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.

Characteristics and outcomes of neonates with intrapartum asphyxia managed with therapeutic hypothermia in a public tertiary hospital in South Africa.

BACKGROUND: In randomized clinical trials, therapeutic hypothermia (TH) has been shown to reduce death and/or moderate-to-severe disability in neonates with hypoxic ischemic encephalopathy (HIE) in high-income countries, while this has not consistently been the case in low-and middle-income countries (LMICs). Many studies reporting on outcomes of neonates with HIE managed with TH are those conducted under controlled study conditions, and few reporting in settings where this intervention is offered as part of standard of care, especially from LMICs. In this study we report on short-term outcomes of neonates with moderate-to-severe HIE where TH was offered as part of standard of care. OBJECTIVE: To determine characteristics and mortality rate at hospital discharge in neonates with moderate-to-severe HIE. METHODS: Hospital records of neonates with intrapartum asphyxia were reviewed for clinical findings, management with TH (cooled or non-cooled) and mortality at hospital discharge. Inclusion criteria were birthweight ≥ 1800 g, gestational age ≥ 36 weeks and moderate-to-severe HIE. Comparisons were made between survivors and non-survivors in cooled and/or non-cooled neonates. RESULTS: Intrapartum asphyxia was diagnosed in 856 neonates, with three having no recorded HIE status; 30% (258/853) had mild HIE, and 595/853 (69%) with moderate-to-severe HIE. The overall incidence of intrapartum asphyxia was 8.8/1000 live births. Of the 595 with moderate-to-severe HIE, three had no records on cooling and 67% (399/592) were cooled. Amongst 193 non-cooled neonates, 126 (67%) had documented reasons for not being cooled with common reasons being a moribund neonate (54.0%), equipment unavailability (11.1%), pulmonary hypertension (9.5%), postnatal age > 6 h on admission (8.7%), and improvement in severity of encephalopathy (8.7%). Overall mortality was 29.0%, being 17.0% and 53.4% in cooled and non-cooled infants respectively. On multivariate analysis, the only factor associated with mortality was severe encephalopathy. CONCLUSION: Overall mortality in neonates with moderate-to-severe HIE was 29.0% and 17.0% in those who were cooled. Cooling was not offered to all neonates mainly because of severe clinical illness, equipment unavailability and delayed presentation, making it difficult to assess overall impact of this intervention. Prospective clinical studies need to be conducted in LMIC to further assess effect of TH in short and long-term outcomes.

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review.

OBJECTIVE: To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa. METHODS: Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available. RESULTS: There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5-0.7];p = <0.001). Gram-negative infection rates increased from 4.3 to 10.8/1000 patient-days (estimated average yearly change 0.7[95%CI,0.6-0.8];p = <0.001). The 2 most commonly isolated Gram-negative organisms were Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];p<0.001). Gram-positive infection rates decreased (estimated average yearly change -0.1[95%CI,-0.2- -0.05];p = <0.001). Staphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%-2%],p< 0.001). Rates of fungal isolates decreased (estimated average yearly change -0.06[95%CI,-0.1 --0.02]);p = 0.007). Candida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated. CONCLUSIONS: There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.

An outbreak of infection due to severe acute respiratory corona virus-2 in a neonatal unit from a low and middle income setting.

Introduction: The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods: Contact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24-72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection. Results: Twelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time. Conclusion: We report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.

Characteristics and Outcomes of Neonates With Blood Stream Infection Due to Listeria monocytogenes.

BACKGROUND: Infection due to Listeria monocytogenes (LM) is rare in neonates; thus, its clinical presentation and outcomes are not commonly reported, especially in low- and middle-income countries. In 2017, South Africa had an outbreak due to LM. OBJECTIVE: To determine demographic characteristics, clinical and laboratory findings and outcomes of all neonates infected with LM during the outbreak period. METHODS: This is a retrospective analytic study. Clinical and laboratory records of neonates admitted at Chris Hani Baragwanath Academic Hospital from January 2017 to May 2018 with positive blood and cerebrospinal fluid culture with LM were reviewed for demographic characteristics, clinical presentation, ancillary laboratory test results and outcomes at hospital discharge. RESULTS: There were 42 neonates with positive cultures due to LM. Thirty-four (81%) were born preterm. Mode of delivery was vaginal in 78.6% and 31.0% were HIV exposed. All patients presented within the first 6 days of life as an early-onset disease. Common clinical presentation was respiratory depression (52.4%) and respiratory distress (38.1%) with 69% requiring invasive or noninvasive respiratory support. Common abnormal laboratory findings were high C-reactive protein (77.1%) followed by leukopenia (23.8%). Fourteen patients (40%) had features of meningitis based on blood and cerebrospinal fluid findings (4 culture proven). There were 11 deaths at hospital discharge, giving a mortality rate of 26.2%. CONCLUSIONS: The majority of neonates infected with LM were born preterm, raising the possibility that LM itself may have been responsible for preterm labor. All presented in the first 6 days of life and most presented with respiratory distress or depression. A high proportion had meningitis, and there was a high-mortality overall.