In Vitro Susceptibilities of Capnocytophaga Isolates to beta -Lactam Antibiotics and beta -Lactamase Inhibitors

Antibiotics can damage the gut microbiome leading to opportunistic infections and the emergence of antibiotic resistance. Microbiome protection via antibiotic inactivation in the gastrointestinal (GI) tract represents a strategy to limit antibiotic exposure of the colonic microbiota. Proof of concept for this approach was achieved with an orally-administered beta-lactamase enzyme, SYN-004 (ribaxamase), that was demonstrated to degrade ceftriaxone excreted into the GI tract and protect the gut microbiome from antibiotic-mediated dysbiosis. Ribaxamase efficiently degrades penicillin and cephalosporin beta-lactam antibiotics, but is not active against carbapenems. To expand this microbiome protection strategy to include all classes of beta-lactams, three distinct carbapenemases were evaluated for manufacturability, antibiotic degradation spectrum, and stability in human intestinal fluid. E. coli production strains were generated for P2A, a novel metallo-enzyme isolated from B. cereus, New Delhi metallo-beta-lactamase (NDM), and Klebsiella pneumoniae carbapenemase (KPC). While all three enzymes effectively inactivated a broad range of antibiotics, including penicillins, most cephalosporins, and carbapenems in vitro, only P2A retained biological activity when incubated with human chyme. As functional stability in the intestinal tract is a key requirement for an orally-delivered enzyme, P2A was chosen as a potential clinical candidate. An enteric formulation of P2A was developed, called SYN-006, that was inert under high acid conditions, with enzyme dissolution occurring at pH > 5.5. SYN-006 has the potential to expand microbiome protection via antibiotic inactivation to include all classes of beta-lactam antibiotics.

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In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.17.4.757 ◽

1980 ◽

Vol 17 (4) ◽

pp. 757-761 ◽

Cited By ~ 34

Author(s):

C N Baker ◽

C Thornsberry ◽

R N Jones

Keyword(s):

Antimicrobial Activity ◽

Neisseria Gonorrhoeae ◽

Haemophilus Influenzae ◽

Beta Lactamase ◽

Beta Lactam ◽

In Vitro Antimicrobial Activity ◽

Beta Lactam Antibiotics

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Features of resistance formation of gram-negative non-fermenting bacteria to antibiotics

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2018-22(2)-03 ◽

2018 ◽

Vol 22 (2) ◽

pp. 253-256

Author(s):

V.M. Kondratuk ◽

Z.M. Prokopchuk ◽

V.M. Burkot ◽

I.M. Vovk

Keyword(s):

Fourth Generation ◽

Diffusion Method ◽

Beta Lactamase ◽

Beta Lactam ◽

Antibacterial Drugs ◽

Gram Negative ◽

Beta Lactam Antibiotics ◽

Development Of Resistance ◽

Fermenting Bacteria

The problem of the antibiotic resistance development of pathogenic microorganisms to the main groups of antibacterial drugs has evolved from medical to socio-economic. There is a resistance increase of P.aeruginosa, A.baumannii belonging to the group of gram-negative non-fermenting bacteria (GNB), to antibiotics that are used in medicine. The possibility of acquiring GNB resistance to the main groups of antibacterial drugs is related to the ability of bacteria to acquire new genetic information. The production of metal-beta-lactamase by GNB become a widespread problem of resistance to beta-lactam antibiotics. Detection of resistance genes to beta-lactam antibiotics blaVIM, blaOXA 23, blaOXA 40, blaOXA 69 and blaOXA 100 was performed using real time polymerase chain reaction (PCR-RT). Sensitivity of isolated strains of microorganisms to antibiotics was investigated using the standard disco-diffusion method (DDM). Influence of meropenem on formation of microorganism resistance was investigated in vitro by method of microorganisms passage on meat-peptone broth (MPB) with increasing concentrations of antibiotics. In the process of research, 14 clinical strains of P. aeruginosa and 30 strains of A.baumannii were isolated and identified, almost all strains of these types of bacteria, characterized by resistance to antibiotics-carbapenems and third and fourth generation of cephalosporins. At the same time, the three strain-carries of markers of beta-lactamase products exhibited resistance to carbapenems, and one of the strains (P.aeruginosa No. 68) was capable of producing MBL, according to DDM, was sensitive to carbapenems and MCC was 31.2 μg / ml for it. Among the investigated strains of A.baumannii 18 (60%) out of 30 isolated ones were potential producers of beta-lactamases, capable of inactivating carbapenem antibiotics. In this case, only 6 out of 18 strains showed resistance to carbapenems according to DDM. Sensitivity to carbapenems revealed all strains of the beta-lactamase producers OXA 69 and OXA 100 and three strains – OXA 23. In this work, modern ideas about the mechanisms of development of resistance of GNB were described, isolated from patients of medical institutions (Vinnytsa city), the most common are producers of beta-lactamase types of OXA 23, OXA 69, OXA 100 and VIM.

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Tuberculosis and beta-lactam antibiotics

Future Microbiology ◽

10.2217/fmb-2019-0318 ◽

2020 ◽

Vol 15 (10) ◽

pp. 937-944

Author(s):

Mehmet Akif Gun ◽

Bulent Bozdogan ◽

Ahmet Yilmaz Coban

Keyword(s):

Multidrug Resistant ◽

Future Perspective ◽

Cell Wall Biosynthesis ◽

Beta Lactamase ◽

Beta Lactam ◽

Control Programs ◽

Beta Lactam Antibiotics ◽

The World

Tuberculosis (TB) is one of the oldest health problems in the world and it remains unresolved. Multidrug-resistant-TB and extensively resistant-TB are a serious problem for control programs. The evaluation of available antibiotics has gained importance in recent years for the treatment of resistant TB. Beta-lactam antibiotics inhibit cell wall biosynthesis in the bacteria; the presence of beta-lactamase enzyme in TB bacilli raises the question of whether this group of antibiotics can be used in treatment. As a result, it has been reported that the combination of beta-lactam antibiotics with beta-lactamase is effective against Mycobacterium tuberculosis both in vitro and in vivo. The aim of this article is to review and discuss up-to-date knowledge and future perspective on beta-lactam antibiotics and TB.

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