Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN.

BACKGROUND: Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID). METHODS: Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization. RESULTS: Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P < .001) and AST (13.5 [56] vs 44.9 [12.1] hours; P < .001). Median (interquartile range [IQR]) time to first antibiotic modification was faster in the RAPID arm vs the SOC arm for overall antibiotics (8.6 [2.6-27.6] vs 14.9 [3.3-41.1] hours; P = .02) and gram-negative antibiotics (17.3 [4.9-72] vs 42.1 [10.1-72] hours; P < .001). Median (IQR) time to antibiotic escalation was faster in the RAPID arm vs the SOC arm for antimicrobial-resistant BSIs (18.4 [5.8-72] vs 61.7 [30.4-72] hours; P = .01). There were no differences between the arms in patient outcomes. CONCLUSIONS: Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs. CLINICAL TRIALS REGISTRATION: NCT03218397.

Using Modified Team-Based Learning to Teach Antimicrobial Stewardship to Medical Students: One Institution's Approach.

Educational interventions are a critical feature of antimicrobial stewardship programs. Most of these interventions target practicing physicians whose prescribing habits are usually difficult to influence. Consequently, there has been increasing interest in familiarizing early learners with the principles of antimicrobial stewardship. However, there is limited data regarding the utility of active learning interventions, such as team-based learning (TBL), for this purpose. In this article, we report the results of a post-course survey eliciting the opinions of the 168 second year medical students who completed the first implementation of a modified TBL course on antimicrobial stewardship. The course consisted of two 120-min modules, each of which guided participant students through most of the characteristic stages of TBL. The post-course survey was analyzed using qualitative and quantitative methodologies. In general, students found the readiness assurance testing, application activity, and team dynamics of TBL effective and the webcasts, used for pre-class preparation, ineffective. This study offers a first glimpse into the attitudes of pre-clinical medical students toward TBL as a strategy for introducing antimicrobial stewardship. It can serve as a roadmap for educators contemplating the implementation of a similar program at their institution and as a launching pad for research on the effects of this type of intervention on physician prescribing habits.

Beyond Susceptible and Resistant, Part II: Treatment of Infections Due to Gram-Negative Organisms Producing Extended-Spectrum ß-Lactamases.

The production of ß-lactamase is the most common mechanism of resistance to ß-lactam antibiotics among gram-negative bacteria. Extended-spectrum ß-lactamases (ESBLs) are capable of hydrolyzing most penicillins, extended-spectrum cephalosporins, and aztreonam, but their activity is suppressed in the presence of a ß-lactamase inhibitor. Serious infections with ESBL-producing isolates are associated with high rates of mortality, making early detection and adequate medical management essential to ensure optimal patient outcomes. Much controversy has centered on the recommendations for testing and reporting of antibiotic susceptibility of potential ESBL-producing organisms. The latest version of the Clinical Laboratory Standards Institute (CLSI) susceptibility reporting guidelines, published in 2010, no longer advocates for phenotypic testing of ESBL-producing isolates. From newer studies demonstrating a correlation between organism minimum inhibitory concentration (MIC) and clinical outcome, along with pharmacokinetic/pharmacodynamic (PK/PD) modeling demonstrating the importance of the MIC to achieving therapeutic targets, the CLSI has assigned lower susceptibility breakpoints for aztreonam and most cephalosporins. The new guidelines recommend using the lower MIC breakpoints to direct antibiotic selection. This article reviews the microbiology and epidemiology of ESBLs, the recent change in CLSI susceptibility reporting guidelines for ESBLs, and the clinical and PK/PD data supporting the relationship between in vitro susceptibility and clinical outcome. Finally, considerations for antimicrobial selection when treating patients with infections caused by ESBL-producing organisms from various sources are discussed.