PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams.

1996 ◽  
Vol 34 (12) ◽  
pp. 2909-2913 ◽  
Author(s):  
K Senda ◽  
Y Arakawa ◽  
S Ichiyama ◽  
K Nakashima ◽  
H Ito ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Pcr Detection ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
Gram Negative ◽  
Lactamase Gene

scholarly journals Multifocal outbreaks of metallo-beta-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum beta-lactams, including carbapenems.

1996 ◽  
Vol 40 (2) ◽  
pp. 349-353 ◽  
Author(s):  
K Senda ◽  
Y Arakawa ◽  
K Nakashima ◽  
H Ito ◽  
S Ichiyama ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Early Recognition ◽  
Carbapenem Resistance ◽  
Hybridization Analysis ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
Imipenem Resistance ◽  
High Level ◽  
Lactamase Gene

A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.

scholarly journals Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens.

1995 ◽  
Vol 39 (4) ◽  
pp. 824-829 ◽  
Author(s):  
H Ito ◽  
Y Arakawa ◽  
S Ohsuka ◽  
R Wacharotayankun ◽  
N Kato ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
The Other ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
E Coli ◽  
Aichi Prefecture ◽  
Imipenem Resistance ◽  
High Level ◽  
Lactamase Gene ◽  
Moderately Resistant

The distribution of strains producing metallo-beta-lactamase among 105 strains of Serratia marcescens was investigated. All of these strains were isolated in seven general hospitals located in Aichi Prefecture, Japan, from April to May 1993. Southern hybridization analysis suggested that four S. marcescens strains, AK9373, AK9374, AK9385, and AK9391, had a metallo-beta-lactamase genes similar to the blaIMP gene found by our laboratory (E. Osano, Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato, Antimicrob. Agents Chemother. 38:71-78, 1994), and these four strains showed resistance to carbapenems as well as to the other broad-spectrum beta-lactams. In particular, strains AK9373, AK9374, and AK9391 showed an extraordinarily high-level resistance to imipenem (MICs, > or = 64 micrograms/ml), whereas strain AK9385 demonstrated moderate imipenem resistance (MIC, 8 micrograms/ml). The imipenem resistance of AK9373 was transferred to Escherichia coli CSH2 by conjugation with a frequency of 10(-5). The DNA probe of the blaIMP gene hybridized to a large plasmid (approximately 120 kb) transferred into the E. coli transconjugant as well as to the large plasmids harbored by AK9373. On the other hand, although we failed in the conjugational transfer of imipenem resistance from strains AK9374, AK9385, and AK9391 to E. coli CSH2, imipenem resistance was transferred from these strains to E. coli HB101 by transformation. A plasmid (approximately 25 kb) was observed in each transformant which acquired imipenem resistance. The amino acid sequence at the N terminus of the enzyme purified from strain AK9373 was identical to that of the metallo-beta-lactamase IMP-1. In contrast, strains ES9348, AK9386, and AK93101, which were moderately resistant to imipenem (MICs, > or = 4 to < or = 8 micrograms/ml), had no detectable blaIMP gene. As a conclusion, 19% of clinically isolated S. marcescens strains in Aichi Prefecture, Japan, in 1993 were resistant to imipenem (MICs, > or = 2 micrograms/ml), and strains which showed high-level imipenem resistance because of acquisition of a plasmid-mediated blaIMP-like metallo-beta-lactamase gene had already proliferated as nosocomial infections, at least in a general hospital.

scholarly journals AmpN-AmpG Operon Is Essential for Expression of L1 and L2 β-Lactamases in Stenotrophomonas maltophilia

2010 ◽  
Vol 54 (6) ◽  
pp. 2583-2589 ◽  
Author(s):  
Yi-Wei Huang ◽  
Cheng-Wen Lin ◽  
Rouh-Mei Hu ◽  
Yu-Tzu Lin ◽  
Tung-Ching Chung ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Gene Dosage ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Gene Dosage Effect ◽  
Gram Negative ◽  
E Coli ◽  
Murein Sacculus ◽  
Lactamase Gene ◽  
L1 And L2

