Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities

Cefmenoxime, a new semisynthetic cephalosporin structurally similar to cefotaxime, was evaluated for its activities in vitro and in vivo against a Kl Escherichia coli strain in comparison with activities of cefotaxime and ampicillin. In vitro the MICs and MBCs of both cefmenoxime and cefotaxime were the same, 1/16th and 1/32nd those of ampicillin, respectively. The efficacies of cefmenoxime and cefotaxime against experimentally induced E. coli bacteremia and meningitis in newborn rats were similar and significantly better than that of ampicillin as judged by bactericidal titers of blood and cerebrospinal fluid, rapidity of clearance of bacteria from blood and cerebrospinal fluid, and incidence of meningitis in animals with bacteremias. The efficacy of cefmenoxime or cefotaxime measured by impact on mortality was influenced by the size of bacterial populations. The mortality was significantly greater in rats with bacterial counts before therapy of .106 CFU/ml of blood than in animals with lower counts. Overall, the in vivo efficacy of cefmenoxime was similar to that of cefotaxime; thus it could be useful in the therapy of neonatal E. coli infection.It has been shown previously that experimental Escherichia coli bacteremia and meningitis induced in the newborn rat is suitable for evaluating in vivo efficacies of various antimicrobial agents, particular in terms of rates of bacterial clearance from blood and cerebrospinal fluid (CSF) and of mortality (4-6). In these studies, it has been shown the activity of armpicillin against E. coli Kl is limited (4, 5), but that of cefotaxime is excellent. Results of recent studies, however, have shown that the outcome of E. coli infections in this model treated with cefotaxime is not significantly better than that of a conventional therapeutic regimen, ampicillin-gentamicin (K. S. Kim, submitted for publication). Recently, Tsuchiya et al. (12) have shown that cefmenoxime, a new cephalosporin structurally similar to cefotaxime, has greater protective and therapeutic activities than cefotaxime against members of the family Enterobacteriaceae in mice despite their similar activities in vitro. The present study was therefore performed to examine the activity of cefmenoxime in vitro and in vivo against E. coli and to compare the results with those of cefotaxime and ampicillin. MATERIALS AND METHODSOrganisms. A serum-resistant E. coli Kl strain (C5) isolated from the CSF ofa newborn infant with meningitis was used in this study.In vitro studies. The MICs and MBCs were measured in Mueller-Hinton broth (Difco Laboratories, Detroit, Mich.) by a macrobroth dilution mpethQd (13). Antimicrobial agents tested were cefmenoxime hydrochloride (Abbott Laboratories, TAP Pharmaceuticals, North Chicago, Ill.), ampicillin trihydrate (Bristol Laboratories, Syracuse, N.Y.) and cefotaxime sodium (Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.). All antibiotic solutions were serially twofold diluted from 16 to 0.03 ,ug/ml in Mueller-Hinton broth. Late logarithmic-phase cultures of strain C5 c...

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Efficacy of cefmenoxime in experimental Escherichia coli bacteremia and meningitis

Kim¹

1985

“…Ceftriaxone demonstrates good activity against Haemophilus sp., Neiserria gonorrheae, and Neisseria meningitidis and is generally as active as cefotaxime and moxalactam against members of the Enterobacteriaceae (4,19). Broad in vitro activity has also been observed with cefmenoxime (25,27). Cefsulodin was first introduced as an antipseudomonal cephalosporin (26) and, compared with other cephalosporins, is less active than ceftazidime but more active than cefoperazone or cefmenoxime against P. aeruginosa (10,26,27).…”

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confidence: 99%

In vitro susceptibility of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa to Amikacin and selected new beta-lactam agents

McNamara¹,

Meyer²,

Pasiecznik³

1982

Amikacin was evaluated in vitro by agar dilution testing against 148 different clinical isolates of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa in parallel with cephalothin, cefoxitin, moxalactam, N-formimidoyl thienamycin, ceftriaxone, and cefmenoxime. Cefsulodin was also evaluated against 39 isolates of P. aeruginosa. More than 80% of all isolates tested were also gentamicin resistant, as determined by disk testing. Moxalactam and amikacin had comparable high activities against Proteus species, Escherichia coli, Serratia species, and Providencia species, and both amikacin and N-formimidoyl thienamycin had comparably high activities against the Klebsiella-Enterobacter group. N-Formimidoyl thienamycin was the most active agent against P. aeruginosa, followed by cefsulodin and amikacin.

