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The spread of extended-spectrum-␤-lactamase-producing Enterobacteriaceae (ESBL-PE) in low-income countries, where the burden of neonatal sepsis is high, may have a serious impact on neonatal mortality rates. Given the potential for mother-to-child transmission of multiresistant bacteria, this study investigated the ESBL-PE rectal colonization among pregnant women at delivery in the community in Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to 22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo-␤-lactamase-1 (NDM-1) producer. Severe bacterial infections are responsible for a large number of neonatal deaths in low-income countries (LICs) (1, 2), with Enterobacteriaceae most frequently isolated in neonatal sepsis (3,4). The production of plasmid-borne extended-spectrum ␤-lactamases (ESBL) is the main mechanism of resistance against expanded-spectrum cephalosporins (ESC) among Enterobacteriaceae, with the CTX-M-15 variant being the most common enzyme (5). In LICs, where neonatal sepsis caused by ESBL-producing Enterobacteriaceae (ESBL-PE) may be associated with higher fatality rates (6), colonized mothers could represent a source of transmission to neonates. The objectives of this study were to estimate the prevalence of ESBL-PE rectal colonization among pregnant women in Madagascar in an urban area, Antananarivo, and a semirural area, Moramanga, and to identify associated risk factors.This study was conducted in the context of an international pediatric cohort, the BIRDY (bacterial infections and antibiotic resistance disease among young children in low-income countries) program, approved by the Ethics Committees of Ministry of Health, Madagascar, and Institut Pasteur, France. All pregnant women living in the study areas were identified by medical or community workers and enrolled after giving written informed consent. A stool sample was taken at delivery for ESBL-PE screening. Among the women enrolled, 356 gave birth between June 2013 and March 2014 and were included in the present study. A risk factor analysis was conducted on a subset of 231 women who delivered during a 6-month period (June to September 2013 and January to March 2014). Sociodemographic characteristics, previous health care exposure, and antibiotic consumption (collected with prescription documents, remaining tablets, or visual aid) were recorded. Fresh stools were plated onto Drigalski agar supplemented with 3 mg/liter of ceftriaxone at the clinical laboratory of Institut Pasteur of Madagascar. Plates were incubated for 24 to 48 h at 37°C. Every oxidase and Gram-negative colony type was Citation Chereau F, Herindrainy P, Garin B, Huynh B-T, Randrianirina F, Padget M, Piola P, Guillemot D, Delarocque-Astagneau E. 2015. Colonization of extendedspectrum-␤-lactamase-and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates.

BackgroundAntibiotic resistance is a threat in developing countries (DCs) because of the high burden of bacterial disease and the presence of risk factors for its emergence and spread. This threat is of particular concern for neonates in DCs where over one-third of neonatal deaths may be attributable to severe infections and factors such as malnutrition and HIV infection may increase the risk of death. Additional, undocumented deaths due to severe infection may also occur due to the high frequency of at-home births in DCs.MethodsWe conducted a systematic review of studies published after 2000 on community-acquired invasive bacterial infections and antibiotic resistance among neonates in DCs. Twenty-one articles met all inclusion criteria and were included in the final analysis.ResultsNinety percent of studies recruited participants at large or university hospitals. The majority of studies were conducted in Sub-Saharan Africa (n = 10) and the Indian subcontinent (n = 8). Neonatal infection incidence ranged from 2.9 (95% CI 1.9–4.2) to 24 (95% CI 21.8–25.7) for 1000 live births. The three most common bacterial isolates in neonatal sepsis were Staphylococcus aureus, Escherichia coli, and Klebsiella. Information on antibiotic resistance was sparse and often relied on few isolates. The majority of resistance studies were conducted prior to 2008. No conclusions could be drawn on Enterobacteriaceae resistance to third generation cephalosporins or methicillin resistance among Staphylococcus aureus.ConclusionsAvailable data were found insufficient to draw a true, recent, and accurate picture of antibiotic resistance in DCs among severe bacterial infection in neonates, particularly at the community level. Existing neonatal sepsis treatment guidelines may no longer be appropriate, and these data are needed as the basis for updated guidelines. Reliable microbiological and epidemiological data at the community level are needed in DCs to combat the global challenge of antibiotic resistance especially among neonates among whom the burden is greatest.

Severe bacterial infections are a leading cause of death among neonates in low-income countries, which harbor several factors leading to emergence and spread of multidrug-resistant bacteria. Low-income countries should prioritize interventions to decrease neonatal infections; however, data are scarce, specifically from the community. To assess incidence, etiologies, and antimicrobial drug–resistance patterns of neonatal infections, during 2012–2014, we conducted a community-based prospective investigation of 981 newborns in rural and urban areas of Madagascar. The incidence of culture-confirmed severe neonatal infections was high: 17.7 cases/1,000 live births. Most (75%) occurred during the first week of life. The most common (81%) bacteria isolated were gram-negative. The incidence rate for multidrug-resistant neonatal infection was 7.7 cases/1,000 live births. In Madagascar, interventions to improve prevention, early diagnosis, and management of bacterial infections in neonates should be prioritized.

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In low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0–13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns.

Background Antimicrobial resistance is widely considered an urgent global health issue due to associated mortality and disability, societal and healthcare costs. Aim To estimate the past, current and projected future proportion of infections resistant to treatment for eight priority antibiotic-bacterium combinations from 2000 to 2030 for 52 countries. Methods We collated data from a variety of sources including ResistanceMap and World Bank. Feature selection algorithms and multiple imputation were used to produce a complete historical dataset. Forecasts were derived from an ensemble of three models: exponential smoothing, linear regression and random forest. The latter two were informed by projections of antibiotic consumption, out-of-pocket medical spending, populations aged 64 years and older and under 15 years and real gross domestic product. We incorporated three types of uncertainty, producing 150 estimates for each country-antibiotic-bacterium-year. Results Average resistance proportions across antibiotic-bacterium combinations could grow moderately from 17% to 18% within the Organisation for Economic Co-operation and Development (OECD; growth in 64% of uncertainty sets), from 18% to 19% in the European Union/European Economic Area (EU/EEA; growth in 87% of uncertainty sets) and from 29% to 31% in Group of Twenty (G20) countries (growth in 62% of uncertainty sets) between 2015 and 2030. There is broad heterogeneity in levels and rates of change across countries and antibiotic-bacterium combinations from 2000 to 2030. Conclusion If current trends continue, resistance proportions are projected to marginally increase in the coming years. The estimates indicate there is significant heterogeneity in resistance proportions across countries and antibiotic-bacterium combinations.

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