Series Of Cephalosporins Research Articles

ANTIBIOTIC RESISTANCE OF E. COLI IN CLINICAL PRACTICE

Background: Antibiotic-resistance is one of the most important problems in modern medicine. The overuse and misuse of antibiotics caused the development of drug-resistant pathogens. It is the reason for more difficult treatment for patients. Objective: To monitor E.coli sensitivity to antibiotics and to evaluate its antibiotic resistance in a multidisciplinary hospital setting. Methods: The study is presented by a statistical analysis of the results of microbiological examination of materials obtained from patients infected with E.Coli, treated in different departments of Tver Clinical Emergency Hospital (Russia) in 2018-2020. A total of 142 results of microbiological examination of urogenital tract, abdominal cavity and wound surfaces were processed. Results: The number of antibiotics to which the Gram-negative Escherichia Coli is resistant also increases with the age of the patients. Among the investigated antibacterial drugs in terms of the total number of microorganisms with resistance to them, the lowest clinical efficacy was observed in the drugs of the cephalosporin series. Among the most frequent diseases caused by the studied strains of E.coli are intestinal infections and urinary tract infections. In addition, infections caused by persistence of E. coli as a background disease can significantly complicate the underlying disease. Conclusion: The results present a rapid spread of resistance genes in the studied E.coli strains. It is the imperative for the improvement of antibiotic resistance monitoring using various laboratory methods. Based on the results of microbiological research it is necessary to create a database that will allow to select the optimal strategy for the drug treatment of patients according to its resistance profile.

Efficacy of cephalosporins against enterobacteria isolated from patients with chronic osteomyelitis

Long-term antibiotic therapy, as well as inappropriate use of drugs in the treatment of osteomyelitis, can lead to the appearance of pan-resistant strains. The existing antibiotic prophylaxis regimens for purulent-septic complications are outdated and need to be adjusted. In this regard, it is necessary to monitor the resistance of microorganisms in order to identify ineffective antibacterial drugs. To analyze the resistance profiles of Enterobacteriaceae isolated from patients with chronic osteomyelitis to cephalosporin drugs over a three-year period. The resistance profiles of 912 clinical strains of Enterobacteriaceae were analyzed: Klebsiella pneumoniae (n=349), Proteus sp. (n=208), Escherichia coli (n=176), Enterobacter cloacae (n=179) for the period from 2018-2020 to cephalosporin drugs. In 2018, 66.2% of Enterobacteriaceace were resistant to the 1st generation cephalosporins, in 2019 - 78.7%, in 2020 - 79.5%. Generation II cephalosporins were most active against Proteus sp. bacteria, but a decrease in clinical effect was observed by 2020. Among the third generation cephalosporins in 2018, cefotaxime was most active, but in 2020 the number of resistant strains doubled and amounted to 86.3%. Ceftazidime was active against 47.1% of Enterobacteriaceae isolates in 2018, in 2019 - 45% of strains, in 2020 - 37.2% of bacterial strains. High activity of ceftriaxone was noted only in 2018 against Proteus sp. Preparations of the IV generation in 2018 showed the highest activity against bacteria of the genus Proteus, the least - against bacteria K. pneumoniae. In the period from 2019-2020, a significant decrease in the effectiveness of cefepime was observed.The monitoring of the resistance profiles to antibiotics of the cephalosporin series revealed their low efficacy against Enterobacteriaceae isolated from wounds and fistulas of patients with chronic osteomyelitis, which shows the inexpediency of their empirical use.

Enzymatic Destruction of Film Materials on the Basis of Chitosan in the Presence of Cephalosporin Series Antibiotics

Enzymatic Destruction of Film Materials on the Basis of Chitosan in the Presence of Cephalosporin Series Antibiotics

Enzymatic Decomposition of Chitosan-Based Film Materials Modified by Antibiotics of the Cephalosporin Series

The enzymatic decomposition of film materials based on chitosan with inclusions of cephalosporin antibiotics on a substrate impregnated with Ringer–Locke’s solution was studied. The introduction of antibiotics led to a decrease in the rate of the enzymatic decomposition of chitosan, as in the case of chitosan lysis in the presence of aminoglycoside antibiotics. A possible reason for the decrease in the rate of the enzymatic decomposition of chitosan is suppression of polyelectrolyte swelling in the presence of low-molecular electrolytes including medicinal agents. The introduction of drugs in the chitosan-based film is a potential method for selectively decreasing the rate of enzymatic hydrolysis of chitosan for increasing the service life of the film material on a wound surface.

