Human gut microbiota are critical to both the development of and recovery from Clostridioides difficile infection (CDI). Antibiotics are the mainstay of CDI treatment, yet inherently cause further imbalances in the gut microbiota, termed dysbiosis, complicating recovery. A variety of microbiota-based therapeutic approaches are in use or in development to limit disease- and treatment-associated dysbiosis and improve rates of sustained cure. These include the recently FDA-approved fecal microbiota, live-jslm (formerly RBX2660) and fecal microbiota spores, live-brpk (formerly SER-109), which represent a new class of live biotherapeutic products (LBPs), traditional fecal microbiota transplantation (FMT), and ultra-narrow-spectrum antibiotics. Here, we aim to review the microbiome changes associated with CDI as well as a variety of microbiota-based treatment approaches.
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). 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). 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). 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.
While efforts have been made in the United States (US) to optimize antimicrobial use, few studies have explored antibiotic prescribing disparities that may drive future interventions. The objective of this study was to evaluate disparities in antibiotic prescribing among US ambulatory care visits by patient subgroups. This was a retrospective, cross-sectional study utilizing the National Ambulatory Medical Care Survey from 2009 to 2016. Antibiotic use was described as antibiotic visits per 1000 total patient visits. The appropriateness of antibiotic prescribing was determined by ICD-9 or ICD-10 codes assigned during the visit. Subgroup analyses were conducted by patient race, ethnicity, age group, and sex. Over 7.0 billion patient visits were included; 11.3% included an antibiotic prescription. Overall and inappropriate antibiotic prescription rates were highest in Black (122.2 and 78.0 per 1000) and Hispanic patients (138.6 and 79.8 per 1000). Additionally, overall antibiotic prescription rates were highest in patients less than 18 years (169.6 per 1000) and female patients (114.1 per 1000), while inappropriate antibiotic prescription rates were highest in patients 18 to 64 years (66.0 per 1000) and in males (64.8 per 1000). In this nationally representative study, antibiotic prescribing disparities were found by patient race, ethnicity, age group, and sex.
A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.