scholarly journals Penicillinase Plasmid Australia type in Neisseria Gonorrhoeae Isolated in Poland

2021 ◽  
Author(s):  
Szymon Jerzy Walter de Walthoffen
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gene Encoding ◽  
Beta Lactamases ◽  
The World ◽  
Lactamase Gene ◽  
Chromosomal Mutations ◽  
First Time

Abstract Purpose. Neisseria gonorrhoeae is an etiological agent of gonorrhea, which continues to be one of the most important public health problems. Currently, the most important problem in treatment is the mechanisms that determine resistance to drugs of the beta-lactam class, which are recommended for the treatment of gonorrhea. Chromosomal mutations are responsible for resistance to ceftriaxone and cefepime. The possibility of mutations in the gene encoding beta-lactamase (blaTEM) in the penicillinase plasmid may also turn out to be a serious threat. Methods. The occurrence of resistance encoded on penicillinase plasmid has been investigated. For this purpose, the susceptibility of bacteria was determined and the gene for resistance to beta-lactams as well as the plasmids themselves was typed. Results. Of the 333 strains tested, 21 (6.3%) had the beta-lactamase gene and produced penicillinase.The results allow to conclude that among the tested strains of N. gonorrhoeae occurred two of the beta-lactamase: TEM-1 and TEM-135. Most of the known penicillinase plasmid types of N. gonorrhoeae were demonstrated: Asian, African, Toronto/Rio plasmids and Australian variant.Conclusions.In the first three years, TEM-1 beta-lactamases dominated in N. gonorrhoeae, which were replaced by TEM-135 in the following years of the study. Not all molecular methods are capable of varying the types of penicillinase plasmids. A particularly noteworthy observation is the fact that the Australia-type of penicillinase plasmid (3270 bp) was identified for the first time in Europe, and the second time in the world.

scholarly journals Penicillinase plasmid Australia type in Neisseria gonorrhoeae isolated in Poland

2022 ◽  
Vol 204 (2) ◽  
Author(s):  
Szymon Walter de Walthoffen
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Gene Encoding ◽  
Beta Lactamases ◽  
Lactamase Gene ◽  
Chromosomal Mutations ◽  
First Time

Abstract Purpose Neisseria gonorrhoeae is an etiological agent of gonorrhea which remains a major public health problem the mechanisms that determine resistance to drugs of the beta-lactam class, which are recommended for the treatment of gonorrhea, are currently the most important problem in its treatment. Chromosomal mutations are responsible for resistance to ceftriaxone and cefepime. The possibility of mutations in the gene encoding beta-lactamase (blaTEM) in the penicillinase plasmid may also turn out to be a serious threat. Methods The occurrence of resistance encoded on penicillinase plasmid has been investigated. For this purpose, the susceptibility of bacteria was determined and the gene for resistance to beta-lactams as well as the plasmids themselves was typed. Results Of the 333 strains tested, 21 (6.3%) had the beta-lactamase gene and produced penicillinase. Two of the beta-lactamase: TEM-1 and TEM-135 occurred among the tested strains of N. gonorrhoeae. Most of the known penicillinase plasmid types of N. gonorrhoeae were demonstrated: the Asian, the African, the Toronto/Rio plasmids and Australian variants. Conclusions In the first 3 years, TEM-1 beta-lactamases dominated in N. gonorrhoeae, which were replaced by TEM-135 in the following years of the study. Not all molecular methods are capable of varying the types of penicillinase plasmids. A particularly noteworthy observation is the fact that the Australia-type of penicillinase plasmid (3270 bp) was identified for the first time in Europe, and the second time in the world.

scholarly journals Variability of chromosomally encoded beta-lactamases from Klebsiella oxytoca.

1997 ◽  
Vol 41 (8) ◽  
pp. 1641-1648 ◽  
Author(s):  
B Fournier ◽  
P H Roy
Keyword(s):  
Klebsiella Oxytoca ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Main Form ◽  
Extended Spectrum Beta Lactamases ◽  
Lactamase Gene ◽  
Hydrolysis Of ◽  
Substrate Hydrolysis

