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Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013-2014 at the Geneva University Hospitals

Published in European journal of clinical microbiology & infectious diseases. 2017, vol. 36, no. 2, p. 343-350
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.
Keywords Anti-Bacterial Agents/pharmacologyBacterial Proteins/geneticsCephalosporins/pharmacologyDrug Resistance, BacterialGenotypeHospitals, UniversityHumansItaly/epidemiologyMethicillin-Resistant Staphylococcus aureus/classification/drug effects/genetics/isolation & purificationMicrobial Sensitivity TestsMolecular TypingMutationPenicillin-Binding Proteins/geneticsPrevalenceStaphylococcal Infections/epidemiology/microbiology
PMID: 27744604
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Research groups Analyse génomique et fonctionnelle du staphylocoque doré (604)
Endoribonucleases : des outils pour le diagnostic des pathogènes (1004)
Epidémiologie et contrôle de la résistance aux antibiotiques (866)
Staphylococcus aureus: antibiotique résistance et signalisation (1030)
Swiss National Science Foundation: 310030_146540
Swiss National Science Foundation: 310030_149762
Swiss National Science Foundation: 31003A_153474
Autre: 115523
European Commission: COMBACTE-NET
(ISO format)
ANDREY, Diego Olivier et al. Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013-2014 at the Geneva University Hospitals. In: European Journal of Clinical Microbiology & Infectious Diseases, 2017, vol. 36, n° 2, p. 343-350. doi: 10.1007/s10096-016-2807-5 https://archive-ouverte.unige.ch/unige:98886

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Deposited on : 2017-11-10

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