Comparative effectiveness and efficacy of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus Bacteremia: A prospective multi-center cohort study in Korea

Background: There is no controlled trial to evaluate comparative outcomes of cefazolin for methicillin-susceptible S. aureus bacteremia (MSSA). The objective of this study was to determine whether cefazolin is comparable to nafcillin for the treatment of MSSA bacteremia.

Methods: A prospective cohort study was conducted at 10 hospitals in Korea from Sep 2013 to Mar 2015. All adult (≥18yrs) patients with MSSA bacteremia who received cefazolin or nafcillin as definite antibiotics were included excluding informed consent refusers. Treatment failure (non-efficacious and non-effective treatment) rate of propensity score-matched cefazolin and nafcillin groups was compared. Non-efficacious treatment defined as switching of antibiotics due to the clinician’s descretion or bacteremia-associated mortality and non-effective treatment as non-efficacious treatment failure or premature discontinuation of antibiotics due to adverse effects.

Results: Among 1013 S. aureus bacteremia patients satisfying inclusion, 480 were MSSA bacteremia patients and 255 were received cefazolin or nafcillin as definite antibiotics. 2 CNS infection were excluded and 253 patients were analyzed. Mean age of 61.58 ± 15.65 years and 60.4% were male. Bone and joint (36%) was most common site of infection. 61.6% had sepsis (SOFA ≥ 2). Metastatic infection (aOR 3.32, 95%CI 1.28-8.64), SOFA score (6~9: aOR 2.90, 95%CI 1.06-7.98, 10~: aOR 70.93, 95%CI 5.95-845.15) at onset of bacteremia were significant risk factor of treatment failure in multivariable logistic regression. Age, hospital, endovascular infection and SOFA score was significant influencing factors to antibiotics selection and all of these factors were balanced through propensity score matching assigning 75 patients in each group. There was no significant difference in baseline characteristics between 2 matched groups. Non-effective treatment rate was significantly lower in cefazolin group (32% [24/75] vs. 50.7% [38/75], p = 0.02) and non-efficacious treatment rate was not significantly different (17.3% [13/75] vs. 18.7% [14/75], p = 0.832). Effectiveness and efficacy was not significantly different in a subgroup analysis of MSSA sepsis patients.

Conclusion: Cefazolin had superior effectiveness and similar efficacy to nafcillin for MSSA bacteremia. Cefazolin can be recommended first line treatment for MSSA bacteremia.