Prescribing Patterns of Nonrecommended Medications for Children With Acute COVID-19.

OBJECTIVE: Repurposed medications for acute coronavirus disease 2019 (COVID-19) continued to be prescribed after results from rigorous studies and national guidelines discouraged use. We aimed to describe prescribing rates of nonrecommended medications for acute COVID-19 in children, associations with demographic factors, and provider type and specialty. METHODS: In this retrospective cohort of children <18 years in a large United States all-payer claims database, we identified prescriptions within 2 weeks of an acute COVID-19 diagnosis. We calculated prescription rate, performed multivariable logistic regression to identify risk factors, and described prescriber type and specialty during nonrecommended periods defined by national guidelines. RESULTS: We identified 3 082 626 COVID-19 diagnoses in 2 949 118 children between March 7, 2020 and December 31, 2022. Hydroxychloroquine (HCQ) and ivermectin were prescribed in 0.03% and 0.14% of COVID-19 cases, respectively, during nonrecommended periods (after September 12, 2020 for HCQ and February 5, 2021 for ivermectin) with considerable variation by state. Prescription rates were 4 times the national average in Arkansas (HCQ) and Oklahoma (ivermectin). Older age, nonpublic insurance, and emergency department or urgent care visit were associated with increased risk of either prescription. Additionally, residence in nonurban and low-income areas was associated with ivermectin prescription. General practitioners had the highest rates of prescribing. CONCLUSIONS: Although nonrecommended medication prescription rates were low, the overall COVID-19 burden translated into high numbers of ineffective and potentially harmful prescriptions. Understanding overuse patterns can help mitigate downstream consequences of misinformation. Reaching providers and parents with clear evidence-based recommendations is crucial to children's health.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Background: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Methods: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 2023 that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Results: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. Conclusions: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Indication-driven order entry decreases stewardship and pharmacist interventions.

Indication-driven order entry (IDOE) was implemented at our pediatric institution for cefazolin, piperacillin-tazobactam, and meropenem; the 3 most intervened upon antibiotics during prospective audit and feedback (PAF) by the antimicrobial stewardship program (ASP). IDOE was associated with a significant reduction in both ASP PAF recommendations and clinical pharmacist interventions.

Successful enteral administration of crushed posaconazole delayed-release tablets in children.

Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed-release tablets (POS-DRT) show promise in adults; limited evidence exists in children. We used crushed POS-DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS-DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment.

Impact of model-informed precision dosing on achievement of vancomycin exposure targets in pediatric patients with cystic fibrosis.

BACKGROUND: Vancomycin is commonly used to treat acute pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus. Optimizing vancomycin exposure during therapy is essential and area under-the-curve (AUC)-guided dosing is now recommended. Model-informed precision dosing (MIPD) utilizing Bayesian forecasting is a powerful approach that can support AUC-guided dose individualization. The objective of the current study was to examine the impact of implementing an AUC-guided dose individualization approach supported via a MIPD clinical decision support (CDS) tool on vancomycin exposure, target attainment rate, and safety in pediatric patients with CF treated with vancomycin during clinical care. METHODS: A retrospective chart review was performed in patients with CF at a single children's hospital comparing pre- and post-implementation of a MIPD approach for vancomycin supported by a cloud-based, CDS tool integrated into the electronic health record (EHR). In the pre-MIPD period, vancomycin starting doses of 60 mg/kg/day (<13 years) or 45 mg/kg/day (≥13 years) were used. Dose adjustment was guided by therapeutic drug monitoring (TDM) with a target trough 10-20 mg/L. In the post-MIPD period, starting dose and dose adjustment were based on the MIPD CDS tool predictions with a target 24 h AUC (AUC24 ) 400-600 mg*h/L. Exposure and target achievement rates were retrospectively calculated and compared. Rates of acute kidney injury (AKI) were also compared. RESULTS: Overall, 23 patient courses were included in the pre-MIPD period and 21 patient courses in the post-MIPD period. In the post-MIPD period, an individualized MIPD starting dose resulted in 71% of patients achieving target AUC24 compared to 39% in the pre-MIPD period (p < 0.05). After the first TDM and dose adjustment, target AUC24 achievement was also higher post-MIPD versus pre-MIPD (86% vs. 57%; p < 0.05). AKI rates were low and similar between periods (pre-MIPD 8.7% vs. post-MIPD 9.5%; p = 0.9). CONCLUSION: An MIPD approach implemented within a cloud-based, EHR-integrated CDS tool safely supported vancomycin AUC-guided dosing and resulted in high rates of target achievement.

