Daynia Ballot

Use of C-reactive protein to guide duration of empiric antibiotic therapy in suspected early neonatal sepsis

Background. Serial C‐reactive protein (CRP) measurements have been shown to be useful for guiding duration of antibiotic therapy in neonates. This study sought to determine whether this is a safe and practical approach in a developing country. Methods. The study was conducted at the Johannesburg Hospital between September 15, 1998, and January 15, 1999. Subjects included all neonates evaluated for suspected sepsis in the first 24 h of life who had negative initial and repeat CRP values (≤ 10 mg/dl). Repeat CRP measurements were performed between 24 and 48 h after birth. Antibiotic therapy was stopped in these infants at 24 to 48 h, and they were observed until 72 h, when the final blood culture results were available. The number of positive blood cultures in this group was determined. Results. The repeat CRP estimation correctly identified 99 of 100 infants in the study as not requiring further antibiotic therapy (negative predictive value, 99%; 95% confidence intervals, 95.6 to 99.97%). The 1 infant with a positive blood culture was premature with a gestational age of 31 weeks. Eight babies required repeat evaluation for suspected sepsis, 4 presented on Day 3 to 4 and one of these babies died. All these neonates were of ≤33 weeks gestation. Conclusion. The use of serial CRP measurements to guide antibiotic therapy is a safe and practical approach in neonates with suspected sepsis in a developing country.

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

BackgroundAudit 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.MethodsThis 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.ResultsOverall 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).ConclusionsSurvival 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.

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.

Serial Interleukin 6 Measurements in the Early Diagnosis of Neonatal Sepsis

The objective of the present study was to evaluate serial interleukin 6 (IL6) levels in the early diagnosis of neonatal sepsis. Subjects included 255 neonates from the Neonatal Unit of Johannesburg Hospital evaluated for suspected sepsis between February and May 1998. All infants had IL6, full blood count (FBC), C reactive protein (CRP) and blood cultures done at presentation. CRP and IL6 were repeated after 24 h. Infants were categorized into groups according to the likelihood of infection on the basis of clinical presentation, CRP, FBC and culture results, i.e., group 1 (no infection) to group 4 (definite infection). IL6 was compared between the groups by the U-test of Mann-Whitney; stepwise logistic regression was done to establish the best predictors of infection, sensitivity, specificity, positive and negative predictive values were determined. The initial IL6 level was significantly raised in those infants with possible infection [880.67 pg/ml (2966.04), p value 0.0104], probable infection [422.62pg/ml (4077.7), p value 0.0021] and definite infection [11164.39pg/ml (24139.77), p value 0.0000] as compared to those infants without infection [58.65 (182.4)]. The best predictors of infection were the combination of the initial IL6 value and CRP value after 24 h (goodness of fit 97.7 per cent). An initial IL6 value below 20 pg/ml gave a negative predictive value of 90.18 per cent. It is concluded that an IL6 value done at the time of presentation of signs and symptoms suggestive of infection is useful in the early diagnosis of neonatal sepsis. In particular, an initial IL6 value below 20 pg/ml may allow antibiotics to be withheld in a number of infants evaluated for sepsis. There is no benefit in serial determination of IL6 in the diagnosis of neonatal sepsis.

Factors influencing the absorption of iron from soya-bean protein products.

The absorption of iron from soya-bean (Glycine hispida)-based and milk-based infant formulas was assessed in 138 multiparous Indian women, using the erythrocyte utilization of radioactive Fe method. Fe absorption was significantly greater from the basal milk formula (1.5 g protein) than it was from the basal soya-bean formula (2.3 g protein), with geometric mean values of 0.083 and 0.044 respectively. Ascorbic acid markedly increased Fe absorption from the milk-based formula in a dose-dependent fashion. The increase was fivefold when the ascorbic acid:Fe ratio on a weight-for-weight basis was 6:1 and over tenfold when it was 20:1. In contrast, ascorbic acid had a less-marked effect on the absorption of Fe from the soya-bean-based formula, with only a two- to threefold increase at an ascorbic acid:Fe ratio of 20:1. The geometric mean Fe absorption from the soya-bean formula (1.27 mg Fe, 2.3 g isolated soya-bean protein (ISP] was somewhat less than that from the same amounts of ISP and ascorbic acid made up in milk (0.075 and 0.113 respectively). However, a direct comparison between the soya-bean formula in milk and in water showed no significant difference (0.043 and 0.060 respectively). Fe absorption from a drink containing 10 g ISP and 30 mg ascorbic acid was significantly better than that from a similar drink containing the soya-bean flour from which ISP is extracted (0.044 and 0.027 respectively). Heating ISP to 200 degrees for 2 h before its use had no effect on Fe availability.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of Neonatal Sepsis at Johannesburg Hospital

