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

Antiviral Toxicities in Pediatric Solid Organ Transplant Recipients.

2022

08/2022

1600-6143

Prophylaxis with valganciclovir (VGCV) is used routinely to prevent cytomegalovirus (CMV) infections in at-risk pediatric solid organ transplant (SOT) recipients. However, the rate and factors associated with toxicities in this population are not well-described. We conducted a retrospective cohort study of children undergoing SOT at our hospital from January 2012 - June 2018. We evaluated the frequency of hematologic and renal toxicities from day 15 through 1-year post-SOT in relation to antiviral exposures, focused on VGCV prophylaxis. Marginal rate models were used to determine the risk of kidney injury and neutropenia in relation to VGCV prophylaxis. Among 281 SOTs, VGCV prophylaxis was administered on 20.1% of all follow-up days. The incidence rates of kidney injury, leukopenia, and neutropenia were significantly higher during VGCV prophylaxis compared to when no antiviral agents were given. Using multivariable marginal rate models, receipt of VGCV prophylaxis was associated with development of kidney injury (rate ratio [RR] 1.79, 95% confidence interval [CI]: 1.22-2.65) and neutropenia (RR 4.82, 95% CI: 3.08-7.55). VGCV dosing did not impact the development of kidney injury or neutropenia. Toxicities are common with VGCV prophylaxis in pediatric SOT recipients.

10.1111/ajt.17171

Am J Transplant

35971847

Improving Vancomycin Stewardship in Critically Ill Children.

2022

2022 Apr 01

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU.</p>

<p><strong>METHODS: </strong>We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction.</p>

<p><strong>RESULTS: </strong>Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin.</p>

<p><strong>CONCLUSION: </strong>Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.</p>

10.1542/peds.2021-052165

Pediatrics

35362066

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

2022

2022 Feb 02

2048-7207

<p><strong>BACKGROUND: </strong>Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience.</p>

<p><strong>METHODS: </strong>A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion.</p>

<p><strong>RESULTS: </strong>The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults.</p>

<p><strong>CONCLUSIONS: </strong>Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.</p>

10.1093/jpids/piab124

J Pediatric Infect Dis Soc

35107571

CMV infection and management among pediatric solid organ transplant recipients.

2022

e14220

2022 Jan 06

1399-3046

<p><strong>BACKGROUND: </strong>Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established.</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end-organ disease) on negative outcomes (death, re-transplantation, or moderate/severe rejection) within the first year after SOT.</p>

<p><strong>RESULTS: </strong>Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73-14.64; p&nbsp;=&nbsp;.12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19- 10.79; p&nbsp;=&nbsp;.74), although not to a statistically significant degree.</p>

<p><strong>CONCLUSIONS: </strong>Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.</p>

10.1111/petr.14220

Pediatr Transplant

34994041

Incidence of CMV Infection and Disease and Adverse Events Associated with Antiviral Therapy in a Retrospective Cohort of Allogeneic Hematopoietic Cell Transplant Recipients at an Academic Children's Hospital.

2021

2021 Jul 02

2048-7207

<p><strong>BACKGROUND: </strong>Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies.</p>

<p><strong>METHODS: </strong>A single-center retrospective observational cohort of allogeneic HCT recipients at the Children's Hospital of Philadelphia January 1, 2004-December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy.</p>

<p><strong>RESULTS: </strong>Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE.</p>

<p><strong>CONCLUSIONS: </strong>CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.</p>

10.1093/jpids/piab041

J Pediatric Infect Dis Soc

34213545

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of COVID-19 in Children and Adolescents.

2021

2021 Jan 03

2048-7207

<p><strong>BACKGROUND: </strong>In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate COVID-19 in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products.</p>

<p><strong>METHODS: </strong>A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion.</p>

<p><strong>RESULTS: </strong>The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis.</p>

<p><strong>CONCLUSIONS: </strong>Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence, and ensure implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.</p>

10.1093/jpids/piaa175

J Pediatric Infect Dis Soc

33388760

Multicenter interim guidance on use of antivirals for children with COVID-19/SARS-CoV-2.

2020

2020 Sep 12

2048-7207

<p><strong>BACKGROUND: </strong>Although Coronavirus Disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data evaluating agents with potential antiviral activity continue to expand, such that updated guidance is needed regarding use of these agents in children.</p>

<p><strong>METHODS: </strong>A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion.</p>

<p><strong>RESULTS: </strong>Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for non-invasive or invasive mechanical ventilation or extra-corporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or non-invasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children.</p>

<p><strong>CONCLUSIONS: </strong>Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.</p>

10.1093/jpids/piaa115

J Pediatric Infect Dis Soc

32918548