Reducing the use of empiric antibiotic therapy in COVID-19 on hospital admission.

BACKGROUND: Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19. METHODS: This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics. RESULTS: A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes. CONCLUSION: Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

BACKGROUND: The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). METHODS: The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. RESULTS: A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. CONCLUSIONS: Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

Assessing the Concordance of MRSA Carriage Screening With MRSA Infections.

OBJECTIVES: This study focused on children with confirmed methicillin-resistant Staphylococcus aureus (MRSA) infections to determine MRSA screening utility in guiding empirical anti-MRSA treatment of children without history of MRSA infection. We examined the concordance of screens to assess differences by infection type and used statistical analysis to determine significant contributors to concordance. METHODS: Pediatric hospital patients admitted from 2002 through 2022 were included. Subjects had MRSA infections subsequent to MRSA surveillance screens performed the preceding year. Statistical analysis identified associations between MRSA screens and infections. Number needed to treat analysis calculated the utility of rescreening. RESULTS: Among 246 subjects, 39.0% had concordant screens; 151 (61.4%) screens were obtained in the 2 weeks preceding infection. Sensitivity for bacteremia was 50.0% (n = 42), for endotracheal/respiratory 44.4% (n = 81), and 29.4% (n = 102) for skin and soft-tissue infection. For children aged younger than 6 months, sensitivity was 35.9% (n = 78). Multivariable analysis significantly associated days since screening with decreasing likelihood of concordance. Regression modeled the probability of concordance to drop below 50.0% for all infections after 4 days, after 6 days for bacteremia specifically, and 12 days for endotracheal/respiratory infections. CONCLUSIONS: The concordance of screens was far lower than negative predictive values found previously; earlier studies were possibly impacted by low prevalence and exclusion of children at high risk to inform high negative predictive values. We suggest that negative MRSA screens should not invalidate reasonable suspicion for MRSA infection in patients with high pretest probabilities.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

OBJECTIVE: This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. METHODS: This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. RESULTS: A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. CONCLUSIONS: Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

A Preliminary, Single-Center Retrospective Chart Review of Infusion Times of Intravenous Immune Globulin in Kawasaki Disease and Clinical Outcomes.

OBJECTIVE: Patients diagnosed with Kawasaki disease (KD) are at a high risk of developing coronary artery aneurysms. Intravenous immune globulin (IVIG) given in combination with aspirin is the standard of treatment for the prevention of coronary aneurysm. IVIG is recommended to be administered as a dose of 2 g/kg infused during 10 to 12 hours for the prevention of coronary aneurysms in KD; however, this does not always occur in practice. We aimed to investigate if an infusion time of <10 hours is associated with more coronary artery aneurysms than the recommended infusion time of 10 to 12 hours. METHODS: Patients with a diagnosis of and treated for KD with IVIG at the University of Chicago Medicine Comer Children's Hospital were identified by drug use reports that included patients who received IVIG between September 2008 and August 2018. Data were collected though chart review and patients were divided into 2 groups based on duration of infusion (<10 hours and 10-12 hours). The primary outcome was the incidence of coronary artery aneurysm. The secondary outcome was the time to defervescence. The safety outcome was the development of renal dysfunction. RESULTS: A total of 70 patients were screened and 44 were included in the analysis. Coronary aneurysm occurred in 2 of 33 patients (6.0%) in the <10-hour group and no patients in the 10- to 12-hour group (p = 0.558). The median time to defervescence was 0.5 hours in the <10-hour group and 0.95 hours in the 10- to 12-hour group (p = 0.166). The incidence of acute kidney injury was 6% (2 of 33 patients) in the 10-hour group and 9.1% (1 of 11 patients) in the 10- to 12-hour group (p = 0.588). CONCLUSIONS: All incidences of coronary artery aneurysm occurred in the patients who received IVIG with an infusion time of <10 hours. The incidence of acute kidney injury was numerically higher in the 10- to 12-hour group. Based on the recommendations in the American Heart Association KD guideline, our internal hospital policy, and our results, we recommend the infusion of IVIG be administered at a rate of 10 to 12 hours.

Optimizing Oral Medication Schedules for Inpatient Sleep: A Quality Improvement Intervention.

