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.

scholarly journals Biofilm Compared to Conventional Antimicrobial Susceptibility of Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients

2013 ◽  
Vol 57 (3) ◽  
pp. 1546-1548 ◽  
Author(s):  
Kitty Wu ◽  
Yvonne C. W. Yau ◽  
Larissa Matukas ◽  
Valerie Waters
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Dose ◽  
Content Type

ABSTRACTStenotrophomonas maltophiliais a multidrug-resistant organism increasingly isolated from the lungs of cystic fibrosis (CF) patients. One hundred twenty-fiveS. maltophiliaisolates from 85 CF patients underwent planktonic and biofilm susceptibility testing against 9 different antibiotics, alone and in double antibiotic combinations. WhenS. maltophiliaisolates were grown as a biofilm, 4 of the 10 most effective antibiotic combinations included high-dose levofloxacin and 7 of the 10 combinations included colistin at doses achievable by aerosolization.

scholarly journals Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

2004 ◽  
Vol 48 (1) ◽  
pp. 168-171 ◽  
Author(s):  
Pablo San Gabriel ◽  
Juyan Zhou ◽  
Setareh Tabibi ◽  
Yunhua Chen ◽  
Marco Trauzzi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Susceptibility ◽  
Stenotrophomonas Maltophilia ◽  
Antimicrobial Agents ◽  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Resistant Organism ◽  
High Concentrations ◽  
The Impact

ABSTRACT Stenotrophomonas maltophilia is a newly emerging pathogen being detected with increasing frequency in patients with cystic fibrosis (CF). The impact of this multidrug-resistant organism on lung function is uncertain. The optimal treatment for S. maltophilia in CF patients is unknown. We studied the in vitro activity of ten antimicrobial agents, and conducted synergy studies by using checkerboard dilutions of eight pairs of antimicrobial agents against strains isolated from 673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the CF patients in the United States who harbor S. maltophilia annually. Doxycycline was the most active agent and inhibited 80% of 673 initial patient isolates, while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of colistin proved more active than high concentrations of tobramycin and gentamicin. Serial isolates (n = 151) from individual patients over time (median, 290 days) showed minimal changes in resistance. Synergistic or additive activity was demonstrated by trimethoprim-sulfamethoxazole paired with ticarcillin-clavulanate (65% of strains), ciprofloxacin paired with ticarcillin-clavulanate (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of strains), trimethoprim-sulfamethoxazole paired with piperacillin-tazobactam (55% of strains), and doxycycline paired with ticarcillin-clavulanate (49% of strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to all agents in two or more antimicrobial classes) but 473 (91%) of these were inhibited by at least one antimicrobial combination (median, four; range, one to eight). To determine appropriate treatment for patients with CF, it is important to monitor the prevalence, antimicrobial susceptibility, and clinical impact of S. maltophilia in this patient population.

scholarly journals Molecular Identification and Susceptibility Pattern of ClinicalNocardiaSpecies: Emergence ofNocardia crassostreaeas an Agent of Invasive Nocardiosis

2013 ◽  
Vol 24 (2) ◽  
pp. e33-e38 ◽  
Author(s):  
Saad J Taj-Aldeen ◽  
Anand Deshmukh ◽  
Sanjay Doiphode ◽  
Atqah Abdul Wahab ◽  
Mona Allangawi ◽  
...  
Keyword(s):  
Molecular Identification ◽  
Ribosomal Rna ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
16S Ribosomal Rna ◽  
Resistant Organism ◽  
Human Pathogen ◽  
Resistant Species ◽  
Nocardia Otitidiscaviarum

BACKGROUND:Nocardiaspecies are rare, opportunistic organisms that cause disease in both immunocompetent and immunocompromised individuals.OBJECTIVE: To investigate the clinical presentations of variousNocardiainfections based on the 16S ribosomal RNA gene of the isolate, as well as related risk factors and susceptibility patterns to antimicrobial agentsMETHODS: Thirteen patients with a diagnosis of nocardiosis were included in the present study. SevenNocardiaspecies were identified by 16S ribosomal RNA. Susceptibility testing was performed using six antimicrobial agents.RESULTS: Five patients were immunocompromised, and eight were immunocompetent with predisposing factors including cystic fibrosis, tuberculosis and ophthalmic infections.Nocardiacaused pulmonary infections in eight patients (61.5%), invasive systemic infections in three patients (23%) and local (ophthalmic) infections in two patients (15.4%). In the patients with pulmonary disease, nocardiosis was caused by six species (Nocardia cyriacigeorgica,Nocardia otitidiscaviarum,Nocardia farcinica,Nocardia carnea,Nocardia testaceaandNocardia asiatica). The seventh species identified in the present study wasNocardia crassostreae.DISCUSSION:N crassostreaeis a multidrug-resistant organism that was reported to be an emerging human pathogen causing invasive nocardiosis in a patient with non-Hodgkin’s lymphoma.N farcinicawas isolated from blood in a patient with breast cancer. None of theNocardiaisolates were resistant to linezolid. OneN otitidiscaviarumisolate was a multidrug-resistant organism. All patients in the present study were treated with the appropriate antibiotics and their condition resolved without further sequelae.CONCLUSIONS: The present study is the first report onN crassostreaeas a human pathogen. The detection of multidrug-resistant species necessitate molecular identification and susceptibility testing, and should be performed for allNocardiainfections. Nocardiosis manifests various clinical features depending on theNocardiaspecies and underlying conditions.

scholarly journals The Action of Efflux Pump Genes in Conferring Drug Resistance to Klebsiella Species and Their Inhibition

2021 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Klebsiella Species ◽  
Gram Negative ◽  
Multidrug Efflux Pumps

AbstractNosocomial infections caused by Klebsiella species are characterized by high rates of morbidity and mortality. The emergence of the multidrug-resistant (MDR) and extensive drug-resistant (XDR) Gram-negative bacteria reduces the antibiotic efficacy in the treatment of infections caused by the microorganisms. Management of these infections is often difficult, due to the high frequency of strains resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. Efflux systems are significant in conferring intrinsic and acquired resistance to the bacteria. The emergence of increasing drug resistance among Klebsiella pneumoniae nosocomial isolates has limited the therapeutic options for treatment of these infections and hence there is a constant quest for an alternative. In this review, we discuss various resistance mechanisms, focusing on efflux pumps and related genes in conferring resistance to Klebsiella. The role of various efflux pump inhibitors (EPIs) in restoring the antibacterial activity has also been discussed. In specific, antisense oligonucleotides as alternative therapeutics in combatting efflux-mediated resistance in Klebsiella species have focused upon.

scholarly journals Comparative Analysis of Plasmodium falciparum Genotyping via SNP Detection, Microsatellite Profiling, and Whole-Genome Sequencing

2021 ◽  
Author(s):  
Mariko Kanai ◽  
Tomas Yeo ◽  
Victor Asua ◽  
Philip J. Rosenthal ◽  
David A. Fidock ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Sequence Information ◽  
Whole Genome ◽  
Single Nucleotide ◽  
Typing Methods ◽  
Greater Mekong Subregion

Research efforts to combat antimalarial drug resistance rely on quick, robust, and sensitive methods to genetically characterize Plasmodium falciparum parasites. We developed a single-nucleotide polymorphism (SNP)-based genotyping method that can assess 33 drug resistance-conferring SNPs in dhfr, dhps, pfmdr1, pfcrt, and k13 in nine PCR reactions, performed directly from P. falciparum cultures or infected blood. We also optimized multiplexed fragment analysis and gel electrophoresis-based microsatellite typing methods using a set of five markers that can distinguish 12 laboratory strains of diverse geographical and temporal origin. We demonstrate how these methods can be applied to screen for the multidrug-resistant KEL1/PLA1/PfPailin (KelPP) lineage that has been sweeping across the Greater Mekong Subregion, verify parasite in vitro SNP-editing, identify novel recombinant genetic cross progeny, or cluster strains to infer their geographical origins. Results were compared with Illumina-based whole-genome sequence analysis that provides the most detailed sequence information but is cost-prohibitive. These adaptable, simple, and inexpensive methods can be easily implemented into routine genotyping of P. falciparum parasites in both laboratory and field settings.

scholarly journals Whole-Genome Sequence Analysis of Multidrug-Resistant Campylobacter Isolates: a Focus on Aminoglycoside Resistance Determinants

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Adrien Fabre ◽  
Monica Oleastro ◽  
Alexandra Nunes ◽  
Andrea Santos ◽  
Elodie Sifré ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Rrna Gene ◽  
Whole Genome ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Resistance Determinants ◽  
New Genes ◽  
Gentamicin Resistance

ABSTRACT A whole-genome sequencing (WGS) approach was conducted in order to identify the molecular determinants associated with antimicrobial resistance in 12 multidrug-resistant Campylobacter jejuni and Campylobacter coli isolates, with a focus on aminoglycoside resistance determinants. Two variants of a new aminoglycoside phosphotransferase gene [aph(2″)-Ii1 and aph(2″)-Ii2] putatively associated with gentamicin resistance were found. In addition, the following new genes were identified for the first time in Campylobacter: a lincosamide nucleotidyltransferase gene [lnu(G)], likely associated with lincomycin resistance, and two resistance enzyme genes (spw and apmA) similar to those found in Staphylococcus aureus, which may confer spectinomycin and gentamicin resistance, respectively. A C1192T mutation of the 16S rRNA gene that may be involved in spectinomycin resistance was also found in a C. coli isolate. Genes identified in the present study were located either on the bacterial chromosome or on plasmids that could be transferred naturally. Their role in aminoglycoside resistance remains to be supported by genetic studies. Regarding the other antimicrobial agents studied, i.e., ampicillin, ciprofloxacin, erythromycin, and tetracycline, a perfect correlation between antimicrobial phenotypes and genotypes was found. Overall, our data suggest that WGS analysis is a powerful tool for identifying resistance determinants in Campylobacter and can disclose the full genetic elements associated with resistance, including antimicrobial compounds not tested routinely in antimicrobial susceptibility testing.