The beta-lactamase genes of Klebsiella oxytoca were previously divided into two main groups: bla(OXY-1) and bla(OXY-2). The two beta-lactamase groups were each represented by beta-lactamases with four different pIs. In each group, one form of beta-lactamase is more frequent than the others combined. The beta-lactamase gene of each representative beta-lactamase with a different pI that was not yet sequenced (pIs 5.7, 6.8 [OXY-2], 7.1, 8.2, and 8.8 [OXY-1]) was cloned and sequenced. The susceptibility patterns as well as relative rates and kinetic parameters for beta-lactam hydrolysis revealed that OXY-2 enzymes hydrolyzed several of the beta-lactams that were examined (carbenicillin, cephalothin, cefamandole, ceftriaxone, and aztreonam) at a greater rate than the OXY-1 enzymes did. Comparison of K. oxytoca beta-lactamases with plasmid-mediated extended-spectrum beta-lactamases MEN-1 and TOHO-1 implied that the threonine at position 168 present in OXY-2 beta-lactamase instead of the alanine in OXY-1 could be responsible for its modified substrate hydrolysis. In each group, the beta-lactamase with a variant pI differs from the main form of beta-lactamase by one to five amino acid substitutions. The substrate profile and the 50% inhibitory concentrations revealed that all substitutions differing from the main form of beta-lactamase were neutral except one difference in the OXY-1 group. This substitution of an Ala to a Gly at position 237 increases the hydrolysis of some beta-lactams, particularly aztreonam; decreases the hydrolysis of benzylpenicillin, cephaloridine, and cefamandole, and decreases the susceptibility to clavulanic acid (fivefold increase in the 50% inhibitory concentration).

scholarly journals Evaluation of the presence of AmpC (FOX) beta-lactamase gene in clinical strains of Escherichia coli isolated from hospitalized patients in Tabriz, Iran

2021 ◽  
Vol 38 (3) ◽  
pp. 301-304
Author(s):  
Zahra SADEGHI DEYLAMDEH ◽  
Abolfazl JAFARI SALES
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Hospitalized Patients ◽  
Disk Diffusion ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Clinical Strains ◽  
Beta Lactam Antibiotics ◽  
Lactamase Gene

Beta-lactamases are the most common cause of bacterial resistance to beta-lactam antibiotics. AmpC-type beta-lactamases hydrolyze cephalosporins, penicillins, and cephamycins. Therefore, the study aims was to determine antibiotic resistance and to investigate the presence of AmpC beta-lactamase gene in clinical strains of Escherichia coli isolated from hospitalized patients in Tabriz. In this cross-sectional descriptive study, 289 E. coli specimens were collected from clinical specimens. Disk diffusion method and combined disk method were used to determine the phenotype of extended spectrum β-Lactamase producing (ESBLs) strains. Then PCR was used to evaluate the presence of AmpC (FOX) beta-lactamase gene in the strains confirmed in phenotypic tests. Antibiotic resistance was also determined using disk diffusion by the Kibry-Bauer method. A total of 121 isolates were identified as generators of beta-lactamase genes. 72 (59.5 %) isolates producing ESBL and 49 (40.5 %) isolates were identified as AmpC generators. In the PCR test, 31 isolates contained the FOX gene. The highest resistance was related to the antibiotics amoxicillin (76.12%), ceftazidime (70.24%) and nalidixic acid (65.05%). The results indicate an increase in the prevalence of beta-lactamase genes and increased resistance to beta-lactam antibiotics, which can be the result of improper use of antibiotics and not using antibiotic susceptibility tests before starting treatment. Also, using phenotypic and molecular diagnostic methods such as PCR together can be very useful.

scholarly journals In Vitro Activity of the Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 in Combination with Multiple Beta-Lactam Antibiotics against Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Olga Lomovskaya ◽  
Debora Rubio-Aparicio ◽  
Kirk Nelson ◽  
Dongxu Sun ◽  
Ruslan Tsivkovski ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Beta Lactamase ◽  
In Vitro Activity ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Lactamase Inhibitor

QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases. QPX7728 enhances the potency of multiple beta-lactams in beta-lactamase producing Enterobacterales and Acinetobacter spp. In this study we evaluated the in vitro activity of QPX7728 (8 μg/ml) combined with multiple beta-lactams against clinical isolates of Pseudomonas aeruginosa with varying beta-lactam resistance mechanisms. Seven-hundred-ninety clinical isolates were included in this study; 500 isolates, termed a “representative panel”, were selected to be representative the MIC distribution of meropenem (MEM), ceftazidime-avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance for clinical isolates according to 2017 SENTRY surveillance data (representative panel). An additional 290 selected isolates (“challenge panel”), that were either non-susceptible to MEM or were resistant to TOL-TAZ or CAZ-AVI were also tested; 61 strains carried metallo beta-lactamases (MBLs), 211 strains were defective in the carbapenem porin OprD and 185 strains had the MexAB-OprM efflux pump overproduced based on a phenotypic test. Against the representative panel, susceptibility for all QPX7728/beta-lactam combinations was >90%. For the challenge panel, QPX-ceftolozane (TOL) was the most active combination (78.6% susceptible) followed by equipotent QPX-piperacillin (PIP) and QPX-cefepime (FEP), restoring susceptibility in 70.3% of strains (CLSI breakpoints for the beta-lactam compound alone). For MBL-negative strains, QPX-TOL and QPX-FEP restored the MIC values to susceptibility rates in ∼90% and ∼80% of strains, respectively, vs 68-70% for QPX-MEM and QPX-PIP and 63-65% for TOL-TAZ and CAZ-AVI. For MBL-positive strains, QPX-PIP restored the MIC to susceptibility values for ∼70% of strains vs 2-40% for other combinations. Increased efflux and impaired OprD had varying effect on QPX7728 combination depending on the partner beta-lactam tested. QPX7728 enhanced the potency of multiple beta-lactams against P. aeruginosa, with varying results according to the beta-lactamase production and other intrinsic resistance mechanisms.

The Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-lactam Antibiotics against Beta-lactamase Producing Strains of Resistant Enterobacterales

2021 ◽  
Author(s):  
Olga Lomovskaya ◽  
Debora Rubio-Aparicio ◽  
Ruslan Tsivkovski ◽  
Jeff Loutit ◽  
Michael Dudley
Keyword(s):  
Broad Spectrum ◽  
Resistance Mechanisms ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Intrinsic Resistance ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
The Impact ◽  
Lactamase Inhibitor

QPX7728 is a cyclic boronate ultra-broad-spectrum beta-lactamase inhibitor, with potent activity against both serine and metallo beta-lactamases. QPX7728 can be delivered systemically by the IV or oral route of administration. Oral β-lactam antibiotics alone or in combination with QPX7728 were evaluated for 1) sensitivity to hydrolysis by various common beta-lactamases and inhibition of hydrolysis by QPX7728; 2) the impact of non-beta-lactamase-mediated resistance mechanisms on potency of beta-lactams; and 3) in vitro activity against a panel of clinical strains producing diverse beta-lactamases. The carbapenem tebipenem had stability for many serine beta-lactamases from all molecular classes followed by cephalosporin ceftibuten. Addition of QPX7728 to tebipenem, ceftibuten and mecillinam completely reversed beta-lactamase-mediated resistance in cloned beta-lactamases from serine and metallo enzyme classes; the degree of potentiation of other beta-lactams varied according to the beta-lactamase produced. Tebipenem, ceftibuten and cefixime had the lowest MICs against laboratory strains with various combinations of beta-lactamases and the intrinsic drug-resistance mechanisms of porin and efflux mutations. There was a high degree of correlation between potency of various combinations against cloned beta-lactamases and efflux/porin mutants and the activity against clinical isolates, showing the importance of both inhibition of beta-lactamase along with minimal impact of general intrinsic resistance mechanisms affecting the beta-lactam. Tebipenem and ceftibuten appeared to be the best beta-lactam antibiotics when combined with QPX7728 for activity against Enterobacterales that produce serine or metallo beta-lactamases.

scholarly journals Promiscuous Enzyme Activity as a Driver of Allo and Iso Convergent Evolution, Lessons from the β-lactamases

2020 ◽  
Author(s):  
Vivek Keshri ◽  
Eric Chabrière ◽  
Lucile Pinault ◽  
Philippe Colson ◽  
Seydina Diene ◽  
...  
Keyword(s):  
Convergent Evolution ◽  
Character State ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Evolutionary Mechanisms ◽  
Beta Lactamases ◽  
Ancestral Sequences ◽  
Two Factors ◽  
Evolution Type

The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. More the evolution of a character is probable more convergent evolution will be witnessed, consequently, convergent evolution could mean that the convergent character evolution result as a combination of these two factors. We investigate this phenomenon by studying the convergent evolution of biochemical functions. We use for the investigation the case of β-lactamases. β-lactamases hydrolyzes β-lactams which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase superfamily. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further show that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explaining the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part, by positive selection as the organisms having β-lactamase activity allows them to resist to organism secreting β-lactams. Indeed a mutation increasing the β-lactamases activity will be selected as the organisms having this activity will have an advantage over the others.

scholarly journals beta-Lactamases in laboratory and clinical resistance.

