Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 5;73(7):1257-1265.
doi: 10.1093/cid/ciab404.

Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients

Michael J Satlin  1   2 , Liang Chen  3   4 , Claire Douglass  1   5 , Michael Hovan  1   6 , Emily Davidson  1   7 , Rosemary Soave  1 , Marisa La Spina  8 , Alexandra Gomez-Arteaga  9 , Koen van Besien  9 , Sebastian Mayer  9 , Adrienne Phillips  9 , Jing-Mei Hsu  9 , Rianna Malherbe  10 , Catherine B Small  1 , Stephen G Jenkins  1   2 , Lars F Westblade  1   2 , Barry N Kreiswirth  3   4 , Thomas J Walsh  1
Affiliations

Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients

Michael J Satlin et al. Clin Infect Dis. .

Abstract

Background: Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach.

Methods: We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing.

Results: Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum β-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P < .001). Of the 17 gram-negative BSIs in FQRE-colonized patients, 15 (88%) were caused by FQRE isolates that were genetically identical to the colonizing strain.

Conclusions: Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.

Keywords: fluoroquinolone resistance; hematopoietic cell transplant recipient; levofloxacin prophylaxis; neutropenia.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flow diagram of patients included in the study, prevalence of fluoroquinolone-resistant Enterobacterales (FQRE) colonization, and risk of gram-negative bloodstream infection in patients colonized and not colonized with FQRE. Abbreviation: NYPH/WCMC, New York–Presbyterian Hospital/Weill Cornell Medical Center.
Figure 2.
Figure 2.
Proportion of patients who developed fluoroquinolone-resistant Enterobacterales (FQRE) bloodstream infection (BSI), gram-negative BSI, gram-positive BSI, and any BSI, stratified by pretransplant FQRE colonization status. P values represent comparisons between FQRE-colonized and noncolonized patients.
Figure 3.
Figure 3.
Comparison of organisms, multilocus sequence types, single-nucleotide polymorphism differences, fluoroquinolone resistance determinants, and β-lactamase genes among stool and bloodstream fluoroquinolone-resistant Enterobacterales (FQRE) isolates among the 16 FQRE-colonized patients who developed FQRE bloodstream infection. Abbreviations: E. coli, Escherichia coli; GI, gastrointestinal; K. pneumo, Klebsiella pneumoniae; NA, not applicable; SNP, single-nucleotide polymorphism; ST, sequence type.
See this image and copyright information in PMC

Comment in

References

    1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. ; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52:427–31. - PubMed
    1. Taplitz RA, Kennedy EB, Bow EJ, et al. . Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol 2018; 36:3043–54. - PubMed
    1. Klastersky J, Ameye L, Maertens J, et al. . Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents 2007; 30(Suppl 1):S51–9. - PubMed
    1. Gudiol C, Bodro M, Simonetti A, et al. . Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect 2013; 19:474–9. - PubMed
    1. Girmenia C, Bertaina A, Piciocchi A, et al. ; Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI) . Incidence, risk factors and outcomes of pre-engraftment gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an Italian prospective multicenter survey. Clin Infect Dis 2017; 65:1884–96. - PubMed

Publication types

MeSH terms