The role of low-molecular-mass electrolyte drug substances in the modification of the chitosan matrix

The effect of antibiotics of the aminoglycoside and cephalosporin series on the properties of chitosan films formed from acetic acid solutions is studied. It is shown that the introduction of the indicated substances substantially affects the conformational state of chitosan acetate and its supramolecular structure. The modification of chitosan by drug substances, accompanied by loss in solubility of chitosan films in water, leads to a decrease in the rate of desorption of antibiotics from the polymer matrix.

Specific transport properties of medicinal chitosan films

Processes of water-vapor sorption by medicinal chitosan films and the kinetics of release of antibiotics of the cephalosporin series from these films have been studied. It has been found that the structural changes in the polymer matrix that are related particularly to its chemical modification via the interaction with drugs are the most probable cause of the deviation of the mass-transfer mechanism from the classical Fick’s mechanism.

Plant coumarins: VII. Amination of oreoselone trifluoromethanesulfonate

Amination of oreoselone trifluoromethanesulfonate with N-substituted piperazines, anabasine, aniline derivatives, quinolin- and isoquinolinamines, and amino acids of the penicillin and cephalosporin series in the presence of palladium complexes gave the corresponding N-substituted 3-aminofurocoumarins. The yield of the amination products depended on the catalytic system and base used.

ChemInform Abstract: Dual-Action Cephalosporins: Cephalosporin 3′-Quinolone Carbamates.

A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.

Multiple Pharmacokinetic Parameter Prediction for a Series of Cephalosporins

The goal of quantitative structure–pharmacokinetic relationship analyses is to develop useful models that can predict one or more pharmacokinetic properties of a particular compound. In the present study, a multiple‐output artificial neural network model was constructed to predict human half‐life, renal and total body clearance, fraction excreted in urine, volume of distribution, and fraction bound to plasma proteins for a series of cephalosporins. Descriptors generated solely from drug structure were used as inputs for the model, and the six pharmacokinetic parameters were simultaneously predicted as outputs. The final 10 descriptor model contained sufficient information for successful predictions using both internal and external test compounds. Descriptors were found to contribute to individual pharmacokinetic parameters to differing extents, such that descriptor importance was independent of the relationships between pharmacokinetic parameters. This technique provides the advantage of simultaneous prediction of multiple parameters using information obtained by nonexperimental means, with the potential for use during the early stages of drug development.

Reversed-Phase HPLC Determination of Antibiotics of the Cephalosporin Series in Biological Objects (Review)

Reversed-Phase HPLC Determination of Antibiotics of the Cephalosporin Series in Biological Objects (Review)

In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci.

Ro 63-9141 is a new member of the pyrrolidinone-3-ylidenemethyl cephem series of cephalosporins. Its antibacterial spectrum was evaluated against significant gram-positive and gram-negative pathogens in comparison with those of reference drugs, including cefotaxime, cefepime, meropenem, and ciprofloxacin. Ro 63-9141 showed high antibacterial in vitro activity against gram-positive bacteria except ampicillin-resistant enterococci, particularly vancomycin-resistant strains of Enterococcus faecium. Its MIC at which 90% of the isolates tested were inhibited (MIC(90)) for methicillin-resistant Staphylococcus aureus (MRSA) was 4 microg/ml. Ro 63-9141 was bactericidal against MRSA. Development of resistance to the new compound in MRSA was not observed. Ro 63-9141 was more potent than cefotaxime against penicillin-resistant Streptococcus pneumoniae (MIC(90) = 2 microg/ml). It was active against ceftazidime-susceptible strains of Pseudomonas aeruginosa and against Enterobacteriaceae except Proteus vulgaris and some isolates producing extended-spectrum beta-lactamases. The basis for the antibacterial spectrum of Ro 63-9141 lies in its affinity to essential penicillin-binding proteins, including PBP 2' of MRSA, and its stability towards beta-lactamases. The in vivo findings were in accordance with the in vitro susceptibilities of the pathogens. These data suggest the potential utility of Ro 63-9141 for the therapy of infections caused by susceptible pathogens, including MRSA. Since insufficient solubility of Ro 63-9141 itself precludes parenteral administration in humans, a water-soluble prodrug, Ro 65-5788, is considered for development.

