Epidemiology of acinetobacter sepsis in infants admitted to a neonatal unit

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Master in Medicine. Johannesburg 2015Background: Acinetobacter baumannii (A. baumannii) is emerging as one of the pathogens causing sepsis in neonates. Prevalence, antibiotic susceptibilities and case-fatality rate (CFR) of A. baumannii in the neonatal units are not well known. Objective: To determine the prevalence, antibiotic susceptibility patterns and CFR of A. baumannii infection in neonates. Methods: Medical records of neonates admitted to Chris Hani Baragwanath Academic Hospital from 1st October 2007 to 31st October 2011 with a positive blood or cerebrospinal fluid culture due to A. baumannii were reviewed for demographic characteristics, clinical presentation, laboratory findings, antibiotic susceptibility and outcome. Results: There were 399 isolates of A. baumannii, with a prevalence of 4.3/1000 live births or 2/ 1000 patient-days, and accounting for 13% of all bacterial and fungal isolates. Antimicrobial susceptibility results were available for 379 isolates and only 155 medical records could be retrieved for analysis. The mean gestational age and birth weight of infected neonates was 30 weeks and 1400 grams respectively. Thirty seven (24%) were isolated from neonates with early onset sepsis and 118 (76%) from those with late onset sepsis. Sixty four percent of isolates were susceptible to Cephalosporins, 21% to Aminoglycosides and 17% were multi-drug resistant (MDR) isolates. The CFR was 32%. Factors associated with mortality were presence of a central venous catheter prior to onset of sepsis (49% vs 31%, p=0.03); need for ventilatory support (62% vs 36%, p=0.005) and inotropic support (57% vs 17%, p<0.001). Conclusions: A. baumannii is a common pathogen causing sepsis in neonates, with 17% of them being MDR. It is associated with high CFR. These findings highlight the need for strict enforcement of infection control and antibiotic stewardship practices.MB201

Incidence and All-Cause Mortality Rates in Neonates Infected With Carbapenem Resistant Organisms

INTRODUCTION: Multidrug-resistant, Gram-negative infections, particularly due to carbapenem resistant organisms (CRO), have increased globally. Few studies have reported on the burden of CRO in neonates from low-middle income countries (LMIC). This study aimed to determine the incidence and mortality rates of culture-confirmed Gram-negative infections, with a special focus on CRO in a neonatal unit from a LMIC. MATERIALS AND METHODS: Positive bacterial cultures from sterile sites of infants admitted in the neonatal unit from the 1st January 2018 to 31st December 2019, were reviewed retrospectively. Type of organism, susceptibility and outcomes were recorded. Data on Gram-negative isolates, including the CRO, were extracted. Rates and outcomes were analysed. RESULTS: There were 2219 neonates with organisms isolated from sterile sites (blood and cerebrospinal fluid), accounting for 30% of all admissions, giving a neonatal sepsis incidence of 17.9/1000 patient-days. There was a total of 1746 positive isolates (excluding coagulase negative Staphyloccocus). Of these, 1706 (98%) were isolated from blood, and 40 (2%) from cerebrospinal fluid. Overall, 1188 (68%) were Gram-negative, 371 (21%) Gram-positive and 187 (10.7%) fungal isolates. The common Gram-negatives were Acinetobacter baumannii (526/1188;44%) and Klebsiella pneumoniae (469/1188;40%). Carbapenem resistance was observed in 359 (68%) of the Acinetobacter baumannii (CRAB) and in 103 (18%) of the Enterobacterales (CRE) isolates, with 98% of CRE being Klebsiella pneumoniae (CR-Klebs). Twenty-four (41%) of Pseudomonas species were carbapenem resistant. Overall, carbapenem resistance was seen in 42% of all Gram-negative organisms. The rate of CRAB and CRE were 2.9 and 0.8/1000 patient-days respectively. The overall, all-cause in-hospital mortality rate in infants with Gram-negative isolates was 22%, with higher mortality rate in those infected with CRO compared to non-CRO (34% vs 13%; OR 3.44; 95% CI 2.58–4.60; p < 0.001). The mortality rate in infants with CRE was higher than those with CRAB (48% vs 33%; OR 1.85; 95% CI 1.18–2.89; p = 0.007). CONCLUSION: We observed a high incidence of positive cultures from sterile sites. The common organisms isolated were Gram-negatives, and among these carbapenem resistance was high and was associated with high mortality. Mortality was higher in infants with CRE compared to those with CRAB

Appropriate use of colistin in neonates, infants and children : interim guidance

DATA AVAILABILITY : No raw data are available for this guidance document.No abstract available.http://www.sajid.co.zaam2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Antibiotic and antifungal use in paediatric departments at three academic hospitals in South Africa

OBJECTIVES : South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres. METHODS : We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa. RESULTS : We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27). CONCLUSIONS : Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting.UNICEF.http://www.elsevier.com/locate/ijregihj2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Healthcare-associated infections drive antimicrobial prescribing in pediatric departments at three academic hospitals in South Africa

BACKGROUND : The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS : This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS : Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS : The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.UNICEF and in part, supported by a grant awarded by the Carnegie Corporation of New York.https://journals.lww.com/pidj/pages/default.aspxhj2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

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

AVAILABILITY OF DATA AND MATERIALS : The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.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.https://bmcpediatr.biomedcentral.comam2024ImmunologySDG-03:Good heatlh and well-bein

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

IntroductionThe 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.MethodsContact 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.ResultsTwelve (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.ConclusionWe 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

Challenges in the implementation of the NeoOBS study, a global pragmatic observational cohort study, to investigate the aetiology and management of neonatal sepsis in the hospital setting

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network

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)