title: Characterization of trimethoprim-sulfamethoxazole resistance genes and their relatedness to class 1 integron and insertion sequence common region in gram-negative bacilli.
abstract: Trimethoprim-sulfamethoxazole (TMP-SMX) has been used for the treatment of urinary tract infections, but increasing resistance to TMP-SMX has been reported. In this study, we analyzed TMP-SMX resistance genes and their relatedness with integrons and insertion sequence common regions (ISCRs) in uropathogenic gram-negative bacilli. Consecutive nonduplicate TMP-SMX nonsusceptible clinical isolates of E. coli, K. pneumoniae, Acinetobacter spp., and P. aeruginosa were collected from urine. The minimal inhibitory concentration was determined by Etest. TMP-SMX resistance genes (sul and dfr), integrons, and ISCRs were analyzed by PCR and sequencing. A total of 45 E. coli (37.8%), 15 K. pneumoniae (18.5%), 12 Acinetobacter spp. (70.6%), and 9 Pseudomonas aeruginosa (30.0%) isolates were found to be resistant to TMP-SMX. Their MICs were all over 640. In E. coli and K. pneumoniae, sul1 and dfr genes were highly prevalent in relation with integron1. The sul3 gene was detected in E. coli. However, in P. aeruginosa and Acinetobacter spp., only sul1 was prevalent in relation with class 1 integron; however, dfr was not detected and sul2 was less prevalent than in Enterobacteriaceae. ISCR1 and/or ISCR2 were detected in E. coli, K. pneumoniae, and Acinetobacter spp. but the relatedness with TMP-SMX resistance genes was not prominent. ISCR14 was detected in six isolates of E. coli. In conclusion, resistance mechanisms for TMP-SMX were different between Enterobacteriaceae and glucose non-fermenting gram-negative bacilli. Class 1 integron was widely disseminated in uropathogenic gram-negative baciili, so the adoption of prudent use of antimicrobial agents and the establishment of a surveillance system are needed.
authors.affiliation: College of Medicine, Department of Laboratory Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Shin
authors.forename: Jinsook
authors.initials: J
authors.lastname: Lim
authors.forename: Semi
authors.initials: S
authors.lastname: Kim
authors.forename: Jimyung
authors.initials: J
authors.lastname: Kim
authors.forename: Gye Cheol
authors.initials: GC
authors.lastname: Kwon
authors.forename: Sun Hoe
authors.initials: SH
authors.lastname: Koo
mesh_terms: D000150:Acinetobacter / Q000235:genetics / Q000302:isolation & purification; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D032023:Integrons; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D014296:Trimethoprim Resistance / Q000235:genetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*; D014556:Urine / Q000382:microbiology
chemical_list: D004251:DNA Transposable Elements; D015662:Trimethoprim, Sulfamethoxazole Drug Combination