Background: A major challenge for antibiotic stewardship programs is the lack of accurate and accessible electronic data to target interventions. We developed and validated separate electronic algorithms to identify inappropriate antibiotic use for adult outpatients with bronchitis and pharyngitis.

Methods: We used International Classification of Diseases, 10th Revision, diagnostic codes to identify patient encounters for acute bronchitis and pharyngitis at outpatient practices between 3/15/17 and 3/14/18. Exclusion criteria included immunocompromising conditions, complex chronic conditions, and concurrent infections. We randomly selected 300 eligible subjects each with bronchitis and pharyngitis. Inappropriate antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm, which was constructed using only data in the electronic data warehouse. Criteria for appropriate prescribing, choice of antibiotic, and duration were based on established guidelines.

Results: Of 300 subjects with bronchitis, 167 (55.7%) received an antibiotic inappropriately based on chart review. The electronic algorithm demonstrated 100% sensitivity and 95.3% specificity for detection of inappropriate prescribing. Of 300 subjects with pharyngitis, 94 (31.3%) had an incorrect prescribing decision. Among 29 subjects with a positive rapid streptococcal antigen test, 27 (93.1%) received an appropriate antibiotic and 29 (100%) received the correct duration. The electronic algorithm demonstrated very high sensitivity and specificity for all outcomes.

Conclusions: Inappropriate antibiotic prescribing for bronchitis and pharyngitis is common. Electronic algorithms for identifying inappropriate prescribing, antibiotic choice, and duration showed excellent test characteristics. These algorithms could be used to efficiently assess prescribing among practices and individual clinicians. Interventions based on these algorithms should be tested in future work.

OBJECTIVE: Optimal strategies for limiting the transmission of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the hospital setting remain unclear. The objective of this study was to evaluate the impact of a urine culture screening strategy on the incidence of ESBL-EK.

DESIGN: Prospective quasi-experimental study.

SETTING: Two intervention hospitals and one control hospital within a university health system from 2005 to 2009.

PATIENTS AND INTERVENTION: All clinical urine cultures with E. coli or Klebsiella spp were screened for ESBL-EK. Patients determined to be colonized or infected with ESBL-EK were placed in a private room with contact precautions. The primary outcome of interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases occurring more than 48 hours after admission). Changes in monthly ESBL-EK incidence rates were evaluated with mixed-effects Poisson regression models, with adjustment for institution-level characteristics (eg, total admissions).

RESULTS: The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to 2.16/10,000 patient-days during the study period. The incidence of community-acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to 0.92/10,000 patient-days (P < .001). On multivariable analysis, the intervention was not significantly associated with a reduction in nosocomial ESBL-EK incidence (incidence rate ratio, 1.38 [95% confidence interval, 0.83-2.31]; P - .21).

CONCLUSIONS: Universal screening of clinical urine cultures for ESBL-EK did not result in a reduction in nosocomial ESBL-EK incidence rates, most likely because of increases in importation of ESBL-EK cases from the community. Further studies are needed on elucidating optimal infection control interventions to limit spread of ESBL-producing organisms in the hospital setting.

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella species (ESBL-EK) in hospitalized patients. The prevalence of colonization with ESBL-EK was 2.6%. Colonization was associated with cirrhosis, longer duration of hospital stay prior to surveillance, and prior exposure to clindamycin or meropenem.

<p><strong>BACKGROUND: </strong>Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown.</p>

<p><strong>METHODS: </strong>We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on antibiotic prescribing for RTDs. RTDs were grouped into tiers based on appropriateness of antibiotic prescribing: tier 1 (almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated). Providers received education on appropriate RTD prescribing followed by monthly peer comparison feedback on antibiotic prescribing for (1) all tiers and (2) tier 3 RTDs. Chi-squared testing was used to compare the proportion of visits with antibiotic prescriptions before and during the intervention. Mixed-effects multivariable logistic regression analysis was performed to assess the association between the intervention and antibiotic prescribing.</p>

<p><strong>RESULTS: </strong>Across 30 PC practices and 185,755 total visits, overall antibiotic prescribing was reduced with the intervention, from 35.2% to 23.0% of visits (p&lt;0.001). In multivariable analysis, the intervention was associated with a reduced odds of antibiotic prescription for tiers 2 (OR 0.57; 95% CI 0.52 - 0.62) and 3 (OR 0.57; 95% CI 0.53 - 0.61), but not for tier 1 (OR 0.98; 95% CI 0.83 - 1.16).</p>

<p><strong>CONCLUSION: </strong>A provider-focused intervention reduced overall antibiotic prescribing for RTDs without affecting prescribing for infections that likely require antibiotics. Future research should examine the sustainability of such interventions, potential unintended adverse effects on patient health or satisfaction, and provider perceptions and acceptability.</p>

<p><strong>OBJECTIVE: </strong>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.</p>

<p><strong>PARTICIPANTS: </strong>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).</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.</p>

<p><strong>OBJECTIVE: </strong>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.</p>

<p><strong>DESIGN: </strong>Quasi-experimental study.</p>

<p><strong>SETTING: </strong>Quaternary children's hospital.</p>

<p><strong>PATIENTS: </strong>Hospitalized children aged 0-21 years with positive blood culture events 1 year before and 1 year after implementation of BC-GP testing.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

<p><strong>STUDY OBJECTIVE: </strong>Sepsis recognition is a clinical challenge in children. We aim to determine whether peripheral blood gene expression profiles are associated with pathogen type and sepsis severity in children with suspected sepsis.</p>

<p><strong>METHODS: </strong>This was a prospective pilot observational study in a tertiary pediatric emergency department with a convenience sample of children enrolled. Participants were older than 56 days and younger than 18 years, had suspected sepsis, and had not received broad-spectrum antibiotics in the previous 4 hours. Primary outcome was source pathogen, defined as confirmed bacterial source from sterile body fluid or confirmed viral source. Secondary outcome was sepsis severity, defined as maximum therapy required for shock reversal in the first 3 hospital days. We drew peripheral blood for ribonucleic acid isolation at the sepsis protocol activation, obtained gene expression measures with the GeneChip Human Gene 2.0 ST Array, and conducted differential expression analysis.</p>

<p><strong>RESULTS: </strong>We collected ribonucleic acid samples from a convenience sample of 122 children with suspected sepsis and 12 healthy controls. We compared the 66 children (54%) with confirmed bacterial or viral infection and found 558 differentially expressed genes, many related to interferon signaling or viral immunity. We did not find statistically significant gene expression differences in patients according to sepsis severity.</p>

<p><strong>CONCLUSION: </strong>The study demonstrates feasibility of evaluating gene expression profiling data in children evaluated for sepsis in the pediatric emergency department setting. Our results suggest that gene expression profiling may facilitate identification of source pathogen in children with suspected sepsis, which could ultimately lead to improved tailoring of sepsis treatment and antimicrobial stewardship.</p>

<p><strong>Background: </strong>Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection.</p>

<p><strong>Methods: </strong>We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein &lt;4 mg/dL and procalcitonin &lt;1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods.</p>

<p><strong>Results: </strong>We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression.</p>

<p><strong>Conclusions: </strong>Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.</p>

<p><strong>OBJECTIVES: </strong>Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis.</p>

<p><strong>DESIGN: </strong>Cohort study.</p>

<p><strong>SETTING: </strong>The medical and surgical ICUs at an academic medical center.</p>

<p><strong>SUBJECTS: </strong>We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy.</p>

<p><strong>INTERVENTIONS: </strong>We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve &gt; 0.76 for 14-d and 0.74 for total mortality).</p>

<p><strong>CONCLUSIONS: </strong>Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.</p>