Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Antibiotic prescribing for adult bacteriuria and pyuria in community hospital emergency departments.

OBJECTIVE: To describe emergency department (ED) antibiotic prescribing for urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) and to identify improvement opportunities. METHODS: Patients treated for UTI in 16 community hospital EDs were reviewed to identify prescribing that was unnecessary (any treatment for ASB, duration >7 days for cystitis or >14 days for pyelonephritis) or suboptimal [ineffective antibiotics (nitrofurantoin/fosfomycin) or duration <7 days for pyelonephritis]. Duration criteria were based on recommendations for complicated UTI since criteria for uncomplicated UTI were not reviewed. 14-day repeat ED visits were evaluated. RESULTS: Of 250,788 ED visits, UTI was diagnosed in 13,466 patients (5%), and 1427 of these (11%) were manually reviewed. 286/1427 [20%, 95% CI: 18-22%] met criteria for ASB and received 2068 unnecessary antibiotic days [mean (±SD) 7 (2) days]. Mean treatment duration was 7 (2) days for cystitis and 9 (2) days for pyelonephritis. Of 446 patients with cystitis, 128 (29%) were prescribed >7 days (total 396 unnecessary). Of 422 pyelonephritis patients, 0 (0%) were prescribed >14 days, 20 (5%) were prescribed <7 days, and 9 (2%) were given ineffective antibiotics. Overall, prescribing was unnecessary or suboptimal in 443/1427 [31%, 95% CI: 29-33%] resulting in 2464/11,192 (22%) unnecessary antibiotic days and 8 (0.5%) preventable ED visits. CONCLUSIONS: Among reviewed patients, poor UTI prescribing in 16 EDs resulted in unnecessary antibiotic days and preventable readmissions. Key areas for improvement include non-treatment of ASB and shorter durations for cystitis.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin-Resistant Staphylococcus aureus.

The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations-a postdistributive and a trough-are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation-based 2-point monitoring approach. AUCs were either obtained from a single trough concentration-fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify the between-subject variability in vancomycin PK parameters, define the sources of PK variability, and leverage information from the population to improve individual AUC estimates. Twenty-three children with CF received 27 courses of vancomycin. The median age was 12.3 (interquartile range [IQR] 8.5-16.6) years. From the individual vancomycin PK parameter estimates from the population PK model, median AUC was 622 (IQR 529-680) mg·h/L. Values were not significantly different from the AUC calculated using the standard PK equation-based approach (median 616 [IQR 540-663] mg·h/L) (P = .89). A standard PK equation-based approach using 2 concentrations and a population PK model-based approach using a single trough concentration yielded unbiased and precise AUC estimates. Findings suggest that options exist to implement AUC-based pediatric vancomycin dosing in patients with CF. The findings of this study reveal that several excellent options exist for centers to implement AUC-based pediatric vancomycin dosing for patients with CF.

Utilization of antibiotics for methicillin-resistant Staphylococcus aureus infection in cystic fibrosis.

OBJECTIVES: The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx). METHODS: An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool. RESULTS: Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in both pediatric (IV 35/224, 16%; oral 41/224, 18%), and adult (IV 44/235, 19%; oral 38/235, 16%) respondents for inpatient treatment. IV vancomycin was the second most commonly utilized antibiotic by pediatric (70/224, 31%) and adult (71/235, 30%) respondents. Most respondents reported dose titration to achieve a vancomycin trough level of 15-20 mg/L (150/179, 84%). Topical or inhaled antibiotic utilization was reported to be an uncommon practice with approximately 70% of pediatric and adult respondents reporting to use them either rarely or never. The concomitant use of anti-MRSA and anti-pseudomonal antibiotics was common with 96% of pediatric and 99% of adult respondents answering in the affirmative. CONCLUSION: We conclude that anti-MRSA antibiotics are utilized via various dosage regimens by a majority of CF Foundation accredited care programs for the treatment of chronic MRSA in PEx, and there is no consensus on the best treatment approach.

A dynamic postoperative protocol provides efficient care for pediatric patients with non-ruptured appendicitis.

