Genotypic analysis of Italian MRSA strains exhibiting low-level ceftaroline and ceftobiprole resistance.
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ genetics
Cephalosporins
/ pharmacology
Daptomycin
/ pharmacology
Drug Resistance, Multiple, Bacterial
/ genetics
Drug Synergism
Genotype
Humans
Italy
Methicillin-Resistant Staphylococcus aureus
/ drug effects
Microbial Sensitivity Tests
Mutation
Penicillin-Binding Proteins
/ genetics
Staphylococcal Infections
/ microbiology
Ceftaroline
Cephalosporins
Cidal activity
MRSA
Penicillin-binding proteins
Resistance
Journal
Diagnostic microbiology and infectious disease
ISSN: 1879-0070
Titre abrégé: Diagn Microbiol Infect Dis
Pays: United States
ID NLM: 8305899
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
26
03
2019
revised:
29
05
2019
accepted:
06
06
2019
pubmed:
11
7
2019
medline:
28
2
2020
entrez:
11
7
2019
Statut:
ppublish
Résumé
The aim of this study was to address the involvement of PBP mutations in the bactericidal activity to novel cephalosporins, alone and in combination with daptomycin, in not-related multidrug-resistant methicillin-resistant Staphylococcus aureus strains isolated during a nationwide Italian survey. MICs determination and time-killing assays were performed and mecA, pbp1, pbp2, pbp3, pbp4, and gdpP genes were sequenced. Ten strains showed low-level resistance to ceftaroline and ceftobiprole. PBP2a sequence analysis identified four different mutations (N146K; N204K; T235I; E239K) uniquely present in the non-penicillin-binding domain (nPBD). Epidemiologically, this resistance was associated with the most widespread MDR Italian clone ST228-SCCmecI-t001/t041, confirming its proclivity to accumulate mutations, and it is also associated to substitutions in the GdpP signaling protein, involved in the maintenance of di-AMP balance, recently associated with resistance to beta-lactams. Despite these mutations, both drugs retained their potent in vitro bactericidal activity and showed a synergistic effect towards difficult-to-treat isolates.
Identifiants
pubmed: 31288948
pii: S0732-8893(19)30322-0
doi: 10.1016/j.diagmicrobio.2019.06.004
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Cephalosporins
0
Penicillin-Binding Proteins
0
ceftobiprole
5T97333YZK
Daptomycin
NWQ5N31VKK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
114852Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.