Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

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).

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

SACCSG HL-2018. Barriers and enablers of a harmonized treatment protocol for childhood and adolescent Hodgkin lymphoma in South Africa.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

The effects of exposure to HIV in neonates at a referral hospital in South Africa.

BACKGROUND: Fewer infants are infected with HIV through mother-to-child transmission, making HIV-exposed but uninfected (HEU) infants a growing population. HIV-exposure seems to affect immunology, early growth and development, and is associated with higher morbidity and mortality rates. Currently, there is a lack of information regarding the clinical effects of HIV-exposure during the neonatal period. OBJECTIVES: To identify a possible difference in mortality and common neonatal morbidities in HEU neonates compared to HIV-unexposed neonates. METHODS: This was a retrospective, descriptive study of all neonates admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital between 1 January 2017 and 31 December 2018. HEU neonates were compared to HIV-unexposed neonates. RESULTS: There were 3236 neonates included, where 855 neonates were HEU. The HEU neonates had significantly lower birth weight and gestational age. The HEU neonates had higher rates of neonatal sepsis (19.8% vs 14.2%, OR 1.49, p <  0.001), specifically for late onset sepsis, and required more respiratory support. NCPAP and invasive ventilation was more common in the HEU group (36.3% vs 31.3% required NCPAP, p = 0.008, and 20.1% vs 15,0% required invasive ventilation, p <  0.001). Chronic lung disease was more common among HIV-exposed neonates (12.2% vs 8.7%, OR 1.46, p = 0.003). The difference in mortality rates between the study groups was not significant (10.8% of HEU neonates and 13.3% of HIV-unexposed). CONCLUSIONS: HEU neonates had higher rates of neonatal sepsis, particularly late-onset sepsis, required more respiratory support and had higher rates of chronic lung disease. Mortality of HEU neonates was not different HIV-unexposed neonates.

Congenital Rubella Syndrome Surveillance in South Africa Using a Sentinel Site Approach: A Cross-sectional Study.

BACKGROUND: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. METHODS: This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. RESULTS: There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). CONCLUSION: Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14-30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.

Factors associated with carotid intima media thickness in South African children with chronic kidney disease
.

BACKGROUND: Increased carotid intima media thickness (cIMT) is one of the early changes seen in chronic kidney disease (CKD) associated cardiovascular disease. This study aimed to determine cIMT measurements and its association with cardiovascular risk factors, including fibroblast growth factor-23 (FGF-23) and fetuin-A, in South African children with CKD. MATERIALS AND METHODS: 72 children (5 - 18 years) with CKD; 20 with CKD I, 23 with CKD II - IV, 29 with CKD V (on dialysis) were recruited. Each patient had a clinical examination and blood samples assessed for creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, total cholesterol, hemoglobin, C-reactive protein, vitamin D, fetuin-A, and FGF-23. cIMT was measured with high-resolution ultrasound. RESULTS: The mean age was 10.8 (3.5) years, and there were 49 males and 23 females (2 : 1). The overall median (range) cIMT was 0.505 mm (0.380 - 0.675) and was highest in patients with dialysis-dependent CKD (p = 0.003). Mean arterial pressure (MAP), hemoglobin, and PTH showed a significant correlation with cIMT (p < 0.001, p = 0.034, and p = 0.002, respectively). After adjusting for confounders in a multivariable analysis, disease duration, MAP, hemoglobin, and estimated glomerular filtration rate (eGFR) were independently associated with cIMT, p = 0.039, 0.001, 0.006, and 0.001, respectively. No significant relationship between cIMT and plasma levels of fetuin-A and FGF-23 was found. CONCLUSION: This study reports high cIMT measurements and their independent association with disease duration, MAP, hemoglobin, and eGFR. However, no similar association was found with fetuin-A and FGF-23.

Growth of extremely low birth weight infants at a tertiary hospital in a middle-income country.

