Clinical Study
Molecular epidemiology and risk factors for colistin- or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients during a 7-year period

https://doi.org/10.1016/j.diagmicrobio.2018.06.001Get rights and content

Highlights

  • Colistin resistance among bacteraemic K. pneumoniae isolates was 46.4%.

  • Tigecycline resistance among bacteraemic K. pneumoniae isolates was 29.5%.

  • Most isolates were blaKPC positive. No isolate carried mcr-1 gene.

  • Colistin or tigecycline administration predisposed to bacteraemia by such isolates.

  • Mortality wasn't influenced by either colistin or tigecycline resistance.

Abstract

A matched 1:2 case–control study was conducted among critically ill patients in order to identify the risk factors of colistin or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae (ColR-Kp, TigR-Kp) bacteraemia. MIC to colistin and tigecycline were determined by Etest. From 224 bacteraemic patients, 46.4% and 29.5% were resistant to colistin and tigecycline, respectively. PCR revealed that 199 isolates carried the blaKPC gene. PCR revealed that no isolate carried the mcr-1 gene. Risk factors for ColR-Kp bacteraemia as compared to patients with bacteraemia by a colistin-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration and tracheostomy, while TigR-Kp bacteraemia as compared to either patients with bacteraemia by tigecycline-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration, number of comorbidities and prior bacteraemia by a Gram-negative pathogen. Administration of colistin and tigecycline predisposed to development of bacteraemia by either ColR-Kp or TigR-Kp.

Introduction

During the last 2 decades, carbapenemase-producing Gram-negative bacilli have disseminated worldwide (Tzouvelekis et al., 2012). Actually, such isolates are endemic in Greek hospitals and have spread also outside Intensive Care Units (ICUs), to Internal Medicine and Surgical ones (Spyropoulou et al., 2016). Different types of carbapenemase genes have been identified thus far. The most common one in Europe is Klebsiella pneumoniae carbapenemase (KPC), belonging to class A, Verona imipenemase (VIM) and New Delhi metallo-beta-lactamase (NDM), also known as metallo-betalactamases, and oxacillinase-48 (OXA-48) belonging to class D (Queenan and Bush, 2007, Spyropoulou et al., 2016).

The worldwide spread of carbapenemase-producing Gram-negative bacilli has led to increased usage of last resort antibiotics such as colistin and tigecycline, which, together with gentamicin and fosfomycin compose the limited armamentum against such pathogens (Papadimitriou-Olivgeris et al., 2017a, Tzouvelekis et al., 2012). Increased use of these antibiotics is not without disadvantages, since emergence of resistance has been observed (Giacobbe et al., 2015, Nigo et al., 2013, Spyropoulou et al., 2016). Different types of genes have been implicated to tigecycline resistance among K. pneumoniae, including efflux pump genes (acrA, acrB, oqxA and oqxB) or pump regulators (acrR, rarA and ramA) (Giamarellou, 2016, Osei Sekyere et al., 2016). Colistin resistance is mainly conferred by chromosomal mediated mechanisms, while, the only plasmid-mediated colistin resistance is due to mcr (mobilized colistin resistance) gene (Giamarellou, 2016, Liu et al., 2016).

The aim of the present study was to identify risk factors for bloodstream infection by colistin-resistant or tigecycline-resistant carbapenemase-producing K. pneumoniae (ColR-Kp, TigR-Kp) among critically ill patients.

Section snippets

Study design

This study is a 1:2 case–control one that included patients hospitalized in the ICU of the University General Hospital of Patras, Greece, during a 7-year period (2010–16). It was divided into two parts in order to identify risk factors for development of ColR-Kp and TigR-Kp bacteraemia. Patients with at least one positive blood culture for carbapenemase-producing K. pneumoniae were included in the study. The study was carried out under the Hospital Surveillance Programme for infections by

Results

Out of 2414 hospitalized ICU patients during the study period, 224 developed carbapenemase-producing K. pneumoniae BSI resulting to an incidence of 9.4 infections per 1000 patients-days. All isolates were resistant to carbapenems, 132 (58.9%) to gentamicin, 104 (46.4%) to colistin and 66 (29.5%) to tigecycline. MIC distribution of carbapenemase-producing K. pneumoniae to colistin and tigecycline are shown in Fig. 1, Fig. 2, respectively.

In the first part of the study, 104 patients with ColR-Kp

Discussion

In the present study a high percentage of carbapenemase-producing K. pneumoniae bacteraemias resistant to either colistin (46.4%) or tigecycline (29.5%) was observed. In a previous study, active surveillance of ICU patients with rectal cultures revealed that 24.4% were colonized by colistin-resistant KPC-producing K. pneumoniae and 17.9% by tigecycline-resistant (Papadimitriou-Olivgeris et al., 2014). This high colonization rate may explain the incidence of ColR-Kp and TigR-Kp observed in the

Conclusion

In conclusion, colistin and tigecycline resistance rates among carbapenemase-producing K. pneumoniae were high during a 7-year period. No isolate carried the mcr-1 gene. PFGE type B was associated with higher resistance rates to colistin as compared to other types. Administration of colistin and tigecycline predisposed to development of BSI by either ColR-Kp or TigR-Kp, even though a high percentage of patients that developed such infections did not receive aforementioned antibiotics. Previous

Abbreviations

    BSI

    Bloodstream infection

    CI

    confidence interval

    ColR-Kp

    colistin-resistant carbapenemase-producing K. pneumoniae

    ColS-Kp

    colistin-susceptible carbapenemase-producing K. pneumoniae

    ICU

    intensive care unit

    KPC

    Klebsiella pneumoniae carbapenemase

    NDM

    New Delhi metallo-beta-lactamase

    OR

    0dds ratio

    OXA-48

    oxacillinase-48

    PFGE

    Pulsed-field gel electrophoresis

    VIM

    Verona imipenemase

    TigR-Kp

    tigecycline-resistant carbapenemase-producing K. pneumoniae

    TigS-Kp

    tigecycline-susceptible carbapenemase-producing K. pneumoniae

Acknowledgements

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or.

not-for-profit sectors.

Declarations of interest: none.

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