Errors in Antimicrobial Prescription and Administration in Very Low Birth Weight Neonates at a Tertiary South African Hospital.

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, South Africa (1 July 2018 - 31 December 2019), describing antimicrobial type, indication, duration of therapy and BSI outcomes. The prevalence of, and risk factors for prescription (dose, interval) and administration errors (hang-time, delayed/missed doses) were determined. Results: One hundred and sixty-one BSI episodes [16 (9.9%)] early-onset, 145 [90.1%] healthcare-associated) affected 141 neonates (55% male, 25% born to mothers living with HIV, 46% <1,000 g birth weight) with 525 antimicrobial prescription episodes [median 3.0 (IQR 2-4) prescriptions/BSI episode]. The median duration of therapy for primary BSI, BSI-associated with meningitis and BSI-associated with surgical infections was 9, 22, and 28 days, respectively. The prevalence of dose and dosing interval errors was 15.6% (77/495) and 16.4% (81/495), respectively with prescription errors occurring most commonly for piperacillin-tazobactam and vancomycin given empirically. Administration errors were less frequent [3.8% (219/5,770) doses missed; 1.4% (78/5,770) delayed], however 64% had a hang-time (time from sepsis diagnosis to 1st dose of antimicrobial) exceeding 60 min. On multivariable analysis, postnatal age >7 days was associated with prescription errors (p = 0.028). The majority of neonates with BSI required escalation of respiratory support (52%) and 26% required intensive care admission. Despite fair concordance between empiric antimicrobial/s prescription and pathogen susceptibility (74.5%), BSI-attributable mortality in this cohort was 30.4%. Conclusion: VLBW neonates with BSI's were critically ill and had high mortality rates. Hang-time to first antimicrobial administration was delayed in two-thirds of BSI episodes and prescription errors affected almost 1 in 6 prescriptions. Targets for intervention should include reducing hang-time, use of standardized antimicrobial dosing guidelines and implementation of antimicrobial stewardship recommendations.

Healthcare-Associated Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Neonatal Unit: The Importance of Universal Masking, Hand Hygiene, and Symptom Screening in Containment.

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 policies. Both neonates and all staff recovered, with no further healthcare-associated SARS-CoV-2 transmission following the implementation of effective outbreak containment measures.

Optimal Ventilation and Surfactant Therapy in Very-Low-Birth-Weight Infants in Resource-Restricted Regions.

In resource-restricted regions, respiratory distress syndrome (RDS) data are often underreported, making the determination of effective interventions and their outcome difficult. The combination of oxygen, nasal continuous positive airway pressure (CPAP) and surfactant therapy has the potential to prevent 42% of RDS-related deaths in sub-Saharan Africa, despite the financial implications. This article provides a brief overview on the status of RDS management, mainly nasal CPAP and surfactant therapy in very-low-birth-weight infants, in resource-restricted regions of sub-Saharan Africa. Data from the public health sector, as compared to the private health sector, of the Western Cape province, South Africa, are used to illustrate what RDS management strategies are able to accomplish in a resource-restricted region. Upscaling of all components (antenatal care, antenatal corticosteroids, prevention of hypothermia and RDS management strategies) are required to decrease premature infant mortality rates in resource-restricted areas.

Antiretroviral Treatment Initiated in the First Month of Life.

