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The Journal of Antibiotics Nov 1981The cephalosporin beta-lactamase (cephalosporinase) was purified from a strain of Proteus morganii which showed resistance to cephalosporins. The optimal pH was about...
The cephalosporin beta-lactamase (cephalosporinase) was purified from a strain of Proteus morganii which showed resistance to cephalosporins. The optimal pH was about 8.5, and the optimal temperature was 40 degrees C. The isoelectric point was 8.7 and the molecular weight was estimated to be about 41,000 from sodium dodecyl sulfate-acrylamide gel electrophoresis. The enzyme activity was inhibited by cloxacillin, ampicillin, carbenicillin, cefuroxime, cefotaxime, ceftizoxime (FK749), cefmenoxime (SCE-1365), cefoxitin, cefmetazole, YM09330 and moxalactam (6059-S), but not by clavulanic acid or CP-45899. The beta-lactamase also hydrolyzed cephaloridine, cefazolin, cephalothin, cephalexin, cefotiam, cefamandole and benzylpenicillin. These results suggest the possibility that the properties of beta-lactamases may be characterized by measuring the kinetic parameters of the enzyme toward newly-introduced beta-lactam antibiotics and beta-lactamase inhibitors.
Topics: Anti-Bacterial Agents; Cephalosporinase; Drug Resistance, Microbial; Electrophoresis, Polyacrylamide Gel; Isoelectric Focusing; Molecular Weight; Proteus; Substrate Specificity; beta-Lactamases
PubMed: 6976340
DOI: 10.7164/antibiotics.34.1469 -
Antimicrobial Agents and Chemotherapy Feb 1981N-Formimidoyl thienamycin (N-F-thienamycin) and moxalactam were compared with other currently available and investigational antibiotics against 100 clinical isolates of...
N-Formimidoyl thienamycin (N-F-thienamycin) and moxalactam were compared with other currently available and investigational antibiotics against 100 clinical isolates of Bacteroides fragilis by an agar dilution method. N-F-thienamycin was the most active among the beta-lactam agents tested, with a minimal inhibitory concentration for 90% of isolates (MIC90) of 0.25 micrograms/ml. Moxalactam was next in activity, with an MIC90 of 4 micrograms/ml. N-F-thienamycin was somewhat more active, and moxalactam was slightly less active, than metronidazole and clindamycin. An increase in inoculum size caused an increase in the MIC of N-F-thienamycin, cefoperazone, and cefotaxime. This inoculum effect could influence the usefulness of these drugs in certain clinical conditions. The minimal bactericidal concentration was less than two times the MIC for most agents and less than four times the MIC for all beta-lactam agents at each inoculum size tested. Investigation of the mechanism of resistance to beta-lactam agents demonstrated a correlation between the level of resistance and beta-lactamase activity in each strain tested. N-F-thienamycin and cefoxitin were not hydrolyzed, and moxalactam was less susceptible to hydrolysis than the other beta-lactam antibiotics. Moxalactam and N-F-thienamycin may prove to be useful against infections with B. fragilis.
Topics: Anti-Bacterial Agents; Bacteroides fragilis; Cephalosporins; Cephamycins; Drug Resistance, Microbial; Hydrolysis; Imipenem; Microbial Sensitivity Tests; Moxalactam; Thienamycins; beta-Lactamases; beta-Lactams
PubMed: 6214986
DOI: 10.1128/AAC.19.2.248 -
Antimicrobial Agents and Chemotherapy Jul 1982The pharmacokinetics of moxalactam were studied in 86 normal adult male volunteers who received single or multiple doses intravenously or intramuscularly. The short...
The pharmacokinetics of moxalactam were studied in 86 normal adult male volunteers who received single or multiple doses intravenously or intramuscularly. The short absorption half-times and lag times indicate that the intramuscular dose is rapidly absorbed. The mean plasma half-life was 1.85 +/- 0.24 h for intravenous doses and 2.24 +/- 0.44 h for intramuscular doses. The mean renal clearances for intravenous doses were 0.052 and 0.067 liters/kg per h for intramuscular doses. Although moxalactam is eliminated primarily by the kidney a chromatogram of the feces from volunteers who received multiple doses showed that it is also excreted as the parent compound in to the feces via the biliary tract. The pharmacokinetics parameters of moxalactam when administered intravenously or intramuscularly in single and multiple doses clearly show the kinetics of moxalactam are linear over the dosage ranges studied and are independent of dose.
