Colonization With Levofloxacin-resistant Extended-spectrum β-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients

Satlin, Michael J.; Chavda, Kalyan D.; Baker, Thomas; Chen, Liang; Shashkina, Elena; Soave, Rosemary; Small, Catherine B.; Jacobs, Samantha; Shore, Tsiporah B.; Besien, Koen van; Westblade, Lars F.; Schuetz, Audrey N.; Fowler, Vance G.; Jenkins, Stephen G.; Walsh, Thomas J.; Kreiswirth, Barry N.

doi:10.1093/cid/ciy363

Cited by 44 publications

(69 citation statements)

References 28 publications

(24 reference statements)

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“…During allogeneic stem cell transplant, the diversity and stability of the intestinal flora are disrupted, resulting in specific bacterial domination and subsequent bacteremia . A recent study describing transplant patients on fluoroquinolone prophylaxis, 30% of patients colonized with ESBL developed a subsequent bacteremia with ESBL, suggesting a role for fecal surveillance pre‐transplant and role for empirical antibiotic therapy in the immunosuppressed patient. Given the high percentage of documented infections being due to gram‐negative bacteria, rapid deterioration with high mortality with MDR strains, and in the an absence of culture positivity to guide antibiotic practice, we undertook this study to analyze the impact of fecal surveillance cultures on subsequent blood culture positivity in the immunocompromised host, in an attempt to guide antibiotic policy and antibiotic stewardship with an emphasis on regional microbial prevalence.…”

Section: Discussioncontrasting

confidence: 45%

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

Korula

Perumalla

Devasia

et al. 2020

Transplant Infectious Dis

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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.

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Section: Discussioncontrasting

confidence: 45%

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

Korula

Perumalla

Devasia

et al. 2020

Transplant Infectious Dis

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“…Cross-resistance between FQs in VGS infections can also occur; in one study of 48 neutropenic patients undergoing HSCT, levofloxacin-resistant VGS recovered from the oropharynx increased from 11% to 59% for all VGS isolates after only 8 days of gatifloxacin or moxifloxacin prophylaxis [79]. FQ-resistant Gram-negative infections have also been described [80,81]. In a single center study of patients undergoing HSCT, only 25% of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae recovered from perianal swabs were susceptible to levofloxacin prior to HSCT; after HSCT, 32% of patients colonized with ESBL Enterobacteriaceae developed subsequent bacteremia with the same ESBL Enterobacteriaceae, all of which were levofloxacin-resistant [80].…”

Section: Prevention Of Bacterial Infections During Neutropeniamentioning

confidence: 99%

“…FQ-resistant Gram-negative infections have also been described [80,81]. In a single center study of patients undergoing HSCT, only 25% of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae recovered from perianal swabs were susceptible to levofloxacin prior to HSCT; after HSCT, 32% of patients colonized with ESBL Enterobacteriaceae developed subsequent bacteremia with the same ESBL Enterobacteriaceae, all of which were levofloxacin-resistant [80]. In another recent prospective multinational study of Gram-negative rod (GNR) bacteremia in patients undergoing autologous or allogeneic HSCT (auto-, allo-HSCT), half of all GNRs were FQ-resistant, and patients who were on FQs at time of bacteremia after allo-HSCT had 7-fold higher odds of breakthrough, FQ-resistant GNR infection [82].…”

Section: Prevention Of Bacterial Infections During Neutropeniamentioning

confidence: 99%

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

Santos

Rhee

Czapka

et al. 2020

JCM

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Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key "safety net" in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible "safety net" for these immunocompromised hosts.

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“…R esistant Enterobacteriaceae, most notably those that are multidrug resistant (MRE; acquired nonsusceptibility to Ն1 agent in Ն3 antimicrobial categories) (1), are a major threat for hospitalized patients. Infections by Enterobacteriaceae such as Klebsiella pneumoniae frequently begin by colonization of the intestinal tract (2), from where they can disseminate to the bloodstream and endanger patients' lives (3). Intestinal colonization by multidrug-resistant pathogens can promote their dissemination to other patients through fecal contamination of the environment (4).…”

mentioning

confidence: 99%

High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams

Djukovic

González-Barberá

Sanz

et al. 2020

Antimicrob Agents Chemother

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Multidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here, we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as Enterobacteriaceae species that acquired nonsusceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e., meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam (P < 0.001) but not with nonsusceptible strains. We report previously unobserved inter- and intraindividual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut-colonizing pathogens for future clinical studies and in clinical decision-making.

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Colonization With Levofloxacin-resistant Extended-spectrum β-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients

Cited by 44 publications

References 28 publications

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

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

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams

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