BACKGROUND: Earlier diagnosis of HIV-infected infants facilitates earlier access to therapy and improved clinical outcomes. The aim of this study was to describe the management of infants who started antiretroviral therapy (ART) in the first month of life. METHODS: A retrospective review was performed on HIV-infected neonates who started ART within the first month of life between January 2013 and March 2015. RESULTS: A total of 997 neonates had 1 HIV polymerase chain reaction test. Of the 997 neonates, 26 (2.6%) tested positive for HIV and 22 initiated therapy in the first month of life. The median age of first HIV polymerase chain reaction test was 7 days. Neonates were started on ART within a median of 7 days of their first HIV test, which equated to a median age of 13.5 [interquartile range (IQR) 7-20] days of life. Median gestational age was 35 weeks (IQR 33-38 weeks), and birth weight was 2170 g (IQR 1773-2480). Nineteen (86.4%) had low birth weight (<2.5 kg) and 16 (72.7%) were premature. Median baseline HIV viral loads were log 4.444 copies/mL (IQR 3.457-5.125), median CD4 counts were 1338 (IQR 803-1928) and CD4% percentages were 36.1% (22.2-45.4). All children initiated zidovudine and lamivudine, 10 with lopinavir/ritonavir and 12 with nevirapine. All children in care are now receiving lopinavir/ritonavir. Of the 22 neonates initiated on treatment, 11 are in care (mean age, 2.1 years), and 2 of these infants had a viral load of <50 copies/ mL when last measured. CONCLUSIONS: Early ART initiation in neonates is feasible. Challenges include safe, palatable regimens and continued close follow-up of mothers and infants.

The last and first frontier--emerging challenges for HIV treatment and prevention in the first week of life with emphasis on premature and low birth weight infants.

INTRODUCTION: There is new emphasis on identifying and treating HIV in the first days of life and also an appreciation that low birth weight (LBW) and preterm delivery (PTD) frequently accompany HIV-related pregnancy. Even in the absence of HIV, PTD and LBW contribute substantially to neonatal and infant mortality. HIV-exposed and -infected infants with these characteristics have received little attention thus far. As HIV programs expand to meet the 90-90-90 target for ending the HIV pandemic, attention should focus on newborn infants, including those delivered preterm or of LBW. DISCUSSION: In high prevalence settings, infant diagnosis of HIV is usually undertaken after the neonatal period. However, as in utero infection may be diagnosed at birth, earlier initiation of therapy may limit viral replication and prevent early damage. Globally, there is growing awareness that preterm and LBW infants constitute a substantial proportion of births each year. Preterm infants are at high risk for vertical transmission. Feeding difficulties, apnoea of prematurity and vulnerability to sepsis occur commonly. Feeding intolerance, a frequent occurrence, may compromise oral administration of medications. Although there is growing experience with post-exposure prophylaxis for HIV-exposed term newborn infants, there is less experience with preterm and LBW infants. For treatment, there are even fewer options for preterm infants. Only zidovudine has adequate dosing recommendations for treating term and preterm infants and has an intravenous formulation, essential if feeding intolerance occurs. Nevirapine dosing for prevention, but not treatment, is well established for both term and preterm infants.HIV diagnosis at birth is likely to be extremely stressful for new parents, more so if caring for preterm or LBW infants. Programs need to adapt to support the medical and emotional needs of young infants and their parents, where interventions may be lifesaving. CONCLUSIONS: New focus is required for the newborn baby, including those born preterm, with LBW or small for gestational age to consolidate gains already made in early diagnosis and treatment of young children.

Nevirapine concentrations in preterm and low birth weight HIV-exposed infants: implications for dosing recommendations.

World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV-exposed infants <2 kg, but 4-6 mg/kg/d for infants >2 kg. In 116 low birth weight infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe (1 mild possibly related rash) and achieved target plasma concentrations. Concentrations decreased with treatment duration. Routine dose increase at 14 days should be considered.

The outcome of ELBW infants treated with NCPAP and InSurE in a resource-limited institution.

