Improving Short Course Treatment of Pediatric Infections: A Randomized Quality Improvement Trial.

BACKGROUND AND OBJECTIVES: Short courses of antibiotic treatment are effective for pediatric community-acquired pneumonia (CAP) and skin and soft tissue infections (SSTI). We compared the effectiveness of education with performance feedback, clinical decision support (CDS), and the combination in encouraging appropriately short treatment courses by primary care clinicians. METHODS: We designed a site-randomized, quality improvement trial within a large pediatric primary care network. Each practice was randomly assigned to 1 of 4 groups: education and feedback; CDS; both interventions ("combined group"); and control. We performed difference-in-differences analysis to compare the proportion of cases with short course treatment before and after intervention among the 4 groups. RESULTS: For all cases of CAP and SSTI, the proportion in the control group treated with the recommended duration did not change from the baseline period (26.1% [679 of 2603]) to the intervention period (25.8% [196 of 761]; P = .9). For the education and feedback group, the proportion rose from 22.3% (428 of 1925) to 45.0% (239 of 532; P < .001); for the CDS group, from 26.6% (485 of 1824) to 52.3% (228 of 436; P < .001); and for the combined group, from 26.2% (491 of 1875) to 67.8% (314 of 463; P < .001). A difference-in-differences analysis showed that all 3 intervention groups improved performance compared with the control group (P < .001); the combined group had greater improvement than the education and feedback group or the CDS group (P < .001). CONCLUSIONS: In this quality improvement project to encourage shorter duration treatment of CAP and SSTI, both education with performance feedback and CDS were effective in modifying clinician behavior; however, the combination of the two was substantially more effective than either strategy alone.

One size does not fit all: advanced practice provider considerations for the antimicrobial steward.

Advanced practice providers are a diverse and established group of antimicrobial prescribers in both ambulatory and inpatient settings. We outline important considerations for antimicrobial stewardship programs and stewards to consider when engaging this important group of providers.

Characteristics and Outcomes of Culture-Positive and Culture-Negative Pediatric Sepsis.

OBJECTIVES: To compare the outcomes of pediatric severe sepsis and septic shock among patients with culture-positive and culture-negative sepsis and to determine if there are differentiating markers of disease severity between these 2 populations during their initial presentation and emergency department (ED) stay. STUDY DESIGN: Retrospective cohort study of patients ≤21 years of age who presented to the ED of a single children's hospital with severe sepsis or septic shock from June 1, 2017 to June 5, 2019. RESULTS: There were 235 patients who met criteria for severe sepsis or septic shock. Of these, 139 (59.1%) had culture-negative sepsis and 96 (40.9%) had culture-positive sepsis. In the adjusted multivariable model, children with culture-negative sepsis had more intensive care unit (ICU)-free days than those with culture-positive sepsis (27.3 vs 24.1; adjusted median differences [aMD] -2.6 [-4.4, -0.8]). There were no differences in mortality or hospital-free days. On initial presentation, there were no differences in fever, hypothermia, tachycardia, tachypnea, or hypotension between the 2 groups. There were no differences in proportion of patients receiving the following interventions: intravenous (IV) antibiotics, IV fluids, vasoactive medications, CPR, intubation, or time from arrival to provision of these interventions. CONCLUSIONS: Culture-negative sepsis constitutes a substantial proportion of pediatric severe sepsis and septic shock. In this study, patients with culture-negative and culture-positive sepsis presented similarly on arrival to the ED and received similar treatments while there. Patients with culture-negative sepsis had more ICU-free days than those with culture-positive sepsis, although differences in hospital length of stay (LOS) and mortality were not observed.

Benchmarking of Outpatient Pediatric Antibiotic Prescribing: Results of a Multicenter Collaborative.

BACKGROUND: Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally. METHODS: We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data. RESULTS: Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC). CONCLUSIONS: We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.

The Antibiotic Likelihood Index: A New Measure of Antimicrobial Stewardship for Pediatric Primary Care Based on Reason for Visit.

