Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

High Incidence Rates of Early-onset Bacterial Sepsis in Infants Born in Two Brazilian Maternities: A 15-Year Retrospective Analysis.

BACKGROUND: Data on the burden and etiology of neonatal early-onset bacterial sepsis (EOBS) in low-to-middle-income countries are scarce. Surveillance is critical for optimizing prevention and treatment strategies. We aimed to estimate the incidence of EOBS in 2 large Brazilian cohorts of neonates. METHODS: Data were retrospectively obtained from 33,794 neonates born between 2009 and 2017 at low-risk (n = 17,981) and high-risk maternity centers (n = 15,813). Blood cultures were taken within 72 hours of life from neonates with perinatal risk factors for EOBS or suspected EOBS. A positive blood culture for a pathogenic microorganism and a compatible clinical evolution confirmed the diagnosis of EOBS. RESULTS: One-third of the infants born from high-risk and 18.5% from low-risk maternities were investigated for EOBS. Overall, EOBS was more incident in neonates born in the high-risk facilities [66 cases or 4.2/1000 (95% CI: 3.2-5.3)] than in the low-risk facilities [24 cases or 1.3/1000 (95% CI: 0.9-2.0)]. The incidence rate of EOBS increased with decreasing gestational age (<32 weeks: 20.5/1000; 32-36 weeks: 5.6/1000; ≥37 weeks: 1.5/1000). Group B Streptococcus (GBS) was the agent more frequently identified in high-risk and low-risk maternities: 1.8/1000 (95% CI: 1.1-2.4) and 0.4/1000 (95% CI: 0.2-0.9), respectively. EOBS's overall case fatality rate was 17.8% for all the agents and 22% for GBS. CONCLUSIONS: EOBS remains unacceptably high and is frequently fatal in preterm and term infants cared for in high- or low-risk maternities. Because GBS has emerged as the most frequent causative agent, preventive strategies are urgently needed.

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil.

OBJECTIVES: To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. METHODS: Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. RESULTS: Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4-8.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. CONCLUSIONS: The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.