Clinical challenges treating Stenotrophomonas maltophilia infections: an update

Abstract

Stenotrophomonas maltophilia is a non-fermenting, Gram-negative bacillus that has emerged as an opportunistic nosocomial pathogen. Its intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Clinical management is further complicated by its molecular heterogeneity that is reflected in the uneven distribution of antibiotic resistance and virulence determinants among different strains, the shortcomings of available antimicrobial susceptibility tests and the lack of standardized breakpoints for the handful of antibiotics with in vitro activity against this microorganism. Herein, we provide an update on the most recent literature concerning these issues, emphasizing the impact they have on clinical management of S. maltophilia infections.

Figure 1.

Timeline showing the total number of papers listed in PubMed per year about E. coli, P. aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and S. maltophilia. Search terms used were: “Escherichia AND coli”, “Pseudomonas AND aeruginosa”, “Klebsiella AND pneumoniae”, “Acinetobacter OR baumannii” and “Stenotrophomonas OR maltophilia”.

Figure 2.

Schematic representation of the coordinated regulation of L1 and L2 expression by the ampNG-ampDI-nagZ-ampR regulatory circuit. Enlargement and growth of the peptidoglycan layer is achieved by a concerted action of both synthetic enzymes, like the PBP, and lytic enzymes, like lytic transglycosylases in the periplasmic space, and NagZ and AmpD in the cytoplasm. All these enzymes work together to process peptidoglycan fragments back into the sugar precursor of peptidoglycan synthesis. The AmpR transcription regulator is located upstream of bla_L2, and their promoters overlap. Precursors of peptidoglycan synthesis act as co-effector molecules that upon binding to the effector-binding domain of the AmpR, prevent expression of β-lactamases, while allowing transcription of the repressor. However, when the rate of catalysis is higher than the synthesis, for instance due to the action of β-lactams, 1,6-anhydro-muropeptide accumulates and acts as a co-inducer molecule, which upon binding to the repressor causes the complex to relocate upstream of the bla genes, allowing the expression of these genes.