Understanding the role of antibiotic-associated adverse events in influencing antibiotic decision-making.

Objective: To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern. Design: Focus groups. Setting: Academic medical center. Participants: Medical and surgical house staff, attending physicians, and advanced practice practitioners. Methods: Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding. Results: Four focus groups were conducted (n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern. Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.

An Electronic Algorithm to Identify Vancomycin-Associated Acute Kidney Injury.

Background: The burden of vancomycin-associated acute kidney injury (V-AKI) is unclear because it is not systematically monitored. The objective of this study was to develop and validate an electronic algorithm to identify cases of V-AKI and to determine its incidence. Methods: Adults and children admitted to 1 of 5 health system hospitals from January 2018 to December 2019 who received at least 1 dose of intravenous (IV) vancomycin were included. A subset of charts was reviewed using a V-AKI assessment framework to classify cases as unlikely, possible, or probable events. Based on review, an electronic algorithm was developed and then validated using another subset of charts. Percentage agreement and kappa coefficients were calculated. Sensitivity and specificity were determined at various cutoffs, using chart review as the reference standard. For courses ≥48 hours, the incidence of possible or probable V-AKI events was assessed. Results: The algorithm was developed using 494 cases and validated using 200 cases. The percentage agreement between the electronic algorithm and chart review was 92.5% and the weighted kappa was 0.95. The electronic algorithm was 89.7% sensitive and 98.2% specific in detecting possible or probable V-AKI events. For the 11 073 courses of ≥48 hours of vancomycin among 8963 patients, the incidence of possible or probable V-AKI events was 14.0%; the V-AKI incidence rate was 22.8 per 1000 days of IV vancomycin therapy. Conclusions: An electronic algorithm demonstrated substantial agreement with chart review and had excellent sensitivity and specificity in detecting possible or probable V-AKI events. The electronic algorithm may be useful for informing future interventions to reduce V-AKI.

Risk-factor analysis for extended-spectrum beta-lactamase-producing Enterobacterales colonization or infection: Evaluation of a novel approach to assess local prevalence as a risk factor.

OBJECTIVE: To explore an approach to identify the risk of local prevalence of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) on ESBL-E colonization or infection and to reassess known risk factors. DESIGN: Case-control study. SETTING: Johns Hopkins Health System emergency departments (EDs) in the Baltimore-Washington, DC, region. PATIENTS: Patients aged ≥18 years with a culture growing Enterobacterales between April 2019 and December 2021. Cases had a culture growing an ESBL-E. METHODS: Addresses were linked to Census Block Groups and placed into communities using a clustering algorithm. Prevalence in each community was estimated using the proportion of ESBL-E among Enterobacterales isolates. Logistic regression was used to determine risk factors for ESBL-E colonization or infection. RESULTS: ESBL-E were detected in 1,167 of 11,224 patients (10.4%). Risk factors included a history of ESBL-E in the prior 6 months (aOR, 20.67; 95% CI, 13.71-31.18), exposure to a skilled nursing or long-term care facility (aOR, 1.64; 95% CI, 1.37-1.96), exposure to a third-generation cephalosporin (aOR, 1.79; 95% CI, 1.46-2.19), exposure to a carbapenem (aOR, 2.31; 95% CI, 1.68-3.18), or exposure to a trimethoprim-sulfamethoxazole (aOR, 1.54; 95% CI, 1.06-2.25) within the prior 6 months. Patients were at lower risk if their community had a prevalence <25th percentile in the prior 3 months (aOR, 0.83; 95% CI, 0.71-0.98), 6 months (aOR, 0.83; 95% CI, 0.71-0.98), or 12 months (aOR, 0.81; 95% CI, 0.68-0.95). There was no association between being in a community in the >75th percentile and the outcome. CONCLUSIONS: This method of defining the local prevalence of ESBL-E may partially capture differences in the likelihood of a patient having an ESBL-E.

COVID-19 and Outpatient Antibiotic Prescriptions in the United States: A County-Level Analysis.

Background: Declines in outpatient antibiotic prescribing were reported during the beginning of the coronavirus disease 2019 (COVID-19) pandemic in the United States; however, the overall impact of COVID-19 cases on antibiotic prescribing remains unclear. Methods: This was an ecological study using random-effects panel regression of monthly reported COVID-19 county case and antibiotic prescription data, controlling for seasonality, urbanicity, health care access, nonpharmaceutical interventions (NPIs), and sociodemographic factors. Results: Antibiotic prescribing fell 26.8% in 2020 compared with prior years. Each 1% increase in county-level monthly COVID-19 cases was associated with a 0.009% (95% CI, 0.007% to 0.012%; P < .01) increase in prescriptions per 100 000 population dispensed to all ages and a 0.012% (95% CI, -0.017% to -0.008%; P < .01) decrease in prescriptions per 100 000 children. Counties with schools open for in-person instruction were associated with a 0.044% (95% CI, 0.024% to 0.065%; P < .01) increase in prescriptions per 100 000 children compared with counties that closed schools. Internal movement restrictions and requiring facemasks were also associated with lower prescribing among children. Conclusions: The positive association of COVID-19 cases with prescribing for all ages and the negative association for children indicate that increases in prescribing occurred primarily among adults. The rarity of bacterial coinfection in COVID-19 patients suggests that a fraction of these prescriptions may have been inappropriate. Facemasks and school closures were correlated with reductions in prescribing among children, possibly due to the prevention of other upper respiratory infections. The strongest predictors of prescribing were prior years' prescribing trends, suggesting the possibility that behavioral norms are an important driver of prescribing practices.

