In vitro and in vivo antibacterial activity of T-1982, a new semisynthetic cephamycin antibiotic

The antimicrobial activities of BMY-28142, cefbuperazone (BMY-25182; formerly T-1982), and cefpiramide (WY-44635; formerly SM-1652) were compared with those of cefmenoxime, cefoperazone, cefotaxime, ceftizoxime, and moxalactam. BMY-28142 was the most active cephalosporin against the majority of aerobic and facultatively anaerobic microorganisms studied. Its spectrum of activity was very similar to that of cefotaxime. However, BMY-28142, cefbuperazone, cefmenoxime, cefotaxime, ceftizoxime, and moxalactam were equivalent in activity and rate of killing against members of the family Enterobacteriaceae. Cefpiramide was considerably less active than the other cephalosporins against the Enterobacteriaceae.There has been remarkable progress in the development of new P-lactam antibiotics in the past few years (1, 5). These antimicrobial agents possess increased resistance to hydrolysis by bacteria-mediated P-lactamases (10,14), excellent activity against aerobic and facultative anaerobic gramnegative bacteria (10,11,16) 576, 1983). Information on their in vitro spectra of activity, however, is limited (3,8,9,20,21). In this report we compared the in vitro antibacterial activity of these cephalosporins with those of cefmenoxime, cefoperazone, cefotaxime, ceftizoxime, and moxalactam against fresh nosocomial isolates. In addition, the bactericidal activities of these antimicrobial agents were determined by a time-kill assay.The cephalosporins compared in this study were chosen to represent those used clinically and those in the final stages of development. The (ATCC 25923), were used throughout the study as control organisms.MICs were determined by using a microtiter broth dilution technique similar to that described by Gavan and Barry (6). Briefly, each bacterial suspension was obtained by inoculating Mueller-Hinton broth (Difco Laboratories, Detroit, Mich.) with 0.1 ml of an overnight culture, incubating, and adjusting the density of the fresh bacterial suspension with a spectrophotometer to contain 108 CFU per ml.

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confidence: 99%

“…Several 576,1983). Information on their in vitro spectra of activity, however, is limited (3,8,9,20,21). In this report we compared the in vitro antibacterial activity of these cephalosporins with those of cefmenoxime, cefoperazone, cefotaxime, ceftizoxime, and moxalactam against fresh nosocomial isolates.…”

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confidence: 99%

Antimicrobial activities of BMY-28142, cefbuperazone, and cefpiramide compared with those of other cephalosporins

Khan¹,

Bihl²,

Schell³

et al. 1984

“…These inocula, which were prepared from overnight cultures on brain heart infusion agar (Eiken) at 37°C, were suspended in 1/15 M phosphate buffer (pH 7.0) containing 5% gastric mucin (Nacalai Tesque Co., Ltd., Kyoto, Japan); Streptococcus pneumoniae and Escherichia coli, however, were suspended in brain heart infusion broth (Eiken) and saline solution, respectively. In all cases except Streptococcus pneumoniae, a series of doses of the agents, which were increased by twofold increments, were administered orally once at 1 h after infection (15); with Streptococcus pneumoniae the agents were administered twice, at 1 and 3 h after challenge. The total number of surviving mice at day 7 postchallenge was recorded, and the dose of drug that gave protection to 50% of the infected mice was determined by the method of Litchfield and Wilcoxon (9).…”

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confidence: 99%

“…MICs were determined by the twofold agar dilution method (15) with Mueller-Hinton agar (Eiken Chemical Co., Ltd., Tokyo, Japan) which was supplemented with 10% sheep blood to support the growth of streptococci. Chocolate agar, GAM agar (Nissui Seiyaku Co., Ltd., Tokyo, Japan), and buffered starch-yeast extract agar (13) were used for Moraxella catarrhalis and Haemophilus influenzae, obligate anaerobes, and Legionella spp., respectively.…”

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confidence: 99%

In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative

Fukuoka

Ikeda

Yamashiro

et al. 1993

Self Cite

T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 ,Lg/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 ,ug/ml against gram-negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 p,g/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and MoraxeUa; 0.025 ,g/ml against Legionella spp.; and 6.25 to 25 ±g/ml against anaerobes, including Bacteroides fragilis, Clostridium difJicile, and Peptostreptococcus spp. The in vitro activity of T-3761 against these clinical isolates was comparable to or 2-to 32-fold greater than those of ofloxacin and norfloxacin and 2-to 16-fold less and 1-to 8-fold greater than those of ciprofloxacin and tosufloxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2-to 14-fold greater than those of the reference agents.

“…Cephamycins such as cefbuperazone, moxalactam, cefotetan, cefmetazole and cefoxitin are intrinsically stable against various ,3-lactamases (15,18,21). Because of this, these antibiotics were provided with excellent antibacterial activity against bacterial pathogens including Bacteroides fragilis.…”

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confidence: 99%

Cephamycin inactivation due to enzymatic hydrolysis by beta-lactamase from Bacteroides fragilis

Yotsuji¹,

Minami²,

Kakizawa³

et al. 1985

Self Cite

The susceptibility of 53 clinical isolates of Bacteroides fragilis to cephamycins was examined. Judging from the MICs for 50% of the strains tested, moxalactam was the most active, however, judging from the MICs for 90% of the strains tested, cefbuperazone was more effective than moxalactam. A correlation was observed between in vitro activity of benzylpenicillin and cephaloridine and beta-lactamase production. Inactivation due to enzymatic hydrolysis of cephamycins over a short time was not observed; however, inactivation was detected by a double disk diffusion test, and moxalactam was most easily inactivated. We conclude that inactivation due to enzymatic hydrolysis of cephamycins over a long time may play an important role in resistance to some cephamycins in strains of B. fragilis.