BACKGROUND: Quality metrics for antibiotic prescribing by pediatricians are limited. We sought to define a novel measure that assesses clinicians' overall antibiotic prescribing. METHODS: Using electronic health record (EHR) data from 2018 to 2019 for children 3 months to 17 years of age from 53 practices within a large pediatric network, we grouped encounters into Reason for Visit categories using the classification system of the National Ambulatory Medical Care Survey and analyzed the proportion of encounters with an antibiotic prescription. Categories were sorted according to the attributable proportion of encounters with an antibiotic prescribed. The proposed metric-the Antibiotic Likelihood Index (ALI)-was defined as the proportion of encounters with an antibiotic prescribed among categories that accounted for >80% of all encounters with an antibiotic prescribed. The ALI was calculated for the entire network and for individual prescribers, and the distribution among prescribers was described. RESULTS: Six Reason for Visit categories-cough, ear complaints, fever, sore throat, rash, and congestion/upper respiratory infection-accounted for 82.4% of all antibiotics prescribed. Among the 222 682 encounters for the top 6 categories combined, 67 368 (30.3%) had an antibiotic prescribed, defined as the ALI for the entire sample. The index among individual prescribers ranged from 7.5% to 57.2% (interquartile range 24.3% to 34.9%). The correlation for individual prescribers between 2018 and 2019 was high (R2 = 0.80). CONCLUSIONS: The ALI, a proposed new metric of pediatric antibiotic prescribing, can be readily calculated from EHR data and captures the range of antibiotic prescribing among pediatricians for common clinical scenarios.

Utility of specific laboratory biomarkers to predict severe sepsis in pediatric patients with SIRS.

OBJECTIVE: To identify the association between readily available laboratory biomarkers and the development of severe sepsis in children presenting to the emergency department (ED) with systemic inflammatory response syndrome (SIRS). METHODS: In this retrospective cohort study, ED patient encounters from June 2018 to June 2019 that triggered an automated sepsis alert based on SIRS criteria were analyzed. Encounters were included if the patient had any of the following laboratory tests sent within 6 h of ED arrival: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactic acid, and procalcitonin. For each of the biomarkers, a receiver operating characteristic (ROC) curve was created for our primary outcome, severe sepsis within 24 h of ED disposition, and our secondary outcome, severe sepsis with a positive bacterial culture. For each ROC curve, we calculated the area under the curve (AUC) with 95% confidence intervals (95% CI) and created cutoff points to achieve 90% sensitivity and 90% sensitivity for the primary and secondary outcomes. RESULTS: During the study period, 4349/61,195 (7.1%) encounters triggered an automated sepsis alert. Of those, 1207/4349 (27.8%) had one of the candidate biomarkers sent within 6 h of ED arrival and were included in the study. A total of 100/1207 (8.3%) met criteria for severe sepsis within 24 h of arrival, and 41/100 severe sepsis cases (41%) were deemed culture-positive. Procalcitonin had the highest AUC for identifying severe sepsis [0.62 (95% CI 0.52-0.73)] while ESR and CRP had the highest AUC for culture-positive sepsis [0.68 (95% CI 0.47-0.89) and 0.67 (95% CI 0.53-0.81), respectively]. At 90% sensitivity for detecting severe sepsis, all of the biomarker threshold values fell within that laboratory test's normal range. At 90% specificity for severe sepsis, threshold values were as follows: procalcitonin 2.72 ng/mL, CRP 16.79 mg/dL, ESR 79.5 mm/h and lactic acid 3.6 mmol/L. CONCLUSION: Our data indicate that CRP, ESR, lactic acid, and procalcitonin elevations were all specific, but not sensitive, in identifying children in the ED with SIRS who go on to develop severe sepsis.

Use of clinical data to augment healthcare worker contact tracing during the COVID-19 pandemic.

OBJECTIVE: This work examined the secondary use of clinical data from the electronic health record (EHR) for screening our healthcare worker (HCW) population for potential exposures to patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We conducted a cross-sectional study at a free-standing, quaternary care pediatric hospital comparing first-degree, patient-HCW pairs identified by the hospital's COVID-19 contact tracing team (CTT) to those identified using EHR clinical event data (EHR Report). The primary outcome was the number of patient-HCW pairs detected by each process. RESULTS: Among 233 patients with COVID-19, our EHR Report identified 4116 patient-HCW pairs, including 2365 (30.0%) of the 7890 pairs detected by the CTT. The EHR Report also revealed 1751 pairs not identified by the CTT. The highest number of patient-HCW pairs per patient was detected in the inpatient care venue. Nurses comprised the most frequently identified HCW role overall. CONCLUSIONS: Automated methods to screen HCWs for potential exposures to patients with COVID-19 using clinical event data from the EHR (1) are likely to improve epidemiological surveillance by contact tracing programs and (2) represent a viable and readily available strategy that should be considered by other institutions.

Variability in Ceftriaxone Dosing Across 32 US Acute Care Children's Hospitals.

Ceftriaxone is one of the most common antibiotics prescribed for hospitalized children in the United States. However, ceftriaxone is not dosed consistently. Sepsis/serious bacterial infection had high dosing variability. Dosing for central nervous system infection was frequently suboptimal. Future efforts should focus on optimizing and standardizing ceftriaxone dosing.

Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: a Systematic Review and Meta-analysis.

Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. We systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval 1 October 2020) for comparative studies of alternative specimen types (saliva, oropharyngeal [OP], and nasal [NS] swabs) versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in subgroups. The QUADAS 2 tool was used to assess bias. From 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives (NS [82%, 95% CI: 73 to 90%], OP [84%, 95% CI: 57 to 100%], and saliva [88%, 95% CI: 81 to 93%]) than NP swabs, while combined OP/NS matched NP performance (97%, 95% CI: 90 to 100%). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield of positive samples. NP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric versus adult, late versus early in disease course), such that head-to head studies of sampling strategies are urgently needed.

A pilot program to improve vaccination status for hospitalized children.

OBJECTIVES: Screening of immunization status at each health care encounter is recommended to improve immunization coverage rates but is often limited to primary care practices. A pilot intervention study was performed to ascertain the immunization status of hospitalized children and determine if development of an immunization plan before discharge would improve the vaccination status for such children. METHODS: On the basis of power calculations estimated to detect an increase in immunization status from 60% to 70% with 80% power, 356 randomly selected children were enrolled between March 6, 2012 and June 14, 2012. Immunization records were obtained, immunization status determined, and parent/guardian informed if catch-up dose(s) were needed. If parent requested vaccine dose(s), they were administered before discharge. RESULTS: Vaccination status was current per Advisory Committee on Immunization Practices guidelines in 73% of hospitalized children, and 27% children required catch-up dose(s) (200 doses for 95 children). Human papilloma virus vaccine (dose 1), varicella zoster vaccine (dose 2), and meningococcal conjugate vaccine were the most commonly identified dose(s) needed. Of those requiring catch-up dose(s), 25% were caught up, increasing vaccination status to 80% at 1-month post hospital discharge. CONCLUSIONS: This is the first study to determine the immunization status of hospitalized pediatric patients of all ages, including adolescents, providing new data on the immunization status of the inpatient pediatric population. A pilot intervention consisting of obtaining immunization records, determining immunization status, and discussing catch-up dose(s) before discharge resulted in improvement of immunization status, suggesting that the inpatient setting may be used along with many other national strategies to help address missed vaccination opportunities.

Antibiotic Management of Animal Bites in Children During the Methicillin-Resistant Staphylococcus aureus Era.

Children presenting to an emergency department following an animal bite were found to be at risk for infection if they had puncture wounds, crush wounds, or were bitten by a cat. Of the infected wounds that were cultured, methicillin-resistant Staphylococcus aureus was not isolated as a pathogen.

Trends in adverse reactions to trimethoprim-sulfamethoxazole.

OBJECTIVE: To examine temporal trends of adverse drug reactions (ADRs) associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in children. METHODS: We performed a retrospective observational study to characterize TMP-SMX ADRs in children between 2000 and 2009. We completed a chart review at our institution by identifying children diagnosed with TMP-SMX ADRs. To compare local trends to comparable institutions, we estimated the frequency of hospitalizations for TMP-SMX ADRs at 25 tertiary pediatric hospitals utilizing the Pediatric Health Information System database. To determine whether changes in outpatient prescribing rates occurred, we used the National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey. RESULTS: At our institution, 109 children were diagnosed with a TMP-SMX ADR (5 cases from 2000 to 2004 as compared with 104 cases from 2005 to 2009). Fifty-eight percent had been treated for a skin and soft tissue infection (SSTI). A similar trend was observed nationally, where the incidence of TMP-SMX ADRs more than doubled from 2004 to 2009 at comparable pediatric hospitals (P < .001). Although national outpatient data revealed no change in overall TMP-SMX prescribing, the percentage of children prescribed TMP-SMX for SSTI sharply increased during the study period (0%-2% [2000-2004]; 9%-17% [2005-2009]). CONCLUSIONS: The majority of TMP-SMX ADRs at our institution occurred in conjunction with SSTI treatment. TMP-SMX ADRs have occurred more frequently coincident with increased prescribing for SSTI. Increased usage alone may explain the increasing trend of TMP-SMX ADRs in children; however drug-disease interaction may play a role and requires further investigation.

Impact of a guideline on management of children hospitalized with community-acquired pneumonia.

OBJECTIVES: We sought to describe the impact a clinical practice guideline (CPG) had on antibiotic management of children hospitalized with community-acquired pneumonia (CAP). PATIENTS AND METHODS: We conducted a retrospective study of discharged patients from a children's hospital with an ICD-9-CM code for pneumonia (480-486). Eligible patients were admitted from July 8, 2007, through July 9, 2009, 12 months before and after the CAP CPG was introduced. Three-stage least squares regression analyses were performed to examine hypothesized simultaneous relationships, including the impact of our institution\x{2019}s antimicrobial stewardship program (ASP). RESULTS: The final analysis included 1033 patients: 530 (51%) before the CPG (pre-CPG) and 503 (49%) after the CPG (post-CPG). Pre-CPG, ceftriaxone (72%) was the most commonly prescribed antibiotic, followed by ampicillin (13%). Post-CPG, the most common antibiotic was ampicillin (63%). The effect of the CPG was associated with a 34% increase in ampicillin use (P < .001). Discharge antibiotics also changed post-CPG, showing a significant increase in amoxicillin use (P < .001) and a significant decrease in cefdinir and amoxicillin/clavulanate (P < .001), with the combined effect of the CPG and ASP leading to 12% (P < 0.001) and 16% (P < .001) reduction, respectively. Overall, treatment failure was infrequent (1.5% vs 1%). CONCLUSIONS: A CPG and ASP led to the increase in use of ampicillin for children hospitalized with CAP. In addition, less broad-spectrum discharge antibiotics were used. Patient adverse outcomes were low, indicating that ampicillin is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP.

Impact of a Prospective-Audit-With-Feedback Antimicrobial Stewardship Program at a Children's Hospital.

