Carbapenem exposure ups risk of Enterobacterales infections

Prior exposure to carbapenems is a strong risk factor for healthcare-associated infections (HAIs) of carbapenem-nonsusceptible Enterobacterales (CnSE), according to a recent Singapore study.

“Appropriate management of deep-seated Enterobacterales infections and reducing exposure to carbapenems may reduce risk of CnSE-HAIs in Singapore. Efforts to improve antimicrobial therapy in CnSE-HAI patients may improve patient outcomes,” the researchers said.

This multicentre, parallel, matched case-control study included 80 patients with CnSE-HAI and 80 comparators with carbapenem-sensitive Enterobacterales (CSE) infections. Susceptibility was determined according to response to meropenem or imipenem.

The primary outcome was all-cause 30-day mortality, while secondary ones included time to discharge and in-hospital mortality. A parallel group of 240 noninfected controls was also included, and clinical endpoints were compared across groups.

CnSEs commonly caused intra-abdominal infections (28.8 percent), respiratory infections (23.8 percent), and skin and soft tissue infections (18.8 percent). Sixty-eight CnSE isolates were available for genotypic and phenotypic analysis, most of which (66.2 percent) were found to produce carbapenemase. [Front Cell Infect Microbiol 2022;doi:10.3389/fcimb.2022.719421]

Compared with noninfected controls, CnSE-HAI patients had a significantly longer duration of stay in intensive care (adjusted odds ratio [OR], 1.25, 95 percent confidence interval [CI], 1.05–1.47) and were significantly more likely to have had drainage devices in the past (adjusted OR, 2.19, 95 percent CI, 1.29–3.70).

Likewise, prior exposure to antipseudomonal beta-lactam/beta-lactamase inhibitors (adjusted OR, 5.92, 95 percent CI, 1.87–18.7) and to carbapenems (adjusted OR, 17.09, 95 percent CI, 3.06–95.4) significantly increased the risk of CnSE-HAIs. Of note, prior exposure to carbapenems did not exert a similarly significant effect on CSE-HAI patients vs controls.

The researchers reported no significant impact of CnSE-HAIs. The rates of all-cause 30-day mortality were comparable between patients with vs without nonsusceptible infections (26.3 percent vs 20.0 percent, respectively; adjusted OR, 0.92, 95 percent CI, 0.37–2.28). The same was true for all-cause in-hospital mortality (40.0 percent vs 23.8 percent; adjusted OR, 2.00, 95 percent CI, 0.82–4.86).

However, when focusing on patients who were discharged alive, those who had CnSE-HAIs showed significantly longer time to discharge than comparators who were infected with susceptible agents (29 vs 21 days, respectively; adjusted OR, 0.66, 95 percent CI, 0.44–0.98).

“A key finding in our study is any prior receipt of carbapenems (as opposed to duration of carbapenem use) is significant risk factor for development of CnSE-HAIs,” the researchers said. “This is most likely associated with the selective pressure on the microbial environment upon carbapenem exposure.”

“Our findings suggested that strategies to prevent unnecessary carbapenem exposure such as formulary restrictions and computerized decision support systems may play a more vital role in the prevention of CnSE-HAIs, compared to strategies that reduces the duration of carbapenem prescriptions after exposure has occurred,” they added.