scholarly journals Cross resistance to cefiderocol and ceftazidime-avibactam in KPC beta-lactamase mutants and inoculum effect

2021 ◽  
Author(s):  
Claire Amaris Hobson ◽  
Aurélie Cointe ◽  
Hervé Jacquier ◽  
Alaksh Choudhury ◽  
Mélanie Magnan ◽  
...  
Keyword(s):  
Cross Resistance ◽  
Beta Lactamase ◽  
Inoculum Effect

scholarly journals Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications.

1997 ◽  
Vol 10 (4) ◽  
pp. 781-791 ◽  
Author(s):  
H F Chambers
Keyword(s):  
Methicillin Resistance ◽  
Regulatory Elements ◽  
Cross Resistance ◽  
Multiple Drug ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Biochemical Basis ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Investigational Agents

Methicillin resistance in staphylococci is determined by mec, composed of 50 kb or more of DNA found only in methicillin-resistant strains. mec contains mecA, the gene for penicillin-binding protein 2a (PBP 2a); mecI and mecR1, regulatory genes controlling mecA expression; and numerous other elements and resistance determinants. A distinctive feature of methicillin resistance is its heterogeneous expression. Borderline resistance, a low-level type of resistance to methicillin exhibited by strains lacking mecA, is associated with modifications in native PBPs, beta-lactamase hyperproduction, or possibly a methicillinase. The resistance phenotype is influenced by numerous factors, including mec and beta-lactamase (bla) regulatory elements, fem factors, and yet to be identified chromosomal loci. The heterogeneous nature of methicillin resistance confounds susceptibility testing. Methodologies based on the detection of mecA are the most accurate. Vancomycin is the drug of choice for treatment of infection caused by methicillin-resistant strains. PBP 2a confers cross-resistance to most currently available beta-lactam antibiotics. Investigational agents that bind PBP 2a at low concentrations appear promising but have not been tested in humans. Alternatives to vancomycin are few due to the multiple drug resistances typical of methicillin-resistant staphylococci.

scholarly journals Cefazolin inoculum effect among methicillinsusceptible Staphylococcus aureus isolated from patients with skin infections

2021 ◽  
Vol 23 (2) ◽  
pp. 205-211
Author(s):  
Anastasia N. Vaganova ◽  
S.V. Borisenko ◽  
E.V. Nesterova ◽  
N.N. Trofimova ◽  
I.V. Litvinenko ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Real Time ◽  
Real Time Pcr ◽  
Disk Diffusion ◽  
Skin Infections ◽  
Beta Lactamase ◽  
Broth Microdilution ◽  
Diffusion Test ◽  
Disk Diffusion Test ◽  
Inoculum Effect

Objective. To evaluate frequency and intensity of cefazolin inoculum effect among methicillin-susceptible staphylococci isolated from patients with skin infections. Materials and Methods. A total of 80 methicillin susceptible isolates of Staphylococcus aureus were identified by cefoxitin disk-diffusion test and negative results of real-time PCR for mecA gene. Inoculum effect was measured by broth microdilution test with two inocula with concentrations of 5 × 105 CFU/mL and 5 × 107 CFU/mL. The disk-diffusion test with cefoxitin was also performed. Penicillin susceptibility was determined by disk-diffusion method. Beta-lactamase blaZ gene was identified by real-time PCR. Results. The frequency of cefazolin inoculum effect in tested isolates was 30% which is consistent with data from different countries. The MIC values for concentrated inoculum reached CLSI breakpoint for cefazolin resistance in 2.5% of isolates. The isolates with inoculum effect and those without it had the similar MIC values for cefazolin in broth microdilution test for standard inocula and similar diameters of inhibition zone in disk-diffusion test with cefazolin. Penicillin resistance was more frequent in inoculum effect-positive isolates. Beta-lactamase activity is considered as a main cause of cefazolin inoculum effect in staphylococci. The beta-lactamase blaZ gene was identified in the majority of isolates with cefazolin inoculum effect, but it was also prevalent among inoculum effect-negative isolates. Conclusions. Up to 30% of MSSA isolates from skin lesions in dermatological patients from SaintPetersburg are positive for cefazolin inoculum effect. Those isolates are usually characterized by penicillin resistance. Most of the cefazolin inoculum effect-positive isolates also carry beta-lactamase blaZ gene.