BACKGROUND: Survival of extremely low birth weight (ELBW; birth weight less than 1000 g) infants has improved significantly since the 1990s. Consequently, growth monitoring in ELBW infants has gained more relevance. METHODS: We conducted this study to describe the growth of ELBW infants at a tertiary hospital, to audit macronutrient intake and explore the association of prematurity complications with growth. This was a retrospective study on 92 ELBW infants born at Charlotte Maxeke Johannesburg Academic Hospital. The association between good growth (regaining birth weight in 21 days or less and subsequent growth velocity > 15 g/kg/day) and complications of prematurity was explored. RESULTS: Only 11infants (13%) had a discharge weight above the 10th centile when the Fenton growth chart was used compared to 20 infants (22.4%) when the Intergrowth 21st Project growth standard was used. The mean weight velocity was 13.5 g/kg/day and the mean number of days to regain birth weight was 18.2 days. Factors associated with poor growth were late-onset sepsis, persistent patent ductus arteriosus, continuous positive airway pressure for more than 2 days, invasive ventilation, oxygen on day 28 and being kept nil per os. Protein and caloric intake correlate positively with growth velocity. Unlike the Fenton Growth Charts, use of the Intergrowth 21st Project growth standards revealed the association between neonatal factors and poor growth. CONCLUSION: Growth outcome in infants is poor at 36 weeks postmenstrual age at our institution. Intergrowth 21st Project growth standards were superior to Fenton Growth Charts, however a multicentre study is required before adoption.

A review of -multidrug-resistant Enterobacteriaceae in a neonatal unit in Johannesburg, South Africa.

BACKGROUND: Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. AIM: This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. METHODS: This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. RESULTS: There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo-ß lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. CONCLUSIONS: There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

Neurodevelopmental outcome of late preterm infants in Johannesburg, South Africa.

BACKGROUND: Late preterm infants, previously considered low risk, have been identified to be at risk of developmental problems in infancy and early childhood. There is limited information on the outcome of these infants in low and middle income countries. METHODS: Bayley scales of infant and toddler development, version III, were done on a group of late preterm infants in Johannesburg, South Africa. The mean composite cognitive, language and motor sub-scales were compared to those obtained from a group of typically developed control infants. Infants were considered to be "at risk" if the composite subscale score was below 85 and "disabled" if the composite subscale score was below 70. Infants identified with cerebral palsy were also reported. RESULTS: 56 of 73 (76.7%) late preterm infants enrolled in the study had at least one Bayley assessment at a mean age of 16.5 months (95% CI 15.2-17.6). The mean birth weight was 1.9 kg (95%CI 1.8-2.0) and mean gestational age 33.0 weeks (95% CI 32.56-33.51). There was no difference in the mean cognitive subscales between late preterm infants and controls (95.4 9, 95% CI 91.2-99.5 vs 91.9.95% CI 87.7-96.0). There was similarly no difference in mean language subscales (94.5, 95% CI 91.3-97.7 vs 95.9, 95% CI 92.9-99.0) or motor subscales (96.2, 95% CI 91.8-100.7 vs 97.6, 95% CI 94.7-100.5). There were four late preterm infants who were classified as disabled, two of whom had cerebral palsy. None of the control group was disabled. CONCLUSIONS: This study demonstrates that overall developmental outcome, as assessed by the Bayley scales of infant and toddler development, was not different between late preterm infants and a group of normal controls. However, 7.1% of the late preterm infants, had evidence of developmental disability. Thus late preterm infants in low and middle income countries require long term follow up to monitor developmental outcome. In a resource limited setting, this may best be achieved by including a parental screening questionnaire, such as the Ages and Stages Questionnaire, in the routine well baby clinic visits.

Comparison of morbidity and mortality of very low birth weight infants in a Central Hospital in Johannesburg between 2006/2007 and 2013.

