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.

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.

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.

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 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.

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.

Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg.

BACKGROUND: Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting. METHODS: This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival. RESULTS: Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31). CONCLUSIONS: Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.

Use of the Bayley Scales of Infant and Toddler Development, Third Edition, to Assess Developmental Outcome in Infants and Young Children in an Urban Setting in South Africa.

BACKGROUND: The Bayley Scales of Infant and Toddler Development (III) is a tool developed in a Western setting. AIM: To evaluate the development of a group of inner city children in South Africa with no neonatal risk factors using the Bayley Scales of Infant and Toddler Development (III), to determine an appropriate cut-off to define developmental delay, and to establish variation in scores done in the same children before and after one year of age. METHODS: Cohort follow-up study. RESULTS: 74 children had at least one Bayley III assessment at a mean age of 19.4 months (95% CI 18.4 to 20.4). The mean composite cognitive score was 92.2 (95% CI 89.4 to 95.0), the mean composite language score was 94.8 (95% CI 92.5 to 97.1), and mean composite motor score was 98.8 (95% CI 96.8 to 101.0). No child had developmental delay using a cut-off score of 70. In paired assessments above and below one year of age, the cognitive score remained unchanged, the language score decreased significantly (p = 0.001), and motor score increased significantly (p = 0.004) between the two ages. CONCLUSION: The Bayley Scales of Infant and Toddler Development (III) is a suitable tool for assessing development in urban children in southern Africa.

A review of delivery room resuscitation in very low birth weight infants in a middle income country.

BACKGROUND: Advanced levels of delivery room resuscitation in very low birth weight infants are reported to be associated with death and complications of prematurity. In resource limited settings, the need for delivery room resuscitation is often used as a reason to limit care in these infants. METHODS: This was a review of delivery room resuscitation in very low birth weight infants born in a tertiary hospital in South Africa between 01 January 2013 and 30 June 2016. Outcomes included death and serious complications of prematurity. Advanced delivery room resuscitation was defined as the need for intubation, chest compressions or the administration of adrenaline. RESULTS: A total of 1511 very low birth weight infants were included in the study. The majority (1332/1511 (88.2%) required oxygen in the delivery room. Face mask ventilation was needed in 45.2% (683/1511). Advanced delivery room resuscitation was only required in 10.6% (160/1511). More than half the infants who required advanced delivery room resuscitation died (89/160; 55.6%). Advanced delivery room resuscitation was required in significantly more infants <1000 grams at birth than those infants >1000 grams (83/539 (15.4%) vs 77/972 (7.9%) p < 0.001). Advanced delivery room resuscitation was significantly associated with a 5 minute Apgar score < 6 (OR 13.8 (95%CI 8.6-22.0), supplemental oxygen at day 28 (OR 2.2 (95% CI 1.4-3.9), metabolic acidosis (OR 2.3 (95% CI 1.1-4.8) and death (OR 1.9 95% CI 1.1-3.3). Other serious complications of prematurity were not associated with advanced delivery room resuscitation. Mortality was increased in infants with a low admission temperature (35.1 °C (SD 0.92) vs 36.1 °C (SD 1.4) (p < 0.001). CONCLUSION: There was a high mortality rate associated with advanced delivery room resuscitation; however complications of prematurity were not increased in survivors..The need for advanced delivery room resuscitation alone should not be used as a predictor of poor outcome in very low birth weight infants. Survivors of advanced delivery room resuscitation should be afforded ventilatory support if required. Special care must be taken to avoid hypothermia in very low birth weight infants requiring resuscitation at birth.

Exchange Transfusion for Neonatal Hyperbilirubinemia in Johannesburg, South Africa, from 2006 to 2011.

Background. Severe hyperbilirubinaemia requiring exchange transfusion has become less common in recent years; however, kernicterus still occurs. The aim of this study was to review babies undergoing exchange transfusion for severe hyperbilirubinaemia in a Johannesburg hospital. Methodology. This was a retrospective review of babies who required exchange transfusion in both the neonatal and the paediatric wards from June 1, 2006, to December 31, 2011. Results. There were 64 patients who underwent 67 exchange transfusions. Isoimmune haemolysis (both Rh and ABO incompatibility) was the cause of jaundice in 9/64 (14%). Most babies who underwent exchange transfusion were sick or preterm and were admitted in hospital after birth (38/64; 59.5%); three of these babies died, but not during the exchange transfusion (3/38; 7.9%); all three had signs suggestive of neonatal sepsis. The remaining 26 babies (40.6%) were readmitted to the paediatric wards for exchange transfusion. Six of these babies (6/26; 23.0%) had signs of kernicterus. The most significant complication of exchange transfusion was apnoea requiring mechanical ventilation in three patients (3/64; 4.6%). Conclusion. Despite a relatively low number of babies undergoing exchange transfusion, kernicterus still occurs and must be prevented. Proper protocols for screening and management of severe hyperbilirubinaemia need to be enforced.

