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.
Bibliographical noteFunding Information:
The authors declare no conflict of interest. This work was supported by Grant No. HI10C2020 from the National Strategic Coordinating Center for Clinical Research, which is run by the Ministry of Health and Welfare, Korean Government. The measurement of the cefazolin inoculum effect of MSSA isolates was supported by a National Research Foundation of Korea ( NRF ) grant funded by the Korea government (MSIP) (No. NRF-2015R1C1A1A01054293).
We registered the protocol of the KIND-SAB 2013 cohort study (KCT0001070) and this comparative study (KCT0001081) in the Clinical Research Information Service of the Republic of Korea, http://cris.nih.go.kr , in cooperation with the WHO International Clinical Trials Registry Platform. KIND-SAB 2013 cohort which was supported by Ministry of Health and Welfare, Korean Government with project name, ‘Establishment of Network for Clinical Research of Staphylococcus aureus Infection’. This work was summarized in an abstract (Presentation No. 1075) for the ID Week, New Orleans, LA, USA, 2016. We thank the members of the Korea INfectious Diseases (KIND) study group and the associated staff for their cooperation in this study. In addition to the authors, the following individuals participated in the study group: Su-Mi Choi (Chonnam National University Hospital); Kyoung Un Park, Chung Jong Kim, Jeong Eun Cho, Yun Jung Choi, and Jung In Park (Seoul National University Bundang Hospital); Myoung-don Oh, Taek Soo Kim, Pyoeng Gyun Choe, Wan Beom Park, Nak-Hyun Kim, Myung Jin Lee, and Su Jin Choi (Seoul National University Hospital); Jae Hyun Jeon, Dong-Kie Kim, Sae-Am Song, Min Ji Kang, and Jae Gyun Shin (Inje University Haeundae Paik Hospital); Jongyoun Yi, Sohee Park (Pusan National University Hospital); Hee Kyoung Choi and Myung Sook Han (Yonsei University Wonju Severance Christian Hospital); Chong Rae Cho, Hyun Suk Song, and Young Soon Lee (Inje University Ilsan Paik Hospital); Seung-Ji Kang and Hyeon-jeong Hwang, (Chonnam National University Hwasun Hospital); Shinhye Cheon, Jin Hee Hwang, and Seon Jin Yun (Chungnam National University Hospital); and Ki Tae Kwon and Seung Min Shin (Daegu Fatima Hospital). We thank Dr. Soyeon Ahn, a biostatistician of Medical Research Collaborating Center, Seoul National University Bundang Hospital for statistical advice on this work. Appendix A
All Science Journal Classification (ASJC) codes
- Microbiology (medical)
- Infectious Diseases