1995 ◽  
Vol 8 (4) ◽  
pp. 557-584 ◽  
Author(s):  
D M Livermore
Keyword(s):  
Bacterial Resistance ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Producer Strain ◽  
Phenotypic Properties ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
Clinical Resistance ◽  
Gram Negative Organisms

beta-Lactamases are the commonest single cause of bacterial resistance to beta-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are known and may be classified by their sequences or phenotypic properties. The ability of a beta-lactamase to cause resistance varies with its activity, quantity, and cellular location and, for gram-negative organisms, the permeability of the producer strain. beta-Lactamases sometimes cause obvious resistance to substrate drugs in routine tests; often, however, these enzymes reduce susceptibility without causing resistance at current, pharmacologically chosen breakpoints. This review considers the ability of the prevalent beta-lactamases to cause resistance to widely used beta-lactams, whether resistance is accurately reflected in routine tests, and the extent to which the antibiogram for an organism can be used to predict the type of beta-lactamase that it produces.

scholarly journals An allelic variant of the chromosomal gene for class A beta-lactamase K2, specific for Klebsiella pneumoniae, is the ancestor of SHV-1.

1997 ◽  
Vol 41 (12) ◽  
pp. 2705-2709 ◽  
Author(s):  
S Haeggman ◽  
S Löfdahl ◽  
L G Burman
Keyword(s):  
Sequence Data ◽  
Negative Resistance ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Class A ◽  
Cephalosporin Resistance ◽  
Group 2 ◽  
Lactamase Gene ◽  
Type Strains

Fecal Klebsiella isolates from neonates in 22 Swedish special care units were examined by a PCR we developed for detection of the SHV-1 beta-lactamase gene. All 105 K. pneumoniae isolates and all 11 K. pneumoniae reference strains (including the K. pneumoniae subsp. pneumoniae, ozaenae, and rhinoscleromatis type strains) tested were positive, whereas all 67 K. oxytoca isolates and the K. oxytoca, K. planticola, and K. terrigena type strains tested were negative. Resistance to beta-lactams in K. pneumoniae was not transferable by conjugation, and the beta-lactamase gene was never found on a plasmid. Southern blot analysis showed that the gene had a defined chromosomal location. Isoelectric focusing and sequencing of 231-bp PCR amplicons from different isolates revealed many variants of the enzyme, with the two main groups being SHV-1 like (pI 7.6; 68 isolates) and LEN-1 like (pI 7.1; 14 isolates). Clavulanic acid markedly reduced the MICs of ampicillin for all the K. pneumoniae isolates tested. This fact, MIC profiles (penicillin rather than cephalosporin resistance), pIs, and sequence data showed that the chromosomal beta-lactamase of K. pneumoniae is a class A, group 2 enzyme distinct from the chromosomal AmpC enzymes found in several other gram-negative bacteria and from the chromosomal beta-lactamase K1 of K. oxytoca. We propose that the chromosomal beta-lactamase of K. pneumoniae be designated K2 and suggest that an allelic pI 7.6 variant of this enzyme is the ancestor of the SHV family of plasmid-mediated beta-lactamases.

scholarly journals Cloning and nucleotide sequence analysis of a gene encoding an OXA-derived beta-lactamase in Acinetobacter baumannii.

1997 ◽  
Vol 41 (12) ◽  
pp. 2757-2759 ◽  
Author(s):  
J Vila ◽  
M Navia ◽  
J Ruiz ◽  
C Casals
Keyword(s):  
Sequence Analysis ◽  
Nucleotide Sequence ◽  
Acinetobacter Baumannii ◽  
Clinical Strain ◽  
Nucleotide Sequence Analysis ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Gene Encoding ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics

A clinical strain of Acinetobacter baumannii (strain Ab41) that was resistant to all beta-lactam antibiotics tested except ceftazidime, ceftriaxone, ceftizoxime, and imipenem produced three beta-lactamases: a presumptive chromosomal cephalosporinase, a TEM-1-like beta-lactamase (pI 5.4), and a novel OXA-derived beta-lactamase named OXA-21 (pI 7.0). The gene encoding OXA-21 was located in an integron. The nucleotide sequence showed three mutations compared with the sequence of OXA-3, with two being silent; the nonsilent mutation generated a substitution of Ile-217 to Met.

scholarly journals Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors

Pharmacy ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 77 ◽  
Author(s):  
Kayla R. Stover ◽  
Katie E. Barber ◽  
Jamie L. Wagner
Keyword(s):  
Antimicrobial Activity ◽  
Case Reports ◽  
Cross Reactivity ◽  
Allergic Reactions ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Beta Lactamases ◽  
Chemical Structures ◽  
Lactamase Inhibitor

Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.

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