Antibiotic management of infections with multidrug-resistant organisms (MDRO) represents a complex clinical challenge. We report here the first patient with a severe MDRO infection managed with assistance of a novel \"real-time\" 3-day high-throughput screen (HTS) that allowed screening of 9 drugs in 14 combinations in 2,304 total samplings. Identified synergies were used to modify patient therapy with the goal of reducing drug-induced toxicity. The desired clinical outcome was achieved on the HTS-informed therapeutic regimen, supporting the utility of HTS technology to expand standard antimicrobial susceptibility testing.

BACKGROUND: Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) infections are increasing in both adults and children. The aim of this study was to describe the epidemiology of children with ESBL in an ethnically-diverse population, to determine what proportion of these infections were community-onset, and to identify risk factors predisposing children to ESBL acquisition.
METHODS: A case-case-control study of children aged 0-18 years was conducted from 2012 to 2014. Patients with ESBL (detected via VITEK2) were matched 1:1:5 (based on age, sex, specimen source, and healthcare setting) with non-ESBL and uninfected controls. Data on prior antibiotic and healthcare exposure, international travel, prior urinary tract infection (UTI), comorbid gastrointestinal (GI), genitourinary (GU), neurologic, and immunocompromising conditions were collected and compared.
RESULTS: Seventy-six patients were identified with 85 ESBL infections, of which 77 (91%) were E. coli. ESBL was isolated most frequently from urine (n = 72, 85%). Most infections were community-onset (n = 76, 89%) and were managed in the ambulatory setting (n = 47, 62%). On multivariate analysis, international travel (p < 0.001, OR 8.93; CI 2.92-27.78), comorbid GI condition (p = 0.002, OR 2.65, CI 1.36-5.15), Asian race (p = 0.005, OR 2.56, CI 1.34-4.89) and prior UTI (p < 0.001, OR 8.06, CI 3.47-18.87) were significant risk factors for ESBL.
CONCLUSIONS: Most ESBL infections in this study were community-onset. To our knowledge, this is the first description of international travel as a risk factor for ESBL acquisition in children in the United States.