Clinical StudyMolecular epidemiology and risk factors for colistin- or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients during a 7-year period
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.
References (32)
Epidemiology of infections caused by polymyxin-resistant pathogens
Int J Antimicrob Agents
(2016)- et al.
Carbapenem-resistant Klebsiella pneumoniae infections in a Greek intensive care unit: molecular characterisation and treatment challenges
J Glob Antimicrob Resist
(2015) - et al.
Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study
Lancet Infect Dis
(2016) - et al.
Bloodstream infections caused by Acinetobacter species with reduced susceptibility to tigecycline: clinical features and risk factors
Int J Infect Dis
(2017) - et al.
Prevalence of colistin resistance in clinical isolates of Enterobacteriaceae: a four-year cross-sectional study
J Infect
(2017) - et al.
Impact of the colistin resistance gene mcr-1 on bacterial fitness
Int J Antimicrob Agents
(2018) - et al.
Colistin and Polymyxin B susceptibility testing for Carbapenem-resistant and mcr-positive Enterobacteriaceae: comparison of Sensititre, MicroScan, Vitek 2, and Etest with broth microdilution
J Clin Microbiol
(2017) - et al.
A simple phenotypic method for screening of MCR-1-mediated colistin resistance
Clin Microbiol Infect
(2018) Breakpoint tables for interpretation of MICs and zone diameters. Version 7.1. 2017
- et al.
Previous bloodstream infections due to other pathogens as predictors of carbapenem-resistant Klebsiella pneumoniae bacteraemia in colonized patients: results from a retrospective multicentre study
Eur J Clin Microbiol Infect Dis
(2017)
Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study
Clin Microbiol Infect
An update of the evolving epidemic of blaKPC-2-carrying Klebsiella pneumoniae in Greece (2009-10)
J Antimicrob Chemother
Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit
Antimicrob Agents Chemother
Genomic insights into Colistin resistant Klebsiella pneumoniae from a Tunisian teaching hospital
Antimicrob Agents Chemother
Risk Factors, Outcomes, and mechanisms of Tigecycline-nonsusceptible Klebsiella pneumoniae bacteremia
Antimicrob Agents Chemother
Nebulised colistin for ventilator-associated pneumonia prevention
Eur Respir J
Cited by (16)
Risk factors for polymyxin-resistant carbapenemase-producing Enterobacteriaceae in critically ill patients: An epidemiological and clinical study
2020, International Journal of Antimicrobial AgentsCitation Excerpt :The overall mortality rate of patients infected with polymyxin-resistant strains was significantly higher than that reported in previous studies [4,11,13,27]. On the other hand, 30-day mortality was lower than identified in previous studies [27,28]. Although the acquisition of a polymyxin-resistant strain plays an important role in the high mortality rates, this does not constitute the only risk factor responsible for the poor outcomes observed, considering that the patients displayed several unfavourable clinical conditions [22,28].
Risk factors associated with colistin resistance in carbapenemase-producing Enterobacterales: a multicenter study from a low-income country
2023, Annals of Clinical Microbiology and AntimicrobialsRisk Factors and Outcomes for Isolation with Polymyxin B-Resistant Enterobacterales from 2018–2022: A Case-Control Study
2023, Infection and Drug ResistancePopulation pharmacokinetics of tigecycline in critically ill patients
2023, Frontiers in PharmacologyRisk Factors for Colistin-Resistant Carbapenem-Resistant Klebsiella pneumoniae in the Postacute Care Setting
2022, Open Forum Infectious Diseases
- 1
Present address: Department of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland.