Evaluation of in vitro activity of ceftaroline on methicillin resistant Staphylococcus aureus blood isolates from Iran

Negin Abdizadeh; Mehri Haeili; Hossein Samadi Kafil; Amin Ahmadi; Mohammad Mehdi Feizabadi

doi:10.18502/ijm.v13i4.6967

Negin Abdizadeh Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
Mehri Haeili Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
Hossein Samadi Kafil Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Amin Ahmadi Pharmaceutical Nanotechnology Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
Mohammad Mehdi Feizabadi Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijm.v13i4.6967

Keywords: Ceftaroline; Methicillin-resistant Staphylococcus aureus; Penicillin-binding protein 2a; Minimum inhibitory concentration; mecA

Abstract

Background and Objectives: Ceftaroline (CPT) is a novel cephalosporin with potent activity against methicillin-resistant Staphylococcus aureus (MRSA). Despite its recent introduction, CPT resistance in MRSA has been described worldwide. We aimed in the current study to evaluate the in vitro 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 nu- cleotide sequence of the mecA 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 character- ized with MIC=2mg/l and categorized as susceptible dose dependent. Compared to E-test, DD revealed a categorical agree- ment 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 spa 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 mecA mutations is indicative of contribution of secondary chromosomal mutations in resistance development.