BACKGROUND: Health protocols need to be guided by current data on survival and benefits of interventions within the local context. Periodic clinical audits are required to inform and update health care protocols. This study aimed to review morbidity and mortality in very low birth weight (VLBW) infants in 2013 compared with similar data from 2006/2007. METHODS: We performed a retrospective review of patients' records from a neonatal computer database for 562 VLBW infants. These neonates weighed between 500 and 1500 g at birth, and were admitted within 48 hours after birth between 01 January 2013 and 31 December 2013. Patients' characteristics, complications of prematurity, and therapeutic interventions were compared with 2006/2007 data. Univariate analysis and multiple logistic regression were performed to establish significant associations of various factors with survival to discharge for 2013. RESULTS: Survival in 2013 was similar to that in 2006/2007 (73.4% vs 70.2%, p = 0.27). However, survival in neonates who weighed 750-900 g significantly improved from 20.4% in 2006/2007 to 52.4% in 2013 (p = 0.001). The use of nasal continuous positive airway pressure (NCPAP) increased from 20.3% to 62.9% and surfactant use increased from 19.2% to 65.5% between the two time periods (both p < 0.001). Antenatal care attendance improved from 54.4% to 70.6% (p = 0.001) and late onset sepsis (>72 hours after birth) increased from 12.5% to 19% (p = 0.006) between the two time periods. Other variables remained unchanged between 2006/2007 and 2013. The main determinants of survival to discharge in 2013 were birth weight (odds ratio 1.005, 95% confidence interval 1.003-1.0007, resuscitation at birth (2.673, 1.375-5.197), NCPAP (0.247, 0.109-0.560), necrotising enterocolitis (4.555, 1.659-12.51), and mode of delivery, including normal vaginal delivery (0.456, 0.231-0.903) and vaginal breech (0.069, 0.013-0.364). CONCLUSIONS: There was a marked improvement in the survival of neonates weighing between 750 and 900 g at birth, most likely due to provision of surfactant and NCPAP. Provision of NCPAP, prevention of necrotising enterocolitis, and control of infection need to be prioritised in VLBW infants to improve their outcome.

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.

Background changing patterns of neonatal fungal sepsis in a developing country.

BACKGROUND: Candida albicans is the predominant isolate in many neonatal fungal bloodstream infections (BSIs), so fluconazole is used as empiric antifungal therapy. AIM: To determine the predominant organisms, antifungal sensitivity patterns, clinical and demographic risk factors and crude mortality rate in neonatal fungal BSI cases. SUBJECTS AND METHODS: This is a review of all neonatal fungal BSI cases between January 2007 and December 2011. RESULTS: Fifty-nine patients were included in the study. Candida parapsilosis (54.2%) was isolated in majority of the cases, followed by C. albicans (27.1%). Fluconazole resistance was present in 16 of 32 cases of C. parapsilosis versus 1 of 16 cases of C. albicans (P = 0.003). Mortality rate was 45.8%. Surgical problems were present in 55.9%. Death was significantly associated with lower birth weight (P = 0.046) and necrotizing enterocolitis (P = 0.034). CONCLUSIONS: The increase in neonatal fungal BSI and resistant organisms highlights the need to review use of routine empiric fluconazole and to implement preventive measures.

A review of necrotising enterocolitis in very low birth weight babies in a tertiary hospital in Johannesburg.

Introduction: Necrotising enterocolitis (NEC) is the most common gastrointestinal complication in pre-mature infants. There are risk factors and modifying factors that have been identified and studied over the years, but not many studies have been conducted in middle-income countries. Aims and Objectives: This study aimed to describe the maternal, obstetric and neonatal characteristics in very low birth weight (VLBW) babies with NEC in a tertiary neonatal unit in South Africa. The survival to hospital discharge in VLBW babies with NEC was also determined. Materials and Methods: This study was a retrospective, cross-sectional, observational study of VLBW babies admitted to a tertiary neonatal unit between January 2013 and December 2017. The population comprised babies <1500 g and <37 weeks gestation. Maternal and neonatal risk factors of NEC were compared in infants with and without NEC. Results: In this study, 173 out of 2111 (8%) babies were diagnosed with NEC. HIV exposure, late-onset sepsis, respiratory support after initial resuscitation, administration of surfactant and blood transfusion were associated with NEC. Surgery was performed in 48/173 (27.7%) of babies with NEC. The mortality rate in babies with NEC was 49.1%. Death in babies with NEC was associated with surgery for NEC (P = 0.01), mechanical ventilation (P < 0.001) and late-onset sepsis (P = 0.018). Conclusion: Risk factors for NEC in our population are similar to other countries, with some variations such as HIV. Even though some prevention measures have been implemented, the mortality rate remains high.

