scholarly journals The Carbapenemase-Producing Klebsiella pneumoniae Population Is Distinct and More Clonal than the Carbapenem-Susceptible Population

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Andrés Esteban-Cantos ◽  
Belén Aracil ◽  
Verónica Bautista ◽  
Adriana Ortega ◽  
Noelia Lara ◽  
...  
Keyword(s):  
Population Structure ◽  
Klebsiella Pneumoniae ◽  
Population Parameters ◽  
Wild Type ◽  
Susceptible Population ◽  
Content Type ◽  
Resistant Population ◽  
Sequence Types ◽  
Type Strains ◽  
Susceptible Group

ABSTRACT We studied in parallel the population structure of 90 carbapenemase-producing and 88 carbapenemase-susceptible Klebsiella pneumoniae isolates collected in 20 Spanish hospitals, in the context of the EuSCAPE project. Fourteen and 50 multilocus sequence types (MLSTs) were detected among the carbapenemase-producing and carbapenem-susceptible isolates, respectively. ST11 and ST15 clones were more frequent in the carbapenemase-producing group than in the carbapenemase-susceptible group (P < 0.0001). Among the members of the carbapenem-suceptible group, the cefotaxime-resistant population showed population parameters that differed between the populations of the wild-type strains and the carbapenemase producers.

scholarly journals High-Level Resistance to Colistin Mediated by Various Mutations in the crrB Gene among Carbapenemase-Producing Klebsiella pneumoniae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Aurélie Jayol ◽  
Patrice Nordmann ◽  
Adrian Brink ◽  
Maria-Virginia Villegas ◽  
Véronique Dubois ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Wild Type ◽  
Content Type ◽  
Resistance Phenotype ◽  
Two Component ◽  
Genes Encoding ◽  
High Level ◽  
Type Strains ◽  
Level Resistance

ABSTRACT Mutations in crrAB genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates, respectively, producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

scholarly journals Pharmacodynamics of Itraconazole against Aspergillus fumigatus in anIn VitroModel of the Human Alveolus: Perspectives on the Treatment of Triazole-Resistant Infection and Utility of Airway Administration

2012 ◽  
Vol 56 (8) ◽  
pp. 4146-4153 ◽  
Author(s):  
Zaid Al-Nakeeb ◽  
Ajay Sudan ◽  
Adam R. Jeans ◽  
Lea Gregson ◽  
Joanne Goodwin ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Therapeutic Strategies ◽  
Wild Type ◽  
Content Type ◽  
Exposure Response ◽  
Prevention And Treatment ◽  
Resistant Infection ◽  
Resistant Strains ◽  
Type Strains

ABSTRACTItraconazole is used for the prevention and treatment of infections caused byAspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. Anin vitromodel of the human alveolus was used to define the pharmacodynamics of itraconazole. Galactomannan was used as a biomarker. The effect of systemic and airway administration of itraconazole was assessed, as was a combination of itraconazole administered to the airway and systemically administered 5FC. Systemically administered itraconazole against the wild type induced a concentration-dependent decline in galactomannan in the alveolar and endothelial compartments. No exposure-response relationships were apparent for the L98H, M220T, or G138C mutant. The administration of itraconazole to the airway resulted in comparable exposure-response relationships to those observed with systemic therapy. This was achieved without detectable concentrations of drug within the endothelial compartment. The airway administration of itraconazole resulted in a definite but submaximal effect in the endothelial compartment against the L98H mutant. The administration of 5FC resulted in a concentration-dependent decline in galactomannan in both the alveolar and endothelial compartments. The combination of airway administration of itraconazole and systemically administered 5FC was additive. Systemic administration of itraconazole is ineffective against Cyp51 mutants. The airway administration of itraconazole is effective for the treatment of wild-type strains and appears to have some activity against the L98H mutants. Combination with other agents, such as 5FC, may enable the attainment of near-maximal antifungal activity.

scholarly journals Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Saad J. Taj-Aldeen ◽  
Husam Salah ◽  
Winder B. Perez ◽  
Muna Almaslamani ◽  
Mary Motyl ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Hot Spot ◽  
Antifungal Susceptibility ◽  
Tertiary Hospital ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values ◽  
Echinocandin Resistance ◽  
Candida Infections ◽  
Type Strains