CP6679, a new injectable cephalosporin. Part1: Synthesis and structure–activity relationships

A series of cephalosporins bearing a 5,5-fused ring system, an (imidazo[5,1- b]thiazolium-6-yl)methyl group, at the C-3 position were synthesized and evaluated for in vitro antibacterial activities. CP6679 ( 1s) and its analogues showed potent antibacterial activities against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. They were also highly active against methicillin-resistant Staphylococcus aureus (MRSA). CP6679 ( 1s) showed more potent antibacterial activity than ceftazidime (CAZ) or cefpirome (CPR) against Pseudomonas aeruginosa and MRSA.

The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as β-lactamase inhibitors

A series of 3-substituted-7-(alkylidene)cephaloporin sulfones were prepared and evaluated as inhibitors of representative class A and class C serine β-lactamase. Appropriate substituents resulted in a 1000-fold improvement in the inhibition of the class A enzymes and a simultaneous 20-fold improvement in the inhibition of class C. These new compounds have achieved the goal of creating broad scale inhibitors in the cephalosporin series.

Synthesis and activity of cephalosporins containing an oxyiminomethylene functionality in the ortho-position of a phenyl- or phenoxyacetic acid C-7 side chain substituent

A new series of cephalosporins having in the C-7 side chain a phenyl- or a phenoxyacetamido group bearing an oxyiminomethyl function in the ortho-position of the aromatic ring was prepared. Their in vitro activity was tested against both Gram+ and Gram− strains.

Synthesis and structure-activity relationship of C-3 quaternary ammonium cephalosporins exhibiting anti-MRSA activities

Abstract A series of cephalosporins bearing C-3 quaternary ammonium groups were prepared and evaluated for their anti-MRSA activity. They exhibit good to excellent in vitro activity (MICs = 1−8 μg/mL) against MRSA.

Synthesis and structure-activity relationship of C-3 benzoyloxymethyl cephalosporins exhibiting anti-MRSA activities

Abstract A series of cephalosporins bearing C-3 benzoyloxymethyl groups were prepared and evaluated for their anti-MRSA activity and plasma stability. They exhibit excellent in vitro activity (MIC = 0.06 ∼2 μg/mL) against MRSA and excellent stability in human plasma.

Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3′ or C-7 catechol or related aromatics

A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3′ catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6 S,7 S)-7-[2-(2-aminothiazol-4-yl)-2-[( Z)-[(1,5-dihydroxy-4-pyridon-2-yl)methoxy] imino]acetamido]-3-[[[(4-methyl-5-carboxymethyl)thiazol-2-yl]thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P. aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P. aeruginosa. A series of cephalosporins, 2-isocephems, and 2-oxaisocephems and C-3′ or C-7 catechol or related aromatics have been prepared and evaluated for antibacterial activity.

Carbon–hydrogen and carbon–carbon coupling patterns in the cephalosporin series

The 13C NMR spectra of the skeleton of 7-amino-3-cephem-4-carboxylic acid derivatives and the 2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetyl substituent were analysed searching for the rules which might be helpful in the structure determination of new cephalosporin antibiotics and their isomers. The 13C NMR decoupled spectra were fully interpreted on the basis of 13C–1H and 13C–13C coupling patterns. The method for unambiguous assignment of the Z/E geometry of 2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetyl groups was established.

Synthesis and Biological Activity of Novel Cephalosporins Containing a (Z)-Vinyl Dimethylphosphonate Group.

A series of cephalosporins containing a novel 7-[2-(Z)-(2-amino-thiazol-4- yl)-3-(dimethoxy-phosphoryl)-acryloylamino] group were prepared and their antibacterial activity measured against a range of pathogens. In general the compounds displayed a broad spectrum of activity against both Gram positive and Gram negative organisms, except Pseudomonas aeruginosa. Activity against the latter could be achieved by introducing a catechol moiety at the 3 position of the cephalosporin. The methyl phosphonates in general were stable to a wide range of beta-lactamases, including the TEM enzymes and the Enterobacter cloacae P99 chromosomal enzyme. In addition, they showed the advantage of being highly water soluble.

Synthesis and biological properties of 3-[( [formula omitted])-2-(1,2,3-Thiadiazolyl)ethenyl]-substituted cephalosporins and related compounds: new oral cephalosporins

A series of cephalosporins possessing a [( Z -2-(1,2,3-thiadiazolyl)ethenl] moiety at C-3 were synthesized and their biological properties were examined. SC-002 ( 1a) exhibited excellent activity against both Gram-positive and Gram-negative bacteria. The ester SC-004 ( 1b) showed good bioavailability after oral administration in mice and rats.