Molecular mechanisms of fluoroquinolone resistance in Streptococcus pneumoniae isolates from Iran

Background: Due to recent reports of resistance to β-lactams and macrolides, the use of fluoroquinolones (FQs) for treating Streptococcus pneumoniae infections has increased. This study aimed to evaluate the molecular mechanisms of FQ resistance in pneumococcal isolates.
Materials & Methods: This study was conducted on 131 pneumococcal isolates (67 nasopharyngeal isolates from healthy individuals and 64 clinical isolates) collected in Tehran, Iran, in 2023. Susceptibility to FQs was determined, and quinolone resistance–determining regions (QRDRs) of gyrA, gyrB, parC, and parE in resistant isolates were amplified and sequenced.
Findings: Disk diffusion testing showed that 23 (17.5%) and five (3.8%) isolates were resistant to norfloxacin (5µg) and ofloxacin (5µg), respectively. Minimum inhibitory concentration (MIC) test confirmed resistance in 22 of 23 norfloxacin-resistant isolates. All five ofloxacin-resistant isolates were distinct from the norfloxacin-resistant group, and their resistance was also confirmed by MIC testing. Overall, 28 non-overlapping resistant isolates were selected for sequencing. Among these isolates, mutations in parC and gyrA were detected in four (14.28%) and five (17.85%) isolates, respectively, while two (7.14%) isolates harbored simultaneous mutations in both genes. The most frequent substitutions were Ser81→Leu in parC and Glu85→Lys and Ser81→His/Thr in gyrA. No statistically significant difference was observed between nasopharyngeal (healthy flora) and clinical isolates regarding FQ resistance patterns.
Conclusion: This study identified key molecular mechanisms of fluoroquinolone resistance in S. pneumoniae, primarily involving mutations in parC and gyrA, including double mutations. Notably, all isolates remained susceptible to moxifloxacin, supporting its effectiveness in treating pneumococcal infections.