Overexpression of SmeGH contributes to the acquired MDR of Stenotrophomonas maltophilia

2019 ◽  
Vol 74 (8) ◽  
pp. 2225-2229 ◽  
Author(s):  
Li-Hua Li ◽  
Man-San Zhang ◽  
Chao-Jung Wu ◽  
Yi-Tsung Lin ◽  
Tsuey-Ching Yang
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Real Time Quantitative Pcr ◽  
Resistant Mutants ◽  
High Level

Abstract Background Stenotrophomonas maltophilia displays high-level resistance to various antibiotics. Fluoroquinolone is among the few treatment options for S. maltophilia infection. Overexpression of SmeDEF, SmeVWX and SmQnr are the main mechanisms responsible for fluoroquinolone resistance in S. maltophilia. Objectives To reveal the unidentified fluoroquinolone resistance mechanisms in S. maltophilia. Methods Fluoroquinolone-resistant spontaneous mutants were selected by spreading KJΔDEFΔ5, a SmeDEF- and SmeVWX-null double mutant, on ciprofloxacin- or levofloxacin-containing medium. Antibiotic susceptibility was assessed by the agar dilution method. Outer membrane protein profiles of fluoroquinolone-resistant mutants were assayed by SDS-PAGE and significant protein was characterized by LC-MS/MS. The expression of tolCsm, smeH, smeK, smeN, smeP, smeZ and smQnr was investigated by real-time quantitative PCR. The contribution of SmeGH overexpression to antibiotic resistance was verified by ΔsmeH mutant construction and smeGH complementation assay. Results Most fluoroquinolone-resistant mutants displayed MDR. The TolCsm protein and smeH transcript were concomitantly overexpressed in some MDR mutants. smeH deletion increased the susceptibility of the MDR mutants to fluoroquinolone, macrolide, chloramphenicol and tetracycline, and the resistance compromise was partially reversed by complementation with a plasmid containing smeGH. SmeGH overexpression was found in some fluoroquinolone-resistant clinical S. maltophilia isolates whose SmeDEF, SmeVWX and SmQnr proteins were not or were lowly expressed. Conclusions Overexpression of SmeGH contributes to the acquired resistance of S. maltophilia to fluoroquinolone, macrolide, chloramphenicol and tetracycline.

scholarly journals Doripenem versus Pseudomonas aeruginosa In Vitro: Activity against Characterized Isolates, Mutants, and Transconjugants and Resistance Selection Potential

2004 ◽  
Vol 48 (8) ◽  
pp. 3086-3092 ◽  
Author(s):  
Shazad Mushtaq ◽  
Yigong Ge ◽  
David M. Livermore
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Laboratory ◽  
Acquired Resistance ◽  
Single Step ◽  
Cross Resistance ◽  
National Committee ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Resistant Mutants

ABSTRACT Doripenem is a broad-spectrum parenteral carbapenem under clinical development in Japan and North America. Its activities against (i) Pseudomonas aeruginosa isolates with graded levels of intrinsic efflux-type resistance, (ii) mutants with various combinations of AmpC and OprD expression, (iii) PU21 transconjugants with class A and D β-lactamases, and (iv) P. aeruginosa isolates with metallo-β-lactamases were tested by the agar dilution method of the National Committee for Clinical Laboratory Standards. Selection of resistant P. aeruginosa mutants was investigated in single- and multistep procedures. Doripenem MICs for isolates without acquired resistance mostly were 0.12 to 0.5 μg/ml, whereas meropenem MICs were 0.25 to 0.5 μg/ml and imipenem MICs were 1 to 2 μg/ml. The MICs of doripenem, meropenem, ertapenem, and noncarbapenems for isolates with increased efflux-type resistance were elevated, whereas the MICs of imipenem were less affected. The MICs of doripenem were increased by the loss of OprD but not by derepression of AmpC; nevertheless, and as with other carbapenems, the impermeability-determined resistance caused by the loss of OprD corequired AmpC activity and was lost in OprD− mutants also lacking AmpC. The TEM, PSE, PER, and OXA enzymes did not significantly protect P. aeruginosa PU21 against the activity of doripenem, whereas MICs of ≥16 μg/ml were seen for clinical isolates with VIM and IMP metallo-β-lactamases. Resistant mutants seemed to be harder to select with doripenem than with other carbapenems (or noncarbapenems), and the fold increases in the MICs were smaller for the resistant mutants. Single-step doripenem mutants were mostly resistant only to carbapenems and had lost OprD; multistep mutants had broader resistance, implying the presence of additional mechanisms, putatively including up-regulated efflux. Most mutants selected with aminoglycosides and quinolones had little or no cross-resistance to carbapenems, including doripenem.

scholarly journals Prevalence and characterization of extended spectrum beta-lactamase-producing Enterobacter cloacae strains in Algeria

2013 ◽  
Vol 7 (11) ◽  
pp. 804-811 ◽  
Author(s):  
Sabrina Nedjai ◽  
Abouddihaj Barguigua ◽  
Nassima Djahmi ◽  
Loubna Jamali ◽  
Khalid Zerouali ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Extended Spectrum Beta Lactamase ◽  
Agar Dilution ◽  
Synergy Test ◽  
High Level ◽  
Genomic Typing ◽  
Microbiological Data

Introduction: Expended spectrum β-lactamase (ESBL)-producing Enterobacter cloacae is an important nosocomial pathogen. In this study, the prevalence and the molecular epidemiology of ESBL producing E. cloacae strains isolated from various hospitals in Annaba, Algeria were investigated. Methodology: The study involved 63 isolates of E. cloacae obtained during 2009 at the four hospitals in Annaba. The detection of ESBL was performed using the double-disk synergy test and the combined disk test. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method. The presence of blaCTX-M, blaSHV, blaTEM, and blaDHA β-lactamase genes was evaluated by PCR, and genomic typing was determined by pulsed-field gel electrophoresis (PFGE) analysis. The clinical and microbiological data were entered into the EpiI Info database. Results: Thirty isolates (47.6%) had an ESBL phenotype. BlaCTX-M group1 (76%); blaTEM (70%) were the most prevalent, followed by blaDHA (16.6%) and blaSHV (10%). Eighteen strains expressed at least two bla genes. MICs revealed a high level of resistance to cefotaxime, ceftazidime, and cefepime.  PFGE revealed an epidemic clonal dissemination of these isolates. Various risk factors associated with the occurrence of ESBL-producing E. cloacae were detected. Conclusions: A higher frequency of ESBL-producing isolates and a diversity of β-lactamases were detected among ESBL-producing E. cloacae; these resulted from an epidemic clonal dissemination and high transference of ESBL genes between bacteria in hospital settings. Strict measures will be required to control the further spread of these pathogens in hospital settings.

Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 25-25
Author(s):  
Hanna Tukachinsky ◽  
Russell Madison ◽  
Jon Chung ◽  
Lucas Dennis ◽  
Bernard Fendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Acquired Resistance ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Cancer Tissue ◽  
Castration Resistant Prostate Cancer ◽  
High Level ◽  
Tumor Dna

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.

scholarly journals Triclosan resistance in clinical isolates of Acinetobacter baumannii

2009 ◽  
Vol 58 (8) ◽  
pp. 1086-1091 ◽  
Author(s):  
Yagang Chen ◽  
Borui Pi ◽  
Hua Zhou ◽  
Yunsong Yu ◽  
Lanjuan Li
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Active Efflux ◽  
Low Level ◽  
High Level ◽  
Resistance Rates ◽  
Triclosan Resistance

The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l−1, and the MIC90 was 0.5 mg l−1, lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs ≥1 mg l−1) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1–2 mg l−1) or high level (MICs ≥4 mg l−1). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.

scholarly journals Antimicrobial Susceptibilities of Clostridium difficile Isolates from 12 Asia-Pacific Countries in 2014 and 2015

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Tanya Lew ◽  
Papanin Putsathit ◽  
Kyung Mok Sohn ◽  
Yuan Wu ◽  
Kentaro Ouchi ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Asia Pacific ◽  
Fluoroquinolone Resistance ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Content Type ◽  
Amoxicillin Clavulanate ◽  
Ongoing Surveillance ◽  
Susceptibility Profiles ◽  
Hospital Acquired

ABSTRACT Clostridium (Clostridioides) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including C. difficile ribotype (RT) 027 in North America and Europe and RT 017, the most common strain in Asia. Despite being the most common cause of hospital-acquired infection in high-income countries, and frequent misuse of antimicrobials in Asia, little is known about CDI in the Asia-Pacific region. We aimed to determine the antimicrobial susceptibility profiles of a collection of C. difficile isolates from the region. C. difficile isolates (n = 414) from a 2014 study of 13 Asia-Pacific countries were tested for susceptibility to moxifloxacin, amoxicillin-clavulanate, erythromycin, clindamycin, rifaximin, metronidazole, vancomycin, and fidaxomicin according to the Clinical and Laboratory Standards Institute’s agar dilution method. All isolates were susceptible to metronidazole, vancomycin, amoxicillin-clavulanate, and fidaxomicin. Moxifloxacin resistance was detected in all countries except Australia, all RT 369 and QX 239 strains, and 92.7% of RT 018 and 70.6% of RT 017 strains. All C. difficile RT 012, 369, and QX 239 strains were also resistant to erythromycin and clindamycin. Rifaximin resistance was common in RT 017 strains only (63.2%) and was not detected in Australian, Japanese, or Singaporean isolates. In conclusion, antimicrobial susceptibility of C. difficile varied by strain type and by country. Multiresistance was common in emerging RTs 369 and QX 239 and the most common strain in Asia, RT 017. Ongoing surveillance is clearly warranted.

scholarly journals In Vitro Derivation of Fluoroquinolone-Resistant Mutants from Multiple Lineages of Haemophilus influenzae and Identification of Mutations Associated with Fluoroquinolone Resistance

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Hiroyuki Honda ◽  
Toyotaka Sato ◽  
Masaaki Shinagawa ◽  
Yukari Fukushima ◽  
Chie Nakajima ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Clinical Setting ◽  
Pathogenic Bacterium ◽  
Fluoroquinolone Resistance ◽  
Novel Mutations ◽  
Content Type ◽  
Resistant Mutants ◽  
High Level ◽  
Current Risk

ABSTRACT Haemophilus influenzae is a pathogenic bacterium that causes respiratory and otolaryngological infections. The increasing prevalence of β-lactamase–negative high-level ampicillin-resistant H. influenzae (high-BLNAR) is a clinical concern. Fluoroquinolones are alternative agents to β-lactams. However, the emergence and increasing prevalence of fluoroquinolone-resistant H. influenzae have been reported. The current risk of fluoroquinolone resistance in H. influenzae (especially in high-BLNAR) has not yet been evaluated. Here, we examined the development of fluoroquinolone resistance in fluoroquinolone-susceptible clinical H. influenzae isolates in vitro during passaging in the presence of moxifloxacin (from 0.03 to 128 mg/liter). Twenty-nine isolates were examined. Seventeen isolates (58.6%) showed reduced moxifloxacin susceptibility, and 10 of these 17 isolates (34.5% of all isolates) exceeded the Clinical and Laboratory Standards Institute breakpoint for moxifloxacin (MIC of >1 mg/liter) after repeat cultivation on moxifloxacin-containing agar. Seven of these ten isolates were high-BLNAR and represented multiple lineages. We identified 56 novel mutations in 45 genes induced during the development of fluoroquinolone resistance, except the defined quinolone resistance-determining regions (Ser84Leu and Asp88Tyr/Gly/Asn in GyrA and Gly82Asp, Ser84Arg, and Glu88Lys in ParC). Glu153Leu and ΔGlu606 in GyrA, Ser467Tyr and Glu469Asp in GyrB, and ompP2 mutations were novel mutations contributing to fluoroquinolone resistance in H. influenzae. In conclusion, H. influenzae clinical isolates from multiple lineages can acquire fluoroquinolone resistance by multiple novel mutations. The higher rate of derivation of fluoroquinolone-resistant H. influenzae from high-BLNAR than β-lactamase-negative ampicillin-susceptible isolates (P = 0.01) raises the possibility of the emergence and spread of fluoroquinolone-resistant high-BLNAR in the clinical setting.

scholarly journals Mechanisms of Acquired Resistance to Savolitinib, a Selective MET Inhibitor in MET-Amplified Gastric Cancer

2020 ◽  
pp. 222-232 ◽  
Author(s):  
Melanie M. Frigault ◽  
Aleksandra Markovets ◽  
Barrett Nuttall ◽  
Kyoung-Mee Kim ◽  
Se Hoon Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Met Inhibitor ◽  
Tumor Dna ◽  
Generation Sequencing

PURPOSE Some gastric cancers harbor MET gene amplifications that can be targeted by selective MET inhibitors to achieve tumor responses, but resistance eventually develops. Savolitinib, a selective MET inhibitor, is beneficial for treating patients with MET-driven gastric cancer. Understanding the resistance mechanisms is important for optimizing postfailure treatment options. PATIENTS AND METHODS Here, we identified the mechanisms of acquired resistance to savolitinib in 3 patients with gastric cancer and MET-amplified tumors who showed a clinical response and then cancer progression. Longitudinal circulating tumor DNA (ctDNA) is useful for monitoring resistance during treatment and progression when rebiopsy cannot be performed. RESULTS Using a next-generation sequencing 100-gene panel, we identified the target mechanisms of resistance MET D1228V/N/H and Y1230C mutations or high copy number MET gene amplifications that emerge when resistance to savolitinib develops in patients with MET-amplified gastric cancer. CONCLUSION We demonstrated the utility of ctDNA in gastric cancer and confirmed this approach using baseline tumor tissue or rebiopsy.

scholarly journals Relation between Genetic Markers of Drug Resistance and Susceptibility Profile of Clinical Neisseria gonorrhoeae Strains

2008 ◽  
Vol 52 (6) ◽  
pp. 2175-2182 ◽  
Author(s):  
Elena N. Ilina ◽  
Vladimir A. Vereshchagin ◽  
Alexandra D. Borovskaya ◽  
Maja V. Malakhova ◽  
Sergei V. Sidorenko ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Genetic Markers ◽  
Predictive Value ◽  
Tetracycline Resistance ◽  
Resistance Mechanisms ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Predictive Values ◽  
Flight Mass Spectrometry ◽  
Polymorphism Discovery

ABSTRACT The main goal of this work is to clarify the predictive value of known genetic markers of Neisseria gonorrhoeae resistance to penicillin, tetracycline, and fluoroquinolones. The correlation between the presence of certain genetic markers and susceptibility of N. gonorrhoeae isolates to penicillin, tetracycline, and fluoroquinolones has been analyzed by means of statistical methods. Susceptibility testing with penicillin, tetracycline, and fluoroquinolones was performed by the agar dilution method. N. gonorrhoeae genomic DNA was isolated. The presence of bla TEM-1 and tet(M) genes was analyzed by PCR. A novel method of polymorphism discovery based on a minisequencing reaction followed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry was applied for the analysis of chromosomal N. gonorrhoeae genes involved in antimicrobial resistance development. Clinical N. gonorrhoeae isolates (n = 464) were collected. Susceptibility levels to penicillin, tetracycline, and fluoroquinolones were found to be 25.9%, 35.9%, and 54.1%, respectively. Among the 19 N. gonorrhoeae isolates with penicillin MICs of ≥4 μg/ml, the bla TEM-1 gene was detected in 12. The Tet(M) determinant was found in 4 of 12 N. gonorrhoeae isolates with tetracycline MICs of ≥16 μg/ml. The chromosomal genetic markers of penicillin and tetracycline resistance were detected especially in isolates with penicillin MICs of 0.25 to 2.0 μg/ml and tetracycline MICs of 0.5 to 4 μg/ml. Mutations in GyrA and ParC were found in 208 of 211 quinolone-resistant N. gonorrhoeae isolates. This work is the first representative molecular research of the N. gonorrhoeae population in Russia. Information about the prevalence of antibiotic resistance mechanisms and the positive predictive value of certain genetic determinants is given. The positive predictive values of the analyzed genetic markers were found to be different for fluoroquinolones (90.3%), penicillin (91.1%), and tetracycline (81.9%).

scholarly journals Detection of OXA-181/OXA-48 carbapenemase producing Enterobacteriaceae in Bangladesh

2016 ◽  
Vol 9 (2) ◽  
pp. 45-51 ◽  
Author(s):  
Rehana Khatun ◽  
SM Shamsuzzaman
Keyword(s):  
Health Concern ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
College Hospital ◽  
Medical College ◽  
Epidemiological Monitoring ◽  
Diffusion Technique ◽  
Genes Encoding ◽  
High Level ◽  
Phenotypic Tests

