Analysis of recurrent urinary tract infection management in women seen in outpatient settings reveals opportunities for antibiotic stewardship interventions

Objectives: We characterized antibiotic prescribing patterns and management practices among recurrent urinary tract infection (rUTI) patients, and we identified factors associated with lack of guideline adherence to antibiotic choice, duration of treatment, and urine cultures obtained. We hypothesized that prior resistance to nitrofurantoin or trimethoprim–sulfamethoxazole (TMP-SMX), shorter intervals between rUTIs, and more frequent rUTIs would be associated with fluoroquinolone or β-lactam prescribing, or longer duration of therapy. Methods: This study was a retrospective database study of adult women with International Classification of Diseases, Tenth Revision (ICD-10) cystitis codes meeting American Urological Association rUTI criteria at outpatient clinics within our academic medical center between 2016 and 2018. We excluded patients with ICD-10 codes indicative of complicated UTI or pyelonephritis. Generalized estimating equations were used for risk-factor analysis. Results: Among 214 patients with 566 visits, 61.5% of prescriptions comprised first-line agents of nitrofurantoin (39.7%) and TMP-SMX (21.5%), followed by second-line choices of fluoroquinolones (27.2%) and β-lactams (11%). Most fluoroquinolone prescriptions (86.7%), TMP-SMX prescriptions (72.2%), and nitrofurantoin prescriptions (60.2%) exceeded the guideline-recommended duration. Approximately half of visits lacked a urine culture. Receiving care through urology via telephone was associated with receiving a β-lactam (adjusted odds ratio [aOR], 6.34; 95% confidence interval [CI], 2.58–15.56) or fluoroquinolone (OR, 2.28; 95% CI, 1.07–4.86). Having >2 rUTIs during the study period and seeking care from a urology practice (RR, 1.28, 95% CI, 1.15–1.44) were associated with longer antibiotic duration. Conclusions: We found low guideline concordance for antibiotic choice, duration of therapy and cultures obtained among rUTI patients. These factors represent new targets for outpatient antibiotic stewardship interventions.

Trends of Clinical Outcomes of Patients with Advanced Hepatocellular Carcinoma Treated with First-line Sorafenib in Randomized Controlled Trials

Background: Sorafenib has consistently served as the control arm in multiple RCTs evaluating novel therapies for advanced HCC for more than a decade. Analyzing trends in clinical outcomes of patients treated with sorafenib for the same indication over time offers the opportunity for unique insight into the evolution of clinical trial conduct and potential non-drug factors impacting outcomes. Methods: We identified RCTs in patients with treatment-naïve advanced HCC where sorafenib was compared to another systemic therapy or placebo. We extracted trial-level demographic, clinicopathologic, and outcome data (OS, progression-free survival (PFS), objective response rate (ORR) and duration of therapy). Sample-weighted linear regression was used to identify temporal trends with significance set at p0.05. Results: Sixteen RCTs (9 phase III and 7 phase II) enrolling 4086 patients treated with sorafenib were included in the analysis. Included trials enrolled patients from 2005-2019. OS has significantly improved by 4.5 months from 2005-2019 (p=0.048) over time. Thirteen studies provided data on PFS using RECIST 1.1, with no significant change over time (p=0.69). ORR assessed by RECIST 1.1 has significantly improved by 6.0% over time (p=0.003). Median duration of therapy with sorafenib has decreased by 53% since the enrollment of the first clinical trial in 2005, from 23.1 weeks to 12.2 weeks (p=0.0037). There was no significant change in patient demographics were identified over time to explain the OS findings. Conclusion: The median OS of patients with advanced HCC treated with sorafenib has improved significantly over 15 years. At the same time, the median duration of therapy with sorafenib has decreased. The reason for these findings was not explained by changing demographics of patients enrolled in these trials and has implications for ongoing clinical trials.

Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study

Background: we have observed the effect of insomnia treatment in clinical and prognostic differences of patients admitted for COVID-19 pneumonia in respiratory sub-intensive units that were administered a prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a group of patients out of therapy. Materials and Methods: We evaluated 40 patients on prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a control group of 40 patients out of therapy. Results: patients in the PRM 2 mg group had a shorter duration of therapy with non-invasive ventilation (5.2 ± 3.0 vs. 12.5 ± 4.2; p < 0.001), with a shorter stay in sub-intensive care (12.3 ± 3.2 vs. 20.1 ± 6.1; p < 0.001), and, therefore, a shorter overall duration of hospitalization (31.3 ± 6.8 vs. 34.3 ± 6.9 p = 0.03). In addition, a lower incidence of delirium was found (2.2 ± 1.1 vs. 3.3 ± 1.3; p < 0.001). Conclusions: A significant increase in sleep hours and a reduction in delirium episodes occurs in hospitalized insomniac patients treated with PRM 2 mg, compared to untreated patients. Based on these preliminary results, we can assume that there are benefits of prolonged-release melatonin 2 mg in COVID-19 therapy.

Infectious Diseases Society of America Guidance on the Treatment of AmpC β-lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections

Background The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. Methods A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggestions and corresponding rationales. In contrast to guidance in the previous document, published data on optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as “suggested approaches” based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Results Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. Conclusions The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of September 17, 2021 and will be updated annually. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.

A multifaceted stewardship intervention helps curb steroid overprescribing in hospitalized patients with acute exacerbations of COPD

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Corticosteroid overprescribing is well documented in real-world practice. There is currently no evidence to guide best practices for steroid stewardship. The aim of this study was to assess the effects of a 3-part stewardship intervention strategy on inpatient steroid prescribing in patients with acute exacerbations of COPD (AECOPD). Summary Investigators implemented a 3-part stewardship initiative consisting of (1) an anonymous survey for providers on steroid prescribing in a simplified case of AECOPD, (2) face-to-face education and review of survey results, and (3) prospective audit and feedback from a clinical pharmacist. This was a quasi-experimental before-and-after study evaluating hospitalized adults diagnosed with AECOPD in two 12-month study periods before (April 2019-March 2020) and after (May 2020-April 2021) implementation. The primary outcome was mean inpatient steroid dosing. Secondary outcomes were duration of therapy, length of stay (LOS), 30-day readmissions, 30-day mortality, and incidence of hyperglycemia. Per power analysis, there were 27 patients per cohort. The interventions resulted in a significant reduction in prednisone equivalents during hospitalization: 118 mg vs 53 mg (P = 0.0003). This decrease was similar in ICU (160 mg vs 61 mg, P = 0.008) and non-ICU (102 mg vs 49 mg, P = 0.004) locations. There was no significant difference in duration of therapy (8 days vs 7 days, P = 0.44), length of stay (3.3 days vs 3.9 days, P = 0.21), 30-day mortality (4% vs 7%, P = 0.55), 30-day readmissions (15% vs 7%, P = 0.39), or rate of hyperglycemia (48% vs 44%, P = 0.78). Conclusion A multifaceted stewardship intervention significantly reduced steroid dosing in hospitalized AECOPD patients. This reduction was not associated with known deleterious effects.

A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity

Purpose Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity. Methods Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1–R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation. Results In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59 years (range 23–85 years). The 5-ring protocol was markedly quicker to perform (1.3 ± 0.2 min; mean (SD)) compared to the 61-hexagon protocol (5.2 ± 0.6 min), p < 0.0001; n = 10 patients. The new R2/R5 ring ratio showed a moderate correlation with daily dose (r = − 0.640), cumulative dose (r = − 0.581) and duration of therapy (r = − 0.417). Similar correlations were observed with the new R2/R4 ring ratio which were not significantly different from the new R2/R5 correlation coefficients. The new R2/R5 ring ratio demonstrated a stronger correlation with daily (p = 0.002) and cumulative dose (p = 0.0001) compared to the 61-hexagon stimulus. Conclusions In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening.

