Assessing antibiotic utilization among pediatric patients in Gaborone, Botswana.

2022

20503121221104437

12/2022

2050-3121

OBJECTIVES: Over the past decade, concerning trends in antimicrobial resistance have emerged in Southern Africa. Given a paucity of pediatric data, our objectives were to (1) describe antibiotic utilization trends at a national referral center in Southern Africa and (2) assess the proportion of patients receiving antibiotics appropriately. In addition, risk factors for inappropriate use were explored.

METHODS: We performed a prospective cohort study on medical and surgical pediatric patients aged below 13 years admitted to the country's tertiary care referral hospital in Gaborone, Botswana. We collected demographics, clinical, laboratory, and microbiology details, in addition to information on antibiotic use. We separately categorized antibiotic prescriptions using the World Health Organization AWaRe Classification of Access, Watch, and Restrict.

RESULTS: Our final cohort of 299 patients was 44% female and 27% HIV-exposed; most (68%) were admitted to the General Pediatrics ward. Infections were a common cause of hospitalization in 29% of the cohort. Almost half of our cohort were prescribed at least one antibiotic during their stay, including 40% on admission; almost half (47%) of these prescriptions were deemed appropriate. At the time of discharge, 52 (21%) patients were prescribed an antibiotic, of which 37% were appropriate. Of all antibiotics prescribed, 42% were from the World Health Organization Access antibiotic list, 58% were from the Watch antibiotic list, and 0% were prescribed antibiotics from the Restrict antibiotic list. Univariate analyses revealed that surgical patients were significantly more likely to have inappropriate antibiotics prescribed on admission. Patients who were treated for diseases for which there was a clinical pathway, or who had blood cultures sent at the time of admission were less likely to have inappropriate antibiotics prescribed. On multivariate analysis, apart from admission to the surgical unit, there were no independent predictors for inappropriate antibiotic use, although there was a trend for critically ill patients to receive inappropriate antibiotics.

CONCLUSION: Our study reveals high rates of antibiotic consumption, much of which was inappropriate. Promising areas for antimicrobial stewardship interventions include (1) standardization of management approaches in the pediatric surgical population and (2) the implementation of feasible and generalizable clinical pathways in this tertiary care facility.

10.1177/20503121221104437

SAGE Open Med

36814934

Severity of illness and mortality among children admitted to a tertiary referral hospital in Botswana: A secondary data analysis of a prospective cohort study.

2023

20503121221149356

12/2023

2050-3121

OBJECTIVES: Data on triage practices of children admitted to Princess Marina Hospital in Gaborone, Botswana is limited. The inpatient triage, assessment, and treatment score was developed for low resource settings to predict mortality in children. We assess its performance among children admitted to Princess Marina Hospital and their demographic, clinical, and risk factors for death.

METHODS: This was a secondary data analysis of a prospective cohort study comprising 299 children ages 1 month to 13 years admitted June to September 2018. Descriptive statistics, bivariate analysis, and multivariate logistic regression were used. Sensitivity and specificity data were generated for the inpatient triage, assessment, and treatment score.

RESULTS: Thirteen children died (13/284, 4.6%). Comorbidity (adjusted odds ratio 4.0,  = 0.020) and high inpatient triage, assessment, and treatment score (adjusted odds ratio 5.0,  = 0.017) increased odds of death. The area under the receiver operating characteristic curve was 0.81. Using inpatient triage, assessment, and treatment cutoff of 4, the sensitivity, specificity, and likelihood ratio were 31%, 94%, and 5.0, respectively.

CONCLUSION: Implementing the inpatient triage, assessment, and treatment score in low resource settings may improve identification, treatment, and evaluation of the sickest children.

10.1177/20503121221149356

SAGE Open Med

36741934

Risk factors for mortality in a hospitalised neonatal cohort in Botswana.

2022

e062776

09/2022

2044-6055

OBJECTIVES: A disproportionate number of neonatal deaths occur in low/middle-income countries, with sepsis a leading contributor of mortality. In this study, we investigate risk factors for mortality in a cohort of high-risk hospitalised neonates in Botswana. Independent predictors for mortality for infants experiencing either a sepsis or a non-sepsis-related death are described.

METHODS: This is a prospective observational cohort study with infants enrolled from July to October 2018 at the neonatal unit (NNU) of Princess Marina Hospital (PMH) in Gaborone, Botswana. Data on demographic, clinical and unit-specific variables were obtained. Neonates were followed to death or discharge, including transfer to another hospital. Death was determined to be infectious versus non-infectious based on primary diagnosis listed on day of death by lead clinician on duty.

RESULTS: Our full cohort consisted of 229 patients. The overall death rate was 227 per 1000 live births, with cumulative proportion of deaths of 22.7% (n=47). Univariate analysis revealed that sepsis, extremely low birth weight (ELBW) status, hypoxic ischaemic encephalopathy, critical illness and infants born at home were associated with an increased risk of all-cause mortality. Our multivariate model revealed that critical illness (HR 3.07, 95% CI 1.56 to 6.03) and being born at home (HR 4.82, 95% CI 1.76 to 13.19) were independently associated with all-cause mortality. Low birth weight status was independently associated with a decreased risk of mortality (HR 0.24, 95% CI 0.11 to 0.53). There was a high burden of infection in the cohort with more than half of infants (140, 61.14%) diagnosed with sepsis at least once during their NNU admission. Approximately 20% (n=25) of infants with sepsis died before discharge. Our univariate subanalysis of the sepsis cohort revealed that ELBW and critical illness were associated with an increased risk of death. These findings persisted in the multivariate model with HR 3.60 (95% CI 1.11 to 11.71) and HR 2.39 (95% CI 1 to 5.77), respectively.

CONCLUSIONS: High rates of neonatal mortality were noted. Urgent interventions are needed to improve survival rates at PMH NNU and to prioritise care for critically ill infants at time of NNU admission, particularly those born at home and/or of ELBW.

10.1136/bmjopen-2022-062776

BMJ Open

36691117

Dodging the bundle-Persistent healthcare-associated rhinovirus infection throughout the pandemic.

2022

1140-1144

05/2022

1527-3296

INTRODUCTION: Healthcare-associated viral infections (HAVI) are a common cause of patient harm in the pediatric population. We implemented a HAVI prevention bundle in 2015, which included 6 core elements: caregiver screening, symptom-based isolation, personal protective equipment (PPE), hand hygiene, staff illness procedures, and monitoring of environmental cleanliness. Enhanced bundle elements were introduced at the start of the COVID-19 pandemic, which provided an opportunity to observe the effectiveness of the bundle with optimal adherence to prevention practices, and to measure the impact on respiratory HAVI epidemiology.

METHODS: Respiratory HAVIs were confirmed through review of medical records and application of the National Health Safety Network (NHSN) surveillance criteria for upper respiratory infections (URIs) with predetermined incubation periods for unit attribution. Descriptive statistics of the study population were examined, and comparative analyses were performed on demographic and process metrics. Data analysis was conducted using R statistical software.

RESULTS: We observed an overall decrease in respiratory HAVI of 68%, with prepandemic rates of 0.19 infections per 1,000 patient significantly decreased to a rate of 0.06 per 1,000 patient days in the pandemic period (P < .01). Rhinovirus made up proportionally more of our respiratory HAVI in the pandemic period (64% vs 53%), with respiratory HAVI secondary only to rhinovirus identified during 8 of 16 months in the pandemic period. Compliance with our HAVI prevention bundle significantly improved during pandemic period.

CONCLUSIONS: Enhancement of our HAVI bundle during the COVID-19 pandemic contributed toward significant reduction in nosocomial transmission of respiratory HAVI. Even with prevention practices optimized, respiratory HAVIs secondary to rhinovirus continued to be reported, likely due to the capacity of rhinovirus to evade bundle elements in hospital, and infection prevention efforts at large in the community, leaving vulnerable patients at continued risk.

10.1016/j.ajic.2022.04.016

Am J Infect Control

35588914

Quantifying Empiric Antibiotic Use in US Children's Hospitals.

2021

2021 Dec 01

2154-1671

<p><strong>OBJECTIVES: </strong>Empirical broad-spectrum antibiotics are routinely administered for short durations to children with suspected bacteremia while awaiting blood culture results. Our aim for this study was to estimate the proportion of broad-spectrum antibiotic use accounted for by these "rule-outs."</p>

<p><strong>METHODS: </strong>The Pediatric Health Information System was used to identify children aged 3 months to 20 years hospitalized between July 2016 and June 2017 who received broad-spectrum antibiotics for suspected bacteremia. Using an electronic definition for a rule-out, we estimated the proportion of all broad-spectrum antibiotic days of therapy accounted for by this indication. Clinical and demographic characteristics, as well as antibiotic choice, are reported descriptively.</p>

<p><strong>RESULTS: </strong>A total of 67 032 episodes of suspected bacteremia across 42 hospitals were identified. From these, 34 909 (52%) patients were classified as having received an antibiotic treatment course, and 32 123 patients (48%) underwent an antibiotic rule-out without a subsequent treatment course. Antibiotics prescribed for rule-outs accounted for 12% of all broad-spectrum antibiotic days of therapy. Third-generation cephalosporins and vancomycin were the most commonly prescribed antibiotics, and substantial hospital-level variation in vancomycin use was identified (range: 16%-58% of suspected bacteremia episodes).</p>

<p><strong>CONCLUSIONS: </strong>Broad-spectrum intravenous antibiotic use for rule-out infections appears common across children's hospitals, with substantial hospital-level variation in the use of vancomycin in particular. Antibiotic stewardship programs focused on intervening on antibiotics prescribed for longer durations may consider this novel opportunity to further standardize antibiotic regimens and reduce antibiotic exposure.</p>

10.1542/hpeds.2021-005950

Hosp Pediatr

34807987

SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021.

2021

2021 Oct 20

<p>The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.</p>

<p><strong>Importance: </strong>SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here we report analysis of 2621 surveillance isolates from xsxpeople diagnosed with COVID-19 in the Delaware Valley in South Eastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a three-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.</p>

10.1101/2021.10.18.21264623

medRxiv

34704098

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

2022

e0378821

2022 Feb 08

2150-7511

<p>The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.</p>

10.1128/mbio.03788-21

mBio

34704098

Center Variability in Acute Rejection and Biliary Complications after Pediatric Liver Transplantation.

2021

2021 Aug 08

1527-6473

<p>Transplant center performance and practice variation for pediatric post-liver transplantation (LT) outcomes other than survival are understudied. This was a retrospective cohort study of pediatric LT recipients between 1/1/2006-5/31/2017 using United Network for Organ Sharing (UNOS) data that was merged with the Pediatric Health Information System database. Center effects at 1 year post-LT for acute rejection (AR1) using UNOS coding and biliary complications (BC1) using inpatient biling claims data were estimated by center-specific rescaled odds ratios that accounted for potential differences in recipient and donor characteristics. There were 2,216 pediatric LT recipients at 24 free-standing children's hospitals in the US during the study period. The median unadjusted center rate of AR1 was 36.92% (IQR: 22.36-44.52%), while that of BC1 was 32.29% (IQR: 26.14-40.44%). Accounting for recipient case-mix and donor factors, 5/24 centers performed better-than-expected with regards to AR1, while 3/24 centers performed worse-than-expected. There was less heterogeneity across the center effects for BC1 than for AR1. There was no relationship observed between center effects for AR1 or BC1 and center volume. CONCLUSION: Beyond recipient and allograft factors, differences in transplant center management are an important driver of center AR1 performance, and less so of BC1 performance. Further research is needed to identify the sources of variability so as to implement the most effective solutions to broadly enhance outcomes for pediatric LT recipients.</p>

10.1002/lt.26259

Liver Transpl

34365719

The Utility of Paired Upper and Lower COVID-19 Sampling in Patients with Artificial Airways.

2021

1-8

2021 May 10

1559-6834

<p>Early in the COVID-19 pandemic, CDC recommended collection of a lower respiratory tract (LRT) specimen for SARS-CoV-2 testing in addition to the routinely recommended upper respiratory tract (URT) testing in mechanically ventilated patients. Significant operational challenges were noted at our institution using this approach. In this report, we describe our experience with routine collection of paired URT and LRT sample testing. Our results revealed a high concordance between the two sources, and that all children tested for SARS-CoV-2 were appropriately diagnosed with URT testing alone. There was no added benefit to LRT testing. Based on these findings, our institutional approach was therefore adjusted to sample the URT alone for most patients, with LRT sampling reserved for patients with ongoing clinical suspicion for SARS-CoV-2 after a negative URT test.</p>

10.1017/ice.2021.222

Infect Control Hosp Epidemiol

33966664

Implementation of a Mandatory Influenza Vaccine Policy: A 10-Year Experience.

2020

2020 Jun 17

1537-6591

<p><strong>BACKGROUND: </strong>Influenza vaccination of healthcare workers (HCWs) has been recommended for more than 30 years. In 2009, HCWs were designated as a priority group by the Centers for Disease Control and Prevention. Current HCW vaccination rates are 78% across all settings and reach approximately 92% among those employed in hospital settings. Over the last decade, it has become clear that mandatory vaccine policies result in maximal rates of HCW immunization.</p>

<p><strong>METHODS: </strong>In this observational 10-year study, we describe the implementation of a mandatory influenza vaccination policy in a dedicated quaternary pediatric hospital setting by a multidisciplinary team. We analyzed 10 years of available data from deidentified occupational health records from 2009-2010 through the 2018-2019 influenza seasons. Descriptive statistics were performed using Stata v15 and Excel.</p>

<p><strong>RESULTS: </strong>Sustained increases in HCW immunization rates above 99% were observed in the 10 years postimplementation, in addition to a reduction in exemption requests and healthcare-associated influenza. In the year of implementation, 145 (1.6%) HCWs were placed on temporary suspension for failure to receive the vaccine without documentation of an exemption, with 9 (0.06%) subsequently being terminated. Since then, between 0 and 3 HCWs are terminated yearly for failure to receive the vaccine.</p>

<p><strong>CONCLUSIONS: </strong>Implementation of our mandatory influenza vaccination program succeeded in successfully increasing the proportion of immunized HCWs at a quaternary care children's hospital, reducing annual exemption requests with a small number of terminations secondary to vaccine refusal. Temporal trends suggest a positive impact on the safety of our patients.</p>

10.1093/cid/ciaa782

Clin Infect Dis

33372217