Antifungal stewardship in practice: Insights from a prospective audit and feedback program.

OBJECTIVE: To identify characteristics of antifungal prospective audit and feedback (PAF) and to compare rates of PAF recommendation and acceptance between antifungal and antibiotic agents. DESIGN: Retrospective cohort study of antifungal and antibiotic audits by a children's hospital antimicrobial stewardship program (ASP) from November 1, 2020, to October 31, 2022. METHODS: Antimicrobial audit data were retrieved from the ASP data warehouse. We characterized antifungal PAF using descriptive statistics. We then compared the overall rates of PAF recommendation and recommendation acceptance between antifungals and antibiotics. We also compared the differences in antifungal and antibiotic PAF recommendation and acceptance rates across various factors, including infectious problem, medical service, and recommendation type. RESULTS: Of 10,402 antimicrobial audits identified during the study period, 8,599 (83%) were for antibiotics and 1,803 (17%) were for antifungals. The highest antifungal recommendation rates were for liposomal amphotericin B, antifungals used for sepsis or respiratory tract infection, and antifungals prescribed in the cardiovascular intensive care unit. The rate of PAF recommendation was higher for antibiotics than for antifungals (29% vs 21%; P < .001); however, the rates of recommendation acceptance were similar. Recommendations to discontinue or for medication monitoring were more common for antifungals. CONCLUSIONS: Our analysis of antifungal PAF identified key opportunities to improve antifungal use, including the optimized use of specific agents and targeted use by certain medical services. Moreover, antifungal PAF, despite identifying fewer recommendations compared to antibiotic PAF, were associated with similarly high rates of acceptance, highlighting a promising opportunity for antifungal stewardship.

Leveraging antimicrobial stewardship programs in response to the coronavirus disease 2019 (COVID-19) public health emergency.

The coronavirus disease 2019 (COVID-19) pandemic has strained antimicrobial stewardship programs (ASPs) but offered new opportunities. This review summarizes the impact of the COVID-19 pandemic on ASPs, review the contributions ASPs have made in the pandemic response, and highlight the potential role of ASPs in future pandemics.

Shedding Light on Amoxicillin, Amoxicillin-clavulanate, and Cephalexin Dosing in Children from a Pharmacist's Perspective.

Selection of an antibiotic and dosing regimen requires consideration of multiple factors including microbiological data, site of infection, pharmacokinetics, and how it relates to the pharmacodynamic target. Given the multiple dosage regimens of amoxicillin with/without clavulanate and cephalexin, we review the principles of dose selection from a pharmacist's perspective.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: 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. RESULTS: 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 noninvasive or invasive mechanical ventilation or extracorporeal 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 noninvasive 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. CONCLUSIONS: 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.

Use of Prospective Audit and Feedback to Reduce Antibiotic Exposure in a Pediatric Cardiac ICU.

