Incidence and clinical impact of extended-spectrum-β-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies
Introduction
Bloodstream infections (BSIs) are among the most common complications observed in patients with lymphomas, leukemias, multiple myeloma, and febrile neutropenia, with a prevalence that ranges from 11% to 38%.1, 2, 3, 4 In 2001, Collin et al. reported BSI occurrence within 5 days of bone marrow infusion in approximately 35% of patients who underwent bone marrow transplantation.5Enterobacteriaceae, in particular Escherichia coli, have been reported, at different frequencies, as the most prevalent gram-negative organisms that cause bacteremia in cancer patients.5, 6, 7, 8, 9, 10, 11
Increasing rates of drug resistance among gram-negative bacteria are reported in several hospitals, including cancer centers.5, 10, 11 In particular, antibiotic-resistant mutant strains that produce extended-spectrum-β-lactamases (ESBLs) have emerged among the Enterobacteriaceae, predominantly Klebsiella pneumoniae and E. coli.12, 13, 14, 15 ESBLs are plasmid-mediated β-lactamases that confer resistance to oxyimino cephalosporins and monobactams.16 These enzymes are globally widespread, but the prevalence and phenotypic characteristics among clinical isolates may vary among geographical areas.17, 18
The routine introduction of antibiotic prophylaxis in high-risk neutropenic patients, especially with fluoroquinolones, significantly reduced infection-related mortality.19 Several studies have reported increasing rates of fluoroquinolone resistance, particularly in Enterobacteriaceae, worldwide throughout the last two decades, and many have identified previous fluoroquinolone exposure as the most significant risk factor.20, 21, 22, 23, 24, 25 Although a recent meta-analysis demonstrated that there is no significant relationship between fluoroquinolone-based prophylaxis and colonization and/or infections by quinolone-resistant bacteria in neutropenic patients,26 the role of fluoroquinolone prophylaxis in the increase in infections caused by fluoroquinolone-resistant gram-negative bacteria and their clinical impact remain unclear.
The aims of the present study, conducted in an Italian university hospital over an eight-year period, were: to evaluate the percentage of ESBL production and resistance to fluoroquinolone among E. coli strains causing BSI in patients with hematological malignancies; to identify the primary characteristics of patients according to ESBL production and/or fluoroquinolone resistance of bacterial isolates; and to evaluate the impact of ESBL production and fluoroquinolone resistance on 30-day mortality.
Section snippets
Setting
The Catholic University Hospital is a 1700-bed university hospital located in Rome, Italy, and admits approximately 60,000 patients per year. The hospital has medical, surgical, and neonatal wards, as well as intensive care and post-surgical units. The hematology ward has a total of 30 beds, 8 of which are reserved for patients undergoing hematopoietic stem cell transplantation (HSCT).
Study design and patients
The computerized database maintained by the hospital microbiology laboratory was used to identify episodes of
Results
During the eight-year study period (2000–2007), there were 107 episodes of BSI caused by gram-negative bacteria in patients with hematological malignancies. Of these, 62 (57.9%) were caused by E. coli.
Higher rates of bacteremia were found in patients with acute myeloid leukemia (31/62, 50%) or non-Hodgkin's diseases (14/62, 22.6%), and who had received allogeneic hematopoietic stem cell transplantation (HSCT; 14/62, 22.6%).
The overall percentage of ESBL production among E. coli isolates was
Discussion
The aim of this study was to identify the incidence and clinical predictors of 30-day mortality resulting from BSIs caused by E. coli in patients suffering from hematological malignancies. Particular attention was focused on the possible roles of ESBL production and/or fluoroquinolone resistance.
The development of resistance to antimicrobial agents is of growing concern in the hospitalized patient population as a whole, and is well recognized in febrile neutropenic patients.5, 10, 32 However,
Conflict of interest
The authors have no conflicts of interest.
Acknowledgments
We would like to thank Paul Kretchmer at San Francisco Edit for revising our English text.
References (48)
- et al.
Microbiological findings in febrile neutropenia
Arch Med Res
(2000) - et al.
Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli
J Infect
(2007) - et al.
Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern
Lancet Infect Dis
(2008) - et al.
CDC definitions for nosocomial infections, 1988
Am J Infect Control
(1988) - et al.
Prognostic factors for neutropenic patients in an intensive care unit: respective roles of underlying malignancies and acute organ failures
Eur J Cancer
(1997) - et al.
A one-year prospective study of nosocomial bacteraemia in ICU and non-ICU patients and its impact on patient outcome
J Hosp Infect
(2000) - et al.
Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (North America)
Diagn Microbiol Infect Dis
(2006) Current attitudes for therapy of febrile neutropenia with consideration to cost-effectiveness
Curr Opin Oncol
(1998)Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia
Infection
(2000)Fever in immunocompromised patients
N Engl J Med
(2000)
Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients
Clin Infect Dis
Prospective study of 288 episodes of bacteremia in neutropenic cancer patients in a single institution
Eur J Clin Microbiol Infect Dis
A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies
Br J Haematol
Bacteremia and fungemia in pediatric versus adult cancer patients after chemotherapy: comparison of etiology, risk factors and outcome
J Chemother
Outcomes of nosocomial bloodstream infections in adult neutropenic patients: a prospective cohort and matched case–control study
Infect Control Hosp Epidemiol
Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States
Clin Infect Dis
Infectious complications in patients with hematological malignancies consulted by the infectious diseases team: a retrospective cohort study (1997–2001)
Support Care Cancer
Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment
Antimicrob Agents Chemother
Bloodstream infections caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome
Antimicrob Agents Chemother
Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge
Clin Infect Dis
Prevalence and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae in Europe
Clin Microbiol Infect
Extended-spectrum beta-lactamases in North America, 1987–2006
Clin Microbiol Infect
Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients
Ann Intern Med
The magnitude of the association between fluoroquinolone use and quinolone-resistant Escherichia coli and Klebsiella pneumoniae may be lower than previously reported
Antimicrob Agents Chemother
Cited by (149)
Extended spectrum cephalosporin resistant enterobacteriaceae carriage and infection in patients admitted with newly-diagnosed acute leukemia
2023, American Journal of Infection ControlCitation Excerpt :The most frequent mechanisms of resistance are the production of extended spectrum β-lactamases (ESBL) and/or expression of AmpC cephalosporin resistance genes. Colonization with ESCRE can be a significant clinical problem, as this may predispose high-risk patients to blood stream infections (BSI) with these organisms, which may be more difficult to treat, more costly, and associated with increased morbidity and mortality.1-3 Patients with newly-diagnosed acute leukemia typically undergo a prolonged initial hospitalization for remission induction chemotherapy that is frequently followed by additional inpatient stays for therapy or therapy/disease-related complications.
Microbiology and prevalence of E<inf>2</inf>SKAPE-resistant strains in catheter-related bloodstream infections in patients with cancer
2020, American Journal of Infection ControlProposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients
2020, Brazilian Journal of Infectious DiseasesCitation Excerpt :Consequently, all outcomes, such as breakthrough bacteremia, 7- and 30-day mortality, were worse in the MDR GNR group. These findings have been previously described.1,2,14,28,40 Thus, for an adequate EAT, risk factors for MDR GNR should be identified.