Retrospective cross-sectional review of survival rates in critically ill children admitted to a combined paediatric/neonatal intensive care unit in Johannesburg, South Africa, 2013-2015.

OBJECTIVE: Report on survival to discharge of children in a combined paediatric/neonatal intensive care unit (PNICU). DESIGN AND SETTING: Retrospective cross-sectional record review. PARTICIPANTS: All children (medical and surgical patients) admitted to PNICU between 1 January 2013 and 30 June 2015. OUTCOME MEASURES: Primary outcome-survival to discharge. Secondary outcomes-disease profiles and predictors of mortality in different age categories. RESULTS: There were 1454 admissions, 182 missing records, leaving 1272 admissions for review. Overall mortality rate was 25.7% (327/1272). Mortality rate was 41.4% (121/292) (95% CI 35.8% to 47.1%) for very low birthweight (VLBW) babies, 26.6% (120/451) (95% CI 22.5% to 30.5%) for bigger babies and 16.2% (86/529) (95% CI 13.1% to 19.3%) for paediatric patients. Risk factors for a reduced chance of survival to discharge in paediatric patients included postcardiac arrest (OR 0.21, 95% CI 0.09 to 0.49), inotropic support (OR 0.085, 95% CI 0.04 to 0.17), hypernatraemia (OR 0.16, 95% CI 0.04 to 0.6), bacterial sepsis (OR 0.32, 95% CI 0.16 to 0.65) and lower respiratory tract infection (OR 0.54, 95% CI 0.30 to 0.97). Major birth defects (OR 0.44, 95% CI 0.26 to 0.74), persistent pulmonary hypertension of the new born (OR 0.44, 95% CI 0.21 to 0.91), metabolic acidosis (OR 0.23, 95% CI 0.12 to 0.74), inotropic support (OR 0.23, 95% CI 0.12 to 0.45) and congenital heart defects (OR 0.29, 95% CI 0.13 to 0.62) predicted decreased survival in bigger babies. Birth weight (OR 0.997, 95% CI 0.995 to 0.999), birth outside the hospital (OR 0.21, 95% CI 0.05 to 0.84), HIV exposure (OR 0.54, 95% CI 0.30 to 0.99), resuscitation at birth (OR 0.49, 95% CI 0.25 to 0.94), metabolic acidosis (OR 0.25, 95% CI 0.10 to 0.60) and necrotising enterocolitis (OR 0.23, 95% CI 0.12 to 0.46) predicted poor survival in VLBW babies. CONCLUSIONS: Ongoing mortality review is essential to improve provision of paediatric critical care.

Uncertainty in Antibiotic Dosing in Critically Ill Neonate and Pediatric Patients: Can Microsampling Provide the Answers?

PURPOSE: With a decreasing supply of antibiotics that are effective against the pathogens that cause sepsis, it is critical that we learn to use currently available antibiotics optimally. Pharmacokinetic studies provide an evidence base from which we can optimize antibiotic dosing. However, these studies are challenging in critically ill neonate and pediatric patients due to the small blood volumes and associated risks and burden to the patient from taking blood. We investigate whether microsampling, that is, obtaining a biologic sample of low volume (<50 µL), can improve opportunities to conduct pharmacokinetic studies. METHODS: We performed a literature search to find relevant articles using the following search terms: sepsis, critically ill, severe infection, intensive care AND antibiotic, pharmacokinetic, p(a)ediatric, neonate. For microsampling, we performed a search using antibiotics AND dried blood spots OR dried plasma spots OR volumetric absorptive microsampling OR solid-phase microextraction OR capillary microsampling OR microsampling. Databases searched include Web of Knowledge, PubMed, and EMbase. FINDINGS: Of the 32 antibiotic pharmacokinetic studies performed on critically ill neonate or pediatric patients in this review, most of the authors identified changes to the pharmacokinetic properties in their patient group and recommended either further investigations into this patient population or therapeutic drug monitoring to ensure antibiotic doses are suitable. There remain considerable gaps in knowledge regarding the pharmacokinetic properties of antibiotics in critically ill pediatric patients. Implementing microsampling in an antibiotic pharmacokinetic study is contingent on the properties of the antibiotic, the pathophysiology of the patient (and how this can affect the microsample), and the location of the patient. A validation of the sampling technique is required before implementation. IMPLICATIONS: Current antibiotic regimens for critically ill neonate and pediatric patients are frequently suboptimal due to a poor understanding of altered pharmacokinetic properties. An assessment of the suitability of microsampling for pharmacokinetic studies in neonate and pediatric patients is recommended before wider use. The method of sampling, as well as the method of bioanalysis, also requires validation to ensure the data obtained reflect the true result.

