scholarly journals Persistence and Epidemic Propagation of a Pseudomonas aeruginosa Sequence Type 235 Clone Harboring an IS26Composite Transposon Carrying theblaIMP-1Integron in Hiroshima, Japan, 2005 to 2012

2015 ◽  
Vol 59 (5) ◽  
pp. 2678-2687 ◽  
Author(s):  
Wataru Shimizu ◽  
Shizuo Kayama ◽  
Shuntaro Kouda ◽  
Yoshitoshi Ogura ◽  
Kanao Kobayashi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Insertion Sequence ◽  
Gene Cassette ◽  
Multidrug Resistant ◽  
Genomic Comparison ◽  
Variable Regions ◽  
Integrase Gene ◽  
Content Type ◽  
History Of ◽  
Lactamase Gene

ABSTRACTA 9-year surveillance for multidrug-resistant (MDR)Pseudomonas aeruginosain the Hiroshima region showed that the number of isolates harboring the metallo-β-lactamase geneblaIMP-1abruptly increased after 2004, recorded the highest peak in 2006, and showed a tendency to decline afterwards, indicating a history of an epidemic. PCR mapping of the variable regions of the integrons showed that this epidemic was caused by the clonal persistence and propagation of an MDRP. aeruginosastrain harboring theblaIMP-1gene and an aminoglycoside 6′-N-acetyltransferase gene,aac(6′)-Iaein a class I integron (In113), whose integrase geneintl1was disrupted by an IS26insertion. Sequence analysis of the representative strain PA058447 resistance element containing the In113-derived gene cassette array showed that the element forms an IS26transposon embedded in the chromosome. It has a Tn21backbone and is composed of two segments sandwiched by three IS26s. In Japan, clonal nationwide expansion of an MDRP. aeruginosaNCGM2.S1 harboring chromosomally encoded In113 with intactintl1is reported. Multilocus sequence typing and genomic comparison strongly suggest that PA058447 and NCGM2.S1 belong to the same clonal lineage. Moreover, the structures of the resistance element in the two strains are very similar, but the sites of insertion into the chromosome are different. Based on tagging information of the IS26present in both resistance elements, we suggest that the MDRP. aeruginosaclone causing the epidemic in Hiroshima for the past 9 years originated from a common ancestor genome of PA058447 and NCGM2.S1 through an IS26insertion intointl1of In113 and through IS26-mediated genomic rearrangements.

scholarly journals Molecular Characterization of Multidrug-Resistant Escherichia coli Isolates from Irish Cattle Farms

2011 ◽  
Vol 77 (20) ◽  
pp. 7121-7127 ◽  
Author(s):  
Maria Karczmarczyk ◽  
Ciara Walsh ◽  
Rosemarie Slowey ◽  
Nola Leonard ◽  
Séamus Fanning
Keyword(s):  
Escherichia Coli ◽  
Gene Cassette ◽  
Multidrug Resistant ◽  
Gene Markers ◽  
Variable Regions ◽  
Content Type ◽  
E Coli ◽  
Virulence Markers ◽  
Class 1 ◽  
Genotypic Characteristics

ABSTRACTThis study describes the genotypic characteristics of a collection of 100 multidrug-resistant (MDR)Escherichia colistrains recovered from cattle and the farm environment in Ireland in 2007. The most prevalent antimicrobial resistance identified was to streptomycin (100%), followed by tetracycline (99%), sulfonamides (98%), ampicillin (82%), and neomycin (62%). Resistance was mediated predominantly bystrA-strB(92%),tetA(67%),sul2(90%),blaTEM(79%), andaphA1(63%) gene markers, respectively. Twenty-seven isolates harbored a class 1 integrase (intI1), whileqacEΔ1andsul1markers were identified in 25 and 26 isolates, respectively. The variable regions of these integrons contained aminoglycoside, trimethoprim, and β-lactam resistance determinants (aadA12,aadB-aadA1,blaOXA-30-aadA1,dfrA1-aadA1,dfrA7). Class 2 integrons were identified less frequently (4%) and contained the gene cassette arraydfrA1-sat1-aadA1. Resistance to ampicillin, neomycin, streptomycin, sulfonamide, and tetracycline was associated with transferable high-molecular-weight plasmids, as demonstrated by conjugation assays. A panel of virulence markers was screened for by PCR, and genes identified includedvt1, K5 in 2 isolates,papCin 10 isolates, and PAI IV536in 37 isolates. MDR commensalE. coliisolates from Irish cattle displayed considerable diversity with respect to the genes identified. Our findings highlight the importance of the commensal microflora of food-producing animals as a reservoir of transferable MDR.

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E. Mendes ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Large Collection ◽  
Content Type ◽  
Negative Results ◽  
Medical Centers ◽  
Extensively Drug Resistant ◽  
Genes Encoding

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

scholarly journals In VitroActivity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Bacterial Ribosome

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.

scholarly journals Genomic comparison of archaeal conjugative plasmids fromSulfolobus

Archaea ◽  
2004 ◽  
Vol 1 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Bo Greve ◽  
Susanne Jensen ◽  
Kim Brügger ◽  
Wolfram Zillig ◽  
Roger A. Garrett
Keyword(s):  
Sequence Similarity ◽  
Comparative Sequence Analysis ◽  
Genomic Comparison ◽  
Variable Regions ◽  
Integrase Gene ◽  
Significant Sequence Similarity ◽  
Genes Encoding ◽  
Putative Origin ◽  
Main Components ◽  
Intercellular Exchange

All of the known self-transmissable plasmids of the Archaea have been found in the genusSulfolobus. To gain more insight into archaeal conjugative processes, four newly isolated self-transmissable plasmids, pKEF9, pHVE14, pARN3 and pARN4, were sequenced and subjected to a comparative sequence analysis with two earlier sequenced plasmids, pNOB8 and pING1. The analyses revealed three conserved and functionally distinct sections in the genomes. Section A is considered to encode the main components of the conjugative apparatus, where two genes show low but significant sequence similarity to sections of genes encoding bacterial conjugative proteins. A putative origin of replication is located in section B, which is highly conserved in sequence and contains several perfect and imperfect direct and inverted repeats. Further downstream, in section C, an operon encoding six to nine smaller proteins is implicated in the initiation and regulation of replication. Each plasmid carries an integrase gene of the type that does not partition on integration, and there is strong evidence for their integration into host chromosomes, where they may facilitate intercellular exchange of chromosomal genes. Two plasmids contain hexameric short regularly spaced repeats (SRSR), which have been implicated in plasmid maintenance, and each plasmid carries multiple recombination motifs, concentrated in the variable regions, which likely provide sites for genomic rearrangements.

scholarly journals Efficacy of Antibiotic Combinations against Multidrug-Resistant Pseudomonas aeruginosa in Automated Time-Lapse Microscopy and Static Time-Kill Experiments

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Anna Olsson ◽  
Pikkei Wistrand-Yuen ◽  
Elisabet I. Nielsen ◽  
Lena E. Friberg ◽  
Linus Sandegren ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Time Lapse ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Positive Interactions ◽  
Synergistic Activity ◽  
Content Type ◽  
Time Lapse Microscopy ◽  
Time Kill ◽  
Antibiotic Combination

ABSTRACT Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria, yet data regarding which combinations are most effective are lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa. We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, linezolid, meropenem, minocycline, rifampin, temocillin, thiamphenicol, or trimethoprim by automated time-lapse microscopy using predefined cutoff values indicating inhibition of growth (≤106 CFU/ml) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments. All strains were intermediate or resistant to polymyxin B, antipseudomonal β-lactams, ciprofloxacin, and amikacin. Genes encoding β-lactamases (e.g., blaPAO and blaOXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol, and trimethoprim. Time-kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem. Positive interactions were frequently found with the tested combinations, against strains that harbored several resistance mechanisms to the single drugs, and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.

scholarly journals Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Ayesha Khan ◽  
William C. Shropshire ◽  
Blake Hanson ◽  
An Q. Dinh ◽  
Audrey Wanger ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Critically Ill Patient ◽  
Whole Genome ◽  
Candida Auris ◽  
Content Type ◽  
Simultaneous Infection ◽  
Polymicrobial Infections ◽  
Selection Of

ABSTRACT We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris. A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.

scholarly journals Molecular Characterization ofblaNDM-1in a Sequence Type 235 Pseudomonas aeruginosa Isolate from France

2013 ◽  
Vol 57 (7) ◽  
pp. 3408-3411 ◽  
Author(s):  
Frédéric Janvier ◽  
Katy Jeannot ◽  
Sophie Tessé ◽  
Marjorie Robert-Nicoud ◽  
Hervé Delacour ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Insertion Sequence ◽  
Variable Region ◽  
Sequence Type ◽  
Common Region ◽  
Class 1 Integron ◽  
Genetic Studies ◽  
Content Type ◽  
Class 1 ◽  
Previous Hospitalization

ABSTRACTAn NDM-1 carbapenemase-producingPseudomonas aeruginosaisolate was recovered from a patient hospitalized in France after a previous hospitalization in Serbia. Genetic studies revealed that theblaNDM-1gene was surrounded by insertion sequence ISAba125and a truncated bleomycin resistance gene. ThisblaNDM-1region was a part of the variable region of a new complex class 1 integron bearing IS common region 1 (ISCR1). The presence of ISPa7upstream of this integron suggests insertion in a chromosomally located Tn402-like structure.

scholarly journals Complete Genome Sequences of 10 Phages Lytic against Multidrug-Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 9 (29) ◽  
Author(s):  
Jason Farlow ◽  
Helen R. Freyberger ◽  
Yunxiu He ◽  
Amanda M. Ward ◽  
Wiriya Rutvisuttinunt ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Complete Genome ◽  
Multidrug Resistant ◽  
Genome Sequences ◽  
Coding Sequences ◽  
Content Type

ABSTRACT We report the genome sequences of 10 Pseudomonas aeruginosa phages studied for their potential for formulation of a therapeutic cocktail; they represent the families Myoviridae, Podoviridae, and Siphoviridae. Genome sizes ranged from 43,299 to 88,728 nucleotides, with G+C contents of 52.1% to 62.2%. The genomes contained 68 to 168 coding sequences.

scholarly journals Influence of the α-Methoxy Group on the Reaction of Temocillin with Pseudomonas aeruginosa PBP3 and CTX-M-14 β-Lactamase

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Michael D. Sacco ◽  
Kyle G. Kroeck ◽  
M. Trent Kemp ◽  
Xiujun Zhang ◽  
Logan D. Andrews ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Active Site ◽  
Methoxy Group ◽  
Complex Structure ◽  
Antibacterial Properties ◽  
Multidrug Resistant ◽  
Binding Modes ◽  
Content Type ◽  
The Stability ◽  
M 14

ABSTRACT The prevalence of multidrug-resistant Pseudomonas aeruginosa has led to the reexamination of older “forgotten” drugs, such as temocillin, for their ability to combat resistant microbes. Temocillin is the 6-α-methoxy analogue of ticarcillin, a carboxypenicillin with well-characterized antipseudomonal properties. The α-methoxy modification confers resistance to serine β-lactamases, yet temocillin is ineffective against P. aeruginosa growth. The origins of temocillin’s inferior antibacterial properties against P. aeruginosa have remained relatively unexplored. Here, we analyze the reaction kinetics, protein stability, and binding conformations of temocillin and ticarcillin with penicillin-binding protein 3 (PBP3), an essential PBP in P. aeruginosa. We show that the 6-α-methoxy group perturbs the stability of the PBP3 acyl-enzyme, which manifests in an elevated off-rate constant (koff) in biochemical assays comparing temocillin with ticarcillin. Complex crystal structures with PBP3 reveal similar binding modes of the two drugs but with important differences. Most notably, the 6-α-methoxy group disrupts a high-quality hydrogen bond with a conserved residue important for ligand binding while also being inserted into a crowded active site, possibly destabilizing the active site and enabling water molecule from bulk solvent to access and cleave the acyl-enzyme bond. This hypothesis is supported by the observation that the acyl-enzyme complex of temocillin has reduced thermal stability compared with ticarcillin. Furthermore, we explore temocillin’s mechanism of β-lactamase inhibition with a high-resolution complex structure of CTX-M-14 class A serine β-lactamase. The results suggest that the α-methoxy group prevents hydrolysis by locking the compound into an unexpected conformation that impedes access of the catalytic water to the acyl-enzyme adduct.

scholarly journals Imipenem/Cilastatin/Relebactam Alone and in Combination against Pseudomonas aeruginosa in the In Vitro Pharmacodynamic Model

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Iris H. Chen ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Pharmacodynamic Model ◽  
Resistance Development ◽  
Content Type ◽  
Combination Studies ◽  
The Mean ◽  
Combined Drugs

ABSTRACT Combination therapy may enhance imipenem/cilastatin/relebactam’s (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible P. aeruginosa isolates in an in vitro pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were −2.52 ± 0.49, −1.49 ± 0.49, −1.15 ± 0.67, and −0.61 ± 0.10 log10 CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic (n = 1) or additive (n = 2) interactions against three isolates with 24-h CFU reductions ranging from −2.62 to −4.67 log10 CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving −0.51- to −3.33-log10 CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant P. aeruginosa, I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some P. aeruginosa, whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.

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