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Efflux-Mediated Macrolide Resistance in Clinical Streptococcus Isolates: A Comparative Molecular Study
Salsabeel M Moshewh1, Salma E Mohamed1, Praveen Kumar2
1Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates.
Background:
Efflux-mediated macrolide resistance represents an emerging threat in Streptococcus infections globally. However, molecular epidemiological data from the Gulf region, particularly the United Arab Emirates (UAE), remain limited. This study addresses this knowledge gap by investigating efflux pump resistance mechanisms in clinical Streptococcus isolates.
Methods:
A cross-sectional study analyzed 100 clinical isolates (99 Streptococcus and 1 Enterococcus) from Thumbay Hospital, Ajman, UAE (October-December 2024). Antimicrobial susceptibility testing for minimum inhibitory concentration (MIC) determination was performed using the DxM 1096 MicroScan WalkAway system (Beckman Coulter Inc., Brea, CA, USA; LabProv4.42). PCR detected mef(A/E), msr(D), and tet(K) resistance genes with sequencing confirmation. Comparative genomic analysis was performed using a total of 30 publicly available Streptococcus genomes: 15 from India and 15 from Saudi Arabia. Statistical analysis employed chi-square tests, Fisher's exact tests, and multivariate logistic regression with Bonferroni correction (α = 0.05).
Results:
Among the isolates, erythromycin resistance occurred in 39 isolates (39%, 95% CI: 29.4-49.2%) and clindamycin resistance in 31 isolates (31%, 95% CI: 22.1-40.9%). The mef(A/E) gene was detected in 31 isolates (31%, 95% CI: 22.1-40.9%), and msr(D) in 3 isolates (3%, 95% CI: 0.6-8.5%), with co-occurrence in 3 isolates (3%). No isolates harbored tet(K). Multivariate analysis identified mef(A/E) as the strongest predictor of macrolide resistance (OR = 18.7, 95% CI: 7.9-44.2, p < 0.001). Regional comparison revealed significant differences: mef(A/E) prevalence was 31% (UAE), 87% (India), and 0% (Saudi Arabia) (p < 0.001).
Conclusions:
This study provides the first molecular characterization of efflux-mediated macrolide resistance in UAE Streptococcus isolates. The predominance of mef(A/E)-mediated resistance with confirmed efflux activity highlights the clinical significance of active surveillance and targeted antimicrobial stewardship in the region.
Insights
Efflux-mediated macrolide resistance in Streptococcus is rising globally. In the UAE, the mef(A/E) gene is the primary driver of this resistance, necessitating enhanced surveillance and antimicrobial stewardship.
Area of Science:
- Microbiology
- Molecular Epidemiology
- Antimicrobial Resistance
Background:
- Efflux-mediated macrolide resistance in Streptococcus poses a growing global health concern.
- Limited molecular epidemiological data exist for this resistance mechanism in the United Arab Emirates (UAE).
Purpose of the Study:
- To investigate efflux pump-mediated macrolide resistance mechanisms in clinical Streptococcus isolates from the UAE.
- To characterize the prevalence of specific resistance genes, including mef(A/E), msr(D), and tet(K).
Main Methods:
- A cross-sectional study of 100 clinical isolates (99 Streptococcus, 1 Enterococcus) from the UAE.
- Antimicrobial susceptibility testing (MIC determination) and PCR for resistance genes (mef(A/E), msr(D), tet(K)) with sequencing.
- Comparative genomic analysis with publicly available Streptococcus genomes from India and Saudi Arabia.
Main Results:
- 39% of isolates were resistant to erythromycin and 31% to clindamycin.
- The mef(A/E) gene was detected in 31% of isolates and was the strongest predictor of macrolide resistance (OR = 18.7, p < 0.001).
- Significant regional differences in mef(A/E) prevalence were observed: 31% (UAE), 87% (India), 0% (Saudi Arabia).
Conclusions:
- This study provides the first molecular characterization of efflux-mediated macrolide resistance in UAE Streptococcus isolates.
- The predominance of mef(A/E)-mediated resistance highlights its clinical significance in the region.
- Active surveillance and targeted antimicrobial stewardship are crucial for managing this resistance.
