Global Antimicrobial Non-Susceptibility Patterns of Streptococcus pneumoniae: A Systematic Literature Review...

Antimicrobial non-susceptibility of Streptococcus pneumoniae is an important global health challenge. While pneumococcal vaccination has significantly lowered the burden of pneumococcal disease, including that caused by antibiotic-resistant strains, non-susceptible S. pneumoniae isolates are still important contributors to morbidity and mortality, complicating treatment. Empiric antibiotic selection for treating pneumococcal disease should consider the local epidemiology and non-susceptibility profile of isolates. To comprehensively characterize the distribution of non-susceptibility to commonly used antibiotics of S. pneumoniae isolates across different age groups, geographical regions and infection types, we conducted a systematic literature review in accordance with PRISMA guidelines. We searched PubMed, Medline, and Embase to retrieve studies published between 2014 and 2023 reporting the proportion of non-susceptible S. pneumoniae isolates detected in patients with pneumococcal disease. Data were analyzed overall and stratified by age groups (pediatric and adult), World Health Organization region, and infection type (any invasive pneumococcal disease, meningitis, bacteremic pneumonia, non-bacteremic pneumonia, bacteremia/septicemia, and acute otitis media). Study quality was assessed using the Newcastle-Ottawa Scale. Due to observed data heterogeneity, meta-analysis was not performed. Of the 1200 publications identified, 128 (113 full-text articles and 15 conference abstracts) were included in the review, comprising antimicrobial susceptibility testing outcomes for >250,000 isolates. Globally, the highest non-susceptibility rates were observed for sulfonamides (52%), macrolides (40%), and lincosamides (30%). Higher rates were reported in the Western Pacific region, with ≥91% of isolates non-susceptible to commonly used antibiotics (lincosamides, tetracyclines, macrolides, and sulfonamides); elevated non-susceptibility to tetracyclines and sulfonamides was also observed in the Southeast Asian region. Non-susceptibility proportions, in general, were higher in the pediatric population than in adults, and they varied markedly by pneumococcal infection type. Up-to-date, stratified information on the non-susceptibility profile of S. pneumoniae isolates causing different types of infection can orient local prescription guidance to use appropriate antibiotics, thereby improving the treatment outcomes and reducing the potential threat of antibiotic resistance.