Topics: Adult; Cephalosporins; Cephamycins; Feces; Humans; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Middle Aged; Moxalactam; Time Factors
PubMed: 6214998
DOI: 10.1128/AAC.22.1.94 -
Antimicrobial Agents and Chemotherapy Mar 1984The bactericidal activity of chloramphenicol against 27 strains of Salmonella typhi and 33 strains of S. enteritidis was compared with those of 11 other antibiotics. The...
The bactericidal activity of chloramphenicol against 27 strains of Salmonella typhi and 33 strains of S. enteritidis was compared with those of 11 other antibiotics. The geometric mean bactericidal concentrations of chloramphenicol against susceptible strains (36.10 and 43.13 micrograms/ml for S. typhi and S. enteritidis, respectively) far exceeded those of the other 11 antibiotics, with cephalothin having the next highest values (2.67 and 8.66 micrograms/ml) and moxalactam (0.09 and 0.28 micrograms/ml), cefotaxime (0.08 and 0.28 micrograms/ml), ceftriaxone (0.07 and 0.16 micrograms/ml), norfloxacin (0.06 and 0.10 micrograms/ml), and aztreonam (0.05 and 0.20 micrograms/ml) having the lowest values. The results for imipenem (0.24 and 0.81 micrograms/ml) and ceftazidime (0.22 and 0.75 micrograms/ml) were lower than those noted for trimethoprim-sulfamethoxazole (1.20 and 5.56 micrograms/ml), cefamandole (0.62 and 3.29 micrograms/ml), and ampicillin (0.55 and 2.78 micrograms/ml). The MBC of chloramphenicol for some isolates decreased with increased incubation times such that the proportion of susceptible isolates killed by chloramphenicol at concentrations within achievable levels in blood increased from 10% after 24 h to 26% after 48 h of incubation. Although the MBC of the other 11 antibiotics for some isolates were also lowered by prolonged incubation, all 24-h values were within achievable levels in blood. The data indicate that chloramphenicol is not uniformly bacteriostatic against S. typhi and S. enteritidis. The in vivo significance of demonstrating delayed killing by chloramphenicol is, however, uncertain.
Topics: Anti-Bacterial Agents; Chloramphenicol; Microbial Sensitivity Tests; Salmonella; Salmonella enteritidis; Salmonella typhi; Time Factors
PubMed: 6372681
DOI: 10.1128/AAC.25.3.327 -
Antimicrobial Agents and Chemotherapy Mar 1980Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in... (Comparative Study)
Comparative Study
Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.
Topics: Ampicillin; Animals; Bacteria; Bacterial Infections; Cephalosporins; Cephamycins; Disease Models, Animal; Gentamicins; Male; Meningitis; Moxalactam; Netilmicin; Rabbits; Species Specificity
PubMed: 6448576
DOI: 10.1128/AAC.17.3.406 -
Antimicrobial Agents and Chemotherapy Jan 1984The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of greater...
The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of greater than or equal to 60 ml/min. Moxalactam was administered in single or multiple intravenous or intramuscular doses. Rapid and complete intramuscular bioavailability was demonstrated in a subgroup of the study population. The mean plasma half-life was 2.9 +/- 0.8 h for intravenous doses and 3.5 +/- 0.9 h for intramuscular doses. Average renal clearances of 0.04 liters/kg per h accounted for 74.0 +/- 15.0% of total plasma clearance. Moxalactam plasma clearance showed a statistically significant (P less than 0.01) correlation with measured and calculated creatinine clearance. The major differences in moxalactam pharmacokinetics seen in the elderly appear to be related to diminishing renal function and highly variable nonrenal elimination. Creatinine clearance can be used in estimating moxalactam doses in the elderly without significant renal impairment, but recommendations for the use of serum creatinine as an estimation of renal function or drug half-life are not valid in this population group.
