Emergence of resistance to last-resort antibiotics in clinical isolates of staphylococci with special reference to daptomycin and linezolid

Abstract

Background: Treatment of staphylococcal infections has been complicated by the continuous emergence of antibiotic-resistant strains. Objective: In this study, we investigated the resistance pattern of clinical isolates of both coagulase-positive and coagulase-negative staphylococci to antibiotics recently introduced to treat staphylococcal infections. Methodology: Minimum inhibitory concentrations of antibiotics were determined by agar dilution or broth microdilution method. Identification of daptomycin- and linezolid-resistant isolates was performed by matrixassisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Moreover, the mechanism of resistance to daptomycin and linezolid was investigated on the molecular basis using PCR and amplicon sequencing. Results: Out of 104 staphylococci, 9 were resistant to ciprofloxacin (8.7%), 68 to clindamycin (65.4%), 2 to daptomycin (1.9%), 54 to erythromycin (51.9%), 6 to linezolid (5.8%), 3 to nitrofurantoin (2.9%), 75 to oxacillin (72.1%), 37 to teichoplanin (35.6%), 69 to tetracycline (66.3%), 51 to tigecycline (49%), and 41 to vancomycin (39.4%). Identification of daptomycin- and linezolid-resistant isolates revealed that they belong to Staphylococcus aureus, S. hominis, S. capitis, and S. epidermidis. In addition, sequencing of the mprF gene conferring daptomycin resistance revealed L431F and S829L point mutations in the two resistant isolates identified as S. aureus and S. hominis, respectively. Furthermore, linezolid resistance was due to optrA gene in two, and cfr in three of the resistant isolates. Conclusion: Resistance to the last-resort antibiotics used to treat staphylococcal infection has emerged. Therefore, the use of daptomycin and linezolid should be restricted to critical cases not susceptible to other available agents.