin as a standard empiric choice in the setting of severe/invasive infections, alternative therapies exist with studies supporting their non-inferiority. This includes the use of linezolid in pneumonia and severe skin and skin structure infections (SSSI) and daptomycin for MRSA bacteremia, endocarditis, SSSIs and bone/joint infections. Additionally, concerns continue to arise in regards to vancomycin, such as increasing isolate MICs, and relatively high rates of clinical failures with vancomycin. Thus, the growing interest in vanomycin alternatives, such as ceftaroline, ceftobribole, dalbavancin, oritavancin, and tedizolid, and their potential role in treating MRSA infections.

Multicenter study of high-dose daptomycin for treatment of enterococcal infections.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

Antibiotic therapy of methicillin-resistant Staphylococcus aureus in critical care.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the critically ill patient is challenging. Data for treatment of critically ill patients are often lacking because many such patients are excluded from industry-sponsored prospective randomized clinical trials. Infections due to MRSA are common in the critical care setting. Up to 24% of patients in intensive care units are colonized with MRSA, and 20% of all nosocomial bloodstream infections are due to MRSA. It is also one of the leading bacterial causes of ventilator- and hospital-acquired pneumonia. Vancomycin has been the drug of choice for treatment of MRSA in the critical care setting. Recent data showing vancomycin resistance, increasing numbers of MRSA isolates with higher vancomycin minumum inhibitory concentrations, and an apparent increase in vancomycin clinical failures have brought vancomycin's utility into question. A variety of treatment options for MRSA are available. Quinupristin-dalfopristin was the first alternative to vancomycin. However, its safety profile and potential for drug interactions limit its use. Linezolid has been shown to be effective in the treatment of pneumonia and skin and skin-structure infections due to MRSA. The drug's potential to cause bone marrow suppression limits its use, especially in treatment durations extending beyond 14 days. Daptomycin has been shown to be effective for the treatment of MRSA bloodstream and of MRSA skin and skin-structure infections. Tigecycline is the newest available drug with MRSA activity. It has demonstrated noninferiority to vancomycin in skin and skin-structure infections. However, its role in the treatment of ventilator- and hospital-acquired pneumonia is still unclear.