Increase in the Prevalence of Resistance Determinants to Trimethoprim/Sulfamethoxazole in Clinical Stenotrophomonas maltophilia Isolates in China.
OBJECTIVE
This study was carried to reveal the genetic mechanisms of trimethoprim/sulfamethoxazole (SXT) resistance.


METHODS
Among 300 clinical Stenotrophomonas maltophilia isolates from China, resistance determinants such as sul and dfrA genes, integrons and transposase were examined using PCR, DNA sequencing and thermal asymmetric interlaced PCR (TAIL-PCR). Data were analyzed using SPSS 20.0.


RESULTS
Of the 300 isolates, 116 (38.7%) were resistant to SXT. An alarming trend of increased resistance to SXT were found over the 10-year period. The positive rates of sul and class 1 integrase (intI1) increased gradually with the development of SXT resistance over the 10-year period. Multiple logistic regression analyses indicated that the genes of qacEΔ1-sul1 (81% vs 46.2%, p = 0.000), sul2 (50.9% vs 9.8%, p = 0.000), intI1 (83.6% vs 65.8%, p = 0.000), dfrA12 (25% vs 3.3%, p = 0.000), dfrA17 (15.5% vs 3.8%, p = 0.000) and dfrA27 (4.3% vs 1.6%, p = 0.01) were more prevalent in SXT-resistant isolates than SXT-susceptible isolates except dfrA1(p = 0.83) and dfrA5(p = 0.18). Sequencing data revealed 12 types of resistance gene cassettes (aar-3-dfrA27, dfrA12-aadA2, dfrA17-aadA5, cmlA1, aacA4, aadA5, arr-3-aacA4, aadA1, aadB-aadA4, aacA4-catB8-aadA1, aadB-aac(6')-II-blaCARB-8 and aac(6')-II-blaCARB-8) located in the class 1 integron in 163 isolates (87% SXT-resistant vs 33.7% SXT-susceptible isolates, p = 0.000). A novel finding was the aar-3-dfrA27 (KC748137) gene cassette. The gene of sul2 linked to transposase in 50 SXT- resistant and 7 SXT- susceptible isolates was detected by TAIL-PCR.


CONCLUSIONS
The findings demonstrated a higher prevalence of sul, dfrA, intI1 and resistance gene cassettes in class 1 integron in SXT-resistant clinical S. maltophilia isolates in China. The sul1 and dfrA genes located in integrons and the sul2 linked to transposase may imply wide and rapid dissemination of resistance gene in bacteria.
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.|Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, China.
Li-Fen
LF
Hu
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Guo-Sheng
GS
Chen
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Qin-Xiang
QX
Kong
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Li-Ping
LP
Gao
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Xi
X
Chen
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.|Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, China.
Ying
Y
Ye
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.|Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, China.|Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Jia-Bin
JB
Li
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002681:China / Q000453:epidemiology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D032023:Integrons; D016015:Logistic Models; D008826:Microbial Sensitivity Tests; D015995:Prevalence; D017422:Sequence Analysis, DNA; D020615:Stenotrophomonas maltophilia / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019895:Transposases / Q000235:genetics / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D019426:Integrases; D019895:Transposases