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To characterize antifungal prescribing patterns, including the indication for antifungal use, in hospitalized children across the United States.
We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a cross-sectional point-prevalence survey conducted between June 2016 and December 2017.
Inpatients aged <18 years with an active systemic antifungal order were included in the analysis. We classified antifungal prescribing by indication (ie, prophylaxis, empiric, targeted), and we compared the proportion of patients in each category based on patient and antifungal characteristics.
Among 34,927 surveyed patients, 2,095 (6%) received at least 1 systemic antifungal and there were 2,207 antifungal prescriptions. Most patients had an underlying oncology or bone marrow transplant diagnosis (57%) or were premature (13%). The most prescribed antifungal was fluconazole (48%) and the most common indication for antifungal use was prophylaxis (64%). Of 2,095 patients receiving antifungals, 79 (4%) were prescribed >1 antifungal, most often as targeted therapy (48%). The antifungal prescribing rate ranged from 13.6 to 131.2 antifungals per 1,000 patients across hospitals (P < .001).
Most antifungal use in hospitalized children was for prophylaxis, and the rate of antifungal prescribing varied significantly across hospitals. Potential targets for antifungal stewardship efforts include high-risk, high-utilization populations, such as oncology and bone marrow transplant patients, and specific patterns of utilization, including prophylactic and combination antifungal therapy.
To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.
Design, setting, and participants:
Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.
Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.
In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.
Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.
We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed children. METHODS/STUDY POPULATION: We analyzed fecal samples from 174 subjects at 12 months of age, of whom 52 were exposed to antibiotics in their first year of life. Of these, 33 subjects were sampled again at 24 months of age. DNA from 200mg of frozen stool (−80C) was isolated with the Qiagen DNeasy PowerSoil kit. Shotgun libraries were generated using the NexteraXT kit and sequenced on the Illumina HiSeq 2500 using 2x125 bp chemistry. Sequence data were analyzed using the Sunbeam metagenomics pipeline. The abundance of bacteria was estimated using Kraken version 2.0.8. Fecal bile acids will be quantified by liquid chromatography–mass spectrometry (LC-MS). RESULTS/ANTICIPATED RESULTS: Overall bacterial community composition at 12 or 24 months was not associated with antibiotic exposure (PERMANOVA test, Bray-Curtis distance). An increase in Enterobacteriaceae, in particular Escherichia coli, is a signature of antibiotic-induced dysbiosis, but also of early infant gut. Children with antibiotic exposure had slightly higher abundance of Escherichia coli compared to those with no exposure (p = 0.03). At 24 months, the abundance of Bacteroides caccae, a commensal gut species, was decreased for children exposed to antibiotics in the first year of life (fdr = 0.02). We will perform further analysis of bile acid modifying bacteria, fecal bile acid concentrations and correlate to GI symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest a significant but nuanced impact of early life antibiotic use on the composition of the gut microbiota. The association of antibiotic exposure with B. caccae and E. coli warrant further attention in the context of the rapidly developing early-life microbiome. CONFLICT OF INTEREST DESCRIPTION: The authors declare no conflicts of interest relevant to this work.
To characterize the current state of antifungal stewardship practices and perceptions of antifungal use among pediatric antimicrobial stewardship programs (ASPs).
We developed and distributed an electronic survey, which included 17 closed-ended questions about institutional antifungal stewardship practices and perceptions, among pediatric ASPs.
ASP physicians and pharmacists of 74 hospitals participating in the multicenter Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.
We sent surveys to 74 hospitals and received 68 unique responses, for a response rate of 92%. Overall, 63 of 68 the respondent ASPs (93%) reported that they conduct 1 or more antifungal stewardship activities. Of these 68 hospital ASPs, 43 (63%) perform prospective audit and feedback (PAF) of antifungals. The most common reasons reported for not performing PAF of antifungals were not enough time or resources (19 of 25, 76%) and minimal institutional antifungal use (6 of 25, 24%). Also, 52 hospitals (76%) require preauthorization for 1 or more antifungal agents. The most commonly restricted antifungals were isavuconazole (42 of 52 hospitals, 80%) and posaconazole (39 of 52 hospitals, 75%). Furthermore, 33 ASPs (48%) agreed or strongly agreed that antifungals are inappropriately used at their institution, and only 25 of 68 (37%) of ASPs felt very confident making recommendations about antifungals.
