Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward.

Infection is the second leading cause of death in patients with cancer. Loss of efficacy in antibiotics due to antibiotic resistance in bacteria is an urgent threat against the continuing success of cancer therapy. In this review, the authors focus on recent updates on the impact of antibiotic resistance in the cancer setting, particularly on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This review highlights the health and financial impact of antibiotic resistance in patients with cancer. Furthermore, the authors recommend measures to control the emergence of antibiotic resistance, highlighting the risk factors associated with cancer care. A lack of data in the etiology of infections, specifically in oncology patients in United States, is identified as a concern, and the authors advocate for a centralized and specialized surveillance system for patients with cancer to predict and prevent the emergence of antibiotic resistance. Finding better ways to predict, prevent, and treat antibiotic-resistant infections will have a major positive impact on the care of those with cancer.

Update on infection control practices in cancer hospitals.

Therapies in oncology have evolved rapidly over the last years. At the same pace, supportive care for patients receiving cancer therapy has also evolved, allowing patients to safely receive the newest advances in treatment in both an inpatient and outpatient basis. The recognition of the role of infection control and prevention (ICP) in the outcomes of patients living with cancer has been such that it is now a requirement for hospitals and involves multidisciplinary groups. Some unique aspects of ICP for patients with cancer that have gained momentum over the past few decades include catheter-related infections, multidrug-resistant organisms, community-acquired viral infections, and the impact of the health care environment on the horizontal transmission of organisms. Furthermore, as the potential for infections to cross international borders has increased, alertness for outbreaks or new infections that occur outside the area have become constant. As the future approaches, ICP in immunocompromised hosts will continue to integrate emerging disciplines, such as antibiotic stewardship and the microbiome, and new techniques for environmental cleaning and for controlling the spread of infections, such as whole-genome sequencing. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society.

In adult inpatients with a UTI, CPOE-based vs. routine stewardship reduced extended-spectrum antibiotic use.

SOURCE CITATION: Gohil SK, Septimus E, Kleinman K, et al. Stewardship prompts to improve antibiotic selection for urinary tract infection: the INSPIRE randomized clinical trial. JAMA. 2024;331:2018-2028. 38639723.

In adult inpatients with pneumonia, CPOE-based vs. routine stewardship reduced extended-spectrum antibiotic use.

SOURCE CITATION: Gohil SK, Septimus E, Kleinman K, et al. Stewardship prompts to improve antibiotic selection for pneumonia: the INSPIRE randomized clinical trial. JAMA. 2024;331:2007-2017. 38639729.

Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid on Antimicrobial Stewardship in Patients With Lower Respiratory Tract Infections: A Retrospective Cohort Study.

BACKGROUND: The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown. METHODS: This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed. RESULTS: A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval, .237-.919]; P = .02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group. CONCLUSIONS: The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs.

Antibiotics on Demand: Advances in Asynchronous Telemedicine Call for Increased Antibiotic Surveillance.

The rapid growth of telehealth services has brought about direct-to-consumer telemedicine platforms, enabling patients to request antibiotics online without a virtual or face-to-face consultation. While telemedicine aims to enhance accessibility, this trend raises significant concerns regarding appropriate antimicrobial use and patient safety. In this viewpoint, we share our first-hand experience with 2 direct-to-consumer platforms, where we intentionally sought inappropriate antibiotic prescriptions for nonspecific symptoms strongly indicative of a viral upper respiratory infection. Despite the lack of clear necessity, requested antibiotic prescriptions were readily transmitted to our local pharmacy following a simple monetary transaction. The effortless acquisition of patient-selected antibiotics online, devoid of personal interactions or consultations, underscores the urgent imperative for intensified antimicrobial stewardship initiatives led by state and national public health organizations in telehealth settings. By augmenting oversight and regulation, we can ensure the responsible and judicious use of antibiotics, safeguard patient well-being, and preserve the efficacy of these vital medications.

What's Hot This Year in Infectious Diseases Clinical Science.

