title: Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort.
abstract: 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 × 107CFU/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.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: S-I
authors.initials: SI
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. ebenezere.lee@gmail.com.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-7652-7093
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Kiem
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea.
authors.forename: Y G
authors.initials: YG
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Yonsei University Medical School, Wonju, Republic of Korea.
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.
authors.forename: H-C
authors.initials: HC
authors.lastname: Jang
authors.affiliation: Division of Infectious Diseases, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea.
authors.forename: H-I
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.|Ewha Woman's University Medical Center, Seoul, Republic of Korea.
authors.forename: C J
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: N J
authors.initials: NJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: M-D
authors.initials: MD
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: H B
authors.initials: HB
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology*; D002437:Cefazolin / Q000494:pharmacology* / Q000627:therapeutic use; D002981:Clindamycin / Q000494:pharmacology; D004917:Erythromycin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017211:Treatment Failure; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D004917:Erythromycin; D001618:beta-Lactamases; D002437:Cefazolin