title: Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints.
abstract: Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.
authors.affiliation: Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Hsieh
authors.affiliation: Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Chung-Hsun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Hong
authors.affiliation: Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; Department of Medicine, Medical College, National Cheng Kung University, Tainan 704, Taiwan. Electronic address: chich@mail.ncku.edu.tw.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chi
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; Department of Medicine, Medical College, National Cheng Kung University, Tainan 704, Taiwan. Electronic address: chichingbm85@gmail.com.
authors.forename: Ching-Chi
authors.initials: CC
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D002439:Cefotaxime / Q000494:pharmacology / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002439:Cefotaxime
keywords: Bacteraemia; Breakpoints; Clinical and Laboratory Standards Institute; Empirical therapy; Enterobacteriaceae; Third-generation cephalosporins