“…Several investigators have reported that B. fragilis strains produce a ,B-lactamase which has cephalosporinase activity and that it plays a significant role in the resistance of these organisms to B-lactam compounds (2,11,13,17,22). On the other hand, several newlactam compounds have been developed in recent years for the treatment of infections caused by resistant organisms which produce a ,-lactamase (1,7,9,20). Prominent among such compounds are cefoxitin, cefmetazole, moxalactam, and cefotetan, which are grouped as 7a-methoxy cephalosporins, and cefotaxime, ceftizoxime, and cefmenoxime, which are included in the 7p-methoxyiminoacetamido cephalosporin group.…”

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confidence: 99%

Comparative antibacterial activities of 7 alpha-methoxy cephalosporins and 7 beta-methoxyiminoacetamido cephalosporins against Bacteroides fragilis

Kesado¹,

Watanabe²,

Asahi³

et al. 1984

The in vitro antibacterial activities of the newly developed 7a-methoxy cephalosporins and 7I-methoxyiminoacetamido cephalosporins against 67 clinical isolates of Bacteroides fragilis and their resistance to the hydrolytic action of a ,-lactamase produced by B. fragilis were simultaneously compared. The minimal inhibitory concentrations that inhibited 90% of the 7a-methoxy cephalosporins, cefoxitin, cefmetazole, moxalactam, and cefotetan, against the isolates were 4, 8, 8, and 16 jig/ml, respectively, and these antibiotics were entirely resistant to hydrolysis by ,-lactamases (0.10 ,umol/h per mg of protein) of the isolates. By contrast, 7p-methoxyiminoacetamido cephalosporins represented by cefotaxime, ceftizoxime, and cefmenoxime were not effective, as indicated by the minimal inhibitory concentrations that inhibited 90%, 64, 32, and 128 ,ug/ml, respectively. Their antibacterial activities clearly corresponded to their resistance to the hydrolytic action of the P-lactamase: namely, the correlation coefficients in regression curves of cefotaxime, ceftizoxime, and cefmenoxime, which were expressed by the antibacterial activity (x axis) and the ,-lactamase activity (y axis) were 0.098, 0.034, and 0.163, respectively.In recent years, anaerobic bacteria, especially Bacteroides fragilis, have been isolated from clinical specimens with increasing frequency (6,8). Several investigators have reported that B. fragilis strains produce a ,B-lactamase which has cephalosporinase activity and that it plays a significant role in the resistance of these organisms to B-lactam compounds (2,11,13,17,22). On the other hand, several newlactam compounds have been developed in recent years for the treatment of infections caused by resistant organisms which produce a ,-lactamase (1,7,9,20). Prominent among such compounds are cefoxitin, cefmetazole, moxalactam, and cefotetan, which are grouped as 7a-methoxy cephalosporins, and cefotaxime, ceftizoxime, and cefmenoxime, which are included in the 7p-methoxyiminoacetamido cephalosporin group. Both groups are currently in clinical use. The present study was undertaken to compare the in vitro antibacterial activities of 7a-methoxy cephalosporins and 7,3-methoxyiminoacetamido cephalosporins against 67 clinical isolates of B. fragilis and to investigate whether there exists a correlation between their antibacterial activity and the resistance to the hydrolytic action of ,B-lactamases produced by B. fragilis. MATERIALS AND METHODSOrganisms. All of the 67 B. fragilis isolates tested were obtained from clinical specimens and were identified at the Institute of Anaerobic Bacteriology, Gifu University School of Medicine, Japan, according to the criteria of the Virginia Polytechnic Institute Anaerobe Laboratory Manual (21). Organisms were maintained at room temperature in tubes containing GAM semisolid medium (1% peptone, 0.3% soya peptone, 1% proteose peptone, 1.35% serum digest powder, 0.5% yeast extract, 0.22% beef extract powder, 0.12% liver extract powder, 0.3% glucose, 0.25% potassium dehydro...