Association of Insurance Type on Outpatient Copayments and Drug Utilization of Oral Multiple Myeloma Medications Via All-Claims Analysis, 2014-2018

Introduction Currently, there are three FDA-approved novel multiple myeloma (MM) oral agents commonly used in clinical practice in the United States: two immunomodulators (lenalidomide [len] and pomalidomide [pom]) and one proteasome inhibitor (ixazomib [ixa]). The financial burden faced by patients with MM on these drugs can be considerable due to increasing long-term survival and extended periods of continuous single agent maintenance or multidrug combination regimens. To better understand the financial burden associated with extended use of these medications, we sought to leverage a real-world, all-claims insurance database to examine the outpatient drug copayments, associated fill patterns, and duration of therapy of these MM oral agents, stratified by insurance type. We hypothesize that copayments associated with oral MM agents will comprise a major portion of the overall drug copayment per patient, and fill patterns and duration of therapy of these medications will vary across patients of different insurance types. Methods We utilized outpatient drug claims derived from the 2014-2018 IBM/Truven MarketScan Commercial, Medicare Advantage, and Medicaid all-claims databases and extracted all outpatient claims from patients who filled at least one prescription (≥28-day duration) for len, pom, or ixa. Annual outpatient medication copayment and number of outpatient scripts were calculated for each patient, both for oral MM agents only and all outpatient prescriptions. Copayments were normalized to the cost per annum. Multivariable linear regression was used to compare outcomes between patients of the three insurance types. Results From 2014-2018, we identified 10,750 patients on len, 2,355 patients on pom, and 794 patients on ixa. These included patients with commercial insurance (53.5%), Medicare Advantage (37.8%), and Medicaid (8.7%). The average adjusted annual copayment per patient of len was $445 for commercial, $480 for Medicare Advantage, and $48 for Medicaid (Table 1). Len copayment comprised of 77-83% of the total outpatient drug copayment per patient. For pom, adjusted copayments were $460 for commercial, $749 for Medicare Advantage, and $128 for Medicaid. Pom copayment comprised 54-90% of the total. For ixa, adjusted copayments were $584 for commercial, $448 for Medicare Advantage and $2 for Medicaid. Ixa copayment comprised 7-48% of the total. Patients with commercial insurance generally filled more scripts for oral MM agents per year (6 len, 4 pom, 5 ixa) compared to those with Medicare Advantage (5 len, 5 pom, 4 ixa) and Medicaid (4 len, 4 pom, 4 ixa) (Table 2). However, patients with commercial insurance filled fewer overall outpatient scripts per year (31-37) compared to Medicare Advantage (35-42) and Medicaid (40-52). Insurance type was associated with the number of scripts filled for len (p&lt;0.0001) and ixa (p=0.01) after adjustment for age, but not pom (p=0.14). Among patients on oral MM therapy for more than one year, insurance type was associated with time on therapy for len (828 days for commercial, 873 days for Medicare Advantage, and 791 days for Medicaid, p=0.0004) (Table 3). However, insurance type was not associated with time on therapy for pom (p=0.83) or ixa (p=0.11). Discussion Our results demonstrate that copayments for oral MM agents comprise the majority of total outpatient drug copayments for patients with MM, suggesting that the out-of-pocket costs of these agents may be a key driver of financial burden. In addition to differences observed in the oral MM drug copayments, insurance type was also associated with the number of scripts filled and time on therapy for patients taking len. Thus, this suggests insurance type is also linked to drug utilization patterns and may indicate a differential financial burden in patients with MM on chronic oral therapy. Reducing the cumulative impact of financial toxicity for patients with MM is an important consideration for prescribers, payors, and health systems to achieve optimal clinical outcomes. Although our current dataset lacks diagnostic and treatment data, further correlative studies incorporating care utilization data, including inpatient admissions and outpatient clinical visits, are in progress. Figure 1 Figure 1. Disclosures Pianko: Karyopharm: Honoraria.

