Meningitis is a serious problem in newborn infants and has high mortality and frequent neurological sequelae. In neonates, signs and symptoms of serious infections are often obscure and clinical ...examination cannot distinguish septicemic babies with or without meningitis. Therefore, lumbar puncture is often not done in time and thus diagnosis of meningitis is missed. This study aimed to discover the prevalence of meningitis among these cases based on laboratory investigation. We prospectively enrolled the blood culture positive septicaemia cases which were not labeled as cases of meningitis during routine clinical evaluation. Out of 30 septicemic cases, eight (26.7%) had abnormal CSF cytology and biochemistry suggestive of meningitis. Among these eight cases, four had positive CSF culture; Klebsiella pneumoniae (n = 3) and Pseudomonas aeruginosa (n = 1), which were similar to the blood isolate of the respective patient. The clinical manifestations were similar in both septicemia and meningitis cases. Mortality was high among the meningitis cases compared with those having septicemia alone (37.5% vs. 13.3%), indicating the need for early diagnosis of this disease. Our data confirmed that it is important to do a lumbar puncture, along with blood culture, for all suspected septicemia cases.
There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, ...and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.
Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability.
Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis.
ClinicalTrials.gov, (NCT03721302).
Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well ...characterized.
Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques.
Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0-6 days of age and 5712 7-59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0-6 days of age (44/424) and 10.9% of infants 7-59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%).
This large study of young infants aged 0-59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.
Background There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical ...outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1—Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2—“Low” Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3—“Medium” Watch), 18.0% (n = 566) started a carbapenem (Group 4—“High” Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration ClinicalTrials.gov, (NCT03721302). James Neal Russell and colleagues report a global neonatal sepsis observational cohort study (NeoOBS) exploring patterns of antibiotic use, pathogens and prediction of mortality in hospitalised neonates and young infants with sepsis. Author summary Why was this study done? Increasing trends in antimicrobial resistance (AMR) disproportionately affect neonates and young infants with sepsis in LMIC settings and undermine the effectiveness of WHO-recommended antibiotics. Despite this, longitudinal data on antibiotic management strategies and outcomes of hospitalized neonates and young infants with sepsis in low- and middle-income country (LMIC) settings are extremely limited, impeding the design of robust antibiotic trials. There is limited data to define risk stratification, inclusion, and escalation criteria in trials of sepsis in hospitalized neonates and young infants. What did the researchers do and find? In this large global, prospective, hospital-based observational study across 4 continents, including LMIC settings, there was a high mortality among infants with culture positive sepsis (almost 1 in 5), and a significant burden of antibiotic resistance. This study highlights wide variations in standard of care (SOC) for sepsis in neonates and young infants, with more than 200 different antibiotic combinations, significant divergence from WHO-recommended regimens, and frequent switching of antibiotics. A NeoSep Severity Score that defined patterns of mortality risk at baseline was developed from 4 non-modifiable and 6 modifiable factors that are feasible to measure across a range of LMIC hospital contexts. A NeoSep Recovery Score including the same modifiable factors (with the addition of cyanosis) predicted mortality on the following day during treatment. What do these findings mean? These data demonstrate that patterns of routine antibiotic use are now markedly divergent from global guidance. There is an urgent need for large pragmatic randomized controlled trials to address optimal empiric first- and second-line antibiotic treatment strategies in LMIC hospital settings with a significant AMR burden. The wide range of multiple antibiotic regimens routinely used as SOC suggests the need for novel trial designs. The NeoSep Severity Score and NeoSep Recovery Score informed inclusion and escalation criteria in the NeoSep1 antibiotic trial (ISRCTN48721236) that aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis.
The skin is a potential source for invasive infections in neonates from developing countries such as Bangladesh, where the level of environmental contamination is exceedingly high. A randomized ...controlled trial was conducted from 1998 to 2003 in the Special Care Nursery of a tertiary hospital in Bangladesh to test the effectiveness of topical emollient therapy in enhancing the skin barrier of preterm neonates less than 33 weeks of gestational age. In the initial months of the study, the infection and mortality rates were noted to be unacceptably high. Therefore, an infection control program was introduced early in the trial to reduce the rate of nosocomial infections.
After a comprehensive review of neonatal care practices and equipment to identify sources of nosocomial infections, a simple but comprehensive infection control program was introduced that emphasized education of staff and caregivers about measures to decrease risk of contamination, particularly hand-washing, proper disposal of infectious waste, and strict asepsis during procedures, as well as prudent use of antibiotics.
Infection control efforts resulted in declines in episodes of suspected sepsis (47%), cases of culture-proven (61%) sepsis, patients with a clinical diagnosis of sepsis (79%), and deaths with clinical (82%) or culture-proven sepsis (50%).
The infection control program was shown to be a simple, low-cost, low-technology intervention to reduce substantially the incidence of septicemia and mortality in the nursery.
