Elsevier

Journal of Infection

Volume 58, Issue 4, April 2009, Pages 299-307
Journal of Infection

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

https://doi.org/10.1016/j.jinf.2009.02.002Get rights and content

Summary

Objectives

To identify risk factors for mortality in patients suffering from hematological malignancies with concurrent bacteremia caused by Escherichia coli. Particular attention was focused on defining the impact of extended-spectrum-β-lactamase (ESBL) production and fluoroquinolone resistance by the bacterial isolates on mortality.

Materials and methods

A retrospective eight-year cohort study design was employed. The outcome measured was death within 30 days of the first positive blood culture. Survivor and non-survivor subgroups were compared to identify predictors of mortality.

Results

A total of 62 episodes of bacteremia caused by E. coli were analyzed. The overall incidences of ESBL production and fluoroquinolone resistance were 41.9% and 62.9%, respectively. The overall 30-day mortality rate was 20.9% (13/62). In a multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (OR = 14.96, 95% CI 1.95–114.51; P = 0.009), infection caused by ESBL-producing isolates (OR = 8.84, 95% CI 1.48–52.91; P = 0.01), and prolonged neutropenia (OR = 8.10, 95% CI 1.29–50.57; P = 0.02).

Conclusions

Sound knowledge of the local distribution of pathogens and their susceptibility patterns and prompt initiation of effective antimicrobial treatment are essential in patients suffering from hematological malignancies with BSIs caused by E. coli.

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.

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