title: Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013-2014 at the Geneva University Hospitals.
abstract: Ceftaroline is a broad-spectrum antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Ceftaroline susceptibility of an MRSA set archived between 1994 and 2003 in the Geneva University Hospitals detected a high percentage (66 %) of ceftaroline resistance in clonotypes ST228 and ST247 and correlated with mutations in PBP2a. The ceftaroline mechanism of action is based on the inhibition of PBP2a; thus, the identification of PBP2a mutations of recently circulating clonotypes in our institution was investigated. We analyzed ceftaroline susceptibility in MRSA isolates (2013 and 2014) and established that resistant strains correlated with PBP2a mutations and specific clonotypes. Ninety-six MRSA strains were analyzed from independent patients and were isolated from blood cultures (23 %), deep infections (38.5 %), and superficial (skin or wound) infections (38.5 %). This sample showed a ceftaroline minimum inhibitory concentration (MIC) range between 0.25 and 2 μg/ml and disk diameters ranging from 10 to 30 mm, with a majority of strains showing diameters ≥20 mm. Based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 76 % (73/96) of isolates showed susceptibility to ceftaroline. Nevertheless, we still observed 24 % (23/96) of resistant isolates (MIC = 2 μg/ml). All resistant isolates were assigned to clonotype ST228 and carried the N146K mutation in PBP2a. Only two ST228 isolates showed ceftaroline susceptibility. The decreasing percentage of ceftaroline-resistant isolates in our hospital can be explained by the decline of ST228 clonotype circulating in our hospital since 2008. We present evidence that ceftaroline is active against recent MRSA strains from our hospital; however, the presence of PBP2a variants in particular clonotypes may affect ceftaroline efficacy.
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
authors.forename: D O
authors.initials: DO
authors.lastname: Andrey
authors.affiliation: Genomic Research Laboratory, Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: François
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Manzano
authors.affiliation: Genomic Research Laboratory, Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bonetti
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.|Infection Control Program, Geneva University Hospitals and Medical School, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Harbarth
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.|Genomic Research Laboratory, Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland.|Bacteriology Laboratory, Department of Laboratories and Genetic Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schrenzel
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, Geneva University, Geneva, Switzerland.
authors.forename: W L
authors.initials: WL
authors.lastname: Kelley
authors.affiliation: Service of Infectious Diseases, Department of Medical Specialties, Geneva University Hospitals and Medical School, Geneva, Switzerland. Adriana.Renzoni@hcuge.ch.|Service of Infectious Diseases, Geneva University Hospital and Medical School, 4 Rue Gabrielle Perret Gentil, Geneva, Switzerland. Adriana.Renzoni@hcuge.ch.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-4897-5208
authors.initials: A
authors.lastname: Renzoni
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002511:Cephalosporins / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D007558:Italy / Q000453:epidemiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000235:genetics; D015995:Prevalence; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000097583:Ceftaroline; C487789:mecA protein, Staphylococcus aureus