The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 ...million deaths occurring in those aged 1-59 months 53% of all deaths in children aged <5 years). More detailed characterization of childhood deaths could inform interventions to improve child survival.
To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia.
The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021.
The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies.
In this study, MITS was performed in 632 deceased children (mean SD age at death, 1.3 0.3 years; 342 54.1% male). The 6 most common underlying causes of death were malnutrition (104 16.5%), HIV (75 11.9%), malaria (71 11.2%), congenital birth defects (64 10.1%), lower respiratory tract infections (LRTIs; 53 8.4%), and diarrheal diseases (46 7.2%). When considering immediate causes only, sepsis (191 36.7%) and LRTI (129 24.8%) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths 28.2%; 127 81.9% considered nosocomial), Plasmodium falciparum (122 of 549 22.2%), and Streptococcus pneumoniae (109 of 549 19.9%). Other organisms, such as cytomegalovirus (57 10.4%) and Acinetobacter baumannii (39 7.1%; 35 of 39 89.7% considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions.
In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death.
The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical ...information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1–59 months enrolled in the CHAMPS Network.
In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24–72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards.
Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4–19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 35·3%), Klebsiella pneumoniae (78 25·5%), and non-typeable Haemophilus influenzae (37 12·1%). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 43·0%), Acinetobacter baumannii (19 12·8%), S pneumoniae (15 10·1%), and Pseudomonas aeruginosa (15 10·1%). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus.
Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens.
Bill & Melinda Gates Foundation.
IMPORTANCE: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and ...Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. OBJECTIVE: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. MAIN OUTCOMES AND MEASURES: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). RESULTS: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths 49.4%, 496 of 1340 neonatal deaths 37.0%), clinical management and quality of care (stillbirths, 280 23.5%; neonates, 498 37.2%; infants and children, 393 of 860 45.7%), health-seeking behavior (infants and children, 237 27.6%), and health education (infants and children, 262 30.5%). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns.
y, mainly due to infections and complications of prematurity. The present article is a descriptive analysis of the most common reasons for hospital admission of VLBW infants, morbidity during ...hospital stay, and their immediate outcome at a community level medical college hospital in Bangladesh. Sixty VLBW neonates (< 1,500 grams weight), 37 males and 23 females, < 72 hours of age were enrolled prospectively from March 2005 to February 2007; 4 babies were excluded. Thirty-four babies were hospital born and 26 home delivered cases admitted postnatally. The mean birth weight and gestational age of the newborns were 1270 ± 169 grams and 30.9 ± 2.9 weeks respectively. Forty-one of 60 cases (68.3%) mothers received at least one antenatal care visit. Common clinical presentations were prematurity alone (36.7%) and its complications like delayed crying (25.0%), feeding problem (23.3%), lethargy (16.7%), hypothermia (10.0%) and respiratory problem (8.3%). The commonest morbidity during hospital stay was neonatal hyperbilirubinemia requiring phototherapy (26.7%), apnoea of prematurity (15.0%), and septicaemia (11.7%). The overall survival rate was 56.7%; most of the deceased cases were those < 1250 grams (15/28, 53.6%) and < 30 weeks of gestation (17/30, 56.7%). No infant with a birth weight < 850 grams or a gestational age < 28 weeks survived. The most common cause of death was birth asphyxia (38.5%), followed by extreme prematurity (26.9%), and septicaemia (19.2%). Very low birth weight infants had relatively higher survival rates probably due to low infection rate. DOI: 10.3329/jbcps.v26i3.4196 J Bangladesh Coll Phys Surg 2008; 26: 128-134
BACKGROUND:The etiology of >90% of cases of suspected neonatal infection remains unknown. We conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region ...in Bangladesh from June 2006 to September 2007 to assess the incidence and etiology of community-acquired viral infections among neonates.
METHODS:Community health workers (CHWs) assessed neonates at home on days 0, 2, 5 and 8 after birth and referred cases of suspected illness to the hospital (CHW surveillance). Among neonates with clinically suspected upper respiratory tract infection (URTI), pneumonia, sepsis and/or meningitis, virus identification studies were conducted on nasal wash, cerebrospinal fluid and/or blood specimens. In the hospital-based surveillance, similar screening was conducted among all neonates (referred by CHWs and self-referred) who were admitted to the hospital.
RESULTS:CHW surveillance found an incidence rate of 15.6 neonatal viral infections per 1000 live births with 30% of infections identified on the day of birth. Among neonates with suspected sepsis, a viral etiology was identified in 36% of cases, with enterovirus accounting for two-thirds of those infections. Respiratory syncytial virus was the most common etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was a low incidence (1.2%) of influenza in this rural population.
CONCLUSION:Viral infections are commonly associated with acute newborn illness, even in the early neonatal period. The estimated incidence was 5-fold greater than reported previously for bacterial infections. Low-cost preventive measures for neonatal viral infections are urgently needed.
PDF