scholarly journals A study on susceptibility patterns, resistance mechanisms and cross- resistances of antibiotics against Pseudomonas aeruginosa in a teaching hospital at Puducherry

2021 ◽  
Vol 8 (4) ◽  
pp. 279-284
Author(s):  
Hemalatha Gurumurthy ◽  
G K Poongothai ◽  
K Bhaskaran
Keyword(s):  
Positive Reaction ◽  
Resistance Mechanisms ◽  
The Body ◽  
Diffusion Method ◽  
Cross Resistance ◽  
Beta Lactamase ◽  
Strict Adherence ◽  
Extended Spectrum Beta Lactamase ◽  
Inappropriate Use ◽  
Susceptibility Patterns

, a gram negative bacteria causes lung and nosocomial infections, mostly infect the body after surgery or invasive techniques. There has been a increasing prevalence in drug resistant variants in the recent years. 1. To determine the antibiotic susceptibility patterns of ; 2. To assess the antibiotics used against and the cross-resistence pattern existing between them; 3. To evaluate the possible resistance mechanisms of by phenotypic techniques.Thirty six consecutive, nonduplicate isolates were collected between January to July in the year 2018 from the hospital pus samples. The isolates showed synthesis of pyocyanin and a oxidase positive reaction. Kirby bauer’s disc diffusion method (HIMEDIA). was used for assessing the sensitivity of drugs. Disk approximation test was done to check the prevalence of inducible β-lactamases. Modified Hodge test was done to assess the metallo-β-lactamase activity. Double disk synergy method had been preferred to evaluate the extended-spectrum beta-lactamase (ESBL) activity. The most sensitive antibiotic was found to be ciprofloxacin which is followed by amikacin and ceftazidime (p < 0.05). 36% of the samples were resistant to more than one antibiotic groups. Cross-resistance was observed between the antibiotics. 53% of the samples had Inducible β-lactamases. Eighty percent of the samples which were non-resistant to ceftazidime showed positive reaction for inducible beta-lactamase. 2% isolates by DDS method showed the presence of ESBLs. The study samples did not show the presence of Metallo-β-lactamases.Strict adherence to the recent trend of “reserve drugs” concept and minimizing the misuse of antibiotics can bring down the drug resistance and morbidity. The addressal of irrational and inappropriate use of antimicrobials among the clinician is the need of the hour.

Resistance in Enterobacteriaceae: Results of a Multicenter Surveillance Study, 1995-2000

2003 ◽  
Vol 24 (8) ◽  
pp. 607-612 ◽  
Author(s):  
Ian Friedland ◽  
Lue Stinson ◽  
Margaretmary Ikaiddi ◽  
Sandra Harm ◽  
Gail L. Woods
Keyword(s):  
Escherichia Coli ◽  
Active Agent ◽  
Surveillance Study ◽  
Cross Resistance ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
Highly Active ◽  
Extended Spectrum ◽  
Changes Over Time

AbstractObjectives:To assess changes over time in susceptibility of Enterobacteriaceae from patients in ICUs, compare susceptibility rates of isolates from patients in ICUs with those from inpatients outside ICUs, and explore phenotypic patterns of cross-resistance and co-resistance.Design:From 1995 to 2000, centers participating in the ICU Surveillance Study tested 100 to 200 consecutive nosocomial gram-negative bacilli by broth microdilution.Setting:Each year, 42 to 97 U.S. hospitals tested isolates.Results:In all years, imipenem was the most potent agent tested, followed by amikacin and ertapenem. Extended-spectrum beta-lactam and monobactam agents had good activity against Escherichia coli and Klebsiella species, but limited activity against Enterobacter species. Susceptibility to imipenem and amikacin did not fluctuate during the analysis period, whereas susceptibility to ceftazidime, ceftriaxone, and ciprofloxacin decreased 2% to 5%. The decline was most pronounced for susceptibility of Escherichia coli to ciprofloxacin: 98.7% of ICU isolates were susceptible in 1995 versus 93.2% in 2000. Susceptibility of ICU isolates was lower than that of non-ICU isolates, except for ciprofloxacin, for which the reverse was true. Cross-resistance was common among extended-spectrum cephalosporins and penicillins, but uncommon between imipenem and ertapenem. Only imipenem and ertapenem remained highly active against Enterobacteriaceae with a phenotype suggesting possible production of an extended-spectrum beta-lactamase and those with a phenotype suggesting possible Amp C hyperproduction.Conclusions:Imipenem was the most active agent against nosocomial Enterobacteriaceae. Susceptibility to ciprofloxacin decreased from 1995 to 2000, particularly in Escherichia coli, and, in contrast to other agents, was lower among non-ICU isolates.

