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Background Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production. Methods 205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE). Results 8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05). Conclusions Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria. [ABSTRACT FROM AUTHOR]

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z -scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552–679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93–1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19–0.64; P  = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions. [ABSTRACT FROM AUTHOR]

The mecA gene is commonly used to identify resistance in Staphylococcus aureus , but historically is not used for coagulase-negative staphylococci (CoNS). Analysis of 412 staphylococcal blood cultures (2014–2018) revealed that the absence of mecA had high concordance (100%) with oxacillin susceptibility for S. aureus and CoNS alike. [ABSTRACT FROM AUTHOR]

A direct-from-source rapid musculoskeletal diagnostic panel (MDP) was validated recently. We compared clinical measures to theoretical time points had MDP results been available. The MDP would have significantly decreased the time to pathogen identification (7 hours), time to definitive antimicrobial therapy (22 hours), and hospital length of stay (26.4 hours). [ABSTRACT FROM AUTHOR]

Background Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. Methods We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. Results Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859–923) in the pre-implementation phase to 655 (95% CI 637–694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686–722) to 544 (95% CI 525 –562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49–54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. Conclusions The handshake method is an effective and sustainable approach to stewardship. [ABSTRACT FROM AUTHOR]

Enterococcus gallinarum and casseliflavus have inherent vancomycin resistance and, though known as pathogens, have not been well characterized in pediatric patients. We identified a significant prevalence of these enterococcal species among immunocompromised patients at a large pediatric institution and describe the impact on patient care, antibiotic stewardship, and infection control. [ABSTRACT FROM AUTHOR]

Background Metronidazole is traditionally dosed every 6–8 hours even though in adults it has a long half-life, concentration-dependent killing, and 3-hour postantibiotic effect. Based on this logic, some pediatric hospitals adopted once-daily dosing for appendicitis, despite limited pharmacokinetics-pharmacodynamics (PK/PD) in children. We studied pediatric patients with appendicitis given metronidazole once daily to determine whether this dosing would meet target area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio of ≥70 for Bacteroides fragilis. Methods One hundred pediatric patients aged 4–17 years had an average of 3 blood draws per patient during the first 24 hours after a 30 mg/kg per dose of intravenous metronidazole. Concentrations of drug were determined using validated liquid chromatography and tandem mass spectrometry. A NONMEM model was constructed for determining PK, followed by Monte Carlo simulations to generate a population of plasma concentration-time AUC of metronidazole and hydroxy-metronidazole. Results Simulated AUC values met target attainment (AUC/MIC ratio of ≥70 to B fragilis MICs) for 96%–100% of all patients for an MIC of 2 mcg/mL. For MICs of 4 and 8 mcg/mL, target attainment ranged from 61% to 97% and 9% to 71%, respectively. Areas under the curve were similar to that of adults receiving 1000 mg and 1500 mg q24, or 500 mg q8 hours. Conclusions Metronidazole, 30 mg/kg per dose, once daily achieved AUC target attainment for B fragilis with an MIC of 2 mcg/mL or less in pediatric appendicitis patients. Based on this and studies in adults, there does not seem to be any PK/PD advantage of more frequent dosing in this population. [ABSTRACT FROM AUTHOR]

We instituted a new antimicrobial stewardship approach that involves review of all antimicrobial agents and communication of interventions in person by a pharmacist–physician team termed handshake stewardship. The acceptance rate in this study was 86%, intervention rates were higher with a physician, and interventions on antibiotics not reviewed by other strategies were made frequently. [ABSTRACT FROM AUTHOR]

Background. Though antimicrobial stewardship programs (ASPs) are in place for patient safety, financial justification is often required. In 2016, the Infectious Diseases Society of America (IDSA) recommended that anti-infective costs be measured by patientlevel administration data normalized for patient census. Few publications use this methodology. Here, we aim to compare 3 methods of drug cost analysis during 3 phases of an ASP as an example of this recommendation's implementation. Methods. At a freestanding pediatric hospital, we retrospectively assessed anti-infective cost using pharmacy purchasing data, patient-level administration data from the electronic medical record (EMR), and patient-level administration data from the Pediatric Hospital Information Systems (PHIS) database, all normalized to patient census. Costs pre-ASP, while planning the ASP, and post- ASP were then compared for each method. Results. Significant differences in costs between the methods were observed. Pharmacy purchasing endorsed minimal financial benefit (decrease planning to post-ASP of $590 dollars per 1000 patient-days), while the EMR and PHIS data endorsed a decrease of $12 785 and $21 380 per 1000 patient-days, respectively, for a total yearly cost savings of $54 656 for pharmacy purchasing data, $1 184 336 for EMR data, and $2 117 522 for PHIS data. Conclusions. Pharmacy purchasing data underestimated cost savings compared with EMR and PHIS data, while EMR and PHIS data were comparable in magnitude of savings. At Children’s Hospital Colorado, savings justified the full cost of the ASP. EMR patient-level administration data, normalized to patient census, offers a readily available and standardized measure of anti-infective costs over time. [ABSTRACT FROM AUTHOR]