The field of infectious diseases saw numerous exciting advances in 2023. Trials of new antibiotics and treatment regimens sought to address rising rates of antimicrobial resistance. Other studies focused on the most appropriate use of currently available treatments, balancing the dual goals of providing effective treatment and impactful antimicrobial stewardship. Improvements in disease prevention were made through trials of both new vaccines and new chemoprophylaxis approaches. Concerning trends this year included increasing rates of invasive group A streptococcal infections, medical tourism-associated cases of fungal meningitis, and the return of locally acquired malaria to the United States. This review covers some of these notable trials and clinical developments in infectious diseases in the past year.

Raising AWaRe-ness of Antimicrobial Stewardship Challenges in Pediatric Emergency Care: Results from the PERFORM Study Assessing Consistency and Appropriateness of Antibiotic Prescribing Across Europe.

BACKGROUND: Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. METHODS: Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. RESULTS: Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/ß-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. CONCLUSIONS: Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship.

Nosocomial Infections in Adults Receiving Extracorporeal Membrane Oxygenation: A Review for Infectious Diseases Clinicians.

Over the past 10 years, there has been a rapid expansion in the use of extracorporeal membrane oxygenation (ECMO) in the care of patients with refractory cardiac or respiratory failure. Infectious diseases clinicians must reconcile conflicting evidence from limited studies as they develop practices at their own institutions, which has resulted in considerably different practices globally. This review describes infection control and prevention as well as antimicrobial prophylaxis strategies in this population. Data on diagnostics and treatment for patients receiving ECMO with a focus on diagnostic and antimicrobial stewardship is then examined. This review summarizes gaps in the current ECMO literature and proposes future needs, including developing clear definitions for infections and encouraging transparent reporting of practices at individual facilities in future clinical trials.

Pediatric Antimicrobial Stewardship Programs Reduce Antibiotic Use at Combined Adult-Pediatric Hospitals.

Implementation of dedicated pediatric antimicrobial stewardship programs (ASPs) at 2 combined adult-pediatric hospitals with existing ASPs was associated with sustained decreases in pediatric antibiotic use out of proportion to declines seen in adult inpatient units. ASPs in combined hospitals may not detect excessive pediatric antibiotic use without incorporating pediatric expertise.

Rapid Diagnostic Tests and Antimicrobial Stewardship Programs for the Management of Bloodstream Infection: What Is Their Relative Contribution to Improving Clinical Outcomes? A Systematic Review and Network Meta-analysis.

BACKGROUND: Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BCs) embedded within antimicrobial stewardship programs (ASPs) is unknown. METHODS: We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. RESULTS: Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI], .59-.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI, .63-.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI, .84-.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (-29 hours; 95% CI, -35 to -23), BC + ASP (-18 hours; 95% CI, -27 to -10), and to RDT alone (-12 hours; 95% CI, -20 to -3). CONCLUSIONS: The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC.

A Novel Risk-Adjusted Metric to Compare Hospitals on Their Antibiotic Prescribing at Hospital Discharge.

BACKGROUND: Antibiotic overuse at hospital discharge is common, but there is no metric to evaluate hospital performance at this transition of care. We built a risk-adjusted metric for comparing hospitals on their overall post-discharge antibiotic use. METHODS: This was a retrospective study across all acute-care admissions within the Veterans Health Administration during 2018-2021. For patients discharged to home, we collected data on antibiotics and relevant covariates. We built a zero-inflated, negative, binomial mixed model with 2 random intercepts for each hospital to predict post-discharge antibiotic exposure and length of therapy (LOT). Data were split into training and testing sets to evaluate model performance using absolute error. Hospital performance was determined by the predicted random intercepts. RESULTS: 1 804 300 patient-admissions across 129 hospitals were included. Antibiotics were prescribed to 41.5% while hospitalized and 19.5% at discharge. Median LOT among those prescribed post-discharge antibiotics was 7 (IQR, 4-10) days. The predictive model detected post-discharge antibiotic use with fidelity, including accurate identification of any exposure (area under the precision-recall curve = 0.97) and reliable prediction of post-discharge LOT (mean absolute error = 1.48). Based on this model, 39 (30.2%) hospitals prescribed antibiotics less often than expected at discharge and used shorter LOT than expected. Twenty-eight (21.7%) hospitals prescribed antibiotics more often at discharge and used longer LOT. CONCLUSIONS: A model using electronically available data was able to predict antibiotic use prescribed at hospital discharge and showed that some hospitals were more successful in reducing antibiotic overuse at this transition of care. This metric may help hospitals identify opportunities for improved antibiotic stewardship at discharge.

