Multidrug-resistant (MDR) Enterobacterales colonized in the gastrointestinal (GI) tract was found to be an independent risk factor for infections in patients following liver, lung, or small bowel transplant, according to study results published in Clinical Infectious Diseases. Although the incidence of mortality was low, recurrent infections due to GI-colonizing strains were common, occurring as late as almost 4 years after the original infection.

In this prospective, single-center study conducted at the University of Pittsburgh in Pennsylvania, researchers aimed to determine the long-term outcomes of MDR Enterobacterales, defined as carbapenem-resistant Enterobacterales (CRE) and third-generation cephalosporin-resistant Enterobacterales (3GCREB) colonization and infections among solid organ transplant recipients.

The primary outcomes were colonization and infection caused by GI strains at 100 days and 6 months post-transplant, respectively. Secondary outcomes were mortality and recurrent infections post-transplant. Analyses were conducted using perirectal swabs that were collected and cultured on a weekly basis up to 100 days post-transplant.


Continue Reading

Of the 162 patients (median age, 57 years; 59% men; 89% White) included in the study, lung, liver, and small bowel transplantation occurred in 88, 70, and 4 patients, respectively. Within 100 days post-transplant, 25% (40/162) of patients were colonized with MDR Enterobacterales and 11 were colonized with more than 1 MDR Enterobacterales. Klebsiella pneumoniae was the most common MDR Enterobacterales with K pneumoniae carbapenemases, and CTX-M was the leading cause of CRE and 3GCREB, respectively.

Within 6 months post-transplant, 35% (14/40) of patients who had GI colonization developed infections vs only 2% (3/145) of those without colonization (P <.0001). Colonization and infection rates did not differ between liver and lung recipients nor between CRE and 3GCREB. However, infection rates were higher following CRE than 3GCREB colonization (53% vs 21%; P =.049).

In multivariate analysis, independent risk factors for MDR Enterobacterales and 3GCREB infections were GI colonization (P <.0001 and P =.008, respectively) and high body mass index (P =.004 for both). For CRE infections, independent risk factors were GI colonization (P <.0001) and surgical re-exploration after transplant (P =.016).

With a median follow-up of 4.3 years post-transplant, mortality did not significantly differ between patients with and without infections (29% vs 23%; P =.56). Although mortality was low, recurrent infections occurred in 44% of survivors, with 43% of recurrences occurring between 285 days and 3.9 years after the initial infection.

Whole genome sequencing phylogenetic analyses “revealed that infections were caused by GI-colonizing strains, and suggested unrecognized transmission of novel clonal group-258 sublineage CR-K pneumoniae and horizontal transfer of resistance genes,” noted the researchers.

Limitations included this being a single-center study, not screening patients before transplantation, using perirectal swabs instead of polymerase chain reaction testing, and a lack of patients undergoing kidney transplant.

“High MDR-[Enterobacterales] colonization and infection rates, links between colonization and invasive infection, and evidence of genetic relatedness between colonizing and infection-causing strains provide rationale for routine surveillance of liver, lung, and small bowel recipients,” concluded the researchers.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Nguyen MH, Shields RK, Chen L, et al. Molecular epidemiology, natural history and long-term outcomes of multi-drug resistant Enterobacterales colonization and infections among solid organ transplant recipients. Clin Infect Dis. Published online May 10, 2021. doi:10.1093/cid/ciab427