Background. Acute pediatric musculoskeletal infections are common, leading to significant use of resources and antimicrobial exposure. In order to decrease variability and improve the quality of care, Children's Hospital Colorado implemented a clinical care guideline (CCG) for these infections. The purpose of this study is to evaluate clinical and resource outcomes PRE and POST this CCG. Methods. Retrospective chart review evaluated patients admitted to a large pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis, septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after guideline implementation. Primary outcomes included length of stay and overall antibiotic use, with additional secondary clinical, process, and therapeutic outcomes examined. Results. 82 patients were identified in both the pre-CCG and post-CCG cohorts. There was a reduction in the median of all primary outcomes, including length of stay (0.6 median days decrease, P = .04), length of IV antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric acute musculoskeletal infections to date. Additionally, there was a 24.5 hour reduction in median length of fever (P = .02), faster CRP normalization (P < .0001), 50% decrease in the number of related readmissions (P = .02), 34% decrease in central venous catheters placed (P < .0001), decreased time to first culture (P = .02), and 79% pathogen identification post-CCG (P = .056).Conclusions. Implementation of a CCG for acute musculoskeletal infections improves patient, process and resource outcomes. [ABSTRACT FROM AUTHOR]

Background. Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Children's Hospital Colorado. Methods. A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. Results. The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. Conclusions. Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers. [ABSTRACT FROM AUTHOR]

Implementation of a unique in-person pediatric antimicrobial stewardship program was associated with a significant increase in infectious disease consultations at a quaternary care children's hospital. This study demonstrates that antimicrobial stewardship programs support, and do not compete with, infectious disease programs. [ABSTRACT FROM AUTHOR]

Background. Appendicitis is a common surgical emergency in pediatric patients, and broad-spectrum antibiotic therapy is warranted in their care. A simplified once-daily regimen of ceftriaxone and metronidazole (CTX plus MTZ) is cost effective in perforated patients. The goal of this evaluation is to compare a historic regimen of cefoxitin (CFX) in nonperforated cases and ertapenem (ERT) in perforated and abscessed cases with CTX plus MTZ for all cases in terms of efficacy and cost. Methods. A retrospective review compared outcomes of nonperforated, perforated, and abscessed cases who received the historic regimen or CTX plus MTZ. Length of stay, time to afebrile, time to full feeds, postoperative abscess, and wound infection rates, inpatient readmissions, and antibiotic costs were evaluated. Results. There were a total of 841 cases reviewed (494 nonperforated, 247 perforated, and 100 abscessed). Overall, the CTX plus MTZ group had a shorter time to afebrile (P < .001). Treatment groups did not differ in length of stay. Postoperative abscess rates were similar between groups (4.1% vs 3.3%, not significant). Other postoperative complications were similar between groups. Total antibiotic cost savings were over $110 000 during the study period (from November 2010 to June 2013). Conclusions. Both CFX and/or ERT and CTX plus MTZ result in low abscess and complication rates, suggesting both are effective strategies. Treatment with CTX plus MTZ results in a shorter time to afebrile, while also providing significant antibiotic cost savings. Ceftriaxone plus MTZ is a streamlined, cost-effective regimen in the treatment of nonperforated, perforated, and abscessed appendicitis. [ABSTRACT FROM AUTHOR]

Administrative data are often used as a proxy for medication-administration record (MAR) data. Multicenter MAR data were compared retrospectively with administrative data from January 2010 through June 2013 from the Pediatric Health Information Systems database. We found that administrative data were more concordant with bill-upon-administration than bill-upon-dispense data. [ABSTRACT FROM AUTHOR]

Purpose. The effect of mandatory provider-selected order indications (PSOIs) on appropriateness of antimicrobial ordering in a tertiary pediatric hospital was evaluated. Methods. Mandatory PSOIs for 14 antimicrobials were implemented in September 2013. Data on initial and final orders in the first 24 hours after ordering were collected from the electronic medical record. Orders from pre-PSOI and post-PSOI implementation were randomly selected and compared with documentation at the time of order to elicit the documentation-determined clinical indication (DDCI). Appropriateness of the order for the DDCI was evaluated and compared between groups using 2-sample t tests, chi-square tests, and logistic regression. Results. Among the total 1,304 orders included in the review, 275 (21.1%) were inappropriate based on DDCI. The indications associated with the greatest number of inappropriate orders in both groups were suspected sepsis/bacteremia, meningitis/central nervous system infection, and pneumonia. A total of 128 (18.3%) of 700 initial orders were inappropriate compared with the DDCI in the pre-PSOI period, and 82 (17.8%) of 461 initial orders were inappropriate in the post-PSOI period (p = 0.83). A total of 78 (11.1%) of 700 final orders were inappropriate in the pre-PSOI period, and 29 (6.3%) of 461 final orders were inappropriate in the post-intervention period (p = 0.01). Overall, 84 (12%) of 700 inappropriate orders reached the patient in the pre-PSOI period versus 43 (9.3%) of 461 inappropriate orders in the post-PSOI period (p = 0.15). Conclusion. PSOIs were effective in reducing inappropriate antimicrobial orders in the first 24 hours after ordering if the correct indication was selected. [ABSTRACT FROM AUTHOR]