High Burden of Viridans Streptococcal Endocarditis Linked to Multidrug Resistance and Regional Risk Factors: First Report From Khyber Pakhtunkhwa, Pakistan

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). Antibiotic susceptibility testing was performed. Antibiotic resistance genes ermB , mefA , tetM , tetO , and pbp2x were analyzed by PCR. Socio-demographic and clinical data were collected, and statistical analysis 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%). A high prevalence of penicillin non-susceptibility (25.8%), alongside high resistance to erythromycin (40.3%) and tetracycline (32.3%) was observed. 38.7% of isolates were multidrug-resistant. Genotypic analysis confirmed a high prevalence of the resistance determinants pbp2x (in penicillin-resistant isolates), ermB (40.3%), and tetM (32.3%). The high prevalence of region-specific risk factors, including limited access to dental care (60.0%) and use of smokeless tobacco ( naswar ) (46.6%) was recorded. No significant independent risk factors were found by multivariate analysis, however, prosthetic heart valve implantation (aOR=2.05, 95% CI: 0.74–5.67) and prior antibiotic use (aOR=1.35, 95% CI: 0.64–2.86) showed elevated risks. Conclusion: This is the first comprehensive 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.