Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries.
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SUBMITTER: Sands K
PROVIDER: S-EPMC8007471 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background99% of the approximate 1 million annual neonatal deaths from life-threatening invasive bacterial infections occur in developing countries, at least 50% of which are from home births or community settings. Data concerning aetiology of sepsis in these settings are necessary to inform targeted therapy and devise management guidelines. This review describes and analyses the bacterial aetiology of community-acquired neonatal sepsis in developing countries.MethodsA search of Medline, Embase, Global Health and Web of Knowledge, limited to post-1980, found 27 relevant studies. Data on aetiology were extracted, tabulated and analysed along with data on incidence, risk factors, case fatality rates and antimicrobial sensitivity.ResultsThe most prevalent pathogens overall were Staphylococcus aureus (14.9%), Escherichia coli (12.2%), and Klebsiella species (11.6%). However, variations were observed both between global regions and age-of-onset categories. Staphylococcus aureus and Streptococcus pneumoniae were most prevalent in Africa, while Klebsiella was highly prevalent in South-East Asia. A notably higher prevalence of Group B Streptococcus was present in neonates aged 7 days or less. The highest case fatality rates were recorded in South-East Asia. Klebsiella species showed highest antimicrobial resistance.ConclusionData on community-acquired neonatal sepsis in developing countries are limited. Future research should focus on areas of high disease burden with relative paucity of data. Research into maternal and neonatal vaccination strategies and improved diagnostics is also needed. All of this could contribute to the formulation of community-based care packages, the implementation of which has significant potential to lower overall neonatal mortality and hence advance progress towards the attainment of Millennium Development Goal 4.
| S-EPMC3484773 | biostudies-literature
Project description:BackgroundNeonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR.Methods and findingsAll studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria.ConclusionsGram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.
| S-EPMC8478175 | biostudies-literature
Project description:Klebsiella pnemoniae, Escherichia coli, Serratia marcescens, Enterobacter cloacae Assembly
| PRJNA1077801 | ENA
Project description:BackgroundNeonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs.MethodsThe Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality.FindingsBetween Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life.InterpretationFindings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs.FundingBill & Melinda Gates Foundation.
| S-EPMC9023753 | biostudies-literature
Project description: Not available
| S-EPMC6422246 | biostudies-literature
Project description:BackgroundBiomarkers may enhance diagnostic capability for common paediatric infections, especially in low- and middle-income countries (LMICs) where standard diagnostic modalities are frequently unavailable, but disease burden is high. A comprehensive understanding of the diagnostic capability of commonly available biomarkers for neonatal sepsis in LMICs is lacking. Our objective was to systematically review evidence on biomarkers to understand their diagnostic performance for neonatal sepsis in LMICs.MethodsWe conducted a systematic review and meta-analysis of studies published in English, Spanish, French, German, Dutch, and Arabic reporting the diagnostic performance of C reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and procalcitonin (PCT) for neonatal sepsis. We calculated pooled test characteristics and the area under the curve (AUC) for each biomarker compared with the reference standards blood culture or clinical sepsis defined by each article.ResultsOf 6570 studies related to biomarkers in children, 134 met inclusion criteria and included 23 179 neonates. There were 80 (59.7%) studies conducted in LMICs. CRP of ≥60 mg/L (AUC 0.87, 95% CI 0.76 to 0.91) among 1339 neonates and PCT of ≥0.5 ng/mL (AUC 0.87, 95% CI 0.70 to 0.92) among 617 neonates demonstrated the greatest discriminatory value for the diagnosis of neonatal sepsis using blood culture as the reference standard in LMICs.ConclusionsPCT and CRP had good discriminatory value for neonatal sepsis in LMICs. ESR and WBC demonstrated poor discrimination for neonatal sepsis in LMICs. Future studies may incorporate biomarkers into clinical evaluation in LMICs to diagnose neonatal sepsis more accurately.Prospero registration numberCRD42020188680.
| S-EPMC9835957 | biostudies-literature
Project description:BACKGROUND: Despite recent achievements to reduce child mortality, neonatal deaths continue to remain high, accounting for 41% of all deaths in children under five years of age worldwide, of which over 90% occur in low- and middle-income countries (LMICs). Infections are a leading cause of death and limitations in care seeking for ill neonates contribute to high mortality rates. As estimates for care-seeking behaviors in LMICs have not been studied, this review describes care seeking for neonatal illnesses in LMICs, with particular attention to type of care sought. METHODS AND FINDINGS: We conducted a systematic literature review of studies that reported the proportion of caregivers that sought care for ill or suspected ill neonates in LMICs. The initial search yielded 784 studies, of which 22 studies described relevant data from community household surveys, facility-based surveys, and intervention trials. The majority of studies were from South Asia (n?=?17/22), set in rural areas (n?=?17/22), and published within the last 4 years (n?=?18/22). Of the 9,098 neonates who were ill or suspected to be ill, 4,320 caregivers sought some type of care, including care from a health facility (n?=?370) or provider (n?=?1,813). Care seeking ranged between 10% and 100% among caregivers with a median of 59%. Care seeking from a health care provider yielded a similar range and median, while care seeking at a health care facility ranged between 1% and 100%, with a median of 20%. Care-seeking estimates were limited by the few studies conducted in urban settings and regions other than South Asia. There was a lack of consistency regarding illness, care-seeking, and care provider definitions. CONCLUSIONS: There is a paucity of data regarding newborn care-seeking behaviors; in South Asia, care seeking is low for newborn illness, especially in terms of care sought from health care facilities and medically trained providers. There is a need for representative data to describe care-seeking patterns in different geographic regions and better understand mechanisms to enhance care seeking during this vulnerable time period.