BACKGROUND: The emergence of antibiotic-resistant organisms and the lack of development of new antimicrobials have made it imperative that additional strategies be developed to maintain the effectiveness of these existing antibiotics. The objective of this study was to describe the impact of a prospective-audit-with-feedback antimicrobial stewardship program (ASP) on antibiotic use in a children's hospital. METHOD: A quasi-experimental study design with a control group was performed to assess the impact of a prospective-audit-with-feedback ASP. The control group was the combined antibiotic use at 25 similar children's hospitals that are members of the Child Health Corporation of America. RESULTS: The ASP reviewed 10 460 broad-spectrum or select antibiotics in 8765 patients in the 30 months following the intervention. The most common select antibiotics reviewed were ceftriaxone/cefotaxime (43%), vancomycin (18%), ceftazidime (12%), and meropenem (7%). A total of 2378 recommendations were made in 1703 (19%) patients; the most common recommendation was to stop antibiotics (41%). Clinicians were compliant with agreed-upon ASP recommendations in 92% of patients. When comparing our antibiotic use with that of the control group, a monthly decline in all antibiotics of 7% (P = .045) and 8% (P = .045) was observed for days of therapy (DoT) and length of therapy (LoT) per 1000 patient-days, respectively. An even greater effect was observed in the select antibiotics as the monthly DoT per 1000 patient-days declined 17% (P < .001) and the monthly LoT per 1000 patient-days declined 18% (P < .001). CONCLUSIONS: A prospective-audit-with-feedback ASP can have a significant impact on decreasing antibiotic use at a children's hospital.

Clinicians' Attitudes Towards an Antimicrobial Stewardship Program at a Children's Hospital.

BACKGROUND: In pediatrics, limited data are available on how to develop and implement an antimicrobial stewardship program (ASP). In addition, no data exist on clinicians' impression of such programs. The objectives of this study were to describe the development and implementation of an ASP in a children's hospital and to describe the thoughts and attitudes of the clinicians interacting with the ASP. METHODS: A qualitative description of the development and implementation of an ASP is provided. In addition, 2 years after the implementation of a prospective-audit-with-feedback ASP, an electronic survey was administered to clinicians to assess their attitudes toward the ASP. RESULTS: A 5-step process for developing this ASP included the following: team development; selecting the stewardship strategy(ies) and antimicrobials to monitor; establishing a method to identify patients; program evaluation; and implementation. Of 365 participants surveyed, 205 (56%) responded, and 80% (160 of 199) had never worked with an ASP before its implementation. Clinicians agreed that the ASP decreased inappropriate use of antibiotics (84%, 162 of 194), improved the quality of patient care (82%, 159 of 194), and provided knowledge and education about appropriate antibiotic use (91%, 177 of 194). Negative feelings regarding the ASP included the following: 11% (22 of 194) felt a loss of autonomy; 6% (12 of 194) felt that it interfered with clinical decision-making; and 5% (9 of 194) felt threatened. Clinicians thought that to further decrease inappropriate antibiotic use, guidelines of empiric antibiotic choices (80%, 152 of 189) should be developed, and better training in medical school and residency should be provided (80%, 152 of 189). Finally, our clinicians felt that the problem of antibiotic resistance and inappropriate antibiotic use was worse nationally than at our institution. CONCLUSIONS: A prospective-audit-with-feedback ASP was successfully developed and implemented at a children's hospital. The ASP was perceived by clinicians to reduce inappropriate antibiotic use and to improve the quality of care of hospitalized children, with minimal loss of physician autonomy or interference in clinical decision-making.

Antibiotic management of Staphylococcus aureus infections in US children's hospitals, 1999-2008.

OBJECTIVES: The objective of this study was to describe trends in antibiotic management for Staphylococcus aureus infections among hospitalized children from 1999 to 2008. METHODS: A retrospective study was conducted by using the Pediatric Health Information Systems database to describe antibiotic treatment of inpatients with S aureus infection at 25 children's hospitals in the United States. Patients who were admitted from 1999 to 2008 with International Classification of Diseases, Ninth Revision, Clinical Modification codes for S aureus infection were included. Trends in the use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient-days. RESULTS: A total of 64813 patients had a discharge diagnosis for S aureus infection. The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008. Similar trends were observed by using days of therapy per 1000 patient-days. CONCLUSIONS: Antibiotic prescribing patterns for the treatment of S aureus infections have changed significantly during the past decade, reflecting the emergence of community-associated MRSA. Clindamycin is now the most commonly prescribed antibiotic for S aureus infections among hospitalized children. The substantial use of clindamycin emphasizes the importance of continuous monitoring of local S aureus susceptibility patterns.