PURPOSE: Postoperative management of pediatric patients with non-ruptured appendicitis is highly variable and often includes an overnight stay in the hospital. We implemented a criteria-based postoperative protocol designed to eliminate postoperative antibiotics and facilitate timely discharge by utilizing the bedside nurse to evaluate for readiness for discharge. METHODS: We collected data on all patients with non-ruptured appendicitis at our institution following protocol implementation (May 1, 2012 to April 30, 2013) and compared them to a control group. RESULTS: 580 patients were treated for non-ruptured appendicitis (285 prior protocol, 295 new protocol). Following implementation of our protocol, there was an overall reduction in length of stay from 40.1 (SD 27.5) to 23.5 (SD 20.8)h, and total cost of care per patient also decreased from $5783 (SD $2501) to $4499 (SD $1983) (p<0.001). There was no change in hospital readmission rate (1.1% prior protocol, 1.4% new protocol) or postoperative abscess rate (0.8% prior protocol, 0.3% new protocol). CONCLUSION: Our new protocol reveals the value of eliminating postoperative antibiotics and leveraging the continuous availability of the bedside nurse in the determination of readiness for discharge.

Response-based therapy for ruptured appendicitis reduces resource utilization.

PURPOSE: We examined the effectiveness of a postoperative ruptured appendicitis protocol that eliminated Pseudomonas coverage and based the duration of IV antibiotic treatment and length of hospital stay on the patient's clinical response. METHODS: In our new protocol, IV antibiotics were administered until the patient met discharge criteria: adequate oral intake, pain control with oral medications, and afebrile for 24h. We collected data on all patients with ruptured appendicitis at our institution following protocol implementation (May 1, 2012, to April 30, 2013) and compared them to a control group. RESULTS: 306 patients were treated (154 prior protocol, 152 new protocol). The new clinical response-based protocol led to a decrease in hospital stay from 134h (SD 66.1) to 94.5h (SD 61.7) (p<0.001) and total cost of care per patient also decreased from $13,610 (SD $6859) to $9870 (SD $5670) (p<0.001). CONCLUSION: Our clinical response-based protocol for pediatric patients with ruptured appendicitis decreased LOS, cost, and IV antibiotics use without significant changes in adverse events.

Pharmacokinetic and pharmacodynamic optimisation of intravenous tobramycin dosing among children with cystic fibrosis.

This study aimed to characterize the pharmacokinetics of tobramycin administered one, two, or three times daily and to develop an optimal dosing scheme for children with cystic fibrosis. Therapeutic drug monitoring data were obtained from children hospitalized at three academic medical centres from 2006 to 2012. Population pharmacokinetic models were constructed using NONMEM 7.2. Model-based simulations were performed in Matlab R2012b to identify optimal dosing regimens using pharmacodynamic targets. The pharmacokinetic analysis involved 257 patients with a median age of 8.1 years (range 0.1-18.8). Clearance was estimated as 5.59 L/h and the volume of distribution was 18.90 L. Mean (±SD) maximum serum concentrations were highest among patients dosed once per day (24.1 ± 8.9 µg/mL) and were lower among patients dosed two and three times per day (11.2 ± 1.4 and 8.1 ± 2.4 µg/mL, respectively). Simulations revealed that once daily dosing was the only effective regimen for a Pseudomonas aeruginosa MIC of 1.5 µg/mL and none of the tested regimens reliably achieved the pharmacodynamic target for MICs ≥2 µg/mL. Once daily dosing resulted in higher maximum serum concentrations when compared to multiple-daily dosing. In simulations, once daily dosing was the only regimen to achieve the pharmacodynamic target for all subjects with MICs <2 µg/mL.

Population pharmacokinetics of intermittent vancomycin in children with cystic fibrosis.