Drivers of Geographic Patterns in Outpatient Antibiotic Prescribing in the United States.

In a retrospective, ecological analysis of US medical claims, visit rates explained more of the geographic variation in outpatient antibiotic prescribing rates than per-visit prescribing. Efforts to reduce antibiotic use may benefit from addressing the factors that drive higher rates of outpatient visits, in addition to continued focus on stewardship.

Antibiotic Prescribing Patterns for Respiratory Tract Illnesses Following the Conclusion of an Education and Feedback Intervention in Primary Care.

BACKGROUND: A study previously conducted in primary care practices found that implementation of an educational session and peer comparison feedback was associated with reduced antibiotic prescribing for respiratory tract diagnoses (RTDs). Here, we assess the long-term effects of this intervention on antibiotic prescribing following cessation of feedback. METHODS: RTD encounters were grouped into tiers based on antibiotic prescribing appropriateness: tier 1, almost always indicated; tier 2, possibly indicated; and tier 3, rarely indicated. A χ2 test was used to compare prescribing between 3 time periods: pre-intervention, intervention, and post-intervention (14 months following cessation of feedback). A mixed-effects multivariable logistic regression analysis was performed to assess the association between period and prescribing. RESULTS: We analyzed 260 900 RTD encounters from 29 practices. Antibiotic prescribing was more frequent in the post-intervention period than in the intervention period (28.9% vs 23.0%, P < .001) but remained lower than the 35.2% pre-intervention rate (P < .001). In multivariable analysis, the odds of prescribing were higher in the post-intervention period than the intervention period for tier 2 (odds ratio [OR], 1.19; 95% confidence interval [CI]: 1.10-1.30; P < .05) and tier 3 (OR, 1.20; 95% CI: 1.12-1.30) indications but was lower compared to the pre-intervention period for each tier (OR, 0.66; 95% CI: 0.59-0.73 tier 2; OR, 0.68; 95% CI: 0.61-0.75 tier 3). CONCLUSIONS: The intervention effects appeared to last beyond the intervention period. However, without ongoing provider feedback, there was a trend toward increased prescribing. Future studies are needed to determine optimal strategies to sustain intervention effects.

Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the COVID-19 Outbreak: An Interrupted Time Series Analysis of 2016-2021 Data.

BACKGROUND: No national study has evaluated changes in the appropriateness of US outpatient antibiotic prescribing across all conditions and age groups after the coronavirus disease 2019 (COVID-19) outbreak in March 2020. METHODS: This was an interrupted time series analysis of Optum's de-identified Clinformatics Data Mart Database, a national commercial and Medicare Advantage claims database. Analyses included prescriptions for antibiotics dispensed to children and adults enrolled during each month during 2017-2021. For each prescription, we applied our previously developed antibiotic appropriateness classification scheme to International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes on medical claims occurring on or during the 3 days prior to dispensing. Outcomes included the monthly proportion of antibiotic prescriptions that were inappropriate and the monthly proportion of enrollees with ≥1 inappropriate prescription. Using segmented regression models, we assessed for level and slope changes in outcomes in March 2020. RESULTS: Analyses included 37 566 581 enrollees, of whom 19 154 059 (51.0%) were female. The proportion of enrollees with ≥1 inappropriate prescription decreased in March 2020 (level decrease: -0.80 percentage points [95% confidence interval {CI}, -1.09% to -.51%]) and subsequently increased (slope increase: 0.02 percentage points per month [95% CI, .01%-.03%]), partly because overall antibiotic dispensing rebounded and partly because the proportion of antibiotic prescriptions that were inappropriate increased (slope increase: 0.11 percentage points per month [95% CI, .04%-.18%]). In December 2021, the proportion of enrollees with ≥1 inappropriate prescription equaled the corresponding proportion in December 2019. CONCLUSIONS: Despite an initial decline, the proportion of enrollees exposed to inappropriate antibiotics returned to baseline levels by December 2021. Findings underscore the continued importance of outpatient antibiotic stewardship initiatives.

