The Evolution of the Antimicrobial Resistance of in Tunisia: A Multicentric Analysis over Two Decades (2000-2019).

: is a leading respiratory pathogen responsible for significant morbidity and mortality, particularly among vulnerable populations. Understanding its antimicrobial resistance patterns and serotype distribution is crucial for guiding treatment and prevention strategies. This study aims to examine these trends in isolates from Tunisia over a two-decade period (2000-2019). : A retrospective time series analysis was conducted on data (n = 4284) gathered from eight university hospital centers across Tunisia. Antimicrobial susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Pneumococcal serotypes were determined for a subset of samples from 2012 to 2019 (n = 903) using multiplex PCR and latex agglutination. : Penicillin G resistance decreased from 9-13.7% during 2000-2002 to 4.3% by 2019, while amoxicillin resistance increased until reaching 10% in 2019. Erythromycin resistance initially increased before stabilizing between 61.9% and 66.3% during 2014-2019, whereas tetracycline resistance declined from 2000 to 2008 and fluctuated around 40% during 2009-2019. Levofloxacin resistance did not exceed 1.2% throughout the study period. The most prevalent serotypes were 14, 19F, 19A, 23F, 3, 6B, 6A, and 9V. Among them, serotype 3 was the most susceptible overall. Serotypes 23F, 14, 9V, and 6B displayed the highest levels of multi-drug resistance. : Penicillin G (high-dosage), cefotaxime, and levofloxacin are still effective against most strains in Tunisia, while erythromycin and tetracycline are not reliable options for treating pneumococcal infections. Alarming resistance rates among prevalent serotypes, except serotype 3, underscore the need for preventive measures, rational antibiotic use, and ongoing surveillance.