ABSTRACT AmpG is an inner membrane permease which transports products of murein sacculus degradation from the periplasm into the cytosol in Gram-negative bacteria. This process is linked to induction of the chromosomal ampC beta-lactamase gene in some members of the Enterobacteriaceae and in Pseudomonas aeruginosa. In this study, the ampG homologue of Stenotrophomonas maltophilia KJ was analyzed. The ampG homologue and its upstream ampN gene form an operon and are cotranscribed under the control of the promoter P ampN. Expression from P ampN was found to be independent of β-lactam exposure and ampN and ampG products. A ΔampN allele exerted a polar effect on the expression of ampG and resulted in a phenotype of null β-lactamase inducibility. Complementation assays elucidated that an intact ampN-ampG operon is essential for β-lactamase induction. Consistent with ampG of Escherichia coli, the ampN-ampG operon of S. maltophilia did not exhibit a gene dosage effect on β-lactamase expression. The AmpG permease of E. coli could complement the β-lactamase inducibility of ampN or ampG mutants of S. maltophilia, indicating that both species have the same precursor of activator ligand(s) for β-lactamase induction.

Use of Antimicrobials and Toxicity

2019 ◽  
Author(s):  
Armine Sefton
Keyword(s):  
Immune System ◽  
Broad Spectrum ◽  
Therapeutic Index ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gram Positive ◽  
Gram Negative ◽  
Narrow Spectrum ◽  
Source Of Infection ◽  
Bactericidal Agent

Broad-spectrum antibacterial agents kill most bacteria including gram-positive rods and cocci, gram-negative rods and cocci, and often anaerobes too. Narrow-spectrum agents kill a narrow range of microbes, e.g. benzylpenicillin is mainly active against gram-positive cocci. By and large a narrow-spectrum antimicrobial is less likely to disrupt a patient’s normal flora than a broad-spectrum agent. Hence, if the likely organism is causing an infection it is best to give a narrow-spectrum antimicrobial to treat that specific organism. If a patient presents ‘septic’ and the source of infection is unknown, relevant cultures should be taken followed by broad-spectrum antimicrobial cover. This can later be modified either when the source of infection is found or as a result of microbiology culture results. ● Agents mostly active against gram-positive bacteria include: ■ Penicillin (Also active against Neisseria spp.). ■ Fusidic acid. ■ Macrolides (Also active against Legionella, Campylobacter, Bordetella spp.). ■ Clindamycin. ■ Glycopeptides. ■ Oxazolidinones. ■ Streptogramins. ● Agents mainly active against gram-negative bacteria include: ■ Polymyxin. ■ Trimethoprim. ■ Aminoglycosides (also active against staphylococci and show synergy when combined with beta-lactams against/glycopeptides against streptococci). ■ Monobactams. ■ Temocillin. ● Broad-spectrum antimicrobials include: ■ Beta-lactam plus beta-lactamase inhibitor combinations. ■ Cephalosporins. ■ Carbapenems. ■ Chloramphenicol, Tetracyclines/Glycyclines. A bactericidal agent is a compound that actively kills multiplying bacteria. A bacteriostatic compound inhibits the growth of bacteria. Whether or not an antimicrobial is bactericidal or bacteriostatic depends on a variety of things, including the type of agent, its concentration, and the organism it is being used to treat. It is especially important to try and use a bactericidal agent if the patient’s immune system is impaired or the infection is at a site where it is difficult for the immune system to access, e.g. the heart valves in bacterial endocarditis, the meninges in meningitis. Examples of each are given here: ● Bactericidal agents include beta-lactams, glycopeptides, fluoroquinolones, and aminoglycosides. ● Bacteriostatic agents include macrolides, clindamycin, tetracyclines, trimethoprim, and sulphonamides. The therapeutic index of a drug is the ration of the concentration of drug likely to be toxic to the patient divided by the concentration of drug likely to be clinically effective.

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 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.

Sign in / Sign up

Export Citation Format

Share Document