Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea.

OBJECTIVES: No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. METHODS: A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics. RESULTS: Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group. CONCLUSIONS: Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort.

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 µg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.