OBJECTIVES: We sought to determine whether a prospective audit and feedback intervention decreased antibiotic utilization in a pediatric cardiac ICU and to describe the characteristics of prospective audit and feedback audits and recommendations. DESIGN: Before-after study. SETTING: Pediatric cardiac ICU of a freestanding children's hospital. PATIENTS: All patients admitted to the cardiac ICU. INTERVENTIONS: A prospective audit and feedback program was established in our hospital's pediatric cardiac ICU on December 7, 2015. The antimicrobial stewardship program audited IV antibiotics, communicated prospective audit and feedback recommendations to the cardiac ICU, and regularly reviewed recommendation adherence. Mean monthly antibiotic utilization 18 months before ("preprospective audit and feedback"; from June 1, 2014 to November 30, 2015) and 24 months after ("prospective audit and feedback"; from January 1, 2016 to December 31, 2017) prospective audit and feedback implementation was compared. Antibiotic audit data during the prospective audit and feedback period were reviewed to capture the characteristics of prospective audit and feedback audits, recommendations, and adherence. MEASUREMENTS AND MAIN RESULTS: Mean cardiac ICU IV antibiotic use decreased 20% (701 vs 880 days of therapy per 1,000 patient days, p = 0.001) during the prospective audit and feedback period compared with the preprospective audit and feedback period. There was no difference in mean cardiac ICU length of stay (p = 0.573), mean hospital length of stay (p = 0.722), or the rate of discharge due to death (p = 0.541). There were 988 antibiotic audits and 370 prospective audit and feedback recommendations (37% recommendation rate) during the study period. The most commonly audited antibiotic category was broad-spectrum gram-negative agents and the most common indication for use was sepsis. Broad-spectrum gram-positive agents were more likely to be associated with a recommendation. CONCLUSIONS: There was a significant reduction in antibiotic use following implementation of a prospective audit and feedback program in our pediatric cardiac ICU. Over one-third of antibiotics audited in our cardiac ICU were associated with a prospective audit and feedback recommendation, revealing important targets for future antimicrobial stewardship efforts in this population.

Standardization of post-operative antimicrobials reduced exposure while maintaining good outcomes in pediatric liver transplant recipients.

Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post-operative (post-op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post-op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17-9/30/17 (N = 38) and 3/14/18-12/13/18 (N = 27) were included in the pre-intervention (PreI) and post-intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post-op broad-spectrum gram-negative antibiotics for >48 hours (76% PreI vs 44% PostI OLT recipients, P = .01) and post-op vancomycin use (50% PreI, vs 7.4% PostI, P < .001). There were no statistically significant differences between groups for post-op fever, positive pre-/post-operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post-op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.

Reducing Piperacillin and Tazobactam Use for Pediatric Perforated Appendicitis.

BACKGROUND: Although perforated appendicitis is associated with infectious complications, the choice of antibiotic therapy is controversial. We assess the effectiveness and safety of an intervention to reduce piperacillin and tazobactam (PT) use for pediatric acute perforated appendicitis. METHODS: This is a single-center, retrospective cohort study of children 18 y of age or younger who underwent primary appendectomy for perforated appendicitis between January 01, 2016 and June 30, 2019. An intervention to decrease PT use was implemented: the first phase was provider education (April 19, 2017) and the second phase was modification of electronic antibiotic orders to default to ceftriaxone and metronidazole (July 06, 2017). Preintervention and postintervention PT exposure, use of PT ≥ half of intravenous antibiotic days, and clinical outcomes were compared. RESULTS: Forty children before and 109 after intervention were included and had similar baseline characteristics. PT exposure was 31 of 40 (78%) and 20 of 109 (18%) (P < 0.001), and use ≥ half of intravenous antibiotic days was 31 of 40 (78%) and 14 of 109 (13%) (P < 0.001), in the preintervention and postintervention groups, respectively. There was no significant difference in mean duration of antibiotic therapy (10.8 versus 9.8 d), mean length of stay (6.2 versus 6.5 d), rate of surgical site infection (10% versus 11%), or rate of 30-d readmission and emergency department visit (20% versus 20%) between the preintervention and postintervention periods, respectively. CONCLUSIONS: Provider education and modification of electronic antibiotic orders safely reduced the use of PT for pediatric perforated appendicitis.

Model-Informed Precision Dosing of Vancomycin in Hospitalized Children: Implementation and Adoption at an Academic Children's Hospital.

