Risk factors and outcome associated with infection or colonization due to carbapenem-heteroresistant .

Background: Up to 32% of ESBL-producing Enterobacterales strains display a carbapenem-heteroresistant (cHR) phenotype but its clinical relevance is unknown.

Objectives: To determine risk factors and clinical outcome associated with infection due to cHR ESBL-producing (ESBL-EC).

Methods: A retrospective, case-control study was conducted on patients from whom a pair of clonally related strains were isolated during separate healthcare encounters with (case) or without (control) development of cHR phenotype in the latter strain. Study groups were compared for host and microbial characteristics and carbapenem exposure. Outcome measures included ICU admission, length of hospitalization, and mortality.

Results: Study patients (15 cases, 10 controls) were elderly (median age: 74 years) with half admitted from home (52%), most (80%) having ≥3 comorbid conditions and severe functional impairment. Case patients were more likely to have 'index' ESBL-EC isolating from blood (27% versus 0%; 0.125) and have greater cumulative amount and duration of carbapenem exposure than controls. All control 'subsequent' isolates were from urine whereas five cHR case isolates were from blood or respiratory sources. More hospitalized case patients required ICU admission (23% versus 0%; 0.257) and prolonged hospital stay (>7 days) than controls (62% versus 38%%; 0.387).

Conclusions: Our findings deserve confirmation with a larger study population and call attention to the potential for increased morbidity with cHR ESBL-EC infections, which underscores the need to screen for cHR phenotype in patients with repeated growth of ESBL-EC, particularly from systemic sites and patients that have had extensive carbapenem exposure.