Neonates of HIV-infected mothers have reduced sepsis risk

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Recent findings have shown that, counter-intuitively, neonates born to mothers infected with HIV had a reduced risk for sepsis. “At our centre, we found maternal HIV infection to be independently associated with a reduced risk of neonatal sepsis,” Dr Matthew Bates, of the department of paediatrics and child health at the University Teaching Hospital Zambia said. “We also have unpublished data of over 6,000 neonatal admissions suggesting maternal HIV infection is linked with a 4 percentage point decrease in mortality, possibly due to lower infection rates.”

In 2010, 600,000 children developed sepsis in sub-Saharan Africa, and 140,000 died, the researchers wrote. Bates and colleagues performed a cross-sectional observational study to gain a better understanding on the lack of interventions to prevent sepsis in sub-Saharan hospitals and the shortage of data describing antibiotic resistance.

They reviewed 313 neonates (20% born to mothers with HIV; 54% male) who were admitted to the neonatal ICU with sepsis at the University Teaching Hospital in Zambia from October 2013 to May 2014. The researchers found that maternal HIV infection was associated with a reduced risk for neonatal sepsis (OR = 0.46; 95% CI, 0.23-0.93). Thirty-three percent of the neonates had a positive blood culture indicating sepsis, of which 85% were early-onset sepsis.

Klebsiella spp., particularly K. pneumoniae, accounted for 75% of cases, followed by coagulase-negative staphylococci (6%), Staphylococcus aureus (6%), Escherichia coli (5%) and Candida spp. (5%). For Klebsiella spp., antibiotic resistance ranged from 96% to 99% for WHO-recommended first-line therapy, including gentamicin and ampicillin/penicillin, and ranged from 94% to 97% for third-generation cephalosporins.

Among neonates aged 4 to 7 days, 93% of those with late-onset sepsis and 82% of those with early-onset were admitted to the NICU more than 2 days before symptom onset. In addition, only 25% of culture results were available before discharge or death.

Although mother-to-child transmission of HIV has been greatly reduced, the researchers wrote, it has led to a growing number of infants who are HIV-exposed but uninfected. These patients are known to experience increased morbidity and mortality from impaired growth and development, while being at greater risk for sepsis and other infections. Because the researchers’ results were counterintuitive, Bates said, “We would be interested to hear from other units within the region to see if they also observe this counterintuitive trend.” He also said further in vivo and in vitro studies are warranted.

“In urban African settings, most neonatal deaths occur in hospitals, but interventions to reduce mortality are focused primarily within communities,” Bates said. “Strengthening neonatal units dogged by rampant nosocomial transmission of multidrug-resistant bacterial sepsis should be the central pillar of efforts to reduce neonatal deaths.”

Background: In sub-Saharan Africa there is scanty data on the causes of neonatal sepsis and antimicrobial resistance among common invasive pathogens that might guide policy and practice.
Methods: A cross-sectional observational prevalence and aetiology study of neonates with suspected sepsis admitted to the neonatal intensive care unit, University Teaching Hospital, Lusaka, Zambia, between October 2013 and May 2014. Data from blood cultures and phenotypic antibiotic susceptibility testing were compared with multivariate analysis of risk factors for neonatal sepsis.
Results: Of 313 neonates with suspected sepsis, 54% (170/313) were male. 20% (62/313) were born to HIV positive mothers. 33% (103/313) had positive blood cultures, of which 85% (88/103) were early onset sepsis (EOS).. Klebsiella species was the most prevalent isolate, accounting for 75% (77/103) of cases, followed by coagulase negative staphylococci (6% (7/103)), Staphylococcus aureus (6% (6/103)), Escherichia coli (5% (5/103) and Candida species (5% (5/103). For Klebsiella species antibiotic resistance ranged from 96-99% for WHO-recommended first line therapy (gentamicin and ampicillin/penicillin) to 94-97% for third generation cephalosporins. The prevalence of culture confirmed sepsis increased from 0-39% during the period Dec 2013-Mar 2014, during which time mortality increased 29-47%. 93% (14/15) of late onset sepsis (LOS) and 82% (37/45) of EOS aged 4-7 days were admitted > 2 days prior to onset of symptoms. Culture results for only 25% (26/103) of cases were available before discharge or death. Maternal HIV infection was associated with a reduced risk of neonatal sepsis (OR 0.46 [0.23-0.93], p=0.029).
Conclusion: Outbreaks of nosocomial multi-antibiotic resistant infections are an important cause of neonatal sepsis and associated mortality. Reduced risk of neonatal sepsis associated with maternal HIV infection is counterintuitive and requires further investigation.

Healio material
Pediatric Infectious Disease Journal abstract

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