Pathogen distribution and antimicrobial resistance among neonatal bloodstream infections in Southeast Asia: results from NeoSEAP, a multicentre retrospective study

Abstract

Background: Progress in reducing morbidity and mortality due to neonatal sepsis has slowed in recent decades and is threatened by the global rise of antimicrobial resistance. The populous Southeast Asian region has a high burden of both neonatal sepsis and antimicrobial resistance (AMR). Despite this, there remains a lack of robust data on the epidemiology of neonatal sepsis and the prevalence of AMR within the region.

Methods: We evaluated positive blood cultures and susceptibility profiles responsible for neonatal sepsis across 10 clinical sites in five countries in South and Southeast Asia (Sri Lanka, Indonesia, The Philippines, Malaysia, and Vietnam). Retrospective data on all blood cultures collected from neonates over two years (1st January 2019-31st December 2020) were extracted from laboratory records. Data were also collected on the availability and implementation of infection prevention and control resources, and antimicrobial prescribing practices. Pooled estimates across sites and pathogens were generated, with adjustment for clustering.

Findings: Of 14,804 blood cultures collected over the study period, a total of 2131 positive isolates (including 1483 significant pathogens) were identified. Gram-negative bacteria predominated as causative of neonatal sepsis (78·4%; 1163/1483) with Klebsiella spp. (408/1483; 27·5%) and Acinetobacter spp. (261/1483; 17·6%) most frequently isolated overall. Adjusted pooled non-susceptibility for Klebsiella spp. was 86·7% (95% CI 54·0-98·5) for third-generation cephalosporins (ceftriaxone and/or cefotaxime; 3GC) and 17·1% (95% CI 8·1-24·7) for carbapenems; while non-susceptibility for Escherichia coli was 46·4% (95% CI 20·0-72·0) for 3GC and 15·4% (95% CI 2·7-31·0) for carbapenems. Carbapenem non-susceptibility for Acinetobacter spp. was 76·5% (95% CI 59·4-84·5). Gram-positive bacteria accounted for 13·2% (196/1483) of pathogens causative of neonatal sepsis, whilst Candida spp. accounted for 8·3% (123/1483) of culture-positive sepsis episodes.

Interpretation: Neonatal sepsis in tertiary hospitals in Southeast Asia is predominantly caused by gram-negative bacteria, with high rates of non-susceptibility to commonly prescribed antibiotics.

Funding: This study was supported by an Australian National Health and Medical Research Council (NHMRC) grant. The NHMRC was not involved in the design or conduct of the research.

Keywords: Antimicrobial resistance; Global health; Gram-negative bacteria; Neonatal sepsis; Southeast Asia.

Fig. 1

Map of included countries and study sites. The number preceding each city denotes site number. The number in parentheses denotes number of positive blood cultures at each site for the period of 2019–2020 inclusive. ∗Private hospital.

Fig. 2

Heatmap of resource availability and infection prevention & control (IPC) strategies by site. ∗Criteria: frequency of time: Green (100%), Yellow (50–100%), Red (<50%). ∼Criteria: Green (Sterilisation), Yellow (Disinfection), Red (Soap & water). ˆCriteria: Green (Daily), Yellow (2–3 times per week), Red (Less than 2–3 per week), White (Not applicable). ^&Criteria: Green (76–100%), Yellow (50–75%), Red (<50%). Data based on available hospital records. ^#Country: Indonesia (IN), Philippines (PH), Sri Lanka (SL), Malaysia (ML), Vietnam (VN). IPC: Infection, Prevention and Control; IV: Intravenous; NIV: Non-invasive Ventilation.

Fig. 3

Distribution of culture-positive pathogens isolated across all sites (n = 1483). Pink = gram-positive bacteria, blue = gram-negative bacteria, green = fungi.

Fig. 4

Estimates of combined antimicrobial non-susceptibility across sites for key pathogen-antibiotic combinations before and after adjustment for clustering by site. a) Enterobacterales, b) Gram-negative non-fermenters, c) Gram-positive bacteria. 3GC: Non-antipseudomonal 3rd Generation Cephalosporins.

Fig. 5

Estimates of combined Enterobacterale antimicrobial non-susceptibility for key antimicrobials by site, before and after adjustment for clustering by species. 3GC: Non-antipseudomonal 3rd Generation Cephalosporins.