Evaluation of activity of ceftaroline on methicillin resistant blood isolates from Iran.

BACKGROUND AND OBJECTIVES

Ceftaroline (CPT) is a novel cephalosporin with potent activity against methicillin-resistant (MRSA). Despite its recent introduction, CPT resistance in MRSA has been described worldwide. We aimed in the current study to evaluate the activity of CPT against 91 clinical MRSA and 3 MSSA isolates.

MATERIALS AND METHODS

Susceptibility of isolates to CPT was tested using E-test and disk diffusion (DD) method. The nucleotide sequence of the gene and molecular types of isolates with reduced susceptibility to CPT were further studied to identify resistance conferring mutations in PBP2a and the genetic relatedness of the isolates respectively.

RESULTS

Overall, 92.5% of isolates were found to be CPT susceptible (MICs≤1mg/l) and 7 MRSA isolates were characterized with MIC=2mg/l and categorized as susceptible dose dependent. Compared to E-test, DD revealed a categorical agreement rate of 93.6% and the obtained rates for minor, major /very major error were found to be 6.3% and 0% respectively. The MRSA isolates with increased CPT MICs (n=7), belonged to types t030 (n=6) and t13927 (n=1) and all carried N146K substitution in PBP2a allosteric domain, except for one isolate which harbored a wild-type PBP2a.

CONCLUSION

While resistance to CPT was not detected we found increased CPT MICs in 7.69% of MRSA isolates. Reduced susceptibility to CPT in the absence of mutations is indicative of contribution of secondary chromosomal mutations in resistance development.