ABSTRACT A total of 301 Candida bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all Candida infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% for Candida albicans versus 69.8% for the other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis contained FKS hot spot mutations, including heterozygous mutations in FKS1. For C. tropicalis, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no FKS mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides C. tropicalis, few strains were classified as non-WT for amphotericin B.

scholarly journals Population Structure and Antimicrobial Resistance of Canine UropathogenicEscherichia coli

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Tessa E. LeCuyer ◽  
Barbara A. Byrne ◽  
Joshua B. Daniels ◽  
Dubraska V. Diaz-Campos ◽  
G. Kenitra Hammac ◽  
...  
Keyword(s):  
Population Structure ◽  
Antimicrobial Resistance ◽  
Companion Animals ◽  
Sequence Type ◽  
Content Type ◽  
E Coli ◽  
Extraintestinal Disease ◽  
Human Infections ◽  
Sequence Types

ABSTRACTEscherichia coliis the most common cause of human and canine urinary tract infection (UTI). Clonal groups, often with high levels of antimicrobial resistance, are a major component of theE. colipopulation that causes human UTI. While little is known about the population structure ofE. colithat causes UTI in dogs, there is evidence that dogs and humans can share fecal strains ofE. coliand that human-associated strains can cause disease in dogs. In order to better characterize theE. colistrains that cause canine UTI, we analyzed 295E. coliisolates obtained from canine urine samples from five veterinary diagnostic laboratories and analyzed their multilocus sequence types, phenotypic and genotypic antimicrobial resistance profiles, and virulence-associated gene repertoires. Sequence type 372 (ST372), an infrequent human pathogen, was the predominant sequence type in dogs at all locations. Extended-spectrum β-lactamase-producing isolates withblaCTX-Mgenes were uncommon in canine isolates but when present were often associated with sequence types that have been described in human infections. This provides support for occasional cross-host-species sharing of strains that cause extraintestinal disease and highlights the importance of understanding the role of companion animals in the overall transmission patterns of extraintestinal pathogenicE. coli.

scholarly journals Nisin Resistance of Listeria monocytogenes Is Increased by Exposure to Salt Stress and Is Mediated via LiaR

2013 ◽  
Vol 79 (18) ◽  
pp. 5682-5688 ◽  
Author(s):  
Teresa M. Bergholz ◽  
Silin Tang ◽  
Martin Wiedmann ◽  
Kathryn J. Boor
Keyword(s):  
Salt Stress ◽  
Listeria Monocytogenes ◽  
Safety Concern ◽  
Response Regulator ◽  
Brain Heart Infusion ◽  
Control Measures ◽  
Protective Effects ◽  
Wild Type ◽  
Content Type ◽  
Type Strains

ABSTRACTGrowth ofListeria monocytogeneson refrigerated, ready-to-eat food is a significant food safety concern. Natural antimicrobials, such as nisin, can be used to control this pathogen on food, but little is known about how other food-related stresses may impact how the pathogen responds to these compounds. Prior work demonstrated that exposure ofL. monocytogenesto salt stress at 7°C led to increased expression of genes involved in nisin resistance, including the response regulatorliaR. We hypothesized that exposure to salt stress would increase subsequent resistance to nisin and that LiaR would contribute to increased nisin resistance. Isogenic deletion mutations inliaRwere constructed in 7 strains ofL. monocytogenes, and strains were exposed to 6% NaCl in brain heart infusion broth and then tested for resistance to nisin (2 mg/ml Nisaplin) at 7°C. For the wild-type strains, exposure to salt significantly increased subsequent nisin resistance (P< 0.0001) over innate levels of resistance. Compared to the salt-induced nisin resistance of wild-type strains, ΔliaRstrains were significantly more sensitive to nisin (P< 0.001), indicating that induction of LiaFSR led to cross-protection ofL. monocytogenesagainst subsequent inactivation by nisin. Transcript levels of LiaR-regulated genes were induced by salt stress, and lmo1746 andtelAwere found to contribute to LiaR-mediated salt-induced nisin resistance. These data suggest that environmental stresses similar to those on foods can influence the resistance ofL. monocytogenesto antimicrobials such as nisin, and potential cross-protective effects should be considered when selecting and applying control measures for this pathogen on ready-to-eat foods.

scholarly journals Increased Vancomycin Susceptibility in Mycobacteria: a New Approach To Identify Synergistic Activity against Multidrug-Resistant Mycobacteria

2015 ◽  
Vol 59 (8) ◽  
pp. 5057-5060 ◽  
Author(s):  
Karine Soetaert ◽  
Céline Rens ◽  
Xiao-Ming Wang ◽  
Jacqueline De Bruyn ◽  
Marie-Antoinette Lanéelle ◽  
...  
Keyword(s):  
Lipid Synthesis ◽  
Multidrug Resistant ◽  
Screening Strategy ◽  
Synergistic Activity ◽  
Wild Type ◽  
New Approach ◽  
Content Type ◽  
Phthiocerol Dimycocerosates ◽  
Type Strains ◽  
Phenolic Glycolipids

ABSTRACTMycobacterium tuberculosisis wrapped in complex waxes, impermeable to most antibiotics. ComparingMycobacterium bovisBCG andM. tuberculosismutants that lack phthiocerol dimycocerosates (PDIM) and/or phenolic glycolipids with wild-type strains, we observed that glycopeptides strongly inhibited PDIM-deprived mycobacteria. Vancomycin together with a drug targeting lipid synthesis inhibited multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates. Our study puts glycopeptides in the pipeline of potential antituberculosis (TB) agents and might provide a new antimycobacterial drug-screening strategy.

scholarly journals Differences between Macrolide-Resistant and -Susceptible Streptococcus pyogenes: Importance of Clonal Properties in Addition to Antibiotic Consumption

2012 ◽  
Vol 56 (11) ◽  
pp. 5661-5666 ◽  
Author(s):  
C. Silva-Costa ◽  
A. Friães ◽  
M. Ramirez ◽  
J. Melo-Cristino ◽  
Keyword(s):  
Streptococcus Pyogenes ◽  
Antibiotic Consumption ◽  
Macrolide Resistance ◽  
Typing Method ◽  
Susceptible Population ◽  
Content Type ◽  
Resistant Population ◽  
Changing Patterns ◽  
Group A ◽  
Two Populations

ABSTRACTA steady decline in macrolide resistance amongStreptococcus pyogenes(group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor ofemmtype and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within eachemmtype. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics, independent of the behavior of the susceptible population.

scholarly journals Resistance to Ceftazidime-Avibactam Is Due to Transposition of KPC in a Porin-Deficient Strain of Klebsiella pneumoniae with Increased Efflux Activity

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Kirk Nelson ◽  
Peera Hemarajata ◽  
Dongxu Sun ◽  
Debora Rubio-Aparicio ◽  
Ruslan Tsivkovski ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Detailed Analysis ◽  
Copy Number ◽  
Sequence Type ◽  
Resistant Isolate ◽  
Wild Type ◽  
Content Type ◽  
Beta Lactamases ◽  
Resistance Phenotype

ABSTRACT Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a nonfunctional OmpK35, whereas we demonstrate that a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced the activity of this porin and impacted ceftazidime-avibactam susceptibility. In addition, we demonstrate that the increased expression of bla KPC-3 and bla SHV-12 observed in the ceftazidime-avibactam-resistant isolate was due to transposition of the Tn4401 transposon harboring bla KPC-3 into a second plasmid, pIncX3, which also harbored bla SHV-12, ultimately resulting in a higher copy number of blaKPC -3 in the resistant isolate. pIncX3 plasmid from the ceftazidime-avibactam resistant isolate, conjugated into a OmpK35/36-deficient K. pneumoniae background that harbored a mutation to the ramR regulator of the acrAB efflux operon recreated the ceftazidime-avibactam-resistant MIC of 32 μg/ml, confirming that this constellation of mutations is responsible for the resistance phenotype.

scholarly journals Antimicrobial Resistance in Porcine Enterococci in Australia and the Ramifications for Human Health

2021 ◽  
Vol 87 (10) ◽  
Author(s):  
Terence Lee ◽  
David Jordan ◽  
Shafi Sahibzada ◽  
Rebecca Abraham ◽  
Stanley Pang ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Tetracycline Resistance ◽  
Public Health Issue ◽  
Opportunistic Pathogens ◽  
Wild Type ◽  
Genomic Comparison ◽  
Major Public Health Issue ◽  
Content Type ◽  
Human Sepsis ◽  
Sequence Types

ABSTRACT Enterococci are ubiquitous opportunistic pathogens that have become a major public health issue globally. The increasing prevalence of antimicrobial resistance in hospital-adapted enterococci had been thought to originate from livestock. However, this association between livestock and hospital-adapted enterococci is currently unclear. This study investigates the antimicrobial susceptibilities of enterococci isolated from pig cecal samples and compares the genomic characteristics of Enterococcus faecium from pigs to those of isolates from meat chickens and from human sepsis cases. From 200 cecal samples, antimicrobial susceptibility testing was performed for E. faecium (n = 84), E. hirae (n = 36), and E. faecalis (n = 17). Whole-genome sequencing was performed for all E. faecium isolates, and the sequences were compared to those of previously studied isolates from meat chickens and human sepsis cases through bioinformatics analysis. Resistance (non-wild type) to erythromycin, gentamicin, tetracycline, ampicillin, daptomycin, virginiamycin, and quinupristin-dalfopristin was identified. More importantly, except for a single isolate harboring the vanC operon, no resistance was observed in the three species to vancomycin, teicoplanin, and linezolid, which are critically important antimicrobials used to treat enterococcal infections in humans. The E. faecium isolates from chickens were genetically distinct from human and pig isolates, which were more closely related. Human strains that were closely related to pig strains were not typical “hospital-adapted strains” as previously identified. The results of this study show that enterococci from Australian finisher pigs are not a source of resistance to critically important antimicrobials and that E. faecium from pigs is not part of the current human hospital-adapted population. IMPORTANCE Resistance to the critically important antimicrobials vancomycin, teicoplanin, and linezolid is not found in enterococci collected from Australian finisher pigs. However, some antimicrobial resistance was observed. In particular, resistance to quinupristin-dalfopristin, a combination of two streptogramin class antimicrobials, was identified despite the absence of streptogramin use Australia-wide since 2005. Other observed resistance among enterococci from pigs include chloramphenicol, erythromycin, and tetracycline resistance. Genomic comparison of E. faecium from Australian pigs to isolates collected from previous studies on chickens and humans indicate that E. faecium from pigs are genetically more similar to those of humans than those from chickens. Despite the increased genetic similarities, E. faecium strains from pigs are phylogenetically distinct and did not belong to the dominant sequence types found in hospital-adapted strains causing sepsis in humans. Therefore, the results indicate that Australian finisher pigs are not a source of hospital-adapted E. faecium in Australia.

scholarly journals Proteomic Investigation of the Signal Transduction Pathways Controlling Colistin Resistance in Klebsiella pneumoniae

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Ching Hei Phoebe Cheung ◽  
Punyawee Dulyayangkul ◽  
Kate J. Heesom ◽  
Matthew B. Avison
Keyword(s):  
Klebsiella Pneumoniae ◽  
Protein Production ◽  
Wild Type ◽  
Colistin Resistance ◽  
Reciprocal Effect ◽  
Content Type ◽  
Direct Activation ◽  
Proteomic Investigation ◽  
Two Component Systems ◽  
Operon Expression

ABSTRACT Colistin resistance in Klebsiella pneumoniae is predominantly caused by mutations that increase expression of the arn (also known as pbg or pmrF) operon. Expression is activated by the PhoPQ and PmrAB two-component systems. Constitutive PhoPQ activation occurs directly by mutation or following loss of MgrB. PhoPQ may also cross-activate PmrAB via the linker protein PmrD. Using proteomics, we show that MgrB loss causes a wider proteomic effect than direct PhoPQ activation, suggesting additional targets for MgrB. Different mgrB mutations cause different amounts of Arn protein production, which correlated with colistin MICs. Disruption of phoP in an mgrB mutant had a reciprocal effect to direct activation of PhoQ in a wild-type background, but the regulated proteins showed almost total overlap. Disruption of pmrD or pmrA slightly reduced Arn protein production in an mgrB mutant, but production was still high enough to confer colistin resistance; disruption of phoP conferred wild-type Arn production and colistin MIC. Activation of PhoPQ directly or through mgrB mutation did not significantly activate PmrAB or PmrC production, but direct activation of PmrAB by mutation was able to do this, and also activated Arn production and conferred colistin resistance. There was little overlap between the PmrAB and PhoPQ regulons. We conclude that under the conditions used for colistin susceptibility testing, PhoPQ-PmrD-PmrAB cross-regulation is not significant and that independent activation of PhoPQ or PmrAB is the main reason that Arn protein production increases above the threshold required for colistin resistance.

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