126 research outputs found
The use of polymyxins to treat carbapenem resistant infections in neonates and children.
No full textINTRODUCTION: The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns. Areas covered: In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections. Expert opinion: Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections
The pros and cons of suctioning at the perineum (intrapartum) and post-delivery with and without meconium
No full textThe epidemiology, risk factors and diagnosis of neonatal sepsis
No full textA thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of
Doctor of Philosophy
Johannesburg, South Africa 2017.Background: In sub-Saharan Africa, sepsis is the third most common cause of deaths during the neonatal period. Both maternal human immunodeficiency virus (HIV) infection and vitamin D deficiency (VDD) have been identified as risk factors for infection in children. The relationship of these risk factors, especially VDD among neonates in developing countries is not well documented. The “gold” standard to diagnose sepsis is blood culture; however, it has low sensitivity. Therefore there is a need for tests with improved sensitivity, to improve estimates of the incidence and aetiology of neonatal sepsis. This could enable prompt and targeted use of antibiotics to reduce both mortality and mitigate against emergence of antimicrobial resistance. The aims of this study were to determine the epidemiology of early-onset sepsis (EOS) and community acquired sepsis (CAS) using standard blood culture. Further, we evaluated the role of molecular diagnostic using polymerase chain reaction (PCR) based technology (Taqman array card), and evaluated role of maternal HIV infection and vitamin D status as risk factors for EOS and CAS in neonates born in Soweto, South Africa.
Methods and Procedures: Neonates born and/ or admitted with a diagnosis of possible serious bacterial infection (pSBI) with no previous hospital admission were prospectively enrolled into the study. They were grouped into EOS (onset of sepsis before 3 days of life) and CAS (onset of sepsis between 3-27 days of life). A subgroup of patients who met a predetermined definition of clinical or culture confirmed neonatal sepsis (protocol-defined sepsis), had blood and naso/oro-pharyngeal (NPOP) swabs tested using a PCR- based technique, Taqman array card (TAC) to identify possible causative pathogens. Healthy neonates were enrolled as controls, matched for age-group of cases with sepsis. In a separate cohort, mother-newborn dyads were enrolled soon after birth, and had blood taken to measure serum 25-hydroxyvitamin D [25(OH)D]. These newborns were grouped as being healthy or ill with sepsis. Sepsis in this cohort was defined as presence of clinical signs together with the presence of a positive blood culture and/or high C-reactive protein or interleukin-6. For both cohorts, cases and controls were stratified according to HIV exposure.
Results: There were 34,808 live births in Soweto over the study period, August 2013 to September 2014. A total of 3260 neonates were enrolled, 2624 (80%) and 636 (20%) with a diagnosis of early-onset pSBI (EO-pSBI) and community acquired pSBI (CA-pSBI) respectively. Blood culture positivity rate due to pathogens in neonates with EO-pSBI was 3.7% (96/2624). The incidence (per 1000 live births) of EO-pSBI was 106 (95%CI 102-109
and 3.8 (95% CI 3.2-4.6) for culture-confirmed EOS. More than two thirds of putative pathogens isolated from neonates with culture-confirmed EOS (69.8%) were Gram positive bacteria. The common bacteria were Group B streptococcus (GBS; 35/105; 33%) , Viridans streptococcus (23/105; 22%), Enterococcus species (10/105; 10%) and Escherichia coli (E. coli; 10/105; 10%), with incidences (per 1000 live births) of 1.41 (95%CI 1.06-1.86), 0.92 (95%CI 0.65-1.30), 0.40 (95% CI 0.20-0.61) and 0.40 (95% CI 0.20-0.61) respectively. HIV exposed neonates had higher incidence of sepsis than HIV unexposed for EO-pSBI (OR:1.45; 95%CI 1.34-1.56). The overall case fatality rate was 9.0% (236/2624) for EOS. Blood culture positivity rate due to pathogens in neonates with CA-pSBI was 9% (55/636). The incidence of CA-pSBI and blood/CSF culture confirmed CAS were 33.4 (95%CI 31.6-35.4) and 3.53 (95%CI 2.96-4.22), respectively. More than three-quarters (76.7%) of putative pathogens isolated from CA-pSBI were Gram positive bacteria. Among, the culture-confirmed CAS, common organisms in blood were Viridans streptococci (17/60; 28%), GBS (14/60; 23%), Staphylococcus aureus (12/60; 20%), and E.coli (9/60; 15%); while in CSF the common organisms were GBS (9/25; 36%), Staphylococcus aureus (5/25; 20%), Viridans streptococcus (4/25; 16%) and Enterococcus species (4/25; 16%). The overall incidence for common organisms in blood and/ or CSF for CAS were 0.95 (95%CI 0.67-1.33), 0.90 (95%CI 0.63-1.27), 0.75 (95%CI 0.51-1.10) and 0.58 (95%CI 0.37-0.89) for Staphylococcus aureus, Viridans streptococcus, GBS and Enterococcus species respectively. HIV exposed neonates had higher incidence of blood/CSF culture confirmed CAS than HIV unexposed (OR:1.90;95%CI 1.32-2.74), including specifically for Staphylococcus aureus (OR:2.71; 95% CI 1.35-5.41), GBS (OR:4.82; 95%CI 2.13-10.9) and E.coli (OR:2.71; 95%CI 1.07-6.82). . The case fatality rate for CAS was 1.4% (9/636).
Among protocol-defined sepsis cases tested with TAC, bacteria or viruses were detected in blood in 37.1% of cases with EOS. Although similar organisms were identified in blood of cases and controls, proportion of cases with positive TAC was higher than in controls (37.1% vs 19.5%; OR: 2.35; 95%CI 1.72-3.21). The common organisms identified in blood of EOS cases using TAC were Streptococcus pneumoniae (14.2%), Ureaplasma species (9.2%), Pseudomonas species (8.5%) and GBS (7.0%). In pharyngeal swabs there were fewer cases that tested positive with TAC compared to controls (44.1% vs 53.1%; OR:0.69; 95%CI 0.59-0.90), and the common organisms identified in cases were Ureaplasma species (19.9%), Klebsiella pneumoniae (11.9%) and GBS (8.5%). After applying modelling factoring positive blood culture, one was able to attribute aetiology to a specific pathogen for 26.7% of cases using blood culture and TAC, and therefore 73.3% of cases did not have an identifiable aetiology from the pathogens tested in culture or TAC. Among the positive TAC results in blood and pharyngeal swabs the organisms that were found to be attributable to EOS were Ureaplasma species (5.4%, 95% CI 3.6%-5.1%) , GBS (4.8%, 95%CI 4.1%-5.8%), and Viridans streptococcus (4.2%, 95%CI 3.5%-5.1%). There were no differences in number of cases and controls with positive TAC results between HIV exposed and unexposed neonates.
In neonates with CAS protocol-defined sepsis cases tested with TAC, bacteria or viruses were detected in blood in 45.8% of cases. Proportion of cases with positive TAC in blood was higher than in controls (45.8% vs 27.4%; OR: 2.24; 95%CI 1.30-3.86). The common organisms identified included Streptococcus pneumoniae (15.7%), GBS (14.5%) and E. coli (8.3%). In pharyngeal swabs there were no differences in numbers with positive TAC results between cases and controls (75.0% vs 70.1%, OR:1.28; 95%CI 0.77-2.12), and the common organisms identified in cases were GBS (28.0%), Klebsiella pneumoniae (24.2%) and at equal rates (13.6%) were E. coli, Ureaplasma species and Streptococcus pneumoniae. Viruses were identified in 40% of cases in the pharyngeal swabs. There were no differences in number of cases and controls with positive TAC results between HIV exposed and unexposed neonates.
