Increasing burden of urinary tract infections due to intrinsic colistin-resistant bacteria in hospitals in Marseille, France

https://doi.org/10.1016/j.ijantimicag.2014.10.010Get rights and content

Highlights

  • We investigated whether use of colistin affected the prevalence of infections due to intrinsic colistin-resistant bacteria (CRB) in the university hospitals of Marseille (France).

  • Increasing use of colistin aerosol forms was correlated with the increasing number of infections due to CRB in intensive care units and units of long-term healthcare.

  • We also identified an increasing number of CRB in emergency and short-term healthcare units.

  • Surveillance is warranted to better understand this intriguing epidemiological change.

Abstract

The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a major public health problem, eliciting renewed interest in colistin, an old antibiotic that is now routinely used to treat MDR bacterial infections. Here we investigated whether colistin use has affected the prevalence of infections due to intrinsic colistin-resistant bacteria (CRB) in university hospitals in Marseille (France) over a 5-year period. All data from patients infected by intrinsic CRB were compiled from January 2009 to December 2013. Escherichia coli infections were used for comparison. Colistin consumption data were also collected from pharmacy records from 2008 to 2013. A total of 4847 intrinsic CRB infections, including 3150 Proteus spp., 847 Morganella spp., 704 Serratia spp. and 146 Providencia spp., were collected between 2009 and 2013. During this period, the annual incidence rate of hospital-acquired CRB infections increased from 220 per 1000 patients to 230 per 1000 patients and that of community-acquired CRB infections increased from 100 per 1000 patients to 140 per 1000 patients. In parallel, colistin consumption increased 2.2-fold from 2008 to 2013, mainly because of an increase in the use of colistin aerosol forms (from 50 unitary doses to 2926 unitary doses; P < 10−5) that was significantly correlated with an increase in the number of patients positive for CRB admitted to ICUs and units of long-term care between 2009 and 2013 (r = 0.91; P = 0.03). The global rise in infections due to intrinsic CRB is worrying and surveillance is warranted to better characterise this intriguing epidemiological change.

Introduction

Antimicrobial resistance represents a major public health concern worldwide. Following the appearance in the 1980s of extended-spectrum β-lactamase-producing Gram-negative bacteria, which threaten both hospital settings and the community [1], carbapenems have been considered as the last-resource drugs and have been widely used in healthcare units [2]. However, since the early 2000s, various acquired carbapenemases, primarily Klebsiella pneumoniae carbapenemase (KPC) type [2] or, more recently, the New Delhi metallo-β-lactamase (NDM) [3], have emerged and spread worldwide [4], further limiting therapeutic options. These limits have forced clinicians and researchers to develop new treatment strategies and practices, including the use of alternative treatment options. The polymyxins are cationic cyclic polypeptide antibiotics composed of five chemical compounds (polymyxins A–E) [5], [6]. Polymyxins are bactericidal antibiotics effective against most Gram-negative bacteria except bacteria of the genera Proteus, Providencia, Serratia, Morganella and Burkholderia that are intrinsically resistant [5]. Colistin (polymyxin E) was extensively used between the 1960s and 1980s to treat patients infected by Gram-negative bacteria but was gradually abandoned in the 1980s owing to nephrotoxicity and neurotoxicity [5], [6]. In this context, colistin has recently been reconsidered as a treatment of last resort to treat patients with ventilator-associated pneumonia and bacteraemia due to carbapenemase-producing bacteria, mainly K. pneumoniae, Acinetobacter spp. and Pseudomonas spp. [5], [6], [7]. Unfortunately, the increased use of colistin as a ‘last-line’ therapeutic drug for the treatment of patients infected with these multidrug-resistant (MDR) Gram-negative bacteria has led to the recent emergence of colistin-resistant bacteria (CRB) among these bacterial species [5], [8], [9], [10], [11], [12].

This increasing public health concern led us to investigate whether the use of colistin currently affects the biodiversity of bacterial pathogens isolated from hospitals towards an increase of intrinsic CRB. A 5-year (January 2009 to December 2013) retrospective analysis of data on intrinsic CRB from the four university hospitals of Marseille was performed, using Escherichia coli infections as a control, and these data were correlated with colistin consumption in the four hospitals during the same period.

Section snippets

Study setting

The Assistance Publique–Hôpitaux de Marseille (AP-HM) comprises the four university hospitals (North, South, Conception and Timone Hospitals) of Marseille, which is the second largest city in France (2010 estimated city population, 850 726). Cumulatively, these hospitals include 4000 beds (ca. 1500 beds in Timone Hospital, 900 in the North Hospital, 700 in Conception Hospital and 600 in the South Hospital [13]).

Retrospective analysis of intrinsic colistin-resistant bacteria in the database

To perform this study, a 5-year retrospective Microsoft Excel database (January 2009

Total number of patients infected by intrinsic colistin-resistant strains, genus distribution and global trends

During this 5-year study, 4847 patients in the different units of the university hospitals of Marseille were identified to be infected by at least one CRB. Among the genera of interest, Proteus spp. were the most common pathogens (3150 isolates), followed by Morganella spp. (847 isolates), Serratia spp. (704 isolates) and Providencia spp. (146 isolates) (Table 1). During the same period, 23 436 patients were infected by E. coli (Table 1). The increase in the number of patients infected by CRB

Discussion

To the best of our knowledge, here we present the largest series of human infections due to intrinsic CRB that has been published worldwide. This study allowed us to identify interesting epidemiological changes of intrinsic CRB isolated from the university hospitals of Marseille, with an increasing number of hospital- and community-acquired CRB infections over the study period.

Conclusion

We argue that the extensive use of colistin may lead to the selection of intrinsic CRB and facilitate their spread as nosocomial agents in hospitals. This phenomenon is well known in the context of cystic fibrosis where colistin use by aerosols occasionally has led to the selection of intrinsic CRB, including Inquilinus limosus, Brevundimonas diminuta, Ochrobactrum anthropi, Pandoraea spp., Chryseobacterium indologenes and Burkholderia spp. [5], [24], [25]. However, other factors could be

Acknowledgments

The authors thank American Journal of Experts for English corrections.

Funding: This work was partly funded by the Centre national de la recherche scientifique and the IHU Méditerranée Infection (France).

Competing interests: None declared.

Ethical approval: Not required.

References (30)

  • S. Biswas et al.

    Colistin: an update on the antibiotic of the 21st century

    Expert Rev Anti Infect Ther

    (2012)
  • M.E. Falagas et al.

    Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections

    Clin Infect Dis

    (2005)
  • A. Stein et al.

    Colistin: an antimicrobial for the 21st century?

    Clin Infect Dis

    (2002)
  • S. Mohanty et al.

    Phenotypic characterization and colistin susceptibilities of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp.

    J Infect Dev Ctries

    (2013)
  • E. Lesho et al.

    Emergence of colistin-resistance in extremely drug-resistant Acinetobacter baumannii containing a novel pmrCAB operon during colistin therapy of wound infections

    J Infect Dis

    (2013)
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