| S-EPMC3295826 | biostudies-literature
Project description:Background: Babies born weighing???2500 g account for more than 80% of the births in most resource-limited locations and for nearly 50% of the 28-day neonatal deaths. In contrast, in high-resource settings, 28-day neonatal mortality among this group represents only a small fraction of the neonatal deaths. Yet mortality risks for birth weight of???2500 g is limited. Knowledge regarding the factors associated with mortality in these babies will help in identifying interventions that can reduce mortality.Methods: The Global Network's Maternal Newborn Health Registry (MNHR) is a prospective, population-based observational study that includes all pregnant women and their pregnancy outcomes in defined geographic communities that has been conducted in research sites in six low-middle income countries (India, Pakistan, Democratic Republic of Congo, Guatemala, Kenya and Zambia). Study staff enroll all pregnant women as early as possible during pregnancy and conduct follow-up visits to ascertain delivery and 28-day neonatal outcomes. We analyzed the neonatal mortality rates (NMR) and risk factors for deaths by 28 days among all live-born babies with a birthweight???2500 g from 2010 to 2018 across the Global Network sites.Results: Babies born in the Global Network sites from 2010 to 2018 with a birthweight???2500 g accounted for 84.8% of the births and 45.4% of the 28-day neonatal deaths. Among this group, the overall NMR was 13.1/1000 live births. The overall 28-day NMR for ongoing clusters was highest in Pakistan (29.7/1000 live births) and lowest in the Zambian/Kenyan sites (9.3/1000) for???2500 g infants.???2500 g NMRs declined for Zambia/Kenya and India. For Pakistan and Guatemala, the NMR remained almost unchanged over the period. The???2500 g risks related to maternal, delivery and newborn characteristics varied by site. Maternal factors that increased risk and were common for all sites included nulliparity, hypertensive disease, previous stillbirth, maternal death, obstructed labor, severe postpartum hemorrhage, and abnormal fetal presentation. Neonatal characteristics including resuscitation, hospitalization, congenital anomalies and male sex, as well as lower gestational ages and birthweights were also associated with increased mortality.Conclusions: Nearly half of neonatal deaths in the Global Network sites occurred in infants born weighing???2500 g. The NMR for those infants was 13.1 per 1000 live births, much higher than rates usually seen in high-income countries. The changes in NMR over time varied across the sites. Even among babies born???2500 g, lower gestational age and birthweight were largely associated with increased risk of mortality. Since many of these deaths should be preventable, attention to preventing mortality in these infants should have an important impact on overall NMR.Trial registration: https://ClinicalTrials.gov Identifier: NCT01073475.
| S-EPMC7706246 | biostudies-literature
Project description:Almost half of under-five deaths occur during the neonatal period. Delivery with a skilled attendant, adherence to essential newborn care (ENC) and postnatal care (PNC) standards, and immediate treatment of infections are essential to improve neonatal survival. This article uses Demographic and Health Survey data from 45 low- and middle-income countries to assess 1) levels of ENC and PNC that mothers and newborns receive and how this differs by place of delivery and 2) levels of and sources for care-seeking for neonates sick with fever. For five of the ten ENC and PNC indicators assessed, less than two-thirds of mothers and newborns received care in alignment with global standards. Adherence is higher in private facilities than public facilities for all indicators other than immediate breastfeeding and skin-to-skin contact. Except for immediate breastfeeding, adherence is lowest for newborns born at home with a skilled birth attendant (SBA). Socioeconomic disparities exist in access to skilled delivery and adherence to ENC and PNC, with the largest disparities among newborns delivered at home with a SBA. Private provider adherence to ENC and PNC standards was relatively high for newborns from the wealthiest families, indicating that meeting recommended guidelines is achievable. On average across the 45 countries, half of caregivers for neonates with fever sought care outside the home and 45 percent of those sought care from the private sector. There were substantial socioeconomic disparities in care-seeking for fever, but illness prevalence and sources of care seeking were consistent across wealth quintiles. Closing inequities in neonatal care and care seeking and ensuring that all families, including the poorest, can access high quality maternal and newborn care is crucial to ensure equity and accelerate reductions in neonatal and child mortality.
| S-EPMC9295978 | biostudies-literature
Project description:BackgroundIn low- and middle-income countries (LMIC) Staphylococcus aureus is regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB).MethodsWe characterised GPB isolates from neonatal blood cultures from LMICs in Africa (Ethiopia, Nigeria, Rwanda, and South Africa) and South-Asia (Bangladesh and Pakistan) between 2015-2017. We determined minimum inhibitory concentrations and performed whole genome sequencing (WGS) on Staphylococci isolates recovered and clinical data collected related to the onset of sepsis and the outcome of the neonate up to 60 days of age.ResultsFrom the isolates recovered from blood cultures, Staphylococci species were most frequently identified. Out of 100 S. aureus isolates sequenced, 18 different sequence types (ST) were found which unveiled two small epidemiological clusters caused by methicillin resistant S. aureus (MRSA) in Pakistan (ST8) and South Africa (ST5), both with high mortality (n = 6/17). One-third of S. aureus was MRSA, with methicillin resistance also detected in Staphylococcus epidermidis, Staphylococcus haemolyticus and Mammaliicoccus sciuri. Through additional WGS analysis we report a cluster of M. sciuri in Pakistan identified between July-November 2017.ConclusionsIn total we identified 14 different GPB bacterial species, however Staphylococci was dominant. These findings highlight the need of a prospective genomic epidemiology study to comprehensively assess the true burden of GPB neonatal sepsis focusing specifically on mechanisms of resistance and virulence across species and in relation to neonatal outcome.
| S-EPMC9254428 | biostudies-literature