Topics: Aged; Biological Availability; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Middle Aged; Moxalactam
PubMed: 6703682
DOI: 10.1128/AAC.25.1.33 -
Antimicrobial Agents and Chemotherapy Mar 1998The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam,... (Comparative Study)
Comparative Study
The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.
Topics: Anti-Bacterial Agents; Bacteroides; Bacteroides fragilis; Cephamycins; Clostridioides difficile; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 9517922
DOI: 10.1128/AAC.42.3.495 -
Antimicrobial Agents and Chemotherapy Jun 1982Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or...
Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or proved bacterial infections outside the central nervous system. Six patients infected with Haemophilus influenzae b, nine infected with Staphylococcus aureus, three infected with Streptococcus pneumoniae, one infected with Streptococcus pyogenes, one infected with Enterobacter aerogenes, one infected with Fusobacterium nucleotum, and one infected with Staphylococcus epidermidis, microaerophilic streptococcus, and Propionibacterium sp. were clinically and bacteriologically cured. One patient with polymicrobial pansinusitis did not respond to moxalactam. No patients developed meningitis. All of the isolates tested were inhibited by less than or equal to 5 micrograms of moxalactam per ml, except for one Staphylococcus epidermidis isolate which was resistant to greater than 20 micrograms/ml. Five patients had transient neutropenia which resolved after the drug was discontinued. The mean peak serum level was 106 micrograms/ml at 15 min after a 50-mg/kg dose. The mean elimination half-life was 91.2 min. These data indicate that this dosage of moxalactam is a safe and effective treatment for bacterial infections outside the central nervous system.
Topics: Adolescent; Bacterial Infections; Cephalosporins; Cephamycins; Child; Child, Preschool; Female; Humans; Infant; Injections, Intravenous; Kinetics; Male; Moxalactam
PubMed: 6214210
DOI: 10.1128/AAC.21.6.898 -
Antimicrobial Agents and Chemotherapy Apr 1980Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria... (Comparative Study)
Comparative Study
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.
Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase-positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole.
Topics: Azlocillin; Cefoperazone; Cefotaxime; Cephalosporins; Cephamycins; Haemophilus influenzae; Mezlocillin; Microbial Sensitivity Tests; Moxalactam; Neisseria gonorrhoeae; Penicillin Resistance; Penicillins; beta-Lactamases
PubMed: 6249195
DOI: 10.1128/AAC.17.4.757 -
Journal of Clinical Pathology Sep 1992To compare CCFA (cycloserine, cefoxitin fructose agar) with a new selective medium CDMN (containing cysteine hydrochloride, norfloxacin, and moxalactam) for the... (Comparative Study)
Comparative Study
AIMS
To compare CCFA (cycloserine, cefoxitin fructose agar) with a new selective medium CDMN (containing cysteine hydrochloride, norfloxacin, and moxalactam) for the isolation of Clostridium difficile after direct faecal culture.
METHODS
The minimum inhibitory concentration (MIC) of norfloxacin was determined for 64 strains of C difficile, 17 strains of other Clostridium sp, and 66 various isolates of faecal origin, together with MIC determinations of moxalactam against the 81 strains of Clostridium sp and 15 isolates of Bacteroides sp. Using C difficile agar base with 0.5 g/l of cysteine hydrochloride, norfloxacin and moxalactam were incorporated into the medium and compared with CCFA for the isolation of C difficile after direct faecal culture.
RESULTS
Norfloxacin (12 mg/l) inhibited the growth of enterobacteriaceae and faecal streptococci; moxalactam (32 mg/l) inhibited the growth of most strains of Bacteroides sp tested, together with Clostridium sp other than C difficile. Using the antibiotics in combination (CDMN), the growth and colonial morphology of 64 strains of C difficile were unaffected. When CDMN medium was compared with CCFA for the isolation of C difficile from 832 faeces from inpatients with diarrhoea, the CDMN agar isolated 20% more strains and reduced the number of contaminating colonies by 30%.
CONCLUSIONS
CDMN both improves the isolation rate of C difficile from faecal specimens and reduces the growth of other organisms compared with CCFA.
Topics: Clostridioides difficile; Culture Media; Feces; Humans; Microbial Sensitivity Tests
PubMed: 1401214
DOI: 10.1136/jcp.45.9.812