Prescribing Practices of Recommended Treatment for Trichomonas vaginalis and Chlamydia trachomatis after 2021 STI Treatment Guideline Update.

ABSTRACT: We evaluated the proportion of patients with trichomoniasis and chlamydial infections who received recommended versus non-recommended antibiotic therapy after the updated 2021 Sexually Transmitted Infections Guideline. Of 712 patients, 473 (66%) received recommended therapy. Receipt of emergency department care was independently associated with recommended therapy (adjOR, 2.1; 95% CI 1.5-2.9).

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Leveraging stewardship to promote ceftriaxone use in severe infections with low- and no-risk AmpC Enterobacterales.

AmpC ß-lactamases are associated with development of ceftriaxone resistance despite initial in vitro susceptibility, but the risk of AmpC derepression is not equal among Enterobacterales. The purpose of this study was to evaluate the impact of an AmpC stewardship intervention on the definitive treatment of low- and no-risk Enterobacterales. This was an IRB-approved, single pre-test, post-test quasi-experiment at a 5-hospital system. An AmpC stewardship intervention was implemented in July 2022 and included prescriber education, the removal of microbiology comments indicating potential for ceftriaxone resistance on therapy, and the modification of a blood PCR comment for Serratia marcescens to recommend ceftriaxone. Adults ≥18 years pre-intervention (July 2021 to December 2021) and post-intervention (July 2022 to December 2022) who received ≥72 hours of inpatient definitive therapy and had non-urine cultures growing low- and no-risk organisms (S. marcescens, Providencia spp., Citrobacter koseri, Citrobacter amalonaticus, or Morganella morganii) were included. The primary endpoint was definitive treatment with ceftriaxone. A total of 224 patients were included; 115 (51%) in pre-intervention and 109 (49%) in post-intervention. Definitive ceftriaxone therapy was prescribed more frequently after intervention [6 (5%) vs 72 (66%), P < 0.001]. After adjustment for critical illness, patients in the post-group were more likely to receive definitive ceftriaxone (adjOR, 34.7; 95% CI, 13.9-86.6). The proportion of patients requiring retreatment was 18 (15%) and 11 (10%) for pre- and post-intervention patients (P = 0.22), and ceftriaxone resistance within 30 days occurred in 5 (4%) and 2 (2%) patients in the pre- and post-group (P = 0.45). An antimicrobial stewardship intervention was associated with increased ceftriaxone prescribing and similar patient outcomes for low- and no-risk AmpC Enterobacterales.

Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments.

INTRODUCTION: Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. METHODS: This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. RESULTS: A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7-7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. CONCLUSIONS: AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

Incidence and Predictors of Gram-Negative Bacilli in Hospitalized People Who Inject Drugs with Injection Drug Use-Attributable Infections.

The objective of this study was to quantify incidence and determine predictors of Gram-negative bacilli (GNB) in people who inject drugs (PWID) with injection-drug use (IDU)-related infections. The investigation was a retrospective cohort of hospitalized PWID from January 2017 to December 2019. Inclusion criteria were age of ≥18 years, active IDU, treated IDU-attributable infection, and organism growth from microbiology cultures. Infection types included infective endocarditis (IE), acute bacterial skin/skin structure infection (ABSSSI), osteoarticular infection (OAI), and other bloodstream infections (BSI). Primary outcome was GNB identification from microbiologic culture; descriptive statistics were used to describe the cohort. Multivariable regression was used to identify variables associated with GNB infection. A total of 230 PWID were included, 65 (28%) with GNB infections and 165 (72%) with Gram-positive infections. The median (interquartile range [IQR]) population age was 38 (31 to 45) years. Most patients were women (56%); 37% had no insurance. Infection types were as follows: IE, 41%; ABSSSI, 37%; OAI, 20%; and other BSI, 2%. A total of 278 organisms were isolated from 230 patients. The most common organisms were methicillin-resistant Staphylococcus aureus (43%), Streptococcus spp. (19%), methicillin-susceptible S. aureus (17%), and Serratia marcescens (8%); 10% of infections were mixed GNB and Gram-positive infections. A total of 80% of patients received empirical Pseudomonas aeruginosa coverage; only 7% had P. aeruginosa infections. In multivariable regression, age of >50 years (adjusted odds ratio [adjOR], 2.9; 95% confidence interval [CI], 1.2 to 7.2), prior hospitalization within 90 days (adjOR, 2.2; 95% CI, 1.2 to 4.3), and OAI (adjOR, 3.2; 95% CI, 1.5 to 6.6) were associated with GNB infection. GNB in PWID with IDU-attributable infections were more frequently observed in recently hospitalized, older patients with OAI. The majority of patients received empirical antipseudomonal antibiotic coverage, but P. aeruginosa was infrequent. PWID are a potential population to target improved empirical antibiotic use.

Candida spp. infective endocarditis: Characteristics and outcomes of twenty patients with a focus on injection drug use as a predisposing risk factor.

BACKGROUND: Candida spp. infective endocarditis (CIE) although rare is associated with high morbidity and mortality. Risk factors include prosthetic heart valves and injection drug use (IDU). We reviewed all cases of CIE at our institution to describe the microbiology, treatment and outcomes of patients focusing on IDU as a predisposing factor. METHODS: Retrospective cohort of patients with definite CIE between 2013 and 2019 at a university hospital was analysed. Demographic data collected included IDU, microbiologic, treatment and mortality. The primary outcome of interest was 12-month, all-cause mortality. RESULTS: Twenty patients were included (one had two separate episodes of CIE); CIE accounted for 4% of total infective endocarditis (IE) cases during the study period. The median (IQR) age was 38 (30-58) years, 10 (50%) had a previous history of IE, and 4 (20%) patients had prosthetic heart valves or an implanted cardiac device. Thirteen (65%) patients were IDU. The tricuspid valve was the primary valve involved (8/18, 44%), and C albicans was the most frequently isolated organism (8, 36%). Echinocandin was the most common treatment strategy (8, 40%). Only three (15%) patients underwent valve replacement during hospitalisation. There were no in-hospital fatalities, and 5 (25%) patients died at one year; all were IDU (39% to 0%, p = .11). CONCLUSION: CIE is a rare infectious disease seen more commonly in the IDU population. Cardiac surgery was rarely performed, and long-term mortality was 25%. Additional data are needed to identify ideal management strategies in this population.

Impact of a Plan of Care Protocol on Patient Outcomes in People Who Inject Drugs With Infective Endocarditis.

BACKGROUND: People who inject drugs (PWID) are at increased risk of deleterious sequelae due to infective endocarditis (IE). A standardized, hospital-wide drug use-associated infection protocol targeting medication safety, pain management, and limiting external risk factors was implemented at an academic medical center to improve outcomes in PWID with IE. METHODS: A quasi-experimental study included patients with active injection drug use and definite IE from January 2013 to July 2017 (preintervention group) and from September 2017 to January 2019 (intervention group). The primary outcome of interest was the 90-day all-cause readmission rate. Secondary outcomes included infection-related readmission rates, in-hospital and all-cause mortality rates, and the frequency of patients leaving against medical advice. RESULTS: A total of 168 patients were included, in the 100 preintervention and 68 in the intervention group. Patients in the intervention group had reduced odds of 90-day all-cause readmission (adjusted odds ratio, 0.2; 95% confidence interval, 0.08-0.6) after adjustment for confounding variables. The 12-month all-cause mortality rate was also significantly reduced in the intervention group (adjusted odds ratio, 0.25; 95% confidence interval, .07-.89). The intervention group had a higher proportion of patients leaving against medical advice (6% for the preintervention group vs 35% for the intervention group, P < .001). CONCLUSIONS: A drug use-associated infection protocol demonstrated reduced 90-day all-cause readmission and 12-month all-cause mortality rates in PWID with IE. This study highlights the importance of standardized care processes for improving care in this specialized patient population.

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. METHODS: A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. RESULTS: A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31-5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03-0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. CONCLUSIONS: These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

Elevated troponin level as a predictor of inpatient mortality in patients with infective endocarditis in the Southeast United States.

BACKGROUND: Despite recent improvement in management, infective endocarditis (IE) continues to be associated with considerable risk of morbidity and mortality. Early identification of predictors of inpatient mortality is key in improving patient outcomes in IE. The aim of our study was to evaluate the role of serum troponin levels measurements as a marker of increased mortality. METHODS: A case-control study included adult patients with IE admitted to a tertiary care hospital in east Tennessee between December 2012 and July 2017. Cases were defined as patients with definitive IE who died in-hospital; controls were patients who did not die in hospital. First patient admission was included only. Data collected included the patients' demographic and baseline clinical information, microbiological data, injection drug use status, elevated serum troponins levels. RESULTS: Two hundred eighty three patients with definitive IE were included; median (IQR) age was 41 (30-57) years, and 153 (54%) patients were men. One-hundred sixty-four (58%) were injection drug users. The most frequent IE type was: 167 (59%) right-sided, 86 (30%) left-sided, 24 (9%) both left and right-sided, and 10 (4%) device related. The most commonly isolated organism was Staphylococcus aureus (n = 141), and 64% were methicillin-resistant. Two-hundred twelve (75%) patients had a troponin level obtained, and 57 (27%) had an elevated troponin value. Thirty-six (13%) patients died in-hospital; in-hospital mortality was associated elevated troponin values (adjusted odds ratio [adjOR], 7.3; 95%CI, 3.3-15.9), and methicillin-resistant S. aureus IE (adjOR 2.6; 95%CI, 1.2-5.8). Forty-four (16%) patients received IE valve surgery, and none of these patients died in the hospital. CONCLUSION: Inpatient mortality was higher in patients with IE and elevated cardiac troponin levels compared to patients with normal levels.