OBJECTIVES: Hospitalized children experience frequent nighttime awakenings. Oral medications are commonly administered around the clock despite the comparable efficacy of daytime administration schedules, which promote sleep. With this study, we evaluated the effectiveness of a quality improvement initiative to increase the proportion of sleep-friendly antibiotic administration schedules. METHODS: Interprofessional stakeholders modified computerized provider order entry defaults for 4 oral antibiotic medications, from around the clock to administration occurring exclusively during waking hours. Additionally, care-team members received targeted education. Outcome measures included the proportion of sleep-friendly administration schedules and patient caregiver-reported disruptions to sleep. Pre- and posteducation surveys were used to evaluate education effectiveness. Balancing measures were missed antibiotic doses and related escalations of care. RESULTS: Interrupted time series analysis revealed a 72% increase (interceptpre: 18%; interceptpost: 90%; 95% confidence interval: 65%-79%; P < .001) in intercept for percentage of orders with sleep-friendly administration schedules (orders: n pre = 1014 and n post = 649). Compared with preeducation surveys, care-team members posteducation were more likely to agree that oral medications scheduled around the clock cause sleep disruption (resident: 71% pre, 90% post [P = .01]; nurse: 63% pre, 79% post [P = .03]). Although sleep-friendly orders increased, patient caregivers reported an increase in sleep disruption due to medications (pre 28%, post 46%; P < .001). CONCLUSIONS: A simple, low-cost intervention of computerized provider order entry default modifications and education can increase the proportion of sleep-friendly oral antibiotic administration schedules for hospitalized children. Patient perception of sleep is impacted by multiple factors and often does not align with objective data. An increased focus on improving sleep during hospitalization may result in heightened awareness of disruptions.

Evaluation of Appropriateness and Cost Savings of Pharmacist-Driven Palivizumab Ordering.

OBJECTIVES: Guidelines by the AAP for the use of palivizumab prophylaxis for respiratory syncytial virus (RSV) recommend administration within 72 hours prior to discharge for selected high-risk patient populations. Our institution historically administered palivizumab on a fixed-day schedule of Mondays and Thursdays, but adjusted the practice in fall 2017 to a pharmacist-driven flex-schedule based on anticipated discharge date. This review evaluated the effect of pharmacist-driven palivizumab ordering on the appropriateness of palivizumab administrations, based on AAP and institutional recommendations. Additionally, this review evaluated for effects on institutional cost. METHODS: This was a retrospective single-center evaluation including patients for whom palivizumab was ordered between July 1, 2016, and June 30, 2018. Patients in the 2016-2017 RSV season were in the fixed-day group, while patients in the 2017-2018 RSV season were in the flex-schedule group. RESULTS: A total of 142 palivizumab doses were evaluated. Overall, 97% of administrations were for an appropriate indication. All doses administered inappropriately (n = 4) occurred in the fixed-day group. In the fixed-day group, 48.6% of doses were given within 72 hours prior to discharge, which increased to 70.1% in the flex-schedule group (p = 0.01). The amount of drug saved by batching was 1 vial for every 4.9 patients in the fixed-day group, and 1 vial for every 4.8 patients in the flex-schedule group. CONCLUSIONS: There was a statistically significant improvement in compliance with AAP recommendations following the implementation of pharmacist-driven flex-schedule for palivizumab, compared to a fixed-day batching schedule. There was no significant difference in cost.

Establishment and evaluation of pharmacist-managed admission medication history and reconciliation process for pediatric patients.

OBJECTIVE: This was a single-center, prospective, pilot study aiming to evaluate the impact of pharmacist involvement in the admission medication history and reconciliation process and to quantify discrepancies found by pharmacists when compared to information collected by other health care providers at a pediatric institution. METHODS: A pharmacist completed a thorough medication history and reconciled discrepancies with the medical team. Discrepancies included incorrect medication, dose, route, frequency; omitted information; missing medications; or any other inconsistencies outside of these categories. Information was documented in the electronic medical record via a standardized template, and pertinent discrepancies were communicated with the medical team. RESULTS: Of the 100 medication histories included in the study, a total of 309 discrepancies were identified and corrected in the electronic medical record. The median length of time it took pharmacists to complete the medication history process was 15 minutes per patient (interquartile range, 10-20 minutes). Thirty discrepancies were determined as pertinent and were reported as intervened on and communicated to the medical team. CONCLUSION: This study provides evidence that pharmacist-obtained admission medication histories and reconciliation have the potential to prevent potentially significant adverse drug reactions and have a positive impact on patient care.Index terms admission, history, medication, pharmacist, reconciliation.