A Retrospective Observational Study of the Impact of HIV Status on the Outcome of Paediatric Intensive Care Unit Admissions at a Tertiary Hospital in South Africa (2015-2019).

HIV-infected and HIV-exposed but uninfected (HEU) children have unique health risks. Our study looked at how HIV exposure and infection impact presentation and outcomes in PICU in an era of improved ART. A retrospective analysis of children admitted to PICU was performed. The sample was divided into HIV negative, HEU and HIV infected, and presentation and outcomes were compared with a significance level set at α = 0.05. Our study showed that 16% (109/678) of children admitted to PICU were HEU and 5.2% (35/678) were HIV infected. HIV-infected children were admitted at a younger age (median two months) with an increased incidence of lower respiratory infections than HIV-negative children (p < 0.001); they also required longer ventilation and admission (p < 0.001). HIV-infected children had a higher mortality (40%) (p = 0.02) than HIV-negative (22.7%) children; this difference was not significant when comparing only children with a non-surgical diagnosis (p = 0.273). HEU children had no significant difference in duration of ICU stay (p = 0.163), ventilation (p = 0.443) or mortality (p = 0.292) compared to HIV-negative children. In conclusion, HIV-infected children presented with more severe disease requiring longer ventilation and admission. HEU had similar outcomes to HIV-negative children.

Multidrug-Resistant Bacterial Infections Among Very Low Birthweight Infants With Late-Onset Sepsis in Johannesburg, South Africa.

Background: An estimated 2.4 million babies died within the first 28 days of life in 2020. The third leading cause of neonatal death continues to be neonatal sepsis. Sepsis-causing bacterial pathogens vary temporally and geographically and, with a rise in multidrug-resistant organisms (MDROs), pose a threat to the neonatal population. Methods: This was a single-center, retrospective study of very low birth weight (VLBW) infants with late-onset sepsis (LOS) admitted to a neonatal unit in South Africa. We aimed to calculate the prevalence of multidrug-resistant (MDR) infections in this population. The data collected included demographic and clinical characteristics, length of hospital stay, risk factors for MDRO and mortality, and microbiology results. Logistic regression was used to assess the association between prespecified risk factors with MDR infections and mortality. Results: Of 2570 VLBW infants admitted, 34% had LOS, of which 33% was caused by MDROs. Infection with Acinetobacter spp., Pseudomonas spp., extended-spectrum beta-lactamase Klebsiella spp., or Escherichia coli was associated with the highest mortality in the LOS cohort. Infants with congenital infections (adjusted odds ratio [aOR], 5.13; 95% CI, 1.19-22.02; P = .028) or a history of necrotizing enterocolitis (aOR, 2.17; 95% CI, 1.05-4.49; P = .037) were at significantly higher risk for MDR infections. Conclusions: More than one-third of LOS cases in VLBW infants were caused by MDROs in this study. MDR infections cause substantial neonatal mortality. Antimicrobial stewardship programs, infection control protocols, and ongoing surveillance are needed to prevent further emergence and spread of MDR infections worldwide.

Developmental outcome of very low birth weight infants in a developing country.

BACKGROUND: Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa. METHODS: The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome. RESULTS: 178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69-91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85-90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0-93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome. CONCLUSION: Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age.

Factors influencing survival and short-term outcomes of very low birth weight infants in a tertiary hospital in Johannesburg.