Most pediatric ASPs steward antifungals, but the strategies employed are highly variable across surveyed institutions. Although nearly half of respondents identified inappropriate antifungal use as a problem at their institution, most ASPs do not feel confident making recommendations about antifungals. Future studies are needed to determine the rate of inappropriate antifungal use and the best antifungal stewardship strategies.
Evaluate the clinical impact of the implementation of VERIGENE gram-positive blood culture testing (BC-GP) coupled with antimicrobial stewardship result notification for children with positive blood cultures.
Quaternary children’s hospital.
Hospitalized children aged 0–21 years with positive blood culture events 1 year before and 1 year after implementation of BC-GP testing.
The primary outcome was time to optimal antibiotic therapy for positive blood cultures, defined as receiving definitive therapy without unnecessary antibiotics (pathogens) or no antibiotics (contaminants). Secondary outcomes were time to effective therapy, time to definitive therapy, and time to stopping vancomycin, length of stay, and 30-day mortality. Time-to-therapy outcomes before and after the intervention were compared using Cox regression models and interrupted time series analyses, adjusting for patient characteristics and trends over time. Gram-negative events were included as a nonequivalent dependent variable.
We included 264 preintervention events (191 gram-positive, 73 gram-negative) and 257 postintervention events (168 gram-positive, 89 gram-negative). The median age was 2.9 years (interquartile range, 0.3–10.1), and 418 pediatric patients (80.2%) had ≥1 complex chronic condition. For gram-positive isolates, implementation of BC-GP testing was associated with an immediate reduction in time to optimal therapy and time to stopping vancomycin for both analyses. BC-GP testing was associated with decreased time to definitive therapy in interrupted time series analysis but not Cox modeling. No such changes were observed for gram-negative isolates. No changes in time to effective therapy, length of stay, or mortality were associated with BC-GP.
The implementation of BC-GP testing coupled with antimicrobial stewardship result notification was associated with decreased time to optimal therapy and time to stopping vancomycin for hospitalized children with gram-positive blood culture isolates.
Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.
We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.
Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.
Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
Antimicrobial stewardship programs typically use days of therapy to assess antimicrobial use. However, this metric does not account for the antimicrobial spectrum of activity. We applied an antibiotic spectrum index to a population of very-low-birth-weight infants to assess its utility to evaluate the impact of antimicrobial stewardship interventions.
Infections due to antibiotic-resistant organisms are increasing in prevalence and represent a major public health threat. Antibiotic overuse is a major driver of this epidemic, and antibiotic stewardship an important means of limiting antibiotic resistance. The intensive care unit (ICU) setting presents an intersection of opportunities and challenges for effective antibiotic stewardship, but limited data inform optimal stewardship interventions in this setting. In this review, we present unique considerations for stewardship interventions the ICU setting and summarize available data evaluating the impact of prospective audit and feedback, diagnostic test stewardship, rapid molecular diagnostic tests, and procalcitonin-guided algorithms for antibiotic discontinuation. The existing knowledge gaps ripe for future research are emphasized.
Implementing antimicrobial stewardship programs (ASPs) can be challenging due to prescriber resistance. Although barriers to implementing new ASPs have been identified, little is known about how prescribers perceive established programs. This information is critical to promoting the sustainability of ASPs.
To identify how prescribers perceive an established pediatric inpatient ASP that primarily utilizes prior authorization.
We conducted a cross-sectional survey administered from February through June 2017 in a large children’s hospital. The survey contained closed- and open-ended questions. Descriptive statistics and thematic content analysis approaches were used to analyze responses.
