Multidrug resistance in clinical isolates of Stenotrophomonas maltophilia: roles of integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation
Introduction
Stenotrophomonas maltophilia, a non-fermentative Gram-negative bacillus, is one of the multiresistant opportunistic nosocomial pathogens especially affecting immunocompromised patients and is being isolated worldwide with increasing frequency [1], [2], [3], [4]. Clinical isolates of S. maltophilia are often highly resistant to most of the currently used antimicrobial agents, including carbapenems, and therapy of S. maltophilia infection presents a significant challenge both for clinicians and microbiologists [2], [3], [4]. A variety of antimicrobial resistance determinants have been reported in S. maltophilia, including tripartite efflux pumps (SmeDEF and SmeABC), integrons and phosphoglucomutase (SpgM) [1], [5], [6], [7]. A role in multidrug resistance has been demonstrated for SmeDEF, and other efflux pumps are also known to be involved in resistance but only in some S. maltophilia isolates [8], [9]. Integrons comprise an integrase-encoding gene that allows for site-specific insertion of resistance gene cassettes between two highly conserved adjacent nucleotide sequences [3′ conserved segment (3′CS) and 5′ conserved segment (5′CS)]. Integrons are located on transposons or plasmids that facilitate the rapid spread of integrons to other strains and bacterial species [10], [11], [12]. SpgM, a homologue of AlgC in Pseudomonas aeruginosa associated with lipopolysaccharide (LPS) and alginate biosynthesis, was shown to play a role in virulence and antibiotic resistance of S. maltophilia[7]. Melanin-like pigment and biofilm formation were generally implicated as common causes of antimicrobial resistance [13], [14], [15].
In the present study, we assessed the roles of integrons, efflux pumps, SpgM, melanin and biofilm on multidrug resistance among clinical isolates of S. maltophilia.
Section snippets
Bacterial isolates
Forty clinical multidrug-resistant (MDR) [i.e. resistant to five or more of the six categories of drugs tested, including cephalosporins and β-lactams plus β-lactamase inhibitors, carbapenems, monobactams, aminoglycosides, quinolones and trimethoprim/sulfamethoxazole (SXT)] and 30 non-MDR (i.e. resistant to four or less of the six categories of drugs tested) S. maltophilia isolates were collected at National Taiwan University Hospital (Taipei, Taiwan) during 2002–2003. These isolates were
Bacterial isolates and antimicrobial susceptibility
The RAPD patterns of the 70 isolates were not identical, indicating the diversity of the isolates (i.e. not clonally related). The results of susceptibility testing (Table 1) showed that most of the S. maltophilia isolates were resistant to MER (90%), ATM (89%), GEN (81%), FEP (67%), CIP (64%) and CAZ (61%). Among the agents tested, MDR and non-MDR isolates exhibited minor differences in resistance to MER, ATM and GEN (98% vs. 80%, 98% vs.77% and 90% vs. 70%, respectively). TIM and SXT (79% and
Discussion
Both combined specific resistance genes and multidrug resistance determinants have been described as conferring multidrug resistance in other Gram-negative bacteria [22], [23], [24], [25]. It is expected that such mechanisms are likely to be present in S. maltophilia. In this study, we assessed the contribution of integrons, efflux pumps, SpgM, and melanin and biofilm formation to multidrug resistance of S. maltophilia. A partial correlation was found between the mechanisms studied and
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