Abstract
BACKGROUND: Infective endocarditis (IE) is a life-threatening condition caused by Viridans Group Streptococci (VGS) in low and middle-income countries. Data on epidemiology and molecular resistance mechanisms in the high-risk resource-limited setting of Khyber Pakhtunkhwa (KP), Pakistan, are scarce. This study aimed to determine the prevalence, risk factors, and molecular analysis of antimicrobial resistance in VGS isolated from IE patients in KP. METHODS: A cross-sectional study was done on 350 IE suspected patients admitted to tertiary care hospitals in KP. Blood cultures were performed and isolates were identified using standard microbiological methods followed by species confirmation via PCR (sodA, gtf, gyrB, and rpoB genes). Kirby-Bauer disk diffusion method was performed. Antibiotic resistance genes ermB, mefA, tetM, tetO, and pbp2x were analyzed by PCR. Statistical analyses of socio-demographic and clinical data were was performed using logistic regression. RESULTS: Among the 350 suspected IE patients, 62 (17.7%) were confirmed to have VGS-IE. The Streptococcus mitis group was the predominant species (41.9%) followed by S. sanguinis (19.4%), and the S. anginosus group (16.1%). Overall, 38.7% of isolates were multidrug-resistant Resistance to Penicillin (25.8%), erythromycin (40.3%) and tetracycline (32.3%) was recorded. Penicillin MIC₉₀ (4 µg/mL) reached the resistance breakpoint, suggesting penicillin monotherapy may not be adequate for empirical therapy. Gene pbp2x was detected in all β-lactam-resistant isolates, ermB in 40.3% and mefA in 48% of macrolide-resistant isolates, and tetM/tetO in 65% and 35% of tetracycline-resistant isolates, respectively. No independent risk factors reached statistical significance though elevated (non-significant) odds were observed. Limited access to dental care showed borderline significance (aOR = 2.10; 95% CI: 1.01-4.38; p = 0.05), whereas other variables such as prosthetic heart valves 9(aOR = 2.05, 95% CI: 0.74-5.67) and prior antibiotic use aOR = 1.35, 95% CI: 0.64-2.86) had elevated point estimates but did not remain significant after adjustment. CONCLUSION: This is the first molecular epidemiological study from KP that demonstrates the high prevalence of VGS-IE with considerable multidrug resistance confirmed for genetic determinants. These findings emphasized the urgent need for improved antimicrobial stewardship, access to better dental care, and the integration of region-specific risk factors into preventive strategies to mitigate the burden of IE in regions with low-income settings.