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Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants.

ABSTRACT: BACKGROUND: Predicting antibiotic resistance before it emerges at clinical settings constitutes a novel approach for preventing and fighting resistance of bacterial pathogens. To analyse the possibility that novel plasmid-encoded quinolone resistance determinants (Qnr) can emerge and disseminate among bacterial pathogens, we searched the presence of those elements in nearly 1000 bacterial genomes and metagenomes. RESULTS: We have found a number of novel potential qnr genes in the chromosomes of aquatic bacteria and in metagenomes from marine organisms. Functional studies of the Stenotrophomonas maltophilia Smqnr gene show that plasmid-encoded SmQnr confers quinolone resistance upon its expression in a heterologous host. CONCLUSION: Altogether, the data presented in our work support the notion that predictive studies on antibiotic resistance are feasible, using currently available information on bacterial genomes and with the aid of bioinformatic and functional tools. Our results confirm that aquatic bacteria can be the origin of plasmid-encoded Qnr, and highlight the potential role of S. maltophilia as a source of novel Qnr determinants.

SUBMITTER: Sanchez MB

PROVIDER: S-EPMC2556341 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants.

Sánchez María B MB Hernández Alvaro A Rodríguez-Martínez José M JM Martínez-Martínez Luis L Martínez José L JL

BMC microbiology 20080916

<h4>Background</h4>Predicting antibiotic resistance before it emerges at clinical settings constitutes a novel approach for preventing and fighting resistance of bacterial pathogens. To analyse the possibility that novel plasmid-encoded quinolone resistance determinants (Qnr) can emerge and disseminate among bacterial pathogens, we searched the presence of those elements in nearly 1000 bacterial genomes and metagenomes.<h4>Results</h4>We have found a number of novel potential qnr genes in the ch ...[more]

PMID: 18793450

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Project description:BackgroundStenotrophomonas maltophilia is an important nosocomial pathogen. This pathogen has intrinsic or acquired resistance to a number of antibiotics classes. Furthermore, Stenotrophomonas infections have been associated with high mortality, mainly in immunocompromised patients. Accordingly, we conducted a retrospective cohort study on the clinical data, microbiological characteristics, and outcomes of patients with S. maltophilia (SM) bacteremia.MethodsA retrospective cohort study was conducted at two tertiary care referral hospitals in Seoul, South Korea. Data were collected between January 2006 and December 2015 from electric medical records. Our analysis aimed to identify the risk factors associated with crude mortality, as well as the predictive factors of quinolone-resistant strains in SM bacteremia patients.ResultsA total of 126 bacteremia patients were enrolled in the study. The mortality rate was 65.1%. On multivariable analysis, hypoalbuminemia (odds ratio [OR], 5.090; 95% confidence interval [CI], 1.321-19.621; P = 0.018), hematologic malignancy (OR, 35.567; 95% CI, 2.517-502.515; P = 0.008) and quinolone-resistant strains (OR, 7.785; 95% CI, 1.278-47.432; P = 0.026) were independent risk factors for mortality. Alternatively, usage of an empirical regimen with quinolone (OR, 0.172; 95% CI, 0.034-0.875; P = 0.034) was an independent protective factor for mortality. The multivariable analysis of predictive factors revealed that high Charlson comorbidity index (OR, 1.190; 95% CI, 1.040-1.361; P = 0.011) and indwelling of a central venous catheter (CVC) (OR, 3.303; 95% CI, 1.194-9.139; P = 0.021) were independent predisposing factors associated with quinolone-resistant strains in SM bacteremia patients.ConclusionsOur findings suggest that a high Charlson comorbidity score and indwelling of a CVC were significantly independent predictors of quinolone-resistant strains in SM bacteremia patients. Therefore, we need to carefully consider the antibiotic use in SM bacteremia patients with these predictive factors.

Project description: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.

Dataset Information

Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants.

Publications

Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants.

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