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