Is there a role for microsampling in antibiotic pharmacokinetic studies?

INTRODUCTION: Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 µL) or 'microsampling' may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. AREAS COVERED: The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. EXPERT OPINION: The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a 'contingency approach' with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.

Bacterial bloodstream infections in neonates in a developing country.

Background. Ongoing surveillance of antimicrobial sensitivity patterns of bacteria isolated in bloodstream infections guides empiric antibiotic therapy in neonatal sepsis. Methods. Sensitivity profiles of neonatal bacterial bloodstream infections in a tertiary hospital were reviewed between 01/06/2009 and 30/06/2010 . Results. There were 246 episodes of bloodstream infection in 181 individuals-(14.06 episodes in10.35 patients/1000 patient days or 14.4 episodes in 10.6 babies/1000 live births. The majority were (93.5%) were late onset and most (54.9%) were gram positive. There were 2.28 sepsis-related deaths /1000 patient days or 2.3/1000 live births. Death was significantly associated with gram-negative infections (P < 0.001), multiple gestation (P < 0.001), shock (P = 0.008), NEC (P = 0.002), and shorter duration of hospital stay (P < 0.001). Coagulase-negative staphylococcus was isolated in 19.1%, K. pneumoniae ESBL in 12.1%, and A. baumanni in 10.9%. S. agalactiae predominated in early onset sepsis. Methicillin resistance was present in 86% of CoNS and 69.5% of S. aureus; 46% enterococcal isolates were ampicillin resistant. The majority (65%) of K. pneumoniae isolates were ESBL producers. Ampicillin resistance was present in 96% of E. coli. Conclusions. Penicillin and an aminoglycoside would be suitable empiric therapy for early onset sepsis and meropenem with gentamycin or ceftazidime with amikacin for late onset sepsis.

Intensive care for very low birthweight infants in South Africa: a survey of physician attitudes, parent counseling and resuscitation practices.

Improving outcomes have promoted utilization of intensive care for premature infants in developing countries with available fiscal and technological resources. Physician counseling and decision-making have not been characterized where economic restrictions, governmental guidelines, and physician cultural attitudes may influence decisions about the appropriateness of neonatal intensive care. A cross-sectional survey of all neonatologists and pediatricians providing neonatal care in public and private hospitals in South Africa (n=394) was carried out. Physicians returned 93 surveys (24 per cent response rate). Frequency of counseling increased with increasing gestational age (GA) but was not universally provided at any GA. Morbidity and mortality were consistently discussed and fiscal considerations frequently discussed when antenatal counseling occurred. Resuscitation thresholds were 25-26 weeks and 665-685 g, and were higher in public than in private hospitals. Decisions to limit resuscitation were based more on expected outcome than on patients' wishes or economics. At 24-25 weeks, 91 per cent of physicians would not resuscitate despite parents' wishes; 93 per cent of physicians would resuscitate 28-29-week-old infants over parents' refusal. Parents expecting premature infants are not invariably counseled. In making life-support decisions, physicians consider infants' best interests and, less frequently, financial and emotional burdens. Thresholds for resuscitation and intensive care are higher in public hospitals, and higher than in developed countries. Physicians relegate parents to a passive role in life-support decisions.

Serum procalcitonin as an early marker of neonatal sepsis.

BACKGROUND: It has recently been suggested that procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role of PCT as a single early marker of neonatal sepsis. SETTING: Neonatal Unit, Johannesburg Hospital, and Microbiology Laboratory, National Health Laboratory Service (NHLS), South Africa. SUBJECTS AND METHODS: Neonates undergoing evaluation for sepsis between April and August 2002 were eligible for inclusion. Patients were categorised into 'no infection', 'possible infection' and 'definite infection' on the basis of C-reactive protein (CRP), white cell count (WCC), platelet count and blood culture results. PCT was correlated with infection categories. RESULTS: One hundred and eighty-three neonates were enrolled. One hundred and eighteen had no infection, 52 possible infection and 13 definite infection. PCT differed significantly among infection categories (p < 0.0001) and correlated significantly with CRP at presentation (correlation coefficient 0.404, p < 0.001) and CRP at 24 hours (correlation coefficient 0.343, p < 0.001). PCT predicted 89.5% of definite infection. Receiver operating characteristic (ROC) analysis for PCT to predict definite infection showed odds ratio (OR) 1.145 (95% confidence interval (CI): 1.05-1.25) with an area under the curve of 0.778. PCT had a negative predictive value of 0.95 (95% CI: 0.915-0.988) for definite infection. CONCLUSIONS: Although PCT was significantly related to the category of infection, it is not sufficiently reliable to be the sole marker of neonatal sepsis. PCT would be useful as part of a full sepsis evaluation, but is relatively expensive. A negative PCT on presentation may rule out sepsis, but this needs to be evaluated further.