BACKGROUND: Vancomycin is the drug-of-choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children with cystic fibrosis. However, no studies have characterized the pharmacokinetic profile of vancomycin among pediatric cystic fibrosis patients. OBJECTIVE: To evaluate the pharmacokinetics of intermittent vancomycin administration in children with cystic fibrosis and identify covariates that significantly influence vancomycin efficacy and safety. METHODS: Therapeutic drug monitoring data were obtained from two cystic fibrosis care centers that identified children < 18 years who received vancomycin treatment for an acute pulmonary exacerbation from 2005 to 2010. Trough and peak serum concentrations were determined before and after the third or fourth dose. Nonlinear mixed effects models were developed to evaluate the population pharmacokinetics of vancomycin. RESULTS: Among the 67 children (mean age 12.1 ± 5.3 years), the mean vancomycin dose was 17.4 ± 4.4 mg/kg. The mean trough concentration (Cmin ) was 10.3 ± 3.8 mg/L. The mean daily area under the serum concentration time curve (AUC24 ) was 282.5 ± 816.9 mg·hour/L. A one-compartment model with first-order elimination best described the data. Weight significantly influenced vancomycin clearance (p<0.001). In the final model, clearance was estimated as 5.57 L/hour/70 kg, and the volume of distribution was 44.1 L/70 kg. The between subject variability for clearance and volume of distribution were 27% and 40%, respectively. CONCLUSIONS: Using a one-compartment model to evaluate the pharmacokinetic properties of vancomycin in children with cystic fibrosis, clearance increased with body weight. Pharmacodynamic studies are needed to establish an optimal vancomycin dosing regimen for the treatment of pediatric exacerbations of cystic fibrosis.

A survey of the utilization of anti-pseudomonal beta-lactam therapy in cystic fibrosis patients.

The purpose of this study was to characterize the utilization of anti-pseudomonal beta-lactam antibiotics in the treatment of acute pulmonary exacerbations (APE) among Cystic Fibrosis Foundation (CFF)-accredited care centers. An anonymous national cross-sectional survey of CFF-accredited care centers was performed using an electronic survey tool (SurveyMonkey.com®). One hundred and twenty-one of 261 centers completed the survey (46%) representing 56% (14,856/26,740) of patients in the CFF Patient Registry. One hundred and nineteen of 121 (98%) respondents reported using beta-lactams for the treatment of APE. Intermittent dosing regimens constituted 155/167 (93%) reported regimens, while extended infusions were 12/167 (7%). Ceftazidime was the most commonly utilized beta-lactam comprising 74/167 (44%) of all infusions (intermittent and extended) of which 70/74 (95%) were intermittent infusions. The majority of intermittent ceftazidime regimens (56/70; 80%) were at doses lower than CFF and European guidelines recommended doses. In conclusion, a great majority of respondents use intermittent anti-pseudomonal beta-lactam antibiotics, with over half of respondents utilizing lower than guidelines recommended doses. While this is of concern, it is not known if optimization of dosing strategies according to guidelines recommendations will result in clinical benefit.

Using assessing care of vulnerable elders quality indicators to measure quality of hospital care for vulnerable elders.

OBJECTIVES: To assess the quality of care for hospitalized vulnerable elders using measures based on Assessing Care of Vulnerable Elders (ACOVE) quality indicators (QIs). DESIGN: Prospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: Subjects aged 65 and older hospitalized on the University of Chicago general medicine inpatient service who were defined as vulnerable using the Vulnerable Elder Survey-13 (VES-13), a validated tool based on age, self-reported health, and functional status. MEASUREMENTS: Inpatient interview and chart review using ACOVE-based process-of-care measures referring to 16 QIs in general hospital care and geriatric-prevalent conditions (e.g., pressure ulcers, dementia, and delirium); adherence rates calculated for type of care process (screening, diagnosis, and treatment) and type of provider (doctor, nurse). RESULTS: Six hundred of 845 (71%) older patients participated. Of these, 349 (58%) were deemed vulnerable based on VES-13 score. Three hundred twenty-eight (94%) charts were available for review. QIs for general medical care were met at a significantly higher rate than for pressure ulcer care (81.5%, 95% confidence interval (CI)=79.3-83.7% vs 75.8%, 95% CI=70.5-81.1%, P=.04) and for delirium and dementia care (81.5%, 95% CI=79.3-83.7 vs 31.4% 95% CI=27.5-35.2%, P<.01). According to standard nursing assessment forms, nurses were responsible for high rates of adherence to certain screening indicators (pain, nutrition, functional status, pressure ulcer risk; P<.001 when compared with physicians), although in patients with functional limitations, nurse admission assessments of functional limitations often did not agree with reports of limitations by patients on admission. CONCLUSION: Adherence to geriatric-specific QIs is lower than adherence to general hospital care QIs. Hospital care QIs that focus on screening may overestimate performance by detecting standard nursing or protocol-driven care.