Ertapenem Versus Meropenem for the Treatment of Extended Spectrum Beta-Lactamase-Producing Enterobacterales Bacteremia in Critically Ill Patients.

BACKGROUND: The preferred carbapenem for treatment of infections caused by extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in critically ill patients is debated. OBJECTIVE: The purpose of this study was to evaluate the difference in clinical failure between ertapenem and meropenem for treatment of ESBL-E bacteremia in critically ill patients. Of concern is ertapenem use in hypoalbuminemia given the potential for higher drug clearance. METHODS: This retrospective, matched cohort study compared critically ill patients treated with ertapenem or meropenem for ESBL-E bacteremia between October 2016 and August 2022. Patients were matched on age, sex, lowest albumin, and in a 1:2 ratio of ertapenem to meropenem. The primary outcome, clinical failure, was a composite of 30-day mortality, antibiotic escalation, and microbiological failure. Secondary outcomes included all-cause readmission and development of superinfection. RESULTS: Of 54 patients, 18 received ertapenem and 36 meropenem. Most had a urinary infection source (55.6% vs 41.7%, P = 0.393). There was no difference in clinical failure (50.0% vs 38.9%, P = 0.436). Ertapenem patients had antibiotic escalation more often (33.3% vs 2.8%, P = 0.002). There was no difference in 30-day mortality (11.1% vs 27.8%, P = 0.298), microbiological failure (27.8% vs 11.1%, P = 0.142), all-cause readmission (22.2% vs 13.9%, P = 0.461), or development of superinfection (11.1% vs 13.9%, P = 1.000). CONCLUSION AND RELEVANCE: There was no difference in clinical failure in a small, retrospective cohort of critically ill patients receiving ertapenem or meropenem for ESBL-E bacteremia. Ertapenem may be appropriate in some critically ill and hypoalbuminemic patients, though additional data are needed.

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.

Impact of outpatient antimicrobial stewardship guideline implementation in an urgent care setting.

BACKGROUND: Urgent care medicine is a rapidly growing health care sector where patients are commonly treated for acute infectious diseases-related conditions. However, there are few antimicrobial stewardship interventions described in these settings. OBJECTIVE: The objective of this study is to determine whether implementing outpatient antimicrobial stewardship guidelines would improve antibiotic prescribing for acute upper respiratory tract infections (ARTIs), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) at a single urgent care site. METHODS: This was a pre-post interventional study comparing antibiotic prescribing patterns for ARTI, SSTI, and UTI at a single urgent care site in the preintervention group (November 2019 to January 2020) with the postintervention group (November 2020 to January 2021) after implementation of outpatient stewardship guidelines. A second urgent care site that did not receive any interventions served as a control. The outpatient stewardship guidelines were implemented in October 2020 via didactic provider education and pocket guide distribution. The primary end point was the rate of total guideline-concordant antibiotic prescribing. Secondary end points included the rates of guideline concordance of each component of the prescription, including antibiotic selection, duration, dose, therapy indication, and patient safety outcomes. RESULTS: The primary outcome of total guideline-concordant antibiotic prescribing significantly improved after implementation of outpatient antimicrobial stewardship guidelines at the study site (50% vs. 70%, P < 0.001), which was also reflected when comparing postintervention study site with postperiod control site (70% vs. 48%, P < 0.001). There was a statistically significant improvement in guideline-concordant duration of antibiotic therapy (43% vs. 61%, P = 0.001), driven by a reduction in antibiotic duration for UTI (7 [interquartile range (IQR) 5-7] vs. 5 [IQR 5-7] days, P = 0.007), which was also observed when comparing the postintervention study site with the postperiod control site (61% vs. 48%, P = 0.02). Patient safety outcomes were similar between groups. CONCLUSION: An antimicrobial stewardship intervention comprising institutional outpatient guideline implementation and provider education significantly improved total guideline-concordant antibiotic prescribing by 20% for ARTI, UTI, and SSTI in an urgent care site.

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa.

BACKGROUND: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). METHODS: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). RESULTS: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). CONCLUSIONS: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.

Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections.

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

Prognostic value of combining a quantitative image feature from positron emission tomography with clinical factors in oligometastatic non-small cell lung cancer.

BACKGROUND AND PURPOSE: Oligometastatic non-small cell lung cancer (NSCLC) is a heterogeneous condition with few known risk stratification factors. A quantitative imaging feature (QIF) on positron emission tomography (PET), gray-level co-occurrence matrix energy, has been linked with outcome of nonmetastatic NSCLC. We hypothesized that GLCM energy would enhance the ability of models comprising standard clinical prognostic factors (CPFs) to stratify oligometastatic patients based on overall survival (OS). MATERIALS AND METHODS: We assessed 79 patients with oligometastatic NSCLC (≤3 metastases) diagnosed in 2007-2015. The primary and largest metastases at diagnosis were delineated on pretreatment scans with GLCM energy extracted using imaging biomarker explorer (IBEX) software. Iterative stepwise elimination feature selection based on the Akaike information criterion identified the optimal model comprising CPFs for predicting OS in a multivariate Cox proportional hazards model. GLCM energy was tested for improving prediction accuracy. RESULTS: Energy was a significant predictor of OS (P = 0.028) in addition to the selected CPFs. The c-indexes for the CPF-only and CPF + Energy models were 0.720 and 0.739. CONCLUSIONS: Incorporating Energy strengthened a CPF model for predicting OS. These findings support further exploration of QIFs, including markers of the primary tumor vs. those of the metastatic sites.