Evaluating the Impact of Thrombopoietin Receptor Agonists Medications on Patient Outcomes and Quality of Life in Pediatric Immune Thrombocytopenia

Introduction: The treatment of Immune Thrombocytopenia (ITP) in children has advanced significantly over the last decade with novel therapies and enhanced clinical care guidelines. Recent American Society of Hematology guidelines now recommend the use of thrombopoietin receptor agonist (TPO-RA) medications as the preferred second line therapy for children with ITP. Accompanying this change, recent ASH guidelines also put emphasis on quality of life in managing ITP, acknowledging the detrimental affect ITP and previous managements can have on patient's and family's quality of life. With this change in guidelines, evaluating the impact of these medications on patient reported outcomes outside of clinical trials is important to evaluate the efficacy of therapy. While there is data from adult studies to show that TPO-RAs improve patient's health related quality of life (HRQoL), results were not statistically significant in previous clinical trials in children. Thus, the goal of the present study is to address this gap and describe the real-world experience of using TPO-RAs in pediatric ITP including the impact on patient-reported HRQoL. Methods: We reviewed all children aged 1-18 at our institution with a diagnosis of ITP and started on a TPO-RA medication after March 1, 2017 (date of TPO-RA for pediatric ITP licensure in Canada). A chart review was conducted to collect demographic data (e.g., age, associated diagnoses, previous therapies), TPO-RA data (e.g. dose(s), monitoring, side effects), outcome data (e.g., platelet count, need for emergency treatments). To explore the impact of TPO-RA use on patient-reported HRQoL, semi-structured interviews were conducted by phone with patients over age 7 and/or their guardians with topics including the effects of the TPO-RA on patient symptoms (e.g. bleeding, bruising, need for emergency treatment), activities (e.g. sports, hobbies, social events) mood (e.g. anxiety, stress, fatigue) and financial burden of treatment (e.g. coverage for medication). These interviews were conducted data in parallel to reviewing the Kids ITP Tool (KIT) questionnaire and a qualitative analysis of HRQoL was performed. Results: We identified 25 patients on a TPO-RA medication for pediatric ITP, of these, 3 were on romiplostim, 20 were on eltrombopag and 2 had been on both romiplostim and eltrombopag at different times. The median age at start of TPO-RA was 9 years (range 1 - 16 years). 14/25 responded to TPO-RA medication by meeting platelet count criteria. The average number of treatments per patient in the 6 months prior to commencing a TPO-RA was 3.7 and in the 6 months post commencing a TPO-RA was 0.5. No significant side effects observed with TPO-RA use, although 2 patients had a transient rise in liver enzymes. Of the 25 patients on a TPO-RA, 23 were eligible to participate in the semi-structured interviews (1 family having permanently relocated out of country and was not contactable; one family had a significant language barrier). With interviews ongoing, 11/23 patients and/or families have participated and results to date indicate that the majority (&gt;90%) have seen an improvement in quality of life. All participants interviewed at the time of abstract submission reported improvement in bleeding/bruising symptoms. The majority also noted a reduction in the frequency of emergency treatments and hematology clinic visits. Several participants reported on their ability to resume sports/activities once on a TPO-RA. While there was some reduction in parental stress/worry there was no clear benefit to patient fatigue/mood. Financial concerns about medication costs and duration of therapy were raised, and many parents expressed the cost of medication and source of ongoing funding a significant stressor. There were also concerns related to oral administration for younger children. Discussion: To our knowledge, this is the first post-licensing study to look at the impact of TPO-RA medications on patient-reported HRQoL in children with ITP. At our institution, TPO-RA medications prescribed for pediatric ITP have had a positive impact on patient platelet count and resulted in a reduced need for emergency treatment with minimal noted side effects. There also appears to be a positive impact on patient reported HRQoL reported by the majority of patients and/or families, while issues with medication administration, cost and long-term duration of therapy remain a concern. Disclosures Klaassen: Agios Pharmaceuticals: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Hoffman-La Roche: Consultancy; Novo Nordisk: Consultancy; Octapharma AG: Consultancy; Sanofi: Consultancy; Takeda: Consultancy.