Background: The neonatal mortality rate in South Africa is lower than the global average, but still approximately five times higher than some European and Scandinavian countries. Prematurity, and its complications, is the main cause (35%) of neonatal deaths. Objective: To review the maternal, delivery period and infant characteristics in relation to mortality in very low birth weight (VLBW) infants at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods: This was a retrospective descriptive study of VLBW infants admitted to CMJAH between 1 January 2017 and 31 December 2018. All infants with a birth weight between 500 to ≤ 1,500 grams were included. The characteristics and survival of these infants were described using univariate analysis. Results: Overall survival was 66.5%. Provision of antenatal steroids, antenatal care, Cesarean section, female sex, resuscitation at birth, and 5-min Apgar score more than five was related with better survival to discharge. Among respiratory diagnoses, 82.8% were diagnosed with RDS, 70.8% received surfactant therapy and 90.7% received non-invasive respiratory support after resuscitation. At discharge, 59.5% of the mothers were breastfeeding and 30.8% spent time in kangaroo mother care. Conclusion: The two-thirds survival rate of VLBW infants is similar to those in other developing countries but still remains lower than developed countries. This may be improved with better antenatal care attendance, coverage of antenatal steroids, temperature control after birth, improving infection prevention and control practices, breastfeeding rates and kangaroo mother care. The survival rate was lowest amongst extremely low birth weight (ELBW) infants.

Neurodevelopmental Outcomes of Extremely Low Birth Weight Survivors in Johannesburg, South Africa.

Background: Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes. Objectives: To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa. Methods: This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months. Results: There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2-877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1-27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2-18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1-101.7), language 89.9 (95% CI 87.3-92.5) and motor 97.6 (95% CI 94.5-100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be "at risk" for neurodevelopmental delay. Conclusion: Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.

Growth of a cohort of very low birth weight infants in Johannesburg, South Africa.

BACKGROUND: Little is known about the growth of VLBW infants in South Africa. The aim of this study was to assess the growth of a cohort of VLBW infants in Johannesburg. METHODS: A secondary analysis of a prospective cohort was conducted on 139 VLBW infants (birth weight ≤ 1500 g) admitted to Charlotte Maxeke Johannesburg Academic Hospital. Growth measurements were obtained from patient files and compared with the World Health Organization Child Growth Standards (WHO-CGS) and with a previous cohort of South African VLBW infants. The sample size per analysis ranged from 11 to 81 infants. RESULTS: Comparison with the WHO-CGS showed initial poor growth followed by gradual catch up growth with mean Z scores of 0.0 at 20 months postmenstrual age for weight, -0.8 at 20 months postmenstrual age for length and 0.0 at 3 months postmenstrual age for head circumference. Growth was comparable with that of a previous cohort of South African VLBW infants in all parameters. CONCLUSIONS: Initial poor growth in the study sample was followed by gradual catch up growth but with persistent deficits in length for age at 20 months postmenstrual age relative to healthy term infants.

Prognostic factors affecting survival in children and adolescents with HIV and Hodgkin lymphoma in South Africa.

South African children with Hodgkin lymphoma (HL) and human immunodeficiency virus (HIV) have low 5-year overall survival (OS) rates. In this retrospective multicenter study, 271 South African pediatric patients with HL were studied to determine OS and prognostic factors in those with HIV and HL. Univariate risk factor analysis was performed to analyze prognostic factors. The 29 HIV-infected patients were younger (p = .021), more likely to present with wasting (0.0573), stunting (0.0332), and Stage IV disease (p = .000) than HIV-uninfected patients. The 5- and 10-year OS of HIV-infected patients of 49% and 45% versus 84% and 79%, respectively for HIV-uninfected patients (p = .0001) appeared to be associated with hypoalbuminemia (<20 g/dL) and CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14), and second malignancy (1/14). HIV-infected pediatric patients with HL experience increased mortality due to post-therapy opportunistic and nosocomial infections.