Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis

Abstract

Introduction Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics. Objectives Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis. Methods At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression. Results Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics. Conclusion There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.

Early-Onset Neonatal Sepsis in Low- and Middle-Income Countries: Current Challenges and Future Opportunities

“… 2 , 11 The place of birth, whether the neonate is born within the hospital (ie “inborn”), or the neonate was admitted to hospital with signs of sepsis (ie “outborn”), are often used when analysing the epidemiology and risk factors of neonatal sepsis. 13–15 Data from previous studies suggests that EOS correlates to maternal gut microbiome colonisation with vertical transmission between the mother and neonate. 16–19 …”

Emerging Antibiotic Resistance Patterns in a Neonatal Intensive Care Unit in Pune, India: A 2-Year Retrospective Study

“…Of positive cultures from the same neonates, 50% (5/10) were unique infections with the same organism, but minimal changes to susceptibility patterns were noted on AST. The median time between unique infections for these neonates was 14 days (IQR [9][10][11][12][13][14][15][16][17][18][19].…”

“…There were similar levels of resistance to all drugs within most antibiotic classes, with the exception of aminoglycosides; isolates showed more susceptibility to amikacin, compared to gentamicin. This discrepancy exists in other areas of India as well as in other LMIC countries (12)(13)(14). The high rate of resistance to gentamicin likely is influenced by widespread use driven by its inclusion as a firstline antibiotic for neonatal sepsis in the WHO's guidelines (15).…”

Fighting Antimicrobial Resistance in Neonatal Intensive Care Units: Rational Use of Antibiotics in Neonatal Sepsis

“…Of note, the resistance of Gram-negative bacteria to traditional antibiotics is increasing [ 83 ]. This is due in part to the plasmid-mediated intergenic transfer of new resistance genes that has been observed among resistance genes for extended-spectrum beta-lactamases (ESBL) between Escherichia coli and Klebsiella pneumoniae , as well as among other enterobacteriaceae [ 84 ]. MDR Gram-negative bacteria are the greatest concern in the neonatal population and have very limited therapeutic options [ 84 , 85 ].…”