Browsing by Author "Bekker, Adrie"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Acquired neonatal bronchial stenosis after selective intubation : successful managed with balloon dilatation
    (Wiley Open Access, 2019) Goussard, Pierre; Morrison, Julie; Bekker, Adrie; Fourie, Barend
    ENGLISH ABSTRACT: Premature babies are prone to airway‐related complications. Selective intubation for the management of pulmonary interstitial emphysema may cause acquired bronchial stenosis. Balloon dilatation under fluoroscopy is a safe minimal invasive and successful intervention for acquired bronchial stenosis. Follow‐up bronchoscopy is needed due to risk of restenosis.
  • Thumbnail Image
    Item
    Epidemiology of clinically suspected and laboratory-confirmed bloodstream infections at a South African neonatal unit
    (JIDC, 2021-07) Dramowski, Angela; Bekker, Adrie; Cotton, Mark Frederic; Whitelaw, Andrew Christopher; Coffin, Susan
    Introduction: Data from Africa reporting the epidemiology of infection in hospitalised neonates are limited. Methodology: A prospective study with convenience sampling was conducted to characterise neonates investigated with blood culture/s for suspected infection at a 132-bed neonatal unit in Cape Town, South Africa (1 February-31 October 2018). Enrolled neonates were classified as having proven bloodstream infection (BSI) (blood culture-positive with a pathogen) or presumed infection (clinically suspected but blood culture-negative) or as potentially at risk of infection (maternal risk factors at birth). Results: Of 1299 hospitalised neonates with >1 blood culture sampling episode, 712 (55%) were enrolled: 126 (17.7%) had proven BSI; 299 (42%) had presumed infection and 287 (40.3%) were potentially at risk of infection. Neonates with proven BSI had lower birth weight and higher rates of co-existing surgical conditions versus the presumed/potential infection groups (p < 0.001). Median onset of proven BSI versus presumed infection was at 8 (IQR = 5-13) and 1 (IQR = 0-5) days respectively (p < 0.001). Most proven BSI were healthcare-associated (114/126; 90.5%), with Klebsiella pneumoniae (80.6% extended-spectrum β-lactamase producers) and Staphylococcus aureus (66.7% methicillin-resistant) predominating. Mortality from proven BSI (34/126; 27%) was substantially higher than that observed in presumed (8/299; 2.7%) and potential infections (3/287; 1.0%) (p < 0.001). The odds of death from proven BSI was 3-fold higher for Gram-negatives than for Gram-positive/fungal pathogens (OR = 3.23; 95% CI = 1.17-8.92). Conclusions: Proven BSI episodes were predominantly healthcare-associated and associated with a high case fatality rate. Most neonates with presumed infection or at potential risk of infection had favourable 30-day outcomes.
  • Thumbnail Image
    Item
    Prevention and treatment of perinatal and infant tuberculosis in the HIV era
    (Stellenbosch : Stellenbosch University, 2016-11-18) Bekker, Adrie; Hesseling, Anneke Catharina; Schaaf, Hendrik Simon; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health
    ENGLISH ABSTRACT : Infants (<12 months) born to women with tuberculosis are at high risk of Mycobacterium tuberculosis (M. tuberculosis) exposure, infection and disease early in life. In settings with high prevalence of human immunodeficiency virus (HIV) and tuberculosis, tuberculosis disproportionately affects women of childbearing age. The aim of this dissertation was to comprehensively investigate prevention and treatment strategies for perinatal and infant tuberculosis in a high HIV-prevalence setting. Research objectives included: 1) defining clinical and epidemiological aspects of maternal-infant tuberculosis at a large referral hospital; 2) identifying barriers and solutions to isoniazid preventive therapy (IPT) delivery in tuberculosis-exposed newborns; and 3) obtaining rigorous pharmacokinetic data to guide the dosing of firstline antituberculosis drugs in newborns and infants for the prevention and treatment of tuberculosis. In the first retrospective study, 70 newborns (42 HIV-exposed) were investigated for tuberculosis at Tygerberg Hospital, a large provincial referral hospital in Cape Town. Newborns were mainly screened for tuberculosis because of maternal tuberculosis. Isoniazid preventive therapy (IPT) was initiated in 36/50 (72%) newborns, because of maternal tuberculosis infectious risk and exposure of infants. Few of the newborns who received IPT were traceable at one-year, and of those traced, less than half completed IPT. To generate more rigorous clinical and epidemiological data on maternal-infant tuberculosis, a prospective cohort study was conducted in pregnant and postpartum women receiving tuberculosis treatment at Tygerberg Hospital. Over a one-year period, 74 pregnant and postpartum women, 53 (72%) HIV-infected, were consecutively enrolled. Nearly half of the women, 35 (47%) were diagnosed with tuberculosis only at delivery or postpartum, and a third of women with tuberculosis reported prior tuberculosis treatment. Tuberculosis-exposed newborns were often premature and of low birth weight (LBW; <2500 grams). All deaths occurred in HIVinfected women (n=5) and all stillbirths (n=4) and newborn deaths (n=6) were from HIV-infected women. Favourable maternal tuberculosis treatment outcomes (cure and tuberculosis treatment completion) were documented only in 41/74 (55%) women, while 33 (45%) had unfavourable treatment outcomes (death, treatment failure and loss to follow-up). These poor observed outcomes highlight the need for earlier diagnosis and treatment of tuberculosis during pregnancy, and close follow-up to ensure maternal tuberculosis treatment completion. Improved care for pregnant women with tuberculosis, with and without HIV infection, will likely reduce morbidity and mortality in mothers and tuberculosis-exposed newborns. Delayed maternal tuberculosis diagnosis led to IPT initiation in a large number of newborns. Forty-four newborns on IPT were followed to 6 months. A hospital-based tuberculosis