Of 394 prescribers invited, 160 (41%) responded. Prescribers had an overall favorable impression of the ASP, believing that it improves the quality of care (92.4% agree) and takes their judgment seriously (73.8%). The most common criticism of the ASP was that it threatened efficiency (26.0% agreed). In addition, 68.7% of respondents reported occasionally engaging in workarounds. Analysis of 133 free-text responses revealed that prescribers perceived that interacting with the ASP involved too many phone calls, caused communication breakdowns with the dispensing pharmacy, and led to gaps between approval and dispensing of antibiotics. Reasons given for workarounds included not wanting to change therapy that appears to be working, consultant disagreement with ASP recommendations, and the desire to do everything possible for patients.
Prescribers had a generally favorable opinion of an established ASP but found aspects to be inefficient. They reported engaging in workarounds occasionally for social and emotional reasons. Established ASPs should elicit feedback from frontline prescribers to optimize program impact.
To describe the epidemiology of surgical site infections (SSIs) after pediatric ambulatory surgery.
Observational cohort study with 60 days follow-up after surgery.
The study took place in 3 ambulatory surgical facilities (ASFs) and 1 hospital-based facility in a single pediatric healthcare network.
Children <18 years undergoing ambulatory surgery were included in the study. Of 19,777 eligible surgical encounters, 8,502 patients were enrolled.
Data were collected through parental interviews and from chart reviews. We assessed 2 outcomes: (1) National Healthcare Safety Network (NHSN)–defined SSI and (2) evidence of possible infection using a definition developed for this study.
We identified 21 NSHN SSIs for a rate of 2.5 SSIs per 1,000 surgical encounters: 2.9 per 1,000 at the hospital-based facility and 1.6 per 1,000 at the ASFs. After restricting the search to procedures completed at both facilities and adjustment for patient demographics, there was no difference in the risk of NHSN SSI between the 2 types of facilities (odds ratio, 0.7; 95% confidence interval, 0.2–2.3). Within 60 days after surgery, 404 surgical patients had some or strong evidence of possible infection obtained from parental interview and/or chart review (rate, 48 SSIs per 1,000 surgical encounters). Of 306 cases identified through parental interviews, 176 cases (57%) did not have chart documentation. In our multivariable analysis, older age and black race were associated with a reduced risk of possible infection.
The rate of NHSN-defined SSI after pediatric ambulatory surgery was low, although a substantial additional burden of infectious morbidity related to surgery might not have been captured by standard surveillance strategies and definitions.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.
Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.
The study included 27 transplant centers in freestanding children’s hospitals.
The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.
Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.
Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.
The decision to utilize antimicrobials in end-of-life situations is complex. Understanding the reasons why physicians prescribe antimicrobials in this patient population is important for informing the design of antimicrobial stewardship interventions.
A 51-item survey containing both closed and open-ended questions on end-of-life antimicrobial use was administered to physicians affiliated with the University of Pennsylvania and Children’s Hospital of Philadelphia from January through April 2017. A mixed-methods approach was used to analyze responses.
Of 637 physicians surveyed, 283 responses (44.4%) were received. Most (86.2%) physicians believed that respecting a patient’s wish to continue antimicrobials was important. Approximately half of physicians (49.8%) believed that antimicrobial use at the end of life contributes to resistance. A higher proportion of pediatricians would often or always continue antimicrobial treatment for active infections and for hospice patients whose death was imminent compared to adult physicians (P<.001). Analysis of free-text responses revealed additional reasons why physicians may continue antimicrobials at end of life, including meeting family expectations, wanting to avoid the perception of “giving up,” uncertainty about prognosis, and reducing patient pain or discomfort.
Physician decision making concerning antimicrobial use in patients at the end of life is multifactorial. Clinicians may overweigh the benefits of antimicrobial therapy in end-of-life situations and view the importance of adhering to stewardship policies differently. Pediatric and adult clinicians have different approaches to this patient population. Better understanding of the complex decision making that occurs in the end-of-life patient population can help guide antimicrobial stewardship policies and improve patient care.
Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics.
We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed.