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PubMed1987

[Prophylactic effects of cefmenoxime against postoperative infections after thoracotomy. Studies of cefmenoxime transfer from serum to pleural fluid and of clinical effects of cefmenoxime].

Cefmenoxime (CMX) at a dose of 1 g was administered intravenously to each of 10 patients undergoing thoracotomy, and concentrations of CMX in the serum and pleural fluid were measured. Serum concentration of CMX reached its peak of 43.71 micrograms/ml at 1 hour and decreased to 4.15 micrograms/ml at 3 hours after the administration. The concentration of CMX in the pleural fluid reached its peak of 7.61 micrograms/ml at 3 hours and decreased slowly 5.26 micrograms/ml at 7 hours after the administration. A clinical study with 21 patients was performed to evaluate the effect of CMX as a prophylactic antimicrobial agent in thoracotomy. Patients received intravenous administration of 4 g/day of CMX for 7-10 days following operations. Each patient was evaluated daily for fever, sign of allergic reaction, and wound infection and other symptoms. No apparent infection occurred in those clinical patients except 1 patient with a suspected infection, and 1 case of allergic reaction as exanthema was observed during this study. Prophylactic effect of CMX against postoperative infection after thoracotomy was good.

Adult↗
PubMed1987

[Clinical study of cefmenoxime in thoracic surgery. Transfer of cefmenoxime to lung tissue and pleural fluid and prophylaxis of postoperative infections].

Twenty-six patients who underwent pulmonary resection for the lung disease were administered 1 g of cefmenoxime (CMX) by intravenous drip infusion just before the operation. The CMX levels in the serum, lung tissue and pleural fluid were measured using the agar-well technique. The effect of the drug on the prophylaxis of postoperative infections was investigated. The obtained results are summarized as follows; 1. The peak concentration of CMX in the serum was 58.23 micrograms/ml 1 hour after starting the drip infusion of 1 g of CMX. The serum half-life of CMX (beta-phase) was 2.15 hours. 2. The ratio of the CMX concentration in lung tissue to the peak serum level was 14.9% 202 minutes after starting the drip infusion. In the pulmonary lesion, the ratio was 9.72% at the 201 minutes. In the bronchiole, the ratio was 20.7% 191 minutes after starting the drip infusion. 3. The concentration of CMX in the pleural fluid was 2.53 micrograms/ml 12 hours after starting the drip infusion. 4. CMX is useful as a prophylaxis of postoperative infections after thoracotomy, because no postoperative infectious complications were observed.

Adult↗
PubMed1984

[Clinical laboratory approach for estimating effective administrative dosage of cefmenoxime. Observation on the MICS and cefmenoxime disc susceptibility test].

The in vitro activity of cefmenoxime (CMX) was determined using agar dilution at inoculum level of 10(6) cfu/ml against 333 clinical bacterial isolates. CMX was highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter aerogenes and Haemophilus influenzae and also Streptococcus Pyogenes and Streptococcus pneumoniae with MIC values in the range of 0.024 to 3.13 micrograms/ml. Against Staphylococci and Serratia marcescens, CMX showed the antimicrobial activity with MIC90 6.25 micrograms/ml. However, CMX was not active against Pseudomonas aeruginosa and Acinetobacter anitratus and exhibited no useful activity against Streptococcus faecalis. Reliability of CMX disc diffusion susceptibility test for quantitative estimation of the antimicrobial activity was also investigated, using 8 mm diameter disc (Showa) and 6 mm diameter disc (Wako), both of them containing 30 micrograms of CMX. These disc susceptibility test results were well correlated with MICs, capable of utilizing CMX disc susceptibility test for the estimation of proper administrative dose of CMX. Using 6 mm diameter disc containing 30 micrograms CMX, FUCHS et al. have proposed the following tentative zone size break points: greater than or equal to 22 mm = MIC 8 micrograms/ml, susceptible; 15 to 21 mm = MIC 16 approximately 32 micrograms/ml, moderately susceptible (intermediate); and less than or equal to 14 mm = MIC greater than 32 micrograms/ml, resistant. In this investigation, the following zone size break points have preferred: greater than or equal to 25 mm = MIC less than or equal to 3 micrograms/ml (3+); 20 to 24 mm = MIC greater than 3 to 15 micrograms/ml (2+); 16 to 19 mm = MIC greater than 15 to 60 micrograms/ml (+) and less than or equal to 15 mm = MIC greater than or equal to 60 micrograms/ml (-). Based on CMX pharmacokinetic data currently available, MIC break points proposed, less than or equal to 3 micrograms/ml and less than or equal to 15 micrograms/ml, would be useful for estimating the administrative dose of this antibiotic to obtain the effective blood level (e.g. the bacteriostatic activity in serum 1: greater than or equal to 8 for treatment of severe infection.

Bacteria↗
PubMed1983

[Clinical study of cefmenoxime in acute peritonitis: clinical effect and tissue concentration of cefmenoxime].

A new antibiotic drug of cephalosporin group, with marked resistance of beta-lactamase, cefmenoxime (CMX) for parenteral use was tested in 15 patients with acute peritonitis. CMX in a dose of 500 mg was given intramusculary before the operation, to 8 cases with appendicitis, and 2 cases with intestinal obstruction. In 3 cases with appendicitis and a case with intestinal perforation, CMX in a dose of 500-1,000 mg was given by intravenous injection before or during the operation. And in a case with appendicitis, CMX in a dose of 1 g was given by intravenous drip infusion before the operation. Tissue specimens of different sites or body fluids were taken during the operation and from the removed organs. The materials of purulent ascites were subsequently taken at intervals. Determination of CMX concentration was performed according to cup bioassay method with Proteus mirabilis ATCC 21100 strain. The peak of CMX concentration in purulent ascites of patient with panperitonitis for intestinal perforation was 39.5 microgram/ml at 41 minutes after 1 g intravenous administration. Concentration of CMX in pus in the appendix was 52.5 microgram/ml at 20 minutes after 1 g intravenous administration. In 15 patients with acute peritonitis, 11 patients were given CMX in a dose of 500 mg by intramuscular administration twice a day, and the serious 4 patients were given in a dose of 500 mg to 1 g by intravenous drip infusion twice a day. Clinical response was excellent in 10 cases, good in 5 cases, fair and poor were none.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1984

Effect of protein binding on cefmenoxime steady-state kinetics in critical patients.

The effect of protein binding on cefmenoxime steady-state kinetics was studied in 20 critical patients with gram-negative pneumonia. Sixteen patients were given 1 gm cefmenoxime every 6 hr, two received 2 gm every 6 hr, and two received 2 gm every 8 hr. Serum protein binding was measured by equilibrium dialysis. Assays were by HPLC. Serum cefmenoxime concentration-time data were characterized by a model-independent method based on statistical moment theory. Despite varying renal function in patients, mean cefmenoxime serum concentration-time curves for all three dosing regimens were closely aligned, reflecting successful empiric dosage adjustment. Terminal phase t 1/2 ranged from 0.8 to 2.9 hr and was significantly related to creatinine clearance. Cefmenoxime total clearance was significantly related to both lambda z (2.303 times the slope of the terminal portion of the log-concentration-time curve) and creatinine clearance (CCr). Plasma clearance of free cefmenoxime was more strongly correlated with CCr than the clearance of total cefmenoxime. Drug recovery from 24-hr urine collections at steady state was 76.9 +/- 19.8% of the daily dose (mean +/- SD, n = 13). Cefmenoxime protein binding in patients differed markedly from normal values. A regression equation derived from data on 11 cephalosporins appeared to predict total volume of distribution in the steady state (Vdss-Total) from the fraction of unbound drug accurately. Since cefmenoxime has a high therapeutic index, no clinical consequences are expected to result from variation in protein binding. Observed differences in protein binding between patients and normal subjects could have clinical consequences for highly bound acidic drugs that, unlike cefmenoxime, have narrow therapeutic indices.

Aged↗
PubMed1981

Antimicrobial activity of cefmenoxime (SCE-1365).

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except Staphylococcus aureus. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC(90)) ranged from 0.06 to 8 mug/ml for the Enterobacteriaceae. The MIC(90)s for gram-positive cocci were 0.015 and </=0.008 mug/ml for Streptococcus pneumoniae and Streptococcus pyogenes, respectively, and 2 mug/ml for S. aureus. Group D streptococci were less susceptible. Cefmenoxime was very active against Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis with MIC(90)s ranging from </=0.008 to 0.25 mug/ml. Cefmenoxime, at a concentration of 16 mug/ml, inhibited 78% and 73% of Pseudomonas aeruginosa and Acinetobacter spp., respectively. MICs for anaerobes ranged from 0.5 to >128 mug/ml with good activity against the gram-positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the Enterobacteriaceae and 100% of P. aeruginosa strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, or S. aureus but was less effective against P. aeruginosa.

Animals↗
PubMed1992

Levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery.

It is not known whether a prophylactic antibiotic administered prior to surgery reaches adequate levels in the peritoneum, where peritonitis may take place. This study determined levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery. Fifteen patients who underwent elective gastrointestinal surgery received an intravenous drip infusion of cefmenoxime (2 g) over 1 h prior to surgery. In patients who underwent gastrectomy, the level of cefmenoxime in serum was 130.8 +/- 6.9 micrograms/ml at laparatomy and decreased to 5.0 +/- 0.7 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues at laparotomy were 35.3 +/- 5.2 and 19.2 +/- 3.5 micrograms, respectively, and decreased time dependently. In patients who underwent cholecystectomy, the level of cefmenoxime in serum was 137.9 +/- 7.3 micrograms/ml at laparotomy and decreased to 5.0 +/- 1.2 micrograms/ml at 4 h. Levels in parietal peritoneal and omental tissues were 31.0 +/- 8.4 and 13.7 +/- 3.3 micrograms/g, respectively, and decreased time dependently. The level of cefmenoxime in serum correlated with the levels of cefmenoxime in parietal peritoneum (r = 0.64, P less than 0.01) and in omentum (r = 0.47, P less than 0.02). In patients with appendicitis who received a bolus injection of 2 g of cefmenoxime, the level of drug in inflammatory omental tissue correlated with the level in serum. The levels in peritoneal tissue during surgery lasting up to 2 h were significantly greater than in MIC of cefmenoxime against almost all bacteria reported. A preoperative single dose of 2 g of cefmenoxime probably is effective as a prophylactic for intraoperative contamination.

Cefmenoxime↗
PubMed1981

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

The activity of cefmenoxime (SCE-1365), 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, was compared with that of other cephalosporins. Cefmenoxime exhibited high activity against a wide variety of gram-positive and gram-negative bacteria. The in vitro activity of cefmenoxime against Streptococcus pyogenes, Haemophilus influenzae, and Enterobacteriaceae, including indole-positive Proteus, Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii, was 10 to 1,000 times greater than that of several other cephalosporins. Against Pseudomonas aeruginosa, cefmenoxime showed activity two to four times that of sulbenicillin and carbenicillin but less than that of cefsulodin. Variation in pH, addition of horse serum, and type of growth medium had definite effects on the activity of cefmenoxime, and the inoculum size affected the activity against bacterial species. In Escherichia coli cefmenoxime showed marked affinity for penicillin-binding protein 3 (PBP-3), followed by PBP-1 (1A and 1B). This affinity profile was well correlated with its filamentous cell-forming activity under extremely low drug concentrations and with its bactericidal activity against microorganisms. The high in vitro activity of cefmenoxime was reflected in the degree of protection observed in mice infected intraperitoneally with a wide variety of gram-positive and gram-negative bacteria. Furthermore, cefmenoxime showed good therapeutic activity against infection models in mice such as respiratory tract infection caused by Klebsiella pneumoniae and urinary tract infection caused by Proteus mirabilis.

Animals↗
PubMed1981

Cefmenoxime (SCE-1365), a new cephalosporin: in vitro activity, comparison with other antimicrobial agents, beta-lactamase stability, and disk diffusion testing with tentative interpretive criteria.

The in vitro activity of cefmenoxime (SCE-1365) was evaluated in a multiphased collaborative investigation. Over 7,500 consecutive clinical isolates were tested in five laboratories, and greater than 90% of the following organisms were inhibited by cefmenoxime at the following concentrations: Enterobacteriaceae and non-enterococcal streptococci, </=0.125 mug/ml; Staphylococcus aureus, </=2.0 mug/ml; and nonfermenting gram-negative bacilli and Bacteroides fragilis group, </=32 mug/ml. Both beta-lactamase-producing and -nonproducing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by cefmenoxime at </=0.03 mug/ml. The spectrum of cefmenoxime was similar to that of other, newer cephalosporins, particularly cefotaxime. A pronounced inoculum effect was found with some species upon increasing inocula from 10(5) to 10(7) colony-forming units per ml, resulting in an approximate eightfold increase in minimum inhibitory concentrations. Cefmenoxime was bactericidal when tested with inocula of 10(5) colonyforming units per ml, and mean differences between the minimum inhibitory concentration and the minimum lethal concentration were less than one log(2) dilution. No significant hydrolysis of cefmenoxime by five different beta-lactamases was detectable, and cefmenoxime exhibited marked inhibition of type I beta-lactamases. Regression and error rate-bounded analyses of results of disk diffusion and reference broth microdilution susceptibility tests were performed on 421 bacterial isolates, and the following tentative zone size breakpoints are proposed: >/=22 mm, susceptible; </=14 mm, resistant; and 15 to 21 mm, moderately susceptible (indeterminate). These data and cross-resistance studies with other newer cephalosporins indicate marked similarity of in vitro activity within this group of drugs, particularly between cefmenoxime, moxalactam, and cefotaxime. Any one of these could serve as the representative for the disk diffusion testing of this group of drugs if comparable minimum inhibitory concentration breakpoints were used for each drug.

Bacteria↗
PubMed1980

Absorption, distribution and excretion of cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin, in mice, rats, rabbits and dogs.

The levels of cefmenoxime (SCE-1365) [7 beta-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetr azol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid] and cefotaxime [7 beta-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-acetoxymethyl-ceph -3-em-4-carboxylic acid] in plasma and tissues, and the excretion in urine and bile of experimental animals were compared. A single dose of 20 mg/kg of cephalosporins was administered subcutaneously to mice and intramuscularly to rats, rabbits and dogs. The cefmenoxime and cefotaxime levels in plasma and tissues reached a peak in 15 approximately 30 minutes after administration. The cefmenoxime levels in plasma were slightly higher than that of cefmenoxime in rats and slightly lower in mice, rabbits and dogs. The tissue levels of cefmenoxime, however, were much higher than those of cefotaxime. In mice and rats, cefmenoxime was distributed in high concentration to various tissues in the descending order of the kidney, plasma, liver, lung, spleen and brain; in rabbits, kidney, plasma, lung, liver, spleen and brain; and in dogs, kidney, liver, plasma, lung, spleen and brain. The plasma and tissue levels of cefmenoxime persisted much longer than those of cefotaxime. Both cephalosporins were excreted principally in the urine. A high biliary excretion of cefmenoxime was observed in rats and dogs. In the specimens from animals given cefotaxime, deacetylcefotaxime was found in various amounts.

Absorption↗
PubMed1984

Metabolism of [14C]Cefmenoxime in normal subjects after intramuscular administration.

The metabolism of cefmenoxime (SCE-1365) was studied in four healthy male volunteers after intramuscular administration of a single 500-mg dose of the 14C-labeled drug. Plasma levels of total radioactivity and cefmenoxime peaked at 0.5 and 1.0 h, corresponding to 16.5 micrograms eq/ml and 15.8 micrograms/ml, respectively. Thereafter, parent drug levels declined rapidly, with a terminal elimination half-life of ca. 1.5 h. No significant differences were noted between total radioactivity and parent drug levels up to 2 h after drug administration. After 3 h, low but persistent levels of radioactivity were significantly greater than parent drug levels, indicating metabolism or degradation of cefmenoxime. The terminal elimination half-life of total radioactivity was estimated to be ca. 40 h. The radioactive plasma metabolite(s) remaining at the end of the 5-day study represented only 1% of the administered dose. Urinary excretion was the major route of elimination of cefmenoxime, accounting for ca. 86% of the dose in 12 h. Analysis of cefmenoxime in urine by total radioactivity, high-pressure liquid chromatography, and a microbiological assay showed that 80 to 92% of the excreted dose was parent drug. Radioactivity was also excreted into the feces via the bile and represented ca. 11% of the dose after 5 days. Although extensive degradation of cefmenoxime was found in fecal samples, it was proposed that this may be due to the metabolic activity of the intestinal flora rather than in vivo biotransformation in the liver. This study supports the concept that cefmenoxime undergoes minimal metabolism in humans and is excreted largely as unchanged drug.

Carbon Radioisotopes↗
PubMed1983

Laboratory evaluation of cefmenoxime: a new cephalosporin. In vitro and in vivo antibacterial activities and pharmacokinetic properties.

Cefmenoxime is a new syn-methoxyimino cephalosporin antibiotic derived from cefotiam, which has been proved to be a very effective and useful antibiotic for the treatment of respiratory infections. This bacteriological and pharmacokinetic study was therefore performed in order to evaluate the potency of cefmenoxime in the treatment of respiratory infections. The minimum inhibitory concentrations of cefmenoxime against 179 isolates of respiratory pathogens (Streptococcus pneumoniae 53, Haemophilus influenzae 64, Klebsiella pneumoniae 43, Escherichia coli 9, Enterobacter spp. 10) were less than 0.20 micrograms/ml, and 43 (73%) of 60 Pseudomonas aeruginosa were inhibited by 12.5 micrograms/ml. In vitro antibacterial activity of cefmenoxime was superior to 18 other antibiotics, including cefotiam and cefotaxime tested in this study. Pharmacokinetic studies on tissue distribution in rats, serum levels and urinary excretion in 3 healthy volunteers, and penetration into bronchial secretes of 9 patients with respiratory infections, revealed that cefmenoxime has a higher penetration into the lung and bronchial secretes compared with cefotiam and cefotaxime. In 1 patient with chronic bronchiolitis, the concentration of cefmenoxime in the intra-bronchial secrete reached 12.5 micrograms/ml. From these results, it is concluded that cefmenoxime is a highly potent and useful antibiotic, and may be more effective in the treatment of respiratory infections than many other cephalosporins, including cefazolin, cefotiam and cefotaxime.

Animals↗
PubMed1984

Cefmenoxime versus cefoxitin in the treatment of serious bacterial infections.

A comparative study was conducted using cefmenoxime, a new extended spectrum cephalosporin, versus cefoxitin. Entry into the study was based on a computer-generated randomization (two cefmenoxime to one cefoxitin). An intravenous dose of cefmenoxime (0.5 to 1 g every six hours) or cefoxitin (1 to 2 g every six hours) was administered to patients suspected of having serious bacterial infections. Six patients had urinary tract infections. Four who received cefmenoxime, including two with positive blood cultures, had eradication of bacteremia. One of the two who received cefoxitin had significant bacteriuria, and the urine was clear after treatment. Twenty-four patients were treated for lower respiratory tract infections. All 15 patients who received cefmenoxime had clinical and bacteriologic cures. Two of the nine patients who received cefoxitin continued to have the pathogens at the end of the treatment period. Both patients had a neoplasm of the lung. All 11 patients who had soft tissue infections (nine of whom received cefmenoxime) responded well. Both antibiotics were well tolerated.

Bacterial Infections↗
PubMed1986

Efficacy of cefmenoxime in experimental group B streptococcal bacteraemia and meningitis.

Cefmenoxime, a new semisynthetic cephalosporin, was evaluated in vitro and in vivo in comparison with penicillin G against a type III group B streptococcal strain. In vitro, the minimal inhibitory and minimal bactericidal concentrations of the two drugs were very close (less than or equal to 2 dilutions). In-vivo studies using experimental bacteraemia and meningitis in newborn rats revealed that despite similar drug levels, cefmenoxime had significantly greater bactericidal titres in blood at 6-7 h after administration and bacterial clearance from blood was significantly faster with cefmenoxime than with penicillin G at the end of one day of treatment. In addition, all animals with cefmenoxime therapy had bactericidal titres in cerebrospinal fluid greater than or equal to 1:8 at 1-2 h after administration, whereas most (67%) animals receiving penicillin G had titres less than 1:8. However, overall efficacy of cefmenoxime was similar to that of penicillin G. These findings suggest that cefmenoxime may be an effective alternative against group B streptococcal infection.

Animals↗
PubMed1991

Cefmenoxime and bilirubin: competition for albumin binding.

Certain drugs are known to compete with bilirubin for albumin binding; therefore, all drugs administered to neonates should be tested to determine the degree of competition. The effect of cefmenoxime on bilirubin-albumin binding was determined by comparing the oxidation rate of free bilirubin in the presence and absence of drug. The reserve albumin concentration (RAC) of pooled cord serum was also measured using the MADDS dialysis rate method. We show that cefmenoxime competes with bilirubin for albumin binding with a displacement constant, of 3.1 x 10(3) l/mol. The maximal displacement factor (MDF) is used to determine the clinical effect of the drug at usual serum concentrations. The MDF for cefmenoxime is 1.10, representing approximately a 10% increase in free bilirubin concentration. In comparison, the MDF for a known bilirubin displacing drug, sulfisoxazole, is 2.43. The MADDS method showed an estimated 28% decrease in the RAC at 150 mumol/l, the mean peak serum concentration (MPSC) of cefmenoxime. These results show while cefmenoxime affects bilirubin-albumin binding, the degree of the effect is relatively small. However, cefmenoxime may pose a hazard to very sick, premature infants, especially if the infant is jaundiced.

Bilirubin↗
PubMed1987

Comparative efficacy of cefotiam, cefmenoxime, and ceftriaxone in experimental endocarditis and correlation with pharmacokinetics and in vitro efficacy.

To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Animals↗
PubMed1987

Paradoxical antibacterial activity of cefmenoxime against Proteus vulgaris.

The growth-inhibitory effect of cefmenoxime against Proteus vulgaris was studied by using the broth dilution and paper disk diffusion methods. Cefmenoxime showed growth-inhibitory activity against Proteus vulgaris at low concentrations but not at high concentrations up to a certain limit. This paradoxical antibacterial activity was not observed with cefoperazone and cefbuperazone. The induction of beta-lactamase by cefmenoxime and the rate of hydrolysis of cefmenoxime in the culture broth were proportional to the initial concentration of this antibiotic. At high initial concentrations, cefmenoxime was rapidly inactivated. On the other hand, neither cefoperazone nor cefbuperazone was inactivated irrespective of concentration. We conclude that cefmenoxime induces beta-lactamase in P. vulgaris, perhaps accounting for its paradoxical antibacterial effect.

Cefmenoxime↗