Ann Lab Med.  2015 Mar;35(2):246-249. 10.3343/alm.2015.35.2.246.

The sul1 Gene in Stenotrophomonas maltophilia With High-Level Resistance to Trimethoprim/Sulfamethoxazole

• Chung HS
• Kim K
• Hong SS
• Hong SG
• Lee K
• Chong Y

• KMID: 2363187
• DOI: http://doi.org/10.3343/alm.2015.35.2.246

Abstract

Emerging resistance to trimethoprim/sulfamethoxazole (SXT) poses a serious threat to the treatment of Stenotrophomonas maltophilia infections. We determined the prevalence and molecular characteristics of acquired SXT resistance in recent clinical S. maltophilia isolates obtained from Korea. A total of 252 clinical isolates of S. maltophilia were collected from 10 university hospitals in Korea between 2009 and 2010. Antimicrobial susceptibility was determined by using the CLSI agar dilution method. The sul1, sul2, and sul3 genes, integrons, insertion sequence common region (ISCR) elements, and dfrA genes were detected using PCR. The presence of the sul1 gene and integrons was confirmed through sequence analysis. Among the 32 SXT-resistant isolates, sul1 was detected in 23 isolates (72%), all of which demonstrated high-level resistance (> or =64 mg/L) to SXT. The sul1 gene (varying in size and structure) was linked to class 1 integrons in 15 of the 23 isolates (65%) harboring this gene. None of the SXT-susceptible isolates or the SXT-resistant isolates with a minimum inhibitory concentration of 4 and 8 mg/L were positive for sul1. Moreover, the sul2, sul3, and dfrA genes or the ISCR elements were not detected. The sul1 gene may play an important role in the high-level SXT resistance observed in S. maltophilia.

Keyword

Stenotrophomonas maltophilia; Trimethoprim/sulfamethoxazole; sul; Class 1 integron

MeSH Terms

Anti-Bacterial Agents/pharmacology
Bacterial Proteins/*genetics
Drug Resistance, Bacterial/genetics
Gram-Negative Bacterial Infections/microbiology/pathology
Humans
Integrons/*genetics
Microbial Sensitivity Tests
Stenotrophomonas maltophilia/*drug effects/genetics/isolation & purification
Trimethoprim, Sulfamethoxazole Drug Combination/*pharmacology
Anti-Bacterial Agents
Bacterial Proteins
Trimethoprim, Sulfamethoxazole Drug Combination

Reference

1. Looney WJ, Narita M, Mühlemann K. Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis. 2009; 9:312–323. PMID: 19393961.

2. Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev. 2012; 25:2–41. PMID: 22232370.

3. Farrell DJ, Sader HS, Jones RN. Antimicrobial susceptibilities of a worldwide collection of Stenotrophomonas maltophilia isolates tested against tigecycline and agents commonly used for S. maltophilia infections. Antimicrob Agents Chemother. 2010; 54:2735–2737. PMID: 20368399.

4. Tan CK, Liaw SJ, Yu CJ, Teng LJ, Hsueh PR. Extensively drug-resistant Stenotrophomonas maltophilia in a tertiary care hospital in Taiwan: microbiologic characteristics, clinical features, and outcomes. Diagn Microbiol Infect Dis. 2008; 60:205–210. PMID: 17950557.

5. Al-Jasser AM. Stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: an increasing problem. Ann Clin Microbiol Antimicrob. 2006; 5:23. PMID: 16978420.

6. Barbolla R, Catalano M, Orman BE, Famiglietti A, Vay C, Smayevsky J, et al. Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia isolates. Antimicrob Agents Chemother. 2004; 48:666–669. PMID: 14742234.

7. Toleman MA, Bennett PM, Bennett DM, Jones RN, Walsh TR. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis. 2007; 13:559–565. PMID: 17553270.

8. Hu LF, Chang X, Ye Y, Wang ZX, Shao YB, Shi W, et al. Stenotrophomonas maltophilia resistance to trimethoprim/sulfamethoxazole mediated by acquisition of sul and dfrA genes in a plasmid-mediated class 1 integron. Int J Antimicrob Agents. 2011; 37:230–234. PMID: 21296557.

9. Chang LL, Lin HH, Chang CY, Lu PL. Increased incidence of class 1 integrons in trimethoprim/sulfamethoxazole-resistant clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2007; 59:1038–1039. PMID: 17329265.

10. Song JH, Sung JY, Kwon KC, Park JW, Cho HH, Shin SY, et al. Analysis of acquired resistance genes in Stenotrophomonas maltophilia. Korean J Lab Med. 2010; 30:295–300. PMID: 20603591.

11. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing.Twenty-first informational supplement, M100-S21. Wanye, PA: Clinical and Laboratory Standards Institute;2011.

12. Perreten V. A new sulfonamide resistance gene (sul3) in Escherichia coli is widespread in the pig population of Switzerland. Antimicrob Agents Chemother. 2003; 47:1169–1172. PMID: 12604565.

13. Bae IK, Lee YN, Lee WG, Lee SH, Jeong SH. Novel complex class 1 integron bearing an ISCR1 element in an Escherichia coli isolate carrying the bla_CTX-M-14 gene. Antimicrob Agents Chemother. 2007; 51:3017–3019. PMID: 17517851.

14. Seputiene V, Povilonis J, Ruzauskas M, Pavilonis A, Suziedéliené E. Prevalence of trimethoprim resistance genes in Escherichia coli isolates of human and animal origin in Lithuania. J Med Microbiol. 2010; 59:315–322. PMID: 20007760.

15. Chung HS, Hong SG, Kim YR, Shin KS, Whang DH, Ahn JY, et al. Antimicrobial susceptibility of Stenotrophomonas maltophilia isolates from Korea, and the activity of antimicrobial combinations against the isolates. J Korean Med Sci. 2013; 28:62–66. PMID: 23341713.

16. Baquero F. Low-level antibacterial resistance: a gateway to clinical resistance. Drug Resist Updat. 2001; 4:93–105. PMID: 11512526.