AbstractWe evaluated sepsis in the neonatal unit at Johannesburg Hospital including the time of onset, clinical features, outcome of the treatment of patients, pathogens isolated, and antimicrobial sensitivity to provide site-specific guidelinesfor empiric antibiotic therapy. This was a retrospective study conducted in the neonatal unit of the Johannesburg Hospital between 1 July 2002 and 30 June 2003. All neonates with growth on blood cultures were included. Demographic, clinical, laboratory and microbiological data were reviewed. Of a total of l03 infants with l40 positive blood cultures, eight isolates were most likely to be contaminants. There were thus 132 significant isolates in 96 patients: five presented with early onset sepsis(EOS) and 91 withlate onset sepsis (LOS). Gram-negative bacilli werethe predominant isolatesin EOS and coagulL-negative staphylococci(CoNS)the predominantisolates(63)in LOS (40/63 considered significant, CoNS were not speciated as Staphylococcus epidermidis). Theremaining is...

A Comparison of High versus Low Dose Recombinant Human Erythropoietin versus Blood Transfusion in the Management of Anaemia of Prematurity in a Developing Country

The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.

Correlates of protection of serotype-specific capsular antibody and invasive Group B Streptococcus disease in South African infants.

BACKGROUND Vaccinating pregnant women may prevent invasive Group B Streptococcus (GBS) disease in their young infants. In a low-middle income setting, we sought to determine an association between natural maternal antibody responses and the development of invasive GBS disease. METHODS We undertook a matched case-control study in Johannesburg, South Africa. Maternal and infant antibody concentrations were compared between serotype-specific Ia and III GBS cases and well-baby controls in which the mother was colonized with the same serotype. RESULTS The median maternal serotype Ia and III antibody concentrations (in μg/mL) were 0.05 (IQR: 0.02-0.24; n=27) and 0.14 (IQR: 0.08-0.33; n=29) in cases, and 0.29 (IQR: 0.06-1.60; n=43) and 0.29 (IQR: 0.13-0.58; n=31) in homotypic controls, respectively. A smaller proportion of cases as compared to homotypic controls had higher serotype Ia and III maternal antibody concentrations. Using Bayesian modeling, we demonstrated that the risk of invasive GBS disease was less than 10% with maternal antibody concentrations ≥ 6 μg/mL and ≥ 3 μg/mL for serotypes Ia and III, respectively. CONCLUSIONS Maternal capsular antibody concentrations are associated with the risk of invasive GBS disease in infants. In a low-middle income setting with a high burden of invasive disease, we have demonstrated a sero-correlate of protection for GBS serotypes Ia and III which could facilitate vaccine licensure.

Survival of extremely low-birth-weight infants

Objectives. Survival of extremely low-birth-weight (ELBW) infants in a resource-limited public hospital setting is still low in South Africa. This study aimed to establish the determinants of survival in this weight category of neonates, who, owing to limited intensive care facilities, were not mechanically ventilated. Design. A retrospective study in which patient data were retrieved from the departmental computer database. Setting. The neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. Subjects. Neonates admitted at birth between January 2006 and December 2010 with birth weights of ≤900 g. Outcome measures. Survival at discharge was the major outcome. Maternal variables were age, parity, gravidity, antenatal care, antenatal steroids, place and mode of delivery and HIV status. Neonatal variables were gestational age (GA), birth weight (BW), gender, place of birth, hypothermia, resuscitation at birth, sepsis, necrotising enterocolitis, intraventricular haemorrhage, jaundice, nasal continuous positive airway pressure (NCPAP) with or without surfactant, and Apgar scores. Results. A total of 382 neonates were included in the study. Overall survival was 26.5%. The main causes of death, as per the Perinatal Problem Identification Programme (PPIP) classification, were extreme multi-organ immaturity and respiratory distress syndrome. The main determinants of survival were BW (odds ratio (OR) 0.994; 95% confidence interval (CI) 0.991 - 0.997) and GA (OR 0.827; 95% CI 0.743 - 0.919). Overall the rate of NCPAP use was 15.5%, and NCPAP was not associated with improved survival. Conclusion. Survival of ELBW infants is low. BW and GA were the strongest predictors of survival. Effective steps are required to avoid extreme prematurity, encourage antenatal care, and provide antenatal steroids when preterm birth is anticipated.

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

BackgroundLittle 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.MethodsA 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.ResultsComparison 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.ConclusionsInitial 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.