Drug‐resistant organisms are common in fecal surveillance cultures, predict bacteremia and correlate with poorer outcomes in patients undergoing allogeneic stem cell transplants

Abstract

Background:With the increasing incidence of multidrug-resistant (MDR) organisms and high mortality rates associated with these infections, we describe the spectrum of the major drug-resistant pathogens identified in fecal surveillance, and re-visit the use of fecal surveillance in predicting infection with these organisms post-allogeneic stem cell transplant. Methods: Data from allogeneic stem cell transplant recipients with common drugresistant strains of bacteria in fecal surveillance (Escherichia coli, Klebsiella spp., and Enterococcus spp.) were compared with recipients who did not have the same in fecal surveillance cultures. Baseline characteristics and post-transplant outcomes including similar drug resistance in blood cultures, severe sepsis, and 100-day transplantrelated mortality were compared. Multivariate analysis using logistic regression model was used to determine independent predictors of outcome.Results: In 232 transplants, the prevalence of common drug-resistant isolates in fecal surveillance cultures was 57.7% (134 out of 232 patients-with a single isolate in 115 and ≥2 isolates in the remaining 19 patients. A total of 164 drug-resistant isolates were obtained from 134 patients. Of the 164 isolates, 133 (81%) were positive for ESBL screening, 19 (11.5%) for carbapenem-resistant organisms (CRO) screening, 12 (7.3%) for VRE screening. Patients who had common drug-resistant pathogens detected in fecal surveillance have significantly higher subsequent blood culture positivity with drug resistance, as well as higher 100-day mortality. Factors influencing 100-day mortality included patient's age (P = .001), drug resistance positivity in blood (P < .001), drug resistance in fecal surveillance (P = .011), use of an alternate donor (other than fully matched sibling) (P < .001), GVHD grade 3-4 (P < .001), and severe sepsis (P < .001). On multivariate analysis, only use of an alternate donor (0.024), severe sepsis (P < .001), and grade 3-4 GVHD (P < .001) retained significance in predicting 100-day mortality.

Impact of broad‐spectrum antibiotic exposures and multidrug‐resistant gram‐negative bacteremia on hematopoietic cell transplantation outcomes

“…We report a high incidence of severe acute GVHD (45%) in patients with MDR GNB bacteremia, similar to that reported in studies looking at the association of gut colonization by antibiotic‐resistant bacteria 19 . We also report very high mortality rates of 40% in patients with MDR GNB bacteremia, similar to those reported in other studies 8,20 . Several previous studies confirm the association of antibiotics on gut microbiome alterations leading to MDR bacteremia and GVHD and mortality in high‐income countries 2–5 .…”

“…19 We also report very high mortality rates of 40% in patients with MDR GNB bacteremia, similar to those reported in other studies. 8,20 Several previous studies confirm the association of antibiotics on gut microbiome alterations leading to MDR bacteremia and GVHD and mortality in high-income countries. [2][3][4][5] These studies have demonstrated the negative impact of fluoroquinolone prophylaxis and broad-spectrum antibiotics like carbapenems post-HCT.…”

“…The challenge of drug‐resistant organisms is vital to low‐middle income countries such as India, with reports of 57.7% colonization by MDR organisms, 8 68.8% CRE isolates, 7 and a high incidence in the community 15 . Our study had MDR GNB bacteremia documented in 38% of patients with an equal number of patients pre‐ and post‐HCT.…”

“…4,5 The incidence of extended-spectrum β-lactamase (ESBL)-producing gram-negative bacteria and carbapenemase-producing organisms, including carbapenem-resistant Enterobacterales (CRE), varies by geographic region (10%-40%) 6 and is on the rise in Indian HCT centers. 7,8 The treatment of ESBL and AmpC ß-lactamase producing organisms involves carbapenems, and CRE treatment consists of novel ß-lactam/ß-lactamase inhibitors or polymyxin/ colistin. 9 One reason for the increased occurrence of drug-resistant bacteremia is the higher use of antibiotics in the pre-HCT period.…”

“…These studies show that the use of antibiotics reduces gut microbial diversity and increases the risk of gram‐negative bacteremia, impacting HCT outcomes like acute graft versus host disease (GVHD) and mortality 4,5 . The incidence of extended‐spectrum β‐lactamase (ESBL)–producing gram‐negative bacteria and carbapenemase‐producing organisms, including carbapenem‐resistant Enterobacterales (CRE), varies by geographic region (10%–40%) 6 and is on the rise in Indian HCT centers 7,8 . The treatment of ESBL and AmpC ß‐lactamase producing organisms involves carbapenems, and CRE treatment consists of novel ß‐lactam/ß‐lactamase inhibitors or polymyxin/ colistin 9 .…”