A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species.

The increasing incidence of and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern. Due to the extremely limited therapeutic options available, it is critical to identify and understand the various causes of treatment failure if patient outcomes are to improve. In this study, we examined one potential source of treatment failure: antagonistic drug interactions. Using a simple screen, we systematically identified currently approved medications that undermine the antifungal activity of three major antifungal drugs-fluconazole, caspofungin, and amphotericin B-on four prevalent human fungal pathogens-Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis This revealed that a diverse collection of structurally distinct drugs exhibit antagonistic interactions with fluconazole. Several antagonistic agents selected for follow-up studies induce azole resistance through a mechanism that depends on Tac1p/Pdr1p zinc-cluster transcription factors, which activate the expression of drug efflux pumps belonging to the ABC-type transporter family. Few antagonistic interactions were identified with caspofungin or amphotericin B, possibly reflecting their cell surface mode of action that should not be affected by drug efflux mechanisms. Given that patients at greatest risk of IFIs usually receive a multitude of drugs to treat various underlying conditions, these studies suggest that chemically inducible azole resistance may be much more common and important than previously realized.

You'll have to call the attending: Impact of a longitudinal, "real-time" case-based infectious diseases elective on entrustable professional activities to enhance APPE readiness.

BACKGROUND AND PURPOSE: Transitioning from the didactic to experiential setting is challenging for student pharmacists, perhaps due to lack of experiences providing "real-time" clinician interaction. We describe findings from a semester-long infectious diseases (ID) didactic elective that utilized a national cohort of preceptors and faculty across the United States to mimic clinician interaction and "real-time" ID management of various disease states. The mechanics of this elective provide a framework for others to implement to enhance advanced pharmacy practice experience (APPE) readiness. EDUCATION ACTIVITY AND SETTING: Students enrolled in an ID elective course at a school of pharmacy participated in "real-time" acute care scenarios. They assisted in multidisciplinary management of a patient's infection, mimicking "rounds" on an APPE, via interaction with external pharmacist volunteers (playing the roles of other healthcare personnel). Additionally, students formally presented and discussed their cases within the class, further promoting learning while optimizing presentation skills. Pharmacist volunteers were surveyed to assess student performances as measured by four entrustable professional activities (EPAs). FINDINGS: A total of 48 volunteer opportunities occurred during two course offerings. Results from 43 surveys were analyzed (90% response rate). Of those responses, 22/24 (92%) played the role of attending physician, and 19/24 (79%) played the role of technician. Volunteers agreed that students met the four EPAs evaluated (agreement was 85-100%). SUMMARY: This semester-long elective provided "real-time" experience and feedback for pre-APPE students to enhance APPE readiness and reinforce EPAs. Students are likely to benefit from mimicked intra-professional interaction and augmented critical thinking skills that could be adapted to various disease states within pharmacy curricula.

Impact of time to treatment in first occurrence, non-severe Clostridioides difficile infection for elderly patients: are we waiting too long to treat?

Objective: Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study's purpose was to evaluate the impact of time-to-CDI treatment on disease progression. Methods: A case-control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours. Cases included patients who progressed to severe or fulminant CDI; controls were patients without CDI progression. Time to CDI treatment was evaluated in three ways: a classification and regression tree (CART)-defined threshold, time as a continuous variable, and time as a categorical variable. Results: 272 patients were included; 136 with CDI progression, 136 patients without. The median (IQR) age was 74 (69-81) years, 167 (61%) were women, and 108 (40%) were immunosuppressed. CDI progression patients more commonly were toxin positive (66 [49%] vs 52 [38%], P = .087) with hospital-acquired disease (57 [42%] vs 29 [21%], P < 0.001). A CART-derived breakpoint for optimal time-to-CDI treatment of 64 hours established early (184, 68%) and delayed treatment (88, 32%). When accounting for confounding variables, delayed CDI treatment was associated with disease progression (adjOR, 4.6; 95%CI, 2.6-8.2); this was observed regardless of how time-to-CDI-active therapy was evaluated (continuous adjOR, 1.02; categorical adjOR, 2.11). Conclusion: Delayed CDI treatment was associated with disease progression and could represent an important antimicrobial stewardship measure with future evaluation.

