Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge

ABSTRACT

Introduction: Stenotrophomonas maltophilia is a prototype of bacteria intrinsically resistant to antibiotics. The reduced susceptibility of this microorganism to antimicrobials mainly relies on the presence in its chromosome of genes encoding efflux pumps and antibiotic inactivating enzymes. Consequently, the therapeutic options for treating S. maltophilia infections are limited.

Areas covered: Known mechanisms of intrinsic, acquired and phenotypic resistance to antibiotics of S. maltophilia and the consequences of such resistance for treating S. maltophilia infections are discussed. Acquisition of some genes, mainly those involved in co-trimoxazole resistance, contributes to acquired resistance. Mutation, mainly in the regulators of chromosomally-encoded antibiotic resistance genes, is a major cause for S. maltophilia acquisition of resistance. The expression of some of these genes is triggered by specific signals or stressors, which can lead to transient phenotypic resistance.

Expert opinion: Treatment of S. maltophilia infections is difficult because this organism presents low susceptibility to antibiotics. Besides, it can acquire resistance to antimicrobials currently in use. Particularly problematic is the selection of mutants overexpressing efflux pumps since they present a multidrug resistance phenotype. The use of novel antimicrobials alone or in combination, together with the development of efflux pumps’ inhibitors may help in fighting S. maltophilia infections.

KEYWORDS:

• Stenotrophomonas maltophilia
• multidrug resistance
• beta-lactamase
• transient resistance
• intrinsic resistance

Article highlights

• Stenotrophomonas maltophilia is a prototype of antibiotic-resistant Gram-negative bacterium.

• The presence in the S. maltophilia genome of genes encoding multidrug efflux pumps and antibiotic inactivating enzymes is an important reason for the low susceptibility to antibiotics of this bacterial species.

• While the acquisition of resistance genes is a relevant mechanism for S. maltophilia antibiotic resistance, particularly in the case of co-trimoxazole, genetic mutations are a major cause of the acquisition of resistance by this opportunistic pathogen.

• The overexpression of multidrug efflux pumps, either as a consequence of mutations or because their induction by effectors/growing conditions, reduces simultaneously the susceptibility to a variety of antibiotics commonly in use in clinical practice.

• Quinolones and co-trimoxazole select, independently, mutants overexpressing either SmeDEF or SmeVWX efflux pumps. These efflux systems also confer resistance to tigecycline. Consequently, the selection of a mutant by one of these antibiotics will confer cross-resistance to all of them.

• Co-trimoxazole stands as the main antimicrobial of choice for treating S. maltophilia infections. However, the increasing prevalence of co-trimoxazole-resistant isolates highlights the need of finding new therapeutic approaches.

• Different drug combinations and recent antibiotics, like minocycline, have been proposed as useful alternatives for treating infections by co-trimoxazole-resistant S. maltophilia isolates.

• Given the relevant role of efflux pumps in S. maltophilia antibiotic resistance, and in occasions in virulence, the development of inhibitors of these resistance elements may help in developing more efficient approaches for fighting S. maltophilia infections.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

T. Gil-Gil is the recipient of a FPI fellowship from MINECO. J L Martinez has been supported by grants from the Instituto de Salud Carlos III (Spanish Network for Research on Infectious Diseases [RD16/0016/0011]), from the Spanish Ministry of Economy, Industry and Competitivity [BIO2017-83128-R] and from the Autonomous Community of Madrid [B2017/BMD-3691]. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.