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101
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Introduction
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November 2007 - present
November 2007 - present
Publications
Publications (101)
Adverse event (AE) collection is a key part of evidence generation in clinical trials and an integral element of safety reporting. AE assessment and documentation is particularly challenging in neonates who are a heterogeneous population with high rates of co-morbidities. Neonatal research is finally gaining the attention of regulators regarding dr...
Background
Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited.
Methods
As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and con...
Background and objectives
Healthcare-associated infections (HAI) are a leading contributor to morbidity and mortality in hospitalised neonates. Diagnosing neonatal HAI is challenging owing to non-specific symptoms and lack of definitive diagnostic markers, contributing to high rates of inappropriate antibiotic use. This study evaluated the theoreti...
Background
Neonatal sepsis is a leading cause of death in low- and middle- income countries (LMIC). Increasing antibiotic resistance in early onset (< 72 h of life) bloodstream infection (EO-BSI) pathogens in LMIC has reduced the effectiveness of the recommended empiric antibiotic regimen (ampicillin plus gentamicin).
Methods
We retrospectively an...
Background
Reports of healthcare-associated bloodstream infection (HA-BSI) epidemiology in African neonatal units are limited.
Methods
We conducted a cross-sectional study (2017–2018) in nine neonatal units in the Western Cape Province, South Africa, including central, regional and district hospitals (416 beds) using laboratory and clinical record...
Treatment options for children living with HIV have historically been less effective, less practical and more difficult to implement compared with those for adults, as the research and development of new drugs for children has lagged behind. Significant progress has been achieved in response to the paediatric HIV epidemic over the last decade. Seve...
Background and objectives
Neonatal mortality due to severe bacterial infections is a pressing global issue, especially in low-middle-income countries (LMICs) with constrained healthcare resources. This study aims to validate the Neonatal Healthcare-associated infectiOn Prediction (NeoHoP) score, designed for LMICs, across diverse neonatal populatio...
Background
Short peripheral catheter (SPC)-associated complications occur frequently in hospitalised neonates. Few studies have reported the use of SPC care bundles in resource-limited neonatal units.
Objective
To evaluate the impact of a SPC care bundle on SPC associated complications (infiltration, dislodgement, phlebitis) and catheter dwell tim...
Objectives
To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation.
Methods
Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression...
Background
Vancomycin is a glycopeptide antibiotic that has been used to treat hospital-acquired gram-positive infections for more than 5 decades. However, the literature is divided regarding the therapeutic advantages of vancomycin loading doses in neonates.
Objectives
This study aimed to investigate the effect of vancomycin loading doses on ther...
Background
The smallest dolutegravir (DTG) dose approved is 5 mg once-daily in infants ≥4 weeks and weighing ≥3 to <6kg using a dispersible tablet (DT). Neonates (<28 days of life) may require a lower dose due to immature organ development. We evaluated the aqueous dispersibility of the generic DTG-DT 10 mg scored tablets (Viatris Inc.) to determin...
Background
Healthcare-associated infections account for substantial neonatal in-hospital mortality. Chlorhexidine gluconate (CHG) whole body skin application could reduce sepsis by lowering bacterial colonisation density, although safety and optimal application regimen is unclear. Emollients, including sunflower oil, may independently improve skin...
Background
Study of liquid lopinavir/ritonavir (LPV/r) in young infants has been limited by concerns for its safety in neonates.
Methods
International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1106 was a phase IV, prospective, trial evaluating the safety and pharmacokinetics of antiretroviral medications administered according to...
Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pr...
Background:
Neonatal sepsis is traditionally classified as early-onset sepsis (EOS) and late-onset sepsis (LOS) disease categories. This paradigm was based on observed epidemiological data from high income settings. However, increasing availability of microbiology results from diverse settings challenges these assumptions, necessitating re-examina...
Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an in...
Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an in...
The paucity of population-level neonatal sepsis data hampers development of antibiotic recommendations for neonatal sepsis in Africa with approximately 250,000 African neonates who die from severe bacterial infections annually. Antibiotic resistance rates in Sub-Saharan Africa (SSA) are high, and access to effective antibiotic therapy for neonatal...
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
Hospit...
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....
Introduction:
Maternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, wit...
Background:
Colistin is increasingly prescribed for neonates with carbapenem-resistant Enterobacterales (CRE) infections.
Objectives:
We described patient demographics, infection episodes, treatment and clinical outcomes, colistin related adverse events and relatedness of isolates in neonates with clinically confirmed or clinically suspected CRE...
Background:
Hand hygiene (HH) is a cornerstone of programmes to prevent healthcare associated infections (HAI) globally, but HH interventions are seldom reported from African neonatal units.
Methods:
We conducted a quasi-experimental study evaluating the impact of a multi-modal intervention (SafeHANDS) on HH compliance rates, alcohol-based handr...
Background:
Suboptimal exposure to antituberculosis drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line antituberculosis drug pharmacokinetics in children and adolescents at a global level.
Methods:
We systematically searched MEDLINE, Embase, and Web of Science (1990-20...
Background:
Infection is a leading cause of death among very low birth-weight (VLBW) infants in resource-limited settings.
Methods:
We performed a retrospective review of healthcare-associated infection (HAI) episodes among VLBW infants from January 1, 2016, to December 31, 2017. The epidemiology, causative organisms and short-term outcomes were...
Introduction
Community acquired infection (CAI) is the leading indication for paediatric hospitalization in South Africa.
Methods
We conducted secondary data analysis of prospective, consecutive paediatric admissions to Tygerberg Hospital (May 2015-November 2015). Clinical characteristics, admission diagnosis, appropriateness of diagnostic tests,...
Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to an extended hospital stay and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies...
Although 23 antiretroviral drugs are approved for use in adults, only six are approved by regulatory authorities for use in term neonates born to women with HIV, with even fewer options for preterm neonates. A major hurdle for approvals is the delay in the generation of pharmacokinetic and safety data for antiretrovirals in neonates. The median tim...
Safe and effective paediatric formulations of the most promising antiretroviral drugs are crucial to advance the treatment and prevention of HIV in neonates, infants, children, and adolescents. The WHO Paediatric Drug Optimization for HIV (PADO-HIV) group brings together stakeholders and experts every 2–3 years to identify priority products and def...
Background
Sepsis severity scores are used in clinical practice and trials to define risk groups. There are limited data to derive hospital-based sepsis severity scores for neonates and young infants in high-burden low- and middle-income country (LMIC) settings where trials are urgently required. We aimed to create linked sepsis severity and recove...
Background
Neonatal sepsis is a leading cause of child mortality, and increasing antimicrobial resistance threatens progress towards the Sustainable Development Goals. Evidence to guide antibiotic treatment for sepsis in neonates and young infants from randomized controlled trials or observational studies in low- and middle-income countries (LMICs)...
Background. Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. Methods. We conducted a 6-countr...
BACKGROUND: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS: We conducted a 6-countr...
Background:
Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice.
Methods:
We conducted a 6-cou...
Objectives:
Ethambutol protects against the development of resistance to co-administered drugs in the intensive phase of first-line anti-TB treatment in children. It is especially relevant in settings with a high prevalence of HIV or isoniazid resistance. We describe the population pharmacokinetics of ethambutol in children with TB to guide dosing...
Background:
Antimicrobial prescription and administration-related errors occur frequently in very low birth weight (VLBW; <1,500 g) neonates treated for bloodstream infections (BSI).
Methods:
Antimicrobial prescriptions for the treatment of laboratory-confirmed BSI were retrospectively analyzed for VLBW neonates at Tygerberg Hospital, Cape Town,...
Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients fa...
Background:
Isoniazid (INH) metabolism depends on the N-acetyl transferase 2 (NAT2) enzyme, whose maturation process remains unknown in low birth weight (LBW) and preterm infants. We aimed to assess INH exposure and safety in infants receiving oral tuberculosis prevention.
Methods:
This population pharmacokinetics (PK) analysis used INH and N-ac...
BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previouslyOBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 diffe...
Background:
Antiretroviral options for neonates (< 28 days of life) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the '4-in-1' fixed-dose paediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates.
Methods:
The PETITE study is an ongoing phase I/II, open-label, sin...
Background
No evidence-based optimal dosing guidance is available for abacavir liquid formulation use from birth. We used abacavir pharmacokinetic data from neonates and infants to determine an exact abacavir dosing strategy (mg/kg) for infants aged 0–3 months and to propose dosing by WHO weight band for neonates.
Methods
Abacavir pharmacokinetic...
Background
In 2010, the WHO revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) table of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg , and suggest a new...
Objective
To describe risk factors and outcomes of pregnant women infected with SARS‐CoV‐2 admitted to South African healthcare facilities.
Methods
A population‐based cohort study was conducted utilizing an amended International Obstetric Surveillance System protocol. Data on pregnant women with SARS‐CoV‐2 infection, hospitalized between April 14,...
The South African National Department of Health published updated guidelines in 2019 for the prevention of mother-to-child transmission of communicable diseases. The proposed management of a neonate born to a mother with tuberculosis (TB) was included, and recommended referral of all symptomatic TB-exposed neonates to hospital for TB evaluation. Ho...
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)...
Background
Chlorhexidine gluconate (CHG) body washes and emollient application may modulate bacterial pathogen colonization and prevent neonatal hospital-acquired infections.
Methods
This pilot, non-randomized, open-label trial, enrolled preterm neonates (1000-1500g; day 1-3 of life) at a tertiary hospital in Cape Town, South Africa. Participants...
Background
Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures.
Objective
We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets...
Background
Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings.
Methods
A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention for surfaces and equipment in a 30...
Background
Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices.
Methods
A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital’s neonatal unit in Cape Town, South Africa. Neonatal clinical and...
Following exposure to a healthcare worker with an influenza-like illness, 2 preterm neonates and 6 staff members developed symptoms and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This neonatal unit coronavirus disease 2019 outbreak occurred prior to the implementation of universal masking and symptom screening...
Abstract
Introduction
Epidemiologic data on neonatal bloodstream infections (BSI) in sub-Saharan Africa is extremely limited.
Methods
Comparative analysis of laboratory-confirmed neonatal BSI (LC-BSI) episodes was conducted retrospectively at two large neonatal units in Botswana and South Africa (1 January-31 December 2017). Routine laboratory and...
Background: Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings.
Methods: A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention (NeoCLEAN) for surfaces and equip...
Background: Contamination of the near-patient hospital environment including work surfaces and equipment, contributes to skin colonization and subsequent invasive bacterial infections in hospitalized neonates. In resource-limited settings, cleaning of the neonatal ward environment and equipment is seldom standardized and infrequently audited. Metho...
Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug ex...
Background: Data from Africa reporting the epidemiology of infection in hospitalised neonates are limited.
Methods: We conducted a cross-sectional study with convenience sampling to characterise neonates investigated with blood culture/s for suspected infection at a 124-bed neonatal unit in Cape Town, South Africa (1 February-31 October 2018). Enro...
Abacavir is a potential option for prophylaxis and early treatment of 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.
Despite a substantial decline in childhood mortality rates in South Africa (SA), progress in neonatal mortality reduction has been much slower. Severe bacterial infections remain a leading cause of neonatal morbidity and a direct cause of 13.1% of neonatal deaths among babies >1 kg. The incidence of hospital-acquired infections, antimicrobial resis...
Ethionamide has proven efficacy against both drug-susceptible and some drug-resistant strains of Mycobacterium tuberculosis . Limited information is available on its pharmacokinetics in children, and current doses are extrapolated from weight-based adult doses. Paediatric doses based on more robust evidence is expected to improve antituberculosis t...
Pregnant women and their infants are a vulnerable but neglected population in tuberculosis (TB) control efforts. Recent advances in TB prevention, diagnosis and treatment have implications for their care, despite their frequent exclusion from research. We have conducted a meta-review of current evidence and clinical guidelines for TB prevention, di...
Objective
To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).
Design
A web-based survey using a REDCap database was c...
Background: The only antiretrovirals (ARV) approved to treat HIV- exposed infants below 37 weeks gestational age (GA) are nevirapine (NVP), zidovudine and lamivudine. The NVP concentration target for treatment (3 mcg/mL) is 30-fold that for prophylaxis (0.1 mcg/mL). Preterm infants have reduced NVP clearance compared to term infants; doses of 4 mg/...
A recent fatal case of confirmed nosocomial tuberculosis (TB) transmission to a neonate in a kangaroo mother care (KMC) unit highlighted the infection risk to hospitalised neonates in South Africa, a high-burden TB setting. The index case was a 9-week-old infant who presented to another hospital's intensive care unit with severe respiratory distres...
Key Clinical Message
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 nee...
Introduction
Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK).
Objectives
The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol...
Background. A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world’s largest LM outbreak to date.Methods. We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 201...