BACKGROUND: Model-informed precision dosing (MIPD) can serve as a powerful tool during therapeutic drug monitoring (TDM) to help individualize dosing in populations with large pharmacokinetic variation. Yet, adoption of MIPD in the clinical setting has been limited. Overcoming technologic hurdles that allow access to MIPD at the point-of-care and placing it in the hands of clinical specialists focused on medication dosing may encourage adoption. OBJECTIVE: To describe the hospital implementation and usage of a MIPD clinical decision support (CDS) tool for vancomycin in a pediatric population. METHODS: Within an academic children's hospital, MIPD for vancomycin was implemented via a commercial cloud-based CDS tool that utilized Bayesian forecasting. Clinical pharmacists were recognized as local champions to facilitate adoption of the tool and operated as end-users. Integration within the electronic health record (EHR) and automatic transmission of patient data to the tool were identified as important requirements. A web-link icon was developed within the EHR which when clicked sends users and needed patient-level clinical data to the CDS platform. Individualized pharmacokinetic predictions and exposure metrics for vancomycin are then presented in the form of a web-based dashboard. Use of the CDS tool as part of TDM was tracked and users were surveyed on their experience. RESULTS: After a successful pilot phase in the neonatal intensive care unit, implementation of MIPD was expanded to the pediatric intensive care unit, followed by availability to the entire hospital. During the first 2+ years since implementation, a total of 853 patient-courses (n = 96 neonates, n = 757 children) and 2,148 TDM levels were evaluated using the CDS tool. For the most recent 6 months, the CDS tool was utilized to support 79% (181/230) of patient-courses in which TDM was performed. Of 26 users surveyed, > 96% agreed or strongly agreed that automatic transmission of patient data to the tool was a feature that helped them complete tasks more efficiently; 81% agreed or strongly agreed that they were satisfied with the CDS tool. CONCLUSIONS: Integration of a vancomycin CDS tool within the EHR, along with leveraging the expertise of clinical pharmacists, allowed for successful adoption of MIPD in clinical care.

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 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 best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Clinical Impact of Clostridium difficile PCR Cycle Threshold-Predicted Toxin Reporting in Pediatric Patients.

BACKGROUND: Reliance on tests that detect only the presence of toxigenic Clostridium difficile can result in overdiagnosis and overtreatment of C difficile infection (CDI). The C difficile polymerase chain reaction (PCR) cycle threshold (CT) can sensitively predict the presence of free C difficile toxins; however, the clinical application for this testing strategy remains unexplored. We evaluated the impact of dual PCR and toxin result reporting, as predicted by the CT, on CDI management and outcomes in children. METHODS: Before the intervention, results for C difficile testing at Lucile Packard Children's Hospital Stanford were reported as PCR positive (PCR+) or negative (PCR-) according to the GeneXpert C diff Epi tcdB PCR assay (Cepheid, Sunnyvale, California). Beginning October 5, 2016, the presence of free toxins, as predicted by the CT, was reported also. The CDI treatment rates 1 year before and 18 months after implementation of toxin reporting were compared. Demographic and treatment-related data were collected, and patient outcomes were followed up 8 weeks later. RESULTS: CDI treatment decreased 22% after the intervention (96% [preintervention] vs 74% [postintervention]; P < .001). During the postintervention period, there were 152 PCR+C difficile results, and 94 (62%) of them were toxin positive (toxin+) according to the CT. Of the 58 PCR+/toxin-negative (toxin-) results, 38 (66%) did not result in CDI treatment. Seven (18%) of the untreated PCR+/toxin- patients underwent repeat testing within 8 weeks, and 5 (13%) of them were subsequently PCR+/toxin+ and treated. No CDI-related complications were identified. CONCLUSIONS: Addition of the CT-predicted C difficile toxin result to PCR reporting reduces the proportion of PCR+ children treated for CDI.

Predictors of Antimicrobial Stewardship Program Recommendation Disagreement.

OBJECTIVETo identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children's hospital.DESIGNRetrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.METHODSThe ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.RESULTSIn total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99-15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08-18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92-19.77), or had been admitted for 31-90 days at the time of the audit (OR, 2.08; 95% CI, 1.36-3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01-1.04).CONCLUSIONSEvaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.Infect Control Hosp Epidemiol 2018;806-813.