title: Rapid molecular determination of methicillin resistance in staphylococcal bacteraemia improves early targeted antibiotic prescribing: a randomized clinical trial.
abstract: Empiric therapy of methicillin-susceptible Staphylococcus aureus (MSSA) infections with vancomycin is associated with poorer outcome than targeted therapy with β-lactams. Our objective was to evaluate whether rapid determination of methicillin resistance shortens the time from Gram stain to targeted antimicrobial therapy in staphylococcal bacteraemia, thereby reducing vancomycin overuse. This was a single-centre open parallel RCT. Gram-positive cocci in clusters in positive blood culture underwent real-time PCR for rapid species and methicillin resistance determination parallel to conventional microbiology. Patients were randomized 1:1 so that clinicians would be informed of PCR results (intervention group) or not (control group). Eighty-nine patients (intervention 48, control 41) were analysed. MRSA was identified in seven patients, MSSA in 46, and CoNS in 36. PCR results were highly concordant (87/89) with standard microbiology. Median time (hours) from Gram stain to transmission of methicillin-susceptibility was 3.9 (2.8-4.3) vs. 25.4 (24.4-26-7) in intervention vs. control groups (p <0.001). Median time (hours) from Gram stain to targeted treatment was similar for 'all staphylococci' [6 (3.8-10) vs. 8 (1-36) p 0.13] but shorter in the intervention group when considering S. aureus only [5 (3-7) vs. 25.5 (3.8-54) p <0.001]. When standard susceptibility testing was complete, 41/48 (85.4%) patients in the intervention group were already receiving targeted therapy compared with 23/41 (56.1%) in the control group (p 0.004). There was no significant effect on clinical outcomes. Rapid determination of methicillin resistance in staphylococcal bacteraemia is accurate and reduces significantly the time to targeted antibiotic therapy in the subgroup of S. aureus, thereby avoiding unnecessary exposure to vancomycin.
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: stephane.emonet@hcuge.ch.
authors.forename: S
authors.initials: S
authors.lastname: Emonet
authors.affiliation: Departments of Infectious Diseases and General Medicine, Austin Health, Heidelberg, Australia.
authors.forename: P G
authors.initials: PG
authors.lastname: Charles
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Harbarth
authors.affiliation: Departments of Infectious Diseases and General Medicine, Austin Health, Heidelberg, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Stewardson
authors.affiliation: Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Renzi
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Uckay
authors.affiliation: Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Cherkaoui
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Rougemont
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Bacteriology Laboratory, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; Genomic Research Laboratory, Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schrenzel
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D061665:Time-to-Treatment; D047090:beta-Lactams / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams
keywords: Antimicrobial stewardship; Methicillin resistance; Molecular diagnosis; Rapid microbiology; Staphylococcal bacteraemia; Targeted treatment