linkage to care intervention, led to 29/44 (66%) newborns completing IPT without a study team intervention. A further 8 infants completed IPT after studyteam intervention. Appropriate tuberculosis referral and linkage to care from hospital to local tuberculosis clinic substantially improved IPT completion among tuberculosis-exposed newborns. More pharmacokinetic data regarding the appropriate use of antituberculosis drugs are required in neonates and infants, who undergo considerable physiological changes in the first year of life. An intensive isoniazid (INH) pharmacokinetic study was therefore designed and implemented in premature and LBW infants (n=20). Relatively high median INH peak concentrations of 5.63 μg/ml were achieved in LBW infants (at an INH dose of 10 mg/kg), compared to the adult proposed target value of > 3 μg/ml. INH exposures were higher with longer half-lives in smaller infants, and among genotypically determined N-acetyltransferase-2 (NAT2) slow acetylators, suggesting reduced clearance of INH. This first study of isoniazid use in LBW and premature neonates showed that the INH dose in premature and LBW infants should probably not exceed 10 mg/kg/day. The final study evaluated whether the revised higher 2009 World Health Organization (WHO)-recommended paediatric doses for rifampicin (RMP), INH, pyrazinamide (PZA) and ethambutol (EMB) achieved adequate drug concentrations in infants, compared to current adult pharmacokinetic target concentrations. All 39 infants enrolled achieved the minimum proposed adult target peak concentrations of > 3 μg/ml for INH at a mean dose of 12.8 mg/kg (10.3 - 15.4 mg/kg), and the minimum adult target of > 20 μg/ml for PZA at a mean dose of 33.3 mg/kg (28.5 – 38.5 mg/kg). RMP administered at mean dose of 15.4 mg/kg (10.1 - 20.5 mg/kg) resulted in very low RMP peak concentrations for both RMP formulations used during the study. None of the infants achieved the minimum proposed adult RMP target concentration of > 8 μg/ml. Given the findings of this study, higher doses of RMP in infants should be considered especially given emerging data from adult RMP doseescalation studies showing better efficacy at higher doses with limited toxicity for short-term use. For EMB, only 1 of 16 infants achieved the recommended adult target concentration of > 2 μg/ml when given at a mean dose of 20.2 mg/kg (15.4-24.1 mg/kg). EMB dose-dependent ocular toxicity however poses a concern regarding the recommendation of higher EMB doses in infants where vision testing is challenging. This is the largest pharmacokinetic study of first-line antituberculosis drugs performed in infants to date, which has generated valuable pharmacokinetic data to inform the effective and safe dosing of first-line antituberculosis drugs in infants. Pregnant women in settings with a high burden of tuberculosis and HIV and their infants face a considerable burden of tuberculosis disease in HIV-endemic settings. Maternal-infant tuberculosis care can be improved by health systems strengthening interventions. Data generated from pharmacokinetic studies of antituberculosis drugs in tuberculosis-exposed infants will inform much needed dosing guidelines of firstline antituberculosis drugs for newborns and infants, who have a high risk of tuberculosis and are prone to develop severe forms of tuberculosis.
  • Thumbnail Image
    Item
    Single dose abacavir pharmacokinetics and safety in neonates exposed to human immunodeficiency virus (HIV)
    (Oxford University Press, 2021-06) Bekker, Adrie; Decloedt, Eric H.; Slade, Gretchen; Cotton, Mark F.; Rabie, Helena; Cressey, Tim R.
    Abacavir is a potential option for prophylaxis and early treatment of human immunodeficiency virus (HIV), but no data are available in neonates. Ten neonates administered a single abacavir dose of 8 mg/kg before 15 days of life had substantially higher exposures than those reported in infants and children, with no reported adverse events.
  • Thumbnail Image
    Item
    Tuberculosis disease during pregnancy and treatment outcomes in HIV-infected and uninfected women at a referral hospital in Cape Town
    (Public Library of Science, 2016) Bekker, Adrie; Schaaf, H. Simon; Draper, Heather R.; Kriel, Magdalena; Hesseling, Anneke C.
    Background: Tuberculosis during pregnancy and treatment outcomes are poorly defined in high prevalence tuberculosis and HIV settings. Methods: A prospective cohort study of pregnant and postpartum women identified to be routinely on antituberculosis treatment was conducted at Tygerberg Hospital, Cape Town, South Africa, from January 2011 through December 2011. Maternal tuberculosis disease spectrum and tuberculosis-exposed newborns were characterized by maternal HIV status. Maternal tuberculosis treatment outcomes were documented and a multivariable regression model identified predictors of unfavourable tuberculosis treatment outcomes. Infant outcomes were also described. Results: Seventy-four women with tuberculosis, 53 (72%) HIV-infected, were consecutively enrolled; 35 (47%) were diagnosed at delivery or postpartum and 22 (30%) of women reported previous antituberculosis treatment. HIV-infected women were 5.67 times more likely to have extrapulmonary tuberculosis (95% CI 1.18–27.25, p = 0.03). All 5 maternal deaths were amongst HIV-infected women. Birth outcomes were available for 75 newborns (2 sets of twins, missing data for 1 stillbirth). Of the 75 newborns, 49 (65%) were premature and 44 (59%) were low birth weight (LBW; <2500 grams). All 6 infants who died and the 4 stillbirths were born to HIV-infected women. Unfavourable tuberculosis treatment outcomes were documented in 33/74 (45%) women. Unfavourable maternal tuberculosis outcome was associated with delivery of LBW infants (OR 3.83; 95% CI 1.40–10.53, p = 0.009). Conclusions: A large number of pregnant women with tuberculosis presented at a provincial referral hospital. All maternal and infant deaths occurred in HIV-infected women and their newborns. Maternal tuberculosis treatment outcomes were poor.