scholarly journals Genome Sequence Comparison of Staphylococcus aureus TX0117 and a Beta-Lactamase-Cured Derivative Shows Increased Cationic Peptide Resistance Accompanying Mutations in relA and mnaA

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Mia Jade Sales ◽  
George Sakoulas ◽  
Richard Szubin ◽  
Bernhard Palsson ◽  
Cesar Arias ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Genome Sequence ◽  
Genome Assembly ◽  
Sequence Comparison ◽  
Beta Lactamase ◽  
Cationic Peptide ◽  
Content Type ◽  
Inoculum Effect ◽  
Antimicrobial Peptide Resistance

Staphylococcus aureus strain TX0117 is a methicillin-susceptible bacterium with type A beta-lactamase exhibiting a high cefazolin inoculum effect. TX0117 was cured of blaZ, yielding TX0117c with increased antimicrobial peptide resistance. The sequencing and genome assembly of TX0117 elucidate six mutations between TX0117 and TX0117c, including relA truncation and mnA_1 substitution.

Inoculum effect leads to overestimation of in vitro resistance for artemisinin derivatives and standard antimalarials: a Gambian field study

Parasitology ◽  
1999 ◽  
Vol 119 (5) ◽  
pp. 435-440 ◽  
Author(s):  
M. T. DURAISINGH ◽  
P. JONES ◽  
I. SAMBOU ◽  
L. VON SEIDLEIN ◽  
M. PINDER ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Field Study ◽  
Susceptibility Testing ◽  
Inoculum Size ◽  
Cross Resistance ◽  
Artemisinin Derivatives ◽  
Inoculum Effect ◽  
Measured Sensitivity

Artemisinin (QHS) and its derivatives are new antimalarials which are effective against Plasmodium falciparum parasites resistant to chloroquine (CQ). As these drugs are introduced it is imperative that resistance is monitored. In this paper we demonstrate that the inoculum size used in in vitro testing influences the measured in vitro susceptibility to QHS and its derivative dihydroartemisinin (DHA) and to mefloquine (MEF) and CQ over the range of parasitaemias routinely used in testing with the WHO in vitro microtest. An increase in parasitaemia and/or haematocrit was accompanied by a decrease in the measured sensitivity of 2 laboratory lines. In the context of a field study testing in vitro susceptibility of parasite isolates from patients with uncomplicated malaria in Fajara, The Gambia we demonstrate that failure to control for inoculum size significantly overestimates the level of resistance to QHS and DHA as well as MEF, halofantrine (HAL) and quinine (QUIN). When controlling for the inoculum effect, cross-resistance was observed between QHS, MEF and HAL suggesting the presence of a multidrug resistance-like mechanism. These studies underline the importance of inoculum size in in vitro susceptibility testing.

scholarly journals Whole Transcriptomic Analysis of Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella Pneumoniae Producers of Carbapenemase

2020 ◽  
Author(s):  
Ines Bleriot ◽  
Lucia Blasco ◽  
Mercedes Delgado ◽  
Ana Gual de Torrella ◽  
Anton Ambroa ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Cross Resistance ◽  
Beta Lactamase ◽  
Tolerance Mechanisms ◽  
Clinical Strains ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
High Level

Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under CHLX pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemK/PemI. We characterized this PemK/PemI TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).

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