Pristinamycin-antibiotic combinations against methicillin-resistant Staphylococcus aureus recovered from skin infections

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BACKGROUND: Macrolide-resistant and methicillin-resistant Staphylococcus aureus, particularly those exhibiting pristinamycin resistance, impose significant medical health consequences with limited therapeutic options. This study is designed to determine their prevalence in a major tertiary care hospital in Egypt, antimicrobial susceptibility and evaluate various pristinamycin (PST)-antibiotic combinations. METHODS: Standard procedures were employed for isolation, identification, antimicrobial susceptibility, and molecular analysis of key macrolide- and methicillin-resistant genes. Phenotypic relatedness and antibiotic combinations of pristinamycin with other antimicrobial agents were done using the heatmap analysis and checkerboard assay. RESULTS: Out of 154 positive cultures of S. aureus were collected from different types of skin infections. The lowest resistance was shown for linezolid (5.2%), followed by vancomycin (9.1%), teicoplanin (9.1%), chloramphenicol (12.3%), and doxycycline (14.9%). The MDR isolates (43%, n = 67) showed diverse phenotypic relatedness. They showed multiple antibiotic resistance (MAR) index range from 0.31-1.0, exhibiting 100% non-susceptibility to cefoxitin (MRSA), erythromycin, and clarithromycin known as macrolide resistant S. aureus (McRSA), followed by 80%, 74.6%, and 46.2% for clindamycin, azithromycin, and PST, respectively. All the MDR isolates gave positive nuc, mecA and confirmed MRSA. The ermC, ermA, and msrA, genes were detected in 49.25%, 26.8%, and 23.8% of the MDR isolates, respectively. The PST-doxycycline and PST-levofloxacin combinations were mostly synergistic in 82.13% and 70.14%, while PST-linezolid showed mostly additive effects in 67% of the MDR S. aureus isolates. CONCLUSION: This study highlights the high prevalence of MRSA isolates recovered from various skin infections. Linezolid, vancomycin, teicoplanin, pristinamycin, chloramphenicol, and doxycycline remain effective therapeutic options. Macrolide and methicillin resistance are increasingly developing among S. aureus clinical isolates. The pristinamycin combination with doxycycline or levofloxacin was mostly synergistic and recommended for clinical evaluation.

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