Cefiderocol: early clinical experience for multi-drug resistant gram-negative infections.

Multi-drug resistant gram-negative bacteria present a significant global health threat. Cefiderocol (CFDC), a siderophore cephalosporin, has shown potential in combating this threat, but with the currently available data, its role in therapy remains poorly defined. This multi-center, retrospective cohort study evaluated the real-world application of CFDC across six U.S. medical centers from January 2018 to May 2023. Patients aged ≥18 years and who had received ≥72 hours of CFDC were included. The primary outcome was a composite of clinical success: survival at 30 days, absence of symptomatic microbiologic recurrence at 30 days following CFDC treatment initiation, and resolution of signs and symptoms. Secondary outcomes included time to CFDC therapy and on-treatment non-susceptibility to CFDC. A total of 112 patients were included, with median (interquartile range [IQR]) APACHE II scores of 15 (19-18). Clinical success was observed in 68.8% of patients, with a mortality rate of 16.1% and comparable success rates across patients infected with carbapenem-resistant gram-negative infections. The most common isolated organisms were Pseudomonas aeruginosa (61/112, 54.5%, of which 55/61 were carbapenem-resistant) and carbapenem-resistant Acinetobacter baumannii (32/112, 28.6%). Median (IQR) time to CFDC therapy was 77 (14-141) hours. Two patients experienced a non-anaphylactic rash as an adverse drug reaction. On-treatment non-susceptibility to CFDC was found in six patients, notably due to P. aeruginosa and A. baumannii.IMPORTANCECFDC was safe and clinically effective as a monotherapy or in combination in treating a variety of carbapenem-resistant gram-negative infections. Further prospective studies are warranted to confirm these findings.

Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Weighing the Odds: Novel ß-Lactam/ß-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pseudomonas aeruginosa Pneumonia for Patients Who Are Morbidly Obese.

Background: Pseudomonas aeruginosa is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m2) and non-morbidly obese (<35 kg/m2) and receiving BL/BLI for P aeruginosa HABP/VABP. Methods: This retrospective study was based on a cohort of patients hospitalized at 2 urban academic medical centers in Detroit, Michigan, from August 2014 through February 2021 with P aeruginosa HABP/VABP who were receiving BL/BLI (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam) for ≥72 continuous hours. The primary endpoint was presumed treatment failure, defined as the presence of all-cause in-hospital mortality or the continuation of infectious symptoms. Analyses were adjusted for possible confounding with inverse probability of treatment weighting. Multivariable regression was used to identify predictors of treatment failure. Results: In total, 285 patients with HABP (61.4%) and/or VABP (56.1%) were enrolled (morbidly obese, n = 95; non-morbidly obese, n = 190). The median Acute Physiology and Chronic Health Evaluation II score was 23 (IQR, 13-26), and 60% of patients were admitted to the intensive care unit at index culture collection. Patients who were morbidly obese demonstrated significantly greater odds of presumed treatment failure vs those who were non-morbidly obese (58.9% vs 37.9%, respectively; adjusted odds ratio, 1.675 [95% CI, 1.465-1.979]). In multivariable analysis, morbid obesity (1.06; 95% CI, 1.02-1.79), prolonged time to BL/BLI initiation (1.47; 95% CI, 1.28-2.66), renal dose-adjusted BL/BLI in the first 48 hours of therapy (1.12; 95% CI, 1.09-1.75), and continuous renal replacement therapy during BL/BLI therapy (1.35; 95% CI, 1.06-1.68) were independently associated with increased odds of presumed treatment failure. Conclusions: Among hospitalized patients receiving BL/BLI for P aeruginosa HABP/VABP, those who were morbidly obese had significantly greater odds of presumed treatment failure when compared with those who were non-morbidly obese.

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections.

We compared optimal antibiotic prescribing before and after implementing an interpretive ß-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87).

Cancer is chronic but antimicrobial stewardship is iconic: A retrospective cohort of optimal antibiotic use in ambulatory oncology clinics.

Objective: To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use. Methods: Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin-skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression. Results: In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19-4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P = .057). Conclusions: Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.

Aminopenicillins vs non-aminopenicillins for treatment of enterococcal lower urinary tract infections.

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.