Frequency and Genetic Determinants of Tigecycline Resistance in Clinically Isolated Stenotrophomonas maltophilia in Beijing, China

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.

Simulated sunlight-induced inactivation of tetracycline resistant bacteria and effects of dissolved organic matter

“…As reported in previous studies, the resistance to tetracycline in gram-negative bacteria (e.g. E. coli used in this study) is usually attributed to three different mechanisms: tetracycline-specific efflux pumps (mainly tetA, tetB, tetC, tetG, tetH ), ribosomal protection proteins (mainly tetM, tetO, tetQ, tetT and tetW ), and enzymatic inactivation of tetracycline ( tetX ) ( Alekshun and Levy, 2007 ;Nolivos et al, 2019 ;Zhao et al, 2018 ). Thus, in this study, efflux by tetracycline-specific pumps is the dominant mechanism for tetracycline resistance as AR E. coli with tetA was used as target ARB.…”

Activity of Potential Alternative Treatment Agents for Stenotrophomonas maltophilia Isolates Nonsusceptible to Levofloxacin and/or Trimethoprim-Sulfamethoxazole

“…The MIC 50 and MIC 90 values for eravacycline, omadacycline, and tigecycline were consistently higher against levofloxacin-NS isolates than against those that were levofloxacin susceptible, irrespective of susceptibility to TMP-SMZ (data not shown). This correlation may be due to expression of the SmeDEF efflux pump, which is known to be associated with both levofloxacin and tigecycline susceptibilities in S. maltophilia (33). Third, we observed improved potency of moxifloxacin over levofloxacin and delafloxacin against all 41 isolates.…”

Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review

“… Acinetobacter baumannii ( MDR ) India 26/15 (57.7) Original research Behera et al, 2009 [ 171 ] Acinetobacter baumannii (imipenem-non-susceptible) Taiwan 114/21 (18) Original research Lee et al, 2009 [ 172 ] Acinetobacter baumannii ( MDR ) Thailand 148/4 (2.7) (resistant or intermediately susceptible) Original research Tiengrim et al, 2006 [ 173 ] Acinetobacter baumannii ( MDR ) Israel 82/54 (66) Original research Navon-Venezia et al, 2007 [ 174 ] Acinetobacter baumannii ( MDR ) Taiwan 134/61 (45.5) Original research Chang et al, 2012 [ 175 ] Colistin-resistant Acinetobacter spp. South Korea 145/14 (9.7) (non-susceptible) Original research Park et al, 2009 [ 176 ] OXA carbapenemase-producing Acinetobacter baumannii South Korea 47/11 (23.4) Original research Kim et al, 2010 [ 177 ] Acinetobacter baumannii (MDR) Turkey 82/21 (25.8) Original research Dizbay et al, 2008 [ 178 ] S. aureus India 127/68 (53.5) Original research Swati Sharma.,2017 [ 179 ] Acinetobacter baumannii Taiwan 393/27 (6.9) Original research Liao CH.,2008[ 180 ] Stenotrophomonas maltophilia China 450/61 (13.56) Original research Jin Zhao.,2018[ …”

“…In other gram-negatives, tigecycline resistance was reported in S. maltophilia from Taiwan and China [ 165 , 166 , 181 ] and in 90% of Pseudomonas aeruginosa isolates from India [ 163 ].…”