Phenotypic and genotypic characterization of linezolid resistance and the effect of antibiotic combinations on methicillin-resistant Staphylococcus aureus clinical isolates.

Autor: AbdAlhafiz AI; Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Elleboudy NS; Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Aboshanab KM; Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Aboulwafa MM; Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. mohammad.aboulwafa@ksiu.edu.eg.; Faculty of Pharmacy, King Salman International University, South Sinai, Ras-Sudr, Egypt. mohammad.aboulwafa@ksiu.edu.eg., Hassouna NA; Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Annals of clinical microbiology and antimicrobials [Ann Clin Microbiol Antimicrob] 2023 Apr 03; Vol. 22 (1), pp. 23. Date of Electronic Publication: 2023 Apr 03.
DOI: 10.1186/s12941-023-00574-2
Abstrakt: Background: Methicillin-Resistant Staphylococcus aureus (MRSA) causes life-threatening infections, with narrow therapeutic options including: vancomycin and linezolid. Accordingly, this study aimed to characterize phenotypically and genotypically, the most relevant means of linezolid resistance among some MRSA clinical isolates.
Methods: A total of 159 methicillin-resistant clinical isolates were collected, of which 146 were indentified microscopically and biochemically as MRSA. Both biofilm formation and efflux pump activity were assessed for linezolid-resistant MRSA (LR-MRSA) using the microtiter plate and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) methods, respectively. Linezolid resistance was further characterized by polymerase chain reaction (PCR) amplification and sequencing of domain V of 23 S rRNA; rplC; rplD;and rplV genes. Meanwhile, some resistance genes were investigated: cfr; cfr(B); optrA; msrA;mecA; and vanA genes. To combat LR-MRSA, the effect of combining linezolid with each of 6 different antimicrobials was investigated using the checkerboard assay.
Results: Out of the collected MRSA isolates (n = 146), 5.48% (n = 8) were LR-MRSA and 18.49% (n = 27) were vancomycin-resistant (VRSA). It is worth noting that all LR-MRSA isolates were also vancomycin-resistant. All LR-MRSA isolates were biofilm producers (r = 0.915, p = 0.001), while efflux pumps upregulation showed no significant contribution to development of resistance (t = 1.374, p = 0.212). Both mecA and vanA genes were detected in 92.45% (n = 147) and 6.92% (n = 11) of methicillin-resistant isolates, respectively. In LR-MRSA isolates, some 23 S rRNA domain V mutations were observed: A2338T and C2610G (in 5 isolates); T2504C and G2528C (in 2 isolates); and G2576T (in 1 isolate). Amino acids substitutions were detected: in L3 protein (rplC gene) of (3 isolates) and in L4 protein (rplD gene) of (4 isolates). In addition, cfr(B) gene was detected (in 3 isolates). In 5 isolates, synergism was recorded when linezolid was combined with chloramphenicol, erythromycin, or ciprofloxacin. Reversal of linezolid resistance was observed in some LR-MRSA isolates when linezolid was combined with gentamicin or vancomycin.
Conclusions: LR-MRSA biofilm producers' phenotypes evolved in the clinical settings in Egypt. Various antibiotic combinations with linezolid were evaluated in vitro and showed synergistic effects.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: