Impact of Rectal Colonization With Highly Drug-Resistant Enterobacteriaceae on Post-Transplant Infections: The Carbapenem-Resistant Enterobacteriaceae Carriage in Solid Organ Transplant (CREST) Study

Abstract

Background. Extended-spectrum beta-lactamase-Enterobacteriaceae (ESBL-E) and CRE infections carry high mortality in solid organ transplant patients (SOT pts). Natural history of rectal colonization (R-COL) and subsequent disease (Dz) by ESBL-E and CRE post-SOT is unclear. Methods. Patients ( pts) who underwent SOT from August 2015 to May 2016 were consented. Peri-rectal swabs were collected each week (wk) until 90 days (d) post-SOT, and cultured using KPC and ESBL CHROMagar plates. Resistance was confirmed by MIC. ESBLs and KPCs were detected by PCR. Pts were followed until 6 months (m) post-SOT. Longitudinal isolates underwent MiSeq whole genome sequencing (WGS). Primary endpoint was ESBL-E or CRE Dz. Results. One hundred forty-seven pts were enrolled: 69 lung (Lu), 51 liver (Li), 17 kidney (K), 6 heart (H), 3 small bowel (SB), and 1 liver-kidney transplant. Median age was 60 years. Fifty-six percent were men; 88% were white. Median time from SOT to first swab was 3 d. Median of 3 swabs/pt were collected. Among 121 pts who completed 90 d screening, 21% (26) were R-COL: 10 CRE (K. pneumoniae [Kp] most common), 16 ESBL-E (E. coli, Kp most common). One pt was R-COL with 2 CRE, and 2 pts with 2-3 ESBL-E. All CRE were KPC +. R-COL rates among Lu, Li and SB pts were 23% (16), 18% (9) and 33% (1), versus 0% among K and H pts. Thirty-one percent (2 CRE, 6 ESBL-E) were detected in the first swab. In other pts, median time from SOT to R-COL was 22 d. Seventy-six percent of pts had persistent R-COL (≥2 swabs +). Among 81 Lu, Li and SB pts who reached 6 m post-SOT, 14% (11) developed Dz or COL (non-R) with ESBL-E or CRE. Nine percent (7) had Dz (urinary, 2; intra-abdominal, 2; bacteremia, empyema, surgical site, 1 each). Twenty-three percent (6 of 26) of R-COL pts developed Dz versus 2% (1 of 55) of non-R-COL (p = 0.004). R-COL was the only significant risk factor for Dz. Dz attack rates among R-COL Li and Lu pts were 33% (3 of 9) and 19% (3 of 16), respectively. Longitudinal KPC-Kp R-COL and Dz isolates from 2 pts, and R-COL isolates from 3 pts without Dz were ST258 clones that were indistinguishable by WGS. Seventeen percent of pts with Dz died; stay was significantly prolonged in survivors (median: 75 d). Conclusion. R-COL with CRE or ESBL-E was common among Lu, Li and SB pts, and a significant risk factor for subsequent Dz. Pts developed Dz due to R-COL isolates. 12% of R-COL pts carried >1 ESBL-E or CRE, suggesting horizontal transfer. Sixty-seven percent of R-COL pts were colonized ≥2 wks post-SOT. WGS revealed cryptic nosocomial acquisition of R-COL ST258 KPC-Kp, which later caused Dz. Rectal screening and infection prevention measures are merited among Lu, Li and SB pts.