BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. METHODS: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoietic stem cell transplantation complicated by persistent VRE bacteremia and meningitis. To optimize therapy, various blood and cerebrospinal fluid (CSF) samples were sent to a research laboratory for extensive susceptibility testing, pharmacokinetic analyses, and time-kill experiments. RESULTS: In vitro testing revealed resistance to all first-line treatment options and CSF sampling demonstrated sub-optimal central nervous system concentrations achieved by each antimicrobial agent administered in relation to their respective MIC value. Time-kill analyses at observed CSF concentrations confirmed the lack of bactericidal activity despite use of a four-drug combination regimen. CONCLUSIONS: This work is the first to report CSF concentrations of oritavancin and tedizolid in humans and adds to the limited data regarding in vitro susceptibility of new antimicrobial agents such as eravacycline, omadacycline, and lefamulin against VRE. Our study provides new insights into various aspects of treatment of extensively drug-resistant Enterococcus faecium meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases.

STUDY OBJECTIVE: Clinicians currently do not reliably adhere to antibiotic treatment guidelines, resulting in unnecessary patient exposure to broad-spectrum antimicrobials. Our objective is to determine whether a treatment intervention for the management of nonpurulent skin and soft tissue infections increases clinician adherence and improves patient outcomes. METHODS: Between January 1 and December 31, 2017, patients presenting to 2 emergency departments (EDs) and who had received a diagnosis of a nonpurulent skin and soft tissue infection were enrolled and assigned to a pre- or postintervention cohort with a treatment intervention implemented on June 1. Primary outcomes were percentage of ED providers following the guidelines and percentage of patients admitted to the hospital. Secondary outcomes were patient self-reported treatment failure and hospital readmission. RESULTS: There were 1,360 patients, 665 in the preintervention and 695 in the postintervention cohorts. After algorithm implementation, guideline adherence increased (43.0% versus 55.1%; P < .001) and number of patients admitted to the hospital declined (36.5% versus 12.0%; P < .001). In addition, patients reported fewer treatment failures (26.8% versus 16.5%; P=.02) and fewer readmissions (22.3% versus 12.7%; P=.013). After multivariate adjustment, guideline adherence increased by 22% (adjusted relative risk [RR] 1.22; 95% confidence interval [CI] 1.10 to 1.37), whereas hospital admissions were reduced by 26% (adjusted RR 0.74; 95% CI 0.64 to 0.87). In addition, the risks of treatment failure and readmission were reduced by 46% (adjusted RR 0.64; 95% CI 0.43 to 0.97) and 45% (adjusted RR 0.55; 95% CI 0.34 to 0.87), respectively. CONCLUSION: Among patients with a nonpurulent skin and soft tissue infection, implementing an easy-to-follow treatment algorithm can reduce unnecessary antibiotic exposure by increasing clinician guideline adherence while reducing patient treatment failure rates.