The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) Fellowship, a Novel Training Program in Public Health for Infectious Diseases Physicians.

The severe acute respiratory syndrome coronavirus 2 pandemic demonstrated a critical need for partnerships between practicing infectious diseases (ID) physicians and public health departments. The soon-to-launch combined ID and Epidemic Intelligence Service fellowship can only address a fraction of this need, and otherwise US ID training lacks development pathways for physicians aiming to make careers working with public health departments. The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) fellowship is a model compatible with the current training paradigm with a proven track record of developing careers of long-term collaboration. Established in 2017 by the ID Society of America, Society for Healthcare Epidemiology of America, Pediatric ID Society, and supported by the Centers for Disease Control and Prevention, LEAP is a single-year in-place, structured training for senior trainees and early career ID physicians. In this viewpoint, we describe the LEAP fellowship, its outcomes, and how it could be adapted into ID training.

Retrospective validation study of a machine learning-based software for empirical and organism-targeted antibiotic therapy selection.

Errors in antibiotic prescriptions are frequent, often resulting from the inadequate coverage of the infection-causative microorganism. The efficacy of iAST, a machine-learning-based software offering empirical and organism-targeted antibiotic recommendations, was assessed. The study was conducted in a 12-hospital Spanish institution. After model fine-tuning with 27,531 historical antibiograms, 325 consecutive patients with acute infections were selected for retrospective validation. The primary endpoint was comparing each of the top three of iAST's antibiotic recommendations' success rates (confirmed by antibiogram results) with the antibiotic prescribed by the physicians. Secondary endpoints included examining the same hypothesis within specific study population subgroups and assessing antibiotic stewardship by comparing the percentage of antibiotics recommended that belonged to different World Health Organization AWaRe groups within each arm of the study. All of iAST first three recommendations were non-inferior to doctor prescription in the primary endpoint analysis population as well as the secondary endpoint. The overall success rate of doctors' empirical treatment was 68.93%, while that of the first three iAST options was 91.06% (P < 0.001), 90.63% (P < 0.001), and 91.06% (P < 001), respectively. For organism-targeted therapy, the doctor's overall success rate was 84.16%, and that of the first three ranked iAST options was 97.83% (P < 0.001), 94.09% (P < 0.001), and 91.30% (P < 0.001), respectively. In empirical therapy, compared to physician prescriptions, iAST demonstrated a greater propensity to recommend access antibiotics, fewer watch antibiotics, and higher reserve antibiotics. In organism-targeted therapy, iAST advised a higher utilization of access antibiotics. The present study demonstrates iAST accuracy in predicting antibiotic susceptibility, showcasing its potential to promote effective antibiotic stewardship. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT06174519.

A survey of patient practices regarding leftover antibiotics reveals a potential source of antibiotic overuse.

Taking leftover prescribed antibiotics without consulting a healthcare professional is problematic for the efficacy, safety, and antibiotic stewardship. We conducted a cross-sectional survey of adult patients in English and Spanish between January 2020 and June 2021 in six safety-net primary care clinics and two private emergency departments. We assessed the reasons for stopping prescribed antibiotics early and what was done with the leftover antibiotics. Additionally, we determined 1) prior leftover antibiotic use, 2) intention for future use of leftover antibiotics, and 3) sociodemographic factors. Of 564 survey respondents (median age of 51), 45% (251/564) reported a history of stopping antibiotics early, with 171/409 (42%) from safety net and 80/155 (52%) from the private clinics. The most common reason for stopping prescribed antibiotics early was "because you felt better" (194/251, 77%). Among survey participants, prior use of leftover antibiotics was reported by 149/564 (26%) and intention for future use of leftover antibiotics was reported by 284/564 (51%). In addition, higher education was associated with a higher likelihood of prior leftover use. Intention for future use of leftover antibiotics was more likely for those with transportation or language barriers to medical care and less likely for respondents with private insurance. Stopping prescribed antibiotics early was mostly ascribed to feeling better, and saving remaining antibiotics for future use was commonly reported. To curb nonprescription antibiotic use, all facets of the leftover antibiotic use continuum, from overprescribing to hoarding, need to be addressed.