Maternal and cord blood 25(OH)D levels were 54.7±30.1 and 39.0±21.3 nmol/L respectively, and prevalence of VDD (defined as a 25(OH)D level of <30 nmol/L) among the women and their newborns was 18.8% and 39.8% respectively. There were no significant differences in 25(OH)D levels or VDD between HIV infected and uninfected pregnant women. On multivariate analysis VDD in neonates was not associated with EOS.
Conclusions: There is high burden of neonatal sepsis in Soweto, including significant mortality. Based on blood culture, GBS is the most common pathogen causing EOS; Viridans streptococcus and Staphylococcus aureus the most common causes of culture-confirmed CAS. HIV exposure contributes significantly to a higher burden of bacterial sepsis in neonates. Although molecular detection using the TAC assay identified more bacteria organisms than from blood culture, including non-culturable organisms like Ureaplasma species, its use as a diagnostic tool for sepsis warrants further evaluation due to high positivity rates among healthy neonates for many of the targeted organisms in blood and NPOP swabs. Nevertheless, after correcting for positive controls, a combination of blood culture and TAC improved the detection of organisms in neonates with sepsis. In this study, maternal and newborn VDD was not associated with sepsis; however, this warrants further evaluation since this study had a limited number of neonates with culture confirmed disease.LG201
Promoting physiologic transition at birth: Re-examining resuscitation and the timing of cord clamping
No full textThe profile of ancillary laboratory tests in neonates with positive blood andor cerebrospinal fluid cultures
No full text
Hypothermia among neonates admitted to the neonatal unit at a tertiary hospital in South Africa
No full textAntibiotics needed to treat multidrug-resistant infections in neonates
No full textInfections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared with only six trials recruiting neonates. We review the World Health Organization (WHO) priority pathogens list relevant to neonatal sepsis and propose a WHO multiexpert stakeholder meeting to promote the development of a neonatal priority antibiotic development list. The goal is to develop international, interdisciplinary consensus for an accelerated neonatal antibiotic development programme. This programme would enable focused research on identified priority antibiotics for neonates to reduce the excess morbidity and mortality caused by MDR infections in this vulnerable population
Surfactant Replacement Therapy in Developing Countries
No full text<i>Background:</i> Since the first successful report of surfactant replacement therapy (SRT) in infants with respiratory distress syndrome (RDS), numerous randomized clinical trials have shown that SRT reduces mortality and morbidity in RDS. Surfactant is now a standard therapy for RDS. However, the use of SRT in the developing world has been extremely slow. <i>Objective:</i> The objective of this paper is to review the published information regarding the usage and barriers encountered in the use of SRT in developing countries. <i>Methods:</i> We reviewed the available literature and also gathered information from countries with a high burden of prematurity and high infant mortality rate regarding replacement therapy and the barriers to use of SRT. <i>Results:</i> We reviewed the available literature and found that developing countries bear a high burden of prematurity and RDS that contribute to high neonatal and infant mortality rates. Based on the effectiveness of SRT in RDS, surfactant preparations were included in the Essential Drug List of WHO in 2008. However, the use of SRT in developing countries is still limited because of (1) high cost, (2) lack of skilled personnel to administer SRT, and (3) lack of support systems after the SRT. The cost of SRT may exceed the per-capita GNP (300–500 USD) in some countries. Data from India and South Africa suggests that SRT is limited to rescue therapy in babies with potential for better survival, usually >28 weeks’ gestation. Recent studies show that infants with RDS respond well to initial continuous positive airway pressure (CPAP) followed by SRT for those who do not respond. <i>Conclusions:</i> In developing countries, CPAP may be used as the primary mode of management of RDS. SRT may be reserved for non-responders to CPAP. Alternate simpler methods of delivery of surfactant (aerosol technique) are also being explored. There is a need for further studies to develop and assess efficient and less expensive methods of application of CPAP and SRT in developing countries.</jats:p
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