title: Prevalence of blaZ gene types and the cefazolin inoculum effect among methicillin-susceptible Staphylococcus aureus blood isolates and their association with multilocus sequence types and clinical outcome.
abstract: Cefazolin treatment failures have been described for bacteraemia caused by methicillin-susceptible Staphylococcus aureus (MSSA) with type A β-lactamase and inoculum effect (InE). We investigated the prevalence of blaZ (β-lactamase) gene types and a cefazolin InE among MSSA blood isolates in South Korea and evaluated their association with specific genotypes. The clinical impact of the cefazolin InE was also evaluated. A total of 220 MSSA isolates were collected from a prospective cohort study of S. aureus bacteraemia. A pronounced InE with cefazolin was defined as a ≥4-fold increase in the minimum inhibitory concentration (MIC) between a standard and high inoculum, resulting in a non-susceptible MIC. Sequencing of blaZ and multilocus sequence typing (MLST) were performed. Clinical outcomes were assessed in 77 patients treated with cefazolin. The blaZ gene was detected in 92 % of the 220 MSSA isolates. Type C β-lactamase was the most common (53 %), followed by type B (20 %) and type A (17 %). Certain genotypes were significantly associated with specific β-lactamase types (notably, ST30 and type A β-lactamase). A pronounced cefazolin InE was observed in 13 % of isolates. Most of these (79 %) expressed type A β-lactamase and ST30 was the predominant (55 %) clone amongst them. Cefazolin treatment failure was not observed in patients infected with strains exhibiting a pronounced InE. These strains had no impact on other clinical outcomes. In conclusion, the prevalence of a pronounced InE with cefazolin could be dependent upon distributions of MSSA genotypes. Cefazolin can likely be used for the treatment of MSSA bacteraemia (except endocarditis), without consideration of an InE.
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.
authors.forename: Y P
authors.initials: YP
authors.lastname: Chong
authors.forename: S-J
authors.initials: SJ
authors.lastname: Park
authors.forename: E S
authors.initials: ES
authors.lastname: Kim
authors.forename: K-M
authors.initials: KM
authors.lastname: Bang
authors.forename: M-N
authors.initials: MN
authors.lastname: Kim
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: S-O
authors.initials: SO
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Choi
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jeong
authors.forename: J H
authors.initials: JH
authors.lastname: Woo
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia; D015373:Bacterial Typing Techniques; D002437:Cefazolin / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D015995:Prevalence; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D002437:Cefazolin; D008712:Methicillin