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.

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).

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.

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.

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.

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.

Lessons from the field: Supporting infection prevention and control and antimicrobial stewardship in Amman, Jordan.

BACKGROUND: To reduce antimicrobial resistance (AMR), appropriate antimicrobial prescribing is critical. In conjunction with Infection Prevention & Control (IPC) programs, Antimicrobial Stewardship Programs (ASP) have been shown to improve prescribing practices and patient outcomes. Low- and middle-income countries (LMIC) face challenges related to inadequate ASP policies and guidelines at both the national and healthcare facility (HCF) levels. METHODS: To address this challenge, the World Health Organization (WHO) created a policy guidance and practical toolkit for implementation of ASPs in LMIC. We utilized this document to support a situational analysis and two-day ASP-focused workshop. In follow-up, we invited these attendees, additional HCF and hospital directors to attend a workshop focused on the benefits of supporting these programs. RESULTS: Over the course of a total three days, we recruited hospital directors, ASP team members, and IPC officers from fifteen different healthcare facilities in Jordan. We describe the courses and coordination, feedback from participants, and lessons learned for future implementation. CONCLUSIONS: Future efforts will include more time for panel-type discussion. which will assist in further delineating enablers and barriers. Also planned is a total three-day workshop; with the first two days being with ASP/IPC teams, and the final third day being with hospital directors and leadership. The WHO policy guidance and toolkit are useful tools to address overuse of antimicrobial agents. Strong leadership support is needed for successful implementation of ASP and IPC. Discussions on quality/safety, as well as cost analyses, are important to generate interest of stakeholders.

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.

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.

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.

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.

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.

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC ß-lactamase Production.

Background: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum ß-lactamase (ESBL) concerns. Methods: This was a retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion ß-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). Conclusions: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive ß-lactam therapy.

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).

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure.

The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

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.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections.

INTRODUCTION: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel ß-lactam-ß-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). METHODS: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. RESULTS: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. CONCLUSION: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.

Prevalence and Predictors of Pseudomonas aeruginosa Among Hospitalized Patients With Diabetic Foot Infections.

Background: Diabetic foot infections (DFIs) are commonly associated with antibiotic overuse. Empiric DFI treatment often includes coverage for Pseudomonas aeruginosa (PsA), but the frequency of PsA DFIs is poorly understood. The study objectives were to quantify the prevalence of and determine predictors for PsA DFIs. Methods: This multicenter, retrospective cohort included hospitalized patients with DFI from 2013 through 2020 who were age ≥18 years; diabetes mellitus diagnosis; and DFI based on International Classification of Diseases, Tenth Revision coding, antibiotic treatment, and DFI culture with organism growth. Osteomyelitis was excluded. Patient characteristics were described and compared; the primary outcome was presence of PsA on DFI culture. Predictors of PsA DFI were identified using multivariable logistic regression. Results: Two hundred ninety-two patients were included. The median age was 61 (interquartile range [IQR], 53-69) years; the majority were men (201 [69%]) and White (163 [56%]). The most commonly isolated organisms were methicillin-susceptible Staphylococcus aureus (35%) and streptococci (32%); 147 (54%) cultures were polymicrobial. Two hundred fifty-seven (88%) patients received empiric antibiotics active against PsA, but only 27 (9%) patients had PsA DFI. Immunocompromised status (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.3-16.7]) and previous outpatient DFI antibiotic treatment failure (aOR, 4.8 [95% CI, 1.9-11.9]) were associated with PsA DFI. Conclusions: PsA DFI is uncommon, but most patients receive empiric antipseudomonal antibiotics. Empiric broad-spectrum antibiotics are warranted given the frequency of mixed infections, but patient-specific risk factors should be considered before adding antipseudomonal coverage.

Real-World, Multicenter Case Series of Patients Treated with Oral Omadacycline for Resistant Gram-Negative Pathogens.

INTRODUCTION: Antibiotic-resistant Gram-negative bacteria have been associated with substantial morbidity and mortality and have limited treatment options available. Omadacycline (OMC) is an aminomethylcycline antibiotic that has been shown to exhibit broad in vitro activity against antibiotic-resistant Gram-negative bacteria. Given the lack of real-world data, the primary objective of our report was to describe early experience with OMC for the treatment of resistant Gram-negative infections. METHODS: This was a real-world, multicenter, observational cases series/pilot study conducted in the USA. Inclusion criteria included any adult patient aged ≥ 18 years who received OMC for ≥ 72 h either in the inpatient and/or outpatient setting. Clinical success was defined as a composite of 90-day survival from initiation of OMC, lack of alteration in treatment/addition of other antibiotic due to concerns of OMC failure, and lack of microbiologic recurrence within 30 days from the end of therapy. RESULTS: Oral OMC was used in nine cases primarily for multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacterial infections (55.6% XDR and/or carbapenem-resistant Acinetobacter baumannii [CRAB]). The majority of infections were of bone/joint (55.6%) origin, followed by intra-abdominal (33.3%) origin. Clinical success occurred in 66.7% of cases, with 80.0% success each in infections of bone/joint origin or those caused by CRAB. One patient experienced an adverse effect that was not treatment limiting while on therapy (gastrointestinal). CONCLUSION: The use of oral OMC in MDR/XDR Gram-negative infections exhibited a relatively high success rate with minimal adverse effects. Real-world studies with larger case numbers are needed to confirm our initial findings.