BACKGROUND AND OBJECTIVE: Nasal continuous positive airway pressure (NCPAP) plus intubation, surfactant, and extubation (InSurE) with the option of back-up ventilation for those infants for whom noninvasive ventilatory support failed resulted in a significant increase in survival in extremely low birth weight (ELBW) infants. The authors sought to determine the outcome of ELBW infants treated with NCPAP and InSurE in a neonatal high care ward with limited back-up ventilation. METHODS: Three hundred eighteen inborn infants with birth weight 500-1000 g and gestational age ≥25 weeks who were admitted to the neonatal high care ward were included in this observational study. InSurE was administered to infants with respiratory distress syndrome on NCPAP who had severe in-drawing and recession, apneic spells, or an Fio(2) >0.4 within 1 hour of birth. RESULTS: Two hundred twelve (68.6%) infants could be treated with NCPAP only and 97 (31.4%) required InSurE. Seventeen infants were admitted to the NICU; 90%, 87%, and 74.8% of the infants survived until day 3, 7, and discharge, respectively. Only 2 infants developed a pneumothorax and 2 had chronic lung disease. Seventy-nine percent of the infants of ≥750 g or >26 weeks' gestation survived to discharge compared with 56% and 60% of the infants of <750 g or ≤26 weeks' gestation, respectively. Maternal antenatal steroid administration contributed significantly to the survival of the infants (P = 0.0017, odds ratio 2.7, 95% confidence interval 1.44-5.07). CONCLUSIONS: The use of NCPAP and InSurE in a neonatal high care ward with limited resources can improve the survival of ELBW infants. Maternal antenatal steroid administration contributed significantly to survival.

Trough lopinavir concentrations in preterm HIV-infected infants.

Because of serious adverse effects, the Food and Drug Administration warns against using lopinavir in infants younger than 42 weeks postconception. However, there is an imperative for early treatment. We report on our use of LPV in 8 premature HIV-infected infants. The median age at initiation was 27 days. Trough values guided dosing. Five infants needed doses above 300 mg/m. Although no adverse events were noted, lopinavir usage requires caution and careful monitoring.

Oseltamivir use in low-birth weight infants during the 2009 nH1N1 influenza a outbreak in the Western Cape, South Africa.

Before vaccination against nH1N1 influenza was available in South Africa our hospital experienced an outbreak of nH1N1 infection on the maternal and neonatal platform. Oseltamivir was administered to nine low birth weight infants, five for therapy and four for prophylaxis. The median gestational age was 31 (27-37) weeks and the birth weight was 1660 (720-2360) g. Respiratory function improved in those with confirmed disease and none receiving prophylaxis developed worsening respiratory symptoms. One neonate receiving prophylaxis developed self-limiting conjunctivitis; another succumbed from necrotizing enterocolitis (NEC) three days post completion of oseltamivir treatment. A causal relationship between oseltamivir and NEC, although unlikely, cannot be confirmed or excluded.

Evaluating Antibiotic Use in a Secondary Level Hospital Neonatal Unit in the Western Cape; South Africa

Abstract:Perinatal infection significantly contributes to neonatal morbidity and mortality. There are no reliable rapid diagnostic tests. Drug resistance is increasing in organisms acquired in hospital. There are little data on the indications for antibiotic use and the prevalent organisms in lower resource settings; and none in regional hospitals in South Africa. We conducted a retrospective cohort study of risk factors; indications for and drugs used at Worcester Provincial Hospital Neonatal Unit. A systematic sample of every alternate neonate listed in the admissions register from 1 July 2005 to 30 June 2006 was taken. Charts for all cases were reviewed. Early antibiotic use was defined as therapy within 72 hours of life. One hundred and ninetyfive infants where included; 144 (74) had 194 antibiotic events. Antibiotic events occurred at a rate of 99 events per 100 neonates. Prematurity was common (83 of admissions) and; in conjunction with prolonged rupture of membranes; was the major driver of early antibiotic use. Ceftriaxone use within 72 hours of birth was significantly associated with subsequent antibiotic events; compared with penicillin alone or in combination with an aminoglycoside (p 0.04). Longer duration of treatment for early events was associated with subsequent empiric need for antibiotics (p 0.02). Prematurity is the major driver for antibiotic use at this unit. Antibiotics are prescribed appropriately but earlier discontinuation; which may be complicated by the inability to confirm/refute infection; should be practised. Alternatives to third generation cephalosporins should be available to treat hospital infection at secondary level