Clonally expanded HIV-1 proviruses with 5'-leader defects can give rise to nonsuppressible residual viremia.

BackgroundAntiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible viremia (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% of all proviruses persisting during ART and can express viral genes, but whether they can cause NSV and complicate ART management is unknown.MethodsWe undertook an in-depth characterization of proviruses causing NSV in 4 study participants with optimal adherence and no drug resistance. We investigated the impact of the observed defects on 5'-leader RNA properties, virus infectivity, and gene expression. Integration-site specific assays were used to track these proviruses over time and among cell subsets.ResultsClones carrying proviruses with 5'-leader defects can cause persistent NSV up to approximately 103 copies/mL. These proviruses had small, often identical deletions or point mutations involving the major splicing donor (MSD) site and showed partially reduced RNA dimerization and nucleocapsid binding. Nevertheless, they were inducible and produced noninfectious virions containing viral RNA, but lacking envelope.ConclusionThese findings show that proviruses with 5'-leader defects in CD4+ T cell clones can give rise to NSV, affecting clinical care. Sequencing of the 5'-leader can help in understanding failure to completely suppress viremia.FundingOffice of the NIH Director and National Institute of Dental and Craniofacial Research, NIH; Howard Hughes Medical Institute; Johns Hopkins University Center for AIDS Research; National Institute for Allergy and Infectious Diseases (NIAID), NIH, to the PAVE, BEAT-HIV, and DARE Martin Delaney collaboratories.

Combination of phage therapy and cefiderocol to successfully treat Pseudomonas aeruginosa cranial osteomyelitis.

Background: Pseudomonas aeruginosa has the ability to exhibit resistance to a broad range of antibiotics, highlighting the importance of identifying alternative or adjunctive treatment options, such as phages. Patients and methods: We report the case of a 25-year-old male who experienced an accidental electrocution resulting in exposed calvarium in the left parieto-temporal region, complicated by a difficult-to-treat P. aeruginosa (DTR-P. aeruginosa) infection. Cefiderocol was the sole antibiotic with consistent activity against six bacterial isolates obtained from the infected region over a 38 day period. Results: WGS analysis identified a bla GES-1 gene as well as the MDR efflux pumps MexD and MexX in all six of the patient's ST235 DTR-P. aeruginosa isolates, when compared with the reference genome P. aeruginosa PA01 and a P. aeruginosa ST235 isolate from an unrelated patient. After debridement of infected scalp and bone, the patient received approximately 6 weeks of cefiderocol in conjunction with IV phage Pa14NPøPASA16. Some improvement was observed after the initiation of cefiderocol; however, sustained local site improvement and haemodynamic stability were not achieved until phage was administered. No medication-related toxicities were observed. The patient remains infection free more than 12 months after completion of therapy. Conclusions: This report adds to the growing literature that phage therapy may be a safe and effective approach to augment antibiotic therapy for patients infected with drug-resistant pathogens. Furthermore, it highlights the importance of the GES ß-lactamase family in contributing to inactivation of a broad range of ß-lactam antibiotics in P. aeruginosa, including ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam.

ICI-RS 2015-Is a better understanding of sleep the key in managing nocturia?

AIMS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom. However, the applied treatment modalities do not improve symptoms in about half of the patients. The aim of this report is to generate new ideas for future nocturia research, with special emphasis on the role of sleep physiology and sleep disorders. METHODS: The following is a report of the presentations and subsequent discussion of the Nocturia Think Tank session at the annual meeting of the International Consultation on Incontinence Research Society (ICI-RS), which took place in September 2015 in Bristol. General information about the organization of the ICI-RS meeting can be found on the website "www.ici-rs.org." An overview of challenges within the existing evidence, future research ideas, and results of research with regard to nocturia and sleep were presented. RESULTS AND CONCLUSION: In order to optimize the management of nocturia and nocturnal polyuria (NP), future research has to focus on the development of unambiguous terminology regarding nocturia and NP, the role of renal function profiles and simplified frequency volume charts as guidance of individualized therapy and the role of sleep disorders such as periodic limb movements during sleep and habitual voiding as a response to awakening. Neurourol. Urodynam. 37:2048-2052, 2018. © 2016 Wiley Periodicals, Inc.