scholarly journals Whole-Genome Pyrosequencing of an Epidemic Multidrug-Resistant Acinetobacter baumannii Strain Belonging to the European Clone II Group

2008 ◽  
Vol 52 (7) ◽  
pp. 2616-2625 ◽  
Author(s):  
Michele Iacono ◽  
Laura Villa ◽  
Daniela Fortini ◽  
Roberta Bordoni ◽  
Francesco Imperi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Acquired Resistance ◽  
Relative Number ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Genome Comparison ◽  
Whole Genome ◽  
Acinetobacter Baylyi ◽  
Single Chromosome

ABSTRACT The whole-genome sequence of an epidemic, multidrug-resistant Acinetobacter baumannii strain (strain ACICU) belonging to the European clone II group and carrying the plasmid-mediated bla OXA - 58 carbapenem resistance gene was determined. The A. baumannii ACICU genome was compared with the genomes of A. baumannii ATCC 17978 and Acinetobacter baylyi ADP1, with the aim of identifying novel genes related to virulence and drug resistance. A. baumannii ACICU has a single chromosome of 3,904,116 bp (which is predicted to contain 3,758 genes) and two plasmids, pACICU1 and pACICU2, of 28,279 and 64,366 bp, respectively. Genome comparison showed 86.4% synteny with A. baumannii ATCC 17978 and 14.8% synteny with A. baylyi ADP1. A conspicuous number of transporters belonging to different superfamilies was predicted for A. baumannii ACICU. The relative number of transporters was much higher in ACICU than in ATCC 17978 and ADP1 (76.2, 57.2, and 62.5 transporters per Mb of genome, respectively). An antibiotic resistance island, AbaR2, was identified in ACICU and had plausibly evolved by reductive evolution from the AbaR1 island previously described in multiresistant strain A. baumannii AYE. Moreover, 36 putative alien islands (pAs) were detected in the ACICU genome; 24 of these had previously been described in the ATCC 17978 genome, 4 are proposed here for the first time and are present in both ATCC 17978 and ACICU, and 8 are unique to the ACICU genome. Fifteen of the pAs in the ACICU genome encode genes related to drug resistance, including membrane transporters and ex novo acquired resistance genes. These findings provide novel insight into the genetic basis of A. baumannii resistance.

scholarly journals An Improved Medium for Colistin Susceptibility Testing

2018 ◽  
Vol 56 (5) ◽  
Author(s):  
Konrad Gwozdzinski ◽  
Saina Azarderakhsh ◽  
Can Imirzalioglu ◽  
Linda Falgenhauer ◽  
Trinad Chakraborty
Keyword(s):  
Susceptibility Testing ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Colistin Resistance ◽  
Reliable Determination ◽  
Content Type ◽  
E Coli ◽  
Resistant Species ◽  
Mueller Hinton ◽  
Serovar Typhimurium

ABSTRACTThe plasmid-located colistin resistance genemcr-1confers low-level resistance to colistin, a last-line antibiotic against multidrug-resistant Gram-negative bacteria. Current CLSI-EUCAST recommendations require the use of a broth microdilution (BMD) method with cation-adjusted Mueller-Hinton (CA-MH) medium for colistin susceptibility testing, but approximately 15% of all MCR-1 producers are classified as sensitive in that broth. Here we report on an improved calcium-enhanced Mueller-Hinton (CE-MH) medium that permits simple and reliable determination ofmcr-1-containingEnterobacteriaceae. Colistin susceptibility testing was performed for 50mcr-1-containingEscherichia coliandKlebsiella pneumoniaeisolates, 7 intrinsically polymyxin-resistant species,K. pneumoniaeandE. coliisolates with acquired resistance to polymyxins due tomgrBandpmrBmutations, respectively, and 32mcr-1-negative, colistin-susceptible isolates ofAcinetobacter baumannii,Citrobacter freundii,Enterobacter cloacae,E. coli,K. pneumoniae, andSalmonella entericaserovar Typhimurium. A comparison of the colistin MICs determined in CA-MH medium and those obtained in CE-MH medium was performed using both the BMD and strip-based susceptibility test formats. We validated the data using an isogenic IncX4 plasmid lackingmcr-1. Use of the CE-MH broth provides clear separation between resistant and susceptible isolates in both BMD and gradient diffusion assays; this is true for bothmcr-1-containingEnterobacteriaceaeisolates and those exhibiting either intrinsic or acquired colistin resistance. CE-MH medium is simple to prepare and overcomes current problems associated with BMD and strip-based colistin susceptibility testing, and use of the medium is easy to implement in routine diagnostic laboratories, even in resource-poor settings.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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