Carbapenem resistant Enterobacteriaceae (CRE) is becoming a major public health concern globally. Detection of carbapenem hydrolyzing enzyme carbapenemase in Enterobacteriaceae is important to institute appropriate therapy and to initiate preventive measures. This study was designed to determine the presence of carbapenemase producers among the CRE isolated from patients at Dhaka Medical College Hospital, Bangladesh. Twenty-nine CRE strains detected by disk diffusion technique were included in the study. Minimum inhibitory concentration of imipenem and tigecycline was determined by agar dilution method. Carbapenemase production was phenotypically detected by Modified Hodge test while MBL producers were detected by combined disk and double disk synergy tests. Genes encoding blaNDM-1, blaOXA-181, blaOXA-48, blaKPC, blaCTX-M-15, blaOXA-1-group were identified by polymerase chain reaction (PCR). Out of 29 CRE, nineteen (65.6%) were positive for carbapenemase by any of the three phenotypic tests namely MHT, CD or DD tests. Those 19 isolates were also positive either for blaNDM-1 or blaOXA-181/blaOXA-48 by PCR. Of the 19 PCR positive isolates, the rate of positivity for blaNDM- 1, blaOXA-181/blaOXA-48 and blaNDM-1+ blaOXA-181/blaOXA-48 was 73.7% (14/19), 57.9% (11/19) and 31.6% (6/19) respectively. Both blaOXA-181 and blaOXA-48 co-existed. All the carbapenemase producing organisms harboured blaCTX-M-15 except one C. freundii strain. The rate of resistance to different classes of antibiotics ranged from 63.2% to 100% except colistin and tigecycline. Organisms positive for OXA-181/OXA-48 had a low level of resistance to carbapenem (MIC 1 - 4 ì g/ml) while with NDM-1 had high level resistance to imipenem (MICs 16 - ? 32 ì g/ ml). Out of 19 carbapenemase positive isolates, 12 (63.16%) were extensively drug-resistant (XDR) and were only sensitive to tigecycline and colistin. The result of this study showed the presence of blaOXA-181/ blaOXA-48, blaNDM-1 positive strains in Bangladesh and colistin and tigecycline were the most effective drugs against carbapenemase producing Enterobacteriaceae (CPE). Epidemiological monitoring of carbapenemase producing organisms in Bangladesh is important to prevent their dissemination.Ibrahim Med. Coll. J. 2015; 9(2): 45-51

scholarly journals Clonal transmission and new mechanism of resistance to trimethoprim-sulfamethoxazole in Stenotrophomonas maltophilia strains isolated in a neonatology unit at Antananarivo, Madagascar, deciphered by whole genome sequence analysis

2019 ◽  
Author(s):  
Mamitina Alain Noah Rabenandrasana ◽  
Volasoa Andrianoelina ◽  
Melanie Bonneault ◽  
Perlinot Herindrainy ◽  
Benoit Garin ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Whole Genome Sequence ◽  
Resistant Organism ◽  
Whole Genome ◽  
Single Nucleotide

ABSTRACTStenotrophomonas maltophilia has been recognized as an emerging multidrug resistant organism in hospital settings due to its resistance to a broad range of antimicrobial agents. These include β-lactams and aminoglycosides, afforded by the existence of intrinsic and acquired resistance mechanisms. Trimethoprim/sulfamethoxazole (SXT) is recommended as one of the best treatment choices against S. maltophilia infections; however increasing resistance to SXT has complicated the treatment. From July 2014 to March 2015, individuals and surfaces from a neonatology ward in Antananarivo, Madagascar, were longitudinally followed to assess the transmission of bacteria resistant to antibiotics between neonates, individuals (parents and nurses) and ward environments. Four S. maltophilia strains were successively isolated from a water-tap (N=1), from feces obtained from a newborn (N=1), and nursing staff (N=2). Antimicrobial susceptibility testing and whole genome sequencing were performed on each isolate. Based on coregenome alignment, all strains were identical and belonged to the new sequence type ST-288. They were resistant to trimethoprim-sulfamethoxazole, carbapenems and intermediate to levofloxacin. Each isolate carried the aadB, strA, strB and sul1 genes located in a class I integron but variants of the dfrA gene were absent. We assessed by PROVEAN analysis the single nucleotide mutations found in folA, folC and folM genes and only the mutation in folA (A114T:GCC→ACC) has an effect on the activity of trimethoprim. Our findings demonstrated the prolonged presence of SXT-resistant S. maltophilia in a clinical setting with consecutive transfers from the environment to a newborn and staff based on the isolation dates. We also hypothesized that single nucleotide mutations in folA could be responsible for trimethoprim resistance.

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