Post-surgical mediastinitis due to carbapenem-resistant Enterobacteriaceae: Clinical, epidemiological and survival characteristics

https://doi.org/10.1016/j.ijantimicag.2016.02.015Get rights and content

Highlights

  • Carbapenem-resistant Enterobacteriaceae (CRE) can be a significant cause of post-surgical mediastinitis.

  • CRE mediastinitis is associated with high mortality, particularly in the presence of polymyxin resistance.

Abstract

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P = 0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.

Introduction

Post-sternotomy mediastinitis is a life-threatening infection that occurs in a small proportion (0.5–2.7%) of patients undergoing cardiothoracic surgery [1], [2], [3], [4], resulting in longer hospital stay, higher medical costs, additional surgical procedures and, finally, increased mortality. Recent studies showed that 14–32% of patients who developed post-surgical mediastinitis died, indicative of a higher risk of morbidity and mortality compared with patients who do not experience infectious complications [1], [2], [3], [4], [5]. Although the main micro-organisms implicated are Gram-positive bacteria (e.g. staphylococci), Gram-negative pathogens can also be a relevant cause of mediastinitis at some centres [5]. Importantly, compared with other micro-organisms, mediastinitis associated with Gram-negative pathogens was shown to have higher rates of in-hospital death [5].

Invasive infections associated with carbapenem-resistant Enterobacteriaceae (CRE) pose a serious challenge to clinicians. Treatment with drugs such as polymyxins (polymyxin B or colistin), carbapenems or their combinations are basically supported by observational studies [6], [7], [8]. The emergence of resistance to polymyxins further complicates the situation [9], [10], [11]. Whilst there is an increasing body of evidence on the clinical characteristics of patients with more common CRE infections (e.g. bloodstream infections) [6], [7], we are faced with a lack of clinical information in the case of less frequent but otherwise severe CRE infections such as post-surgical mediastinitis. To the best of our knowledge, this is the first study describing a cohort of patients with post-surgical mediastinitis due to CRE, including patients infected with strains resistant to polymyxins.

Given the lack of evidence described above and the potential occurrence of polymyxin resistance in CRE, this study intended to describe the clinical characteristics of a significant post-sternotomy mediastinitis CRE outbreak population and to compare survival outcomes among polymyxin-resistant and -susceptible isolates.

Section snippets

Study population and setting

This retrospective cohort study was conducted at Instituto Dante Pazzanese de Cardiologia (São Paulo, Brazil) between December 2010 and June 2014. This is a 350-bed hospital specialising in cardiology and cardiovascular surgery that serves as a referral centre for 300 000 patients, 90% of whom are from São Paulo. Patients undergoing surgical procedures at the institution are followed by the institutional teams until the patient recovers or is clinically stable, allowing for external follow-up.

Results

From December 2010 to June 2014, 5933 cardiac surgeries were performed at this single institution. During this period 92 patients (1.6%) were diagnosed with mediastinitis, among which Gram-positive and Gram-negative pathogens were isolated from 45% and 55% of the patients, respectively. Enterobacteriaceae were isolated in 88% of patients infected with Gram-negative pathogens, including 36 patients infected with CRE strains. Three patients were excluded due to insufficient clinical or

Discussion

To the best of our knowledge, this is the first study describing a cohort of patients with post-surgical mediastinitis due to CRE. Several results provided by this investigation have been highlighted here.

In centres with a high volume of cardiothoracic surgery and CRE outbreaks, a significant proportion of post-surgical mediastinitis can be caused by CRE. In this study, approximately one-third of post-surgical mediastinitis were due to CRE strains. Importantly, the rate of mediastinitis

Conclusion

Mediastinitis due to CRE has become an emerging infection in this centre. Antibacterial treatments are usually based on carbapenems, frequently accompanied by polymyxin plus a third agent. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE. Centres with increasing rates of CRE and with a high cardiac surgery volume should be aware of these potentially devastating infections.

Acknowledgements

The authors acknowledge Celia Harumi Hiroshi (secretary) and LEE Laboratory of Epidemiology and Statistics–Instituto Dante Pazzanese de Cardiologia (São Paulo, Brazil).
Funding: This work was funded by a grant [2012/12108-3] from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
Competing interests: MES is or has been a consultant to Achaogen, Astellas, Cempra, Cerexa, Furiex, Nabriva, PRI, Trius and Theravance. All other authors declare no competing interests.
Ethical approval:

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