Abstract
Stenotrophomonas maltophilia is an emerging nosocomial pathogen with high resistance to most clinically used antimicrobials. Tigecycline is a potential alternative antimicrobial for S. maltophilia infection treatment, but its resistance mechanism in clinical isolates is not fully elucidated. We investigated the antimicrobial susceptibility of 450 S. maltophilia isolated during 2012–2015 from three university hospitals in Beijing, China. These strains exhibited high susceptibility to minocycline (98.44%), sulfamethoxazole/trimethoprim (87.56%), tigecycline (77.78 %), doxycycline (81.33%), levofloxacin (67.56%), and ticarcillin/clavulanate (73.00%). The susceptibility of tigecycline-nonsusceptible strains (TNS) to doxycycline and levofloxacin was much lower than that of tigecycline-susceptible strains (TSS) (25.00% vs. 97.71% for doxycycline, P < 0.001; 17.00% vs. 82.00% for levofloxacin, P < 0.001). We further selected 48 TNS and TSS and compared the detection rate of eight tetracycline-specific genes by PCR and the expression level of six intrinsic multidrug resistance efflux pumps by real-time PCR. Only one tetB and two tetH genes in TNS and three tetH genes in TSS were detected, and the detection rate had no difference. The average expression level of smeD in TNS was higher than that in TSS [20.59 (11.53, 112.54) vs. 2.07 (0.80, 4.96), P < 0.001], while the average expression levels of smeA, smeI, smeO, smeV, and smrA were not significantly different, indicating that smeDEF was the predominant resistance genetic determinant in clinical S. maltophilia. Higher smeD expression was also observed in levofloxacin- and doxycycline-nonsusceptible isolates than in their corresponding susceptible isolates [16.46 (5.83, 102.24) vs. 2.72 (0.80, 6.25) for doxycycline, P < 0.001; 19.69 (8.07, 115.10) vs. 3.01(1.00, 6.03), P < 0.001], indicating that smeDEF was also the resistance genetic determinant to levofloxacin and doxycycline. The consistent resistance profile and common resistance genetic determinant highlight the importance of rational use of tigecycline for preventing the occurrence and spread of multidrug resistance.
Highlights
Stenotrophomonas maltophilia is classified by the World Health Organization as one of the leading multidrug resistant organisms in hospital settings, and an increasing infection rate has been reported in worldwide and nationwide surveillance studies during the past 15 years (Fluit et al, 2001; Brooke, 2012, 2014; Sader et al, 2013; Walkty et al, 2014; Chang et al, 2015)
The susceptibility rate of tigecycline-nonsusceptible strains (TNS) strains to doxycycline and levofloxacin was much lower than that of tigecycline-susceptible strains (TSS) strains (25.00% vs. 97.71% for doxycycline, P < 0.001; 17.00% vs. 82.00% for levofloxacin, P < 0.001)
The tigecycline susceptibility rate in Beijing was lower than that reported in the Taiwan Surveillance of Antimicrobial Resistance Study from 1998 to 2008 and in the countries in the SENTRY Antimicrobial Surveillance Program from 2009 to 2012, but similar to that reported in SENTRY from 2011 to 2014 (Wu et al, 2012; Sader et al, 2014, 2016)
Summary
Stenotrophomonas maltophilia is classified by the World Health Organization as one of the leading multidrug resistant organisms in hospital settings, and an increasing infection rate has been reported in worldwide and nationwide surveillance studies during the past 15 years (Fluit et al, 2001; Brooke, 2012, 2014; Sader et al, 2013; Walkty et al, 2014; Chang et al, 2015). Tigecycline has been reported to retain good in vitro activity against S. maltophilia in worldwide surveillance and multicenter studies, and Wei et al (2016) reported that 80.4% of clinical isolates in China, and 72.7% of SXT-resistant isolates were susceptible to tigecycline, making it a promising alternative antimicrobial for infection treatment (Stein and Babinchak, 2013; Rizek et al, 2015; Wei et al, 2015, 2016). The tigecycline resistance mechanism in clinical isolates is unclear, and epidemiological surveys focused on frequency and genetic determinants of tigecycline resistance are needed in clinical isolates of S. maltophilia. These epidemiologic data could help to guide the appropriate use of tigecycline and preventing the occurrence and spread of multidrug resistance
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