Characterization of methicillin-resistant Staphylococcus aureus displaying increased MICs of ceftaroline.
J Antimicrob Chemother
; 67(6): 1321-4, 2012 Jun.
Article
in En
| MEDLINE
| ID: mdl-22398650
ABSTRACT
OBJECTIVES:
To characterize the mechanisms responsible for elevated MICs of ceftaroline for methicillin-resistant Staphylococcus aureus (MRSA).METHODS:
During the 2008 Assessing Worldwide Antimicrobial Resistance Evaluation ('AWARE') surveillance programme, four S. aureus collected from separate patients in Athens, Greece, demonstrated ceftaroline MICs of 4 mg/L. These isolates were clonally related and one strain (13101) was selected for further characterization. Two strains (4981 and 4977) displaying ceftaroline MICs of 1 and 2 mg/L, respectively, were included for comparison. All strains originated from the same hospital. Penicillin-binding protein (PBP) affinities for ceftaroline and comparators were determined. Strains were typed by single-locus typing (i.e. spa typing), multilocus sequence typing ('MLST') and by multiple-locus variable-number tandem repeat fingerprinting (MLVF). The presence of Pantone-Valentine leucocidin and the staphylococcal cassette chromosome mec types was assessed. We also performed nucleotide sequencing of the mecA (encoding PBP2a) promoter and ribosomal binding site (rbs) regions and mecR1.RESULTS:
Ceftaroline demonstrated the highest PBP2a affinity with strain 4981 (ST5-MRSA-II) (IC(50) 0.06 mg/L; MIC 1 mg/L). Strains 4977 and 13101 (both ST239-MRSA-III) showed indistinguishable MLVF profiles. Ceftaroline PBP2a binding affinity in strains 4977 (IC(50) 0.25 mg/L; MIC 2 mg/L) and 13101 (IC(50) 1 mg/L; MIC 4 mg/L) was 4- and 16-fold lower than 4981, respectively. Strain 4981 contains a wild-type PBP2a, while strains 4977 and 13101 have N(146)K and E(150)K alterations in the non-penicillin-binding domain. Additionally, 13101 has one substitution (H(351)N) in the transpeptidase domain. Alterations in the mecR1, mecA promoter or rbs regions were not observed.CONCLUSIONS:
Increased ceftaroline MICs were associated with decreased PBP2a binding affinity and reflected alterations in PBP2a.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcal Infections
/
Cephalosporins
/
Methicillin-Resistant Staphylococcus aureus
/
Anti-Bacterial Agents
Limits:
Humans
Country/Region as subject:
Europa
Language:
En
Journal:
J Antimicrob Chemother
Year:
2012
Document type:
Article
Affiliation country:
United States