Clinical Studies
Bacteraemia due to AmpC β-lactamase-producing Escherichia coli in hospitalized cancer patients: risk factors, antibiotic therapy, and outcomes

https://doi.org/10.1016/j.diagmicrobio.2017.04.006Get rights and content

Highlights

  • Prevalence of AmpC-EC was high in hospitalized cancer patients.

  • Cephalosporins, carbapenems exposure and invasive procedures are risk factors for AmpC-EC.

  • TTP of AmpC-EC bacteraemia tended to be shorter than that of non-AmpC-EC.

Abstract

AmpC β-lactamase-producing Escherichia coli (AmpC-EC) is one of the main antimicrobial resistant pathogens in patients with cancer. A cohort study was performed to evaluate the risk factors, antibiotic therapy, and outcomes of AmpC-EC bacteraemia in hospitalized cancer patients from September 2012 through December 2015. Two hundred forty-eight cases of E. coli bacteraemia were documented in cancer patients, 51 (20.6%) were caused by AmpC-EC and 197 (79.4%) were caused with non-AmpC-EC. Prior exposure to cephalosporins (OR 2.786; 95% CI: 1.094–7.091; P = 0.032), carbapenems (OR 2.296; 95% CI: 1.054–5.004; P = 0.036), and invasive procedures (OR 4.237; 95% CI: 1.731–10.37; P = 0.002) were identified as independent risk factors for AmpC-EC. The time to positivity (TTP) of patients with AmpC-EC bacteraemia tended to be significantly shorter than that of non-AmpC-EC (8.33 ± 2.18 h versus 9.48 ± 3.82 h; P = 0.006), and had a higher 30-day mortality rate in AmpC-EC compared with non-AmpC-EC (25.5% versus 12.2%; P = 0.018). Metastasis (OR = 2.778, 95% CI: 1.078–7.162; P = 0.034), the presence of septic shock (OR = 4.983, 95% CI: 1.761–14.10; P = 0.002), and organ failure (OR = 24.51 95% CI: 9.884–60.81; P < 0.001) were independently associated with the overall mortality. The mortality rate showed a gradual increase when appropriate antibiotic therapy (AAT) was delayed more than 48 h as determined by the trend test (P < 0.001). In conclusion, this study showed that prevalence of AmpC-EC was high in hospitalized cancer patients of our area. Thus, it is necessary to apply appropriate therapeutic approaches and improve outcomes based on the analysis of risk factors for the acquisition of AmpC-EC.

Introduction

The gram-negative bacillus Escherichia coli is one of the most common causes of bacteraemia in patients with cancer (Ha et al., 2011). Recently, acquired AmpC β-lactamase-producing Escherichia coli (AmpC-EC) has emerged as an important pathogen, which is markedly associated with community-onset and hospital-acquired infections worldwide (Lee et al., 2015, Matsumura et al., 2013). Especially plasmid-mediated AmpC-EC has frequently arisen through the transfer of the inducible AmpC β-lactamase gene from chromosome to plasmids. This often results in hydrolyzing all β-lactam antibiotics except cefepime and carbapenems, and conferring resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactam inhibitor combinations (broad multidrug resistance), which has become a major problem in health care settings (Harris, 2015). Cancer patients with immunodeficiency are especially particularly vulnerable to infection by AmpC-producing pathogens, due to the fact that most cancer patients undergo treatments involving invasive surgery, chemotherapy, radiotherapy, immunosuppressive agents, or anticancer drugs during their hospital stay. To the best of our knowledge, information on the characteristics of AmpC-EC, particularly clinic associated data is fairly limited (Lee et al., 2015, Pascual et al., 2015). Therefore, the aim of this study was to assess risk factors, antibiotic therapy, and outcomes of AmpC-EC bacteraemia in hospitalized cancer patients.

Section snippets

Setting and study design

This retrospective study was conducted at the Tianjin Medical University Cancer Institute and Hospital, a 2400 bed tertiary care cancer center in China (http://www.tmucih.org/). The electronic medical record database was twice-reviewed by Dr. Ding Li and Dr. Shan Zheng to accurately identify patients who were diagnosed with cancer and who also had an episode of E. coli bacteraemia between September 2012 and December 2015. Only the first infection episode of each patient was included in the

Clinical characteristics and risk factors for AmpC-EC in cancer patients

During the study period, 325 cases of Escherichia coli bacteraemia in hospitalized cancer patients were identified, 77 patients with ESBL-producing isolates were excluded and 248 were enrolled. The bacteraemia of 197 patients was caused by non-AmpC-EC and 51 were caused by AmpC-EC. AmpC-EC was mainly identified from pancreatic cancer (21.6%), colorectal cancer (15.7%), gastric carcinoma (13.7%), hepatic carcinoma (11.7%), and gynecological cancer patients (13.7%). The mean age of the study

Discussion

The prevalence of AmpC-EC isolates that gain resistance to broad-spectrum cephalosporins has been increasing in recent years (Jacoby, 2009, Liu and Liu, 2016). A limited selection of antimicrobial agents can be used to treat infections caused by these organisms. The present study showed that 51 (20.5%) AmpC-EC infections were isolated in our area (Fig. S2), which was a higher prevalence than Asian and Euro-American countries (Adler et al., 2008, Alvarez et al., 2004, Coudron et al., 2000b, Ding

Funding

This work was supported by the National Natural Science Found of China (No.30700829, No.81373318] the Specialized Research Fund for Doctoral Program of Higher Education of China (No.20130031120037), and the Natural Science Found of Tianjin (No. 16JCYBJC23900). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests

No conflicts of interest.

Ethical Approval

Not required.

Acknowledgement

Thanks to Dr. Edward C. Mignot, Shandong University, for linguistic advice.

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