Cell wall-inhibiting antibiotics resistance in Streptococcus pneumoniae causing invasive diseases: a global systematic review and meta-analysis in pediatric populations

Streptococcus pneumoniae causes diseases such as meningitis and bacteremia, which lead to high morbidity and mortality rates among children under 5 years old. The invasive form of the disease, known as invasive pneumococcal disease, is a significant global health threat to children. Additionally, antimicrobial resistance in this bacterium has greatly hindered worldwide efforts to prevent and treat infections. In this meta-analysis, we reviewed published studies to provide a comprehensive overview of the global status of resistance to anti-cell wall antibiotics among S. pneumoniae strains causing invasive diseases. We searched PubMed, Scopus, and Embase for relevant studies published up to July 25, 2022. All statistical analyses were conducted using the R statistical software package. Our meta-analysis included 54 studies from 23 countries, spanning the period from 1994 to 2022. The average prevalence rates of antibiotic resistance were as follows: 30.1% for penicillin-non-susceptible pneumococci, 1.2% for amoxicillin, 2.5% for amoxicillin-clavulanic acid, 6.1% for ceftriaxone, and 0.6% for vancomycin. No significant differences were observed in resistance rates for vancomycin, amoxicillin-clavulanic acid, or amoxicillin. Additionally, no notable variations were found across age groups, over time, or based on different antibiotic susceptibility testing methods. The high prevalence of penicillin-non-susceptible pneumococci represents a significant challenge for global healthcare systems. Furthermore, our findings highlight considerable geographical variation in antibiotic resistance levels to cell wall-targeting antibiotics among S. pneumoniae isolates globally.