ntimicrobial resistance in bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae (2010–24): a systematic review and meta-analysis
Lazarus G., Caddey B., Dean A., Febrina F., Wangsaputra VK., Radiani SP., Xiong Y., Conly JM., Barkema HW., Pezzoli L., van Kleef E., Tosas Auguet O., Turner P., Kothari KU., Bertagnolio S., Nobrega DB., Hamers RL., Prasetya A., Guzman AJ., Butters A., de Lima A., Dias A., Weyant B., Liaqat C., Kamaliddin C., Nobrega DB., Adesanwo E., van Kleef E., Satria F., Lazarus G., Krisandi G., Brünger G., Akinniyi H., Barkema HW., Maharani IL., Phowira J., Sun J., Yang J., Rattner JI., Conly JM., Takahashi J., Kothari KU., Ngadimin KD., Batalha L., Covington L., Pezzoli L., Radu L., Jokar M., Aurelie N., Wisnu NKP., Auguet OT., Fasiku O., Goddard Q., Hamers RL., Siagian RM., Ruby R., Sinto R., Rezaee S., Fisher S., Bertagnolio S., Tazerji SS., Cong S., Li T., Dirjayanto VJ., Shaukat W., Tong X., Xiong Y.
Background There are fragmented data on the patterns of antimicrobial resistance in the main bacterial pathogens causing meningitis, especially in low-income and middle-income countries (LMICs) where the disease burden is highest. This review aimed to estimate meningitis-specific prevalence of antimicrobial resistance and time trends, globally and for each of the WHO regions, for the main antimicrobials used to treat or prevent meningitis. Methods In this systematic review and meta-analysis, we systematically searched Embase, Global Health Database, and MEDLINE for original, peer-reviewed articles in any language, published between Jan 1, 2010, and May 16, 2024, describing people diagnosed with a microbiologically confirmed meningitis caused by Streptococcus pneumoniae , Neisseria meningitidis , or Haemophilus influenzae , with antimicrobial susceptibility testing results. We excluded reports that did not describe specimen type, sampling period, geographical setting, denominators, or proportions for single-agent and class resistance. We used multilevel random-effect meta-analysis on summary data to estimate the prevalence and time trends of antimicrobial resistance for relevant pathogen–antimicrobial combinations in each WHO region and globally. To assess article quality, we adopted the Microbiology Investigation Criteria for Reporting Objectively (MICRO) checklist. This review was registered with PROSPERO (CRD42019155379). Findings The search yielded 1503 studies. After the removal of 606 duplicates, 665 from title and abstract screening, and 140 from full-text screening, 92 reports were eligible for inclusion. A further four were removed due to duplicate datasets. We included 88 reports and extracted data on 16 441 clinical isolates from 37 countries across all WHO regions, mostly LMICs. For S pneumoniae (81 reports, 13 295 isolates), prevalence of antimicrobial resistance was highest in the Western Pacific and Eastern Mediterranean regions, ranging across WHO regions from 14·7% (95% CI 4·5–29·5) to 58·0% (34·9–79·5) for benzylpenicillin (27·4% [19·0–36·6] globally), and from 3·8% (0·0–13·7) to 20·6% (2·2–50·8) for third-generation cephalosporins (3GCs; 8·8% [4·3–14·6] globally). Benzylpenicillin resistance in S pneumoniae meningitis increased over time in LMICs, whereas benzylpenicillin and 3GC resistance decreased over time in high-income countries. For N meningitidis (11 reports, 3001 isolates), prevalence of antimicrobial resistance was highest in the African region, ranging across WHO regions from 9·4% (7·2–11·8) to 44·9% (0·0–100·0) for benzylpenicillin (24·7% [5·3–52·3] globally, increasing over time); from 0·0% (0·0–0·1) to 17·0% (0·0–100·0) for 3GCs (4·6% [0·0–19·4] globally); and from 0·0% (0·0–0·2) to 17·1% (0·0–100·0) for ciprofloxacin (3·7% [0·0-25·9] globally). Among H influenzae isolates (five reports, 145 isolates), 51·2% (0·0–100·0) were ampicillin resistant and 8·4% (0·1–28·4) were 3GC resistant globally; data were insufficient for WHO regions. None of the included reports described all 13 MICRO mandatory items, with a median of four (range one to six) items missing. Interpretation Treatment of bacterial meningitis is challenged by a rise of antimicrobial-resistant pathogens, particularly affecting patients in LMICs where access to effective treatment might be limited. Our findings call for the strengthening of national antimicrobial resistance surveillance systems to better tailor treatment guidelines and public health interventions. Funding Fleming Fund, US Centers for Disease Control and Prevention (CDC), and WHO.