Low birthweight neonates and those with long hospital stays are most at risk of antimicrobial-resistant Klebsiella pneumoniae infection in Malawi: implications for antibiotic prescribing
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Research in Context
Evidence before this study
We searched PubMed for studies published between Jan 1, 2015, and Dec 31, 2025, using combinations of the terms “ Klebsiella pneumoniae ”, “neonate”, “young infant”, “bloodstream infection”, “sepsis”, “risk factors”, and “sub-Saharan Africa”. Only seven studies were identified. These studies were identified in South Africa, Tanzania, and Ethiopia. They have identified Gram-negative bacteria, including Klebsiella pneumoniae , as important causes of neonatal bloodstream infections and mortality. Previous work has described the epidemiology, antimicrobial resistance profiles, and outcomes of neonatal bloodstream infections, highlighting the increasing burden of multidrug-resistant and extended-spectrum β-lactamase-producing organisms.
Studies have also identified risk factors for neonatal sepsis, including prematurity, low birthweight, healthcare exposure, and invasive procedures. However, no studies in Sub-Saharan Africa have specifically examined risk factors for Klebsiella pneumoniae infection among infants younger than 3 months of age. Furthermore, most available studies have focused on clinical outcomes, antimicrobial resistance, or transmission pathways rather than determinants of Klebsiella pneumoniae infection. Data from sub-Saharan Africa remain limited, particularly for young infants in high-burden settings. To our knowledge, no validated risk prediction tools are available to identify infants at increased risk of Klebsiella pneumoniae infection, and there is limited evidence linking risk stratification approaches to targeted treatment or management strategies. No such data have been reported from Malawi.
Added value of this study
This study investigated risk factors associated with Klebsiella pneumoniae infection among infants younger than 3 months of age in Malawi. We identified factors independently associated with Klebsiella pneumoniae infection in early infancy, and we quantified the risk of neonates getting these Klebsiella pneumoniae infections, and this was done in a setting where rapid microbiological diagnosis is often unavailable. We also linked risk prediction to potential clinical management by evaluating antibiotic susceptibility patterns and identifying antibiotic regimens that may be appropriate for infants classified as being at high risk of Klebsiella pneumoniae infection. Our findings provide evidence from a high-burden African setting where data on pathogen-specific risk prediction and treatment guidance remain scarce.
Implications of all the available evidence
Together with existing evidence, our findings provide further evidence that neonatal sepsis in African settings is commonly healthcare associated and antimicrobial resistant. Antimicrobial stewardship is not simply about restriction to unnecessary therapy, but also enabling access where it has the potential to be life-saving. Neonates do not have the physiological reserve to wait for antimicrobial therapy to be tailored to a blood culture result. Early identification of infants with clinical suspicion of sepsis that are at increased risk of Klebsiella pneumoniae infection could support more targeted clinical management and reduce mortality due to Klebsiella pneumoniae and improve antimicrobial stewardship in high-burden settings.
Background
Klebsiella pneumoniae ( Kpn ) is a major cause of neonatal sepsis in Africa. 3 rd -generation cephalosporin and gentamicin resistant Kpn is the norm in many sites, rendering WHO-recommended first- and second-line antimicrobials ineffective. An understanding of which neonates and infants are most at risk of sepsis caused by Kpn would support the case for improved access to WHO watch and reserve antimicrobials (i.e. carbapenems) for patients most likely to benefit from them.
Methods
A prospective case-control study was conducted at Queen Elizabeth Central Hospital, Malawi. Cases were infants <3 months of age with blood or CSF culture-confirmed Kpn infection. Controls were healthy infants from the same wards and were matched 2:1. Univariate and multivariate logistic regression were performed on mean-centred data to determine risk factors for infection with Kpn.
Results
We analysed data from 38 cases and 76 controls between [insert dates]. Mortality at 3 months of age was 21/38 (29%) for cases, with 14/38 (37%) identified postmortem and 6/76 (7.9%) for controls (OR 14.0 (95% CI 4.59, 49.2, p>0.001). Cases were more likely to be born out of QECH than controls (42% vs. 24%, p = 0.043), and cases had lower birthweights (median 2200g vs. 2850g, p = 0.005). Multivariate logistic regression analysis revealed that increasing birthweight was protective against Kpn infection (OR: 0.858 [95% CI: 0.745–0.987] per 100g increase), while longer hospital stay was associated with increased odds of infection (OR: 1.148 [95% CI: 1.012–1.1.303] per additional day). Most infecting isolates (34/38 [89%]) were resistant to first- and second-line antimicrobial agents, but all were sensitive to meropenem and 33/36 [92%] to amikacin.
Conclusion
Low birthweight infants with prolonged hospital stay were at greatest risk of Kpn infections that were typically resistant to WHO first- and second-line antimicrobial therapy. These infants should be prioritised for antibiotics that have the potential to be life-saving. The overlapping and evolving nature of these risk factors makes it difficult to design a simple tool to support empiric initiation of meropenem. Neonates critically ill with Kpn sepsis cannot, however, afford to wait for blood culture-confirmation before receiving effective treatment. This highlights the need for empiric decision-making frameworks that allow rapid initiation of effective therapy in high-risk neonates.
