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Pharmaceuticals (Basel, Switzerland) Jan 2022Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every... (Review)
Review
Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every year leading to at least 20,000 deaths worldwide. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are β-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens. Among the several oxime based derivatives, cefuroxime, ceftizoxime, cefpodoxime and cefmenoxime are the FDA approved oxime-based antibiotics. Given the pharmacological significance of oximes, in the present paper, we put together all the FDA-approved oximes and discuss their mechanism of action, pharmacokinetics and synthesis.
PubMed: 35056123
DOI: 10.3390/ph15010066 -
Case Reports in Ophthalmological... 2020To present our findings in a case of delayed-onset postoperative endophthalmitis caused by , a rare organism. . A 57-year-old man presented with epiphora and photophobia...
PURPOSE
To present our findings in a case of delayed-onset postoperative endophthalmitis caused by , a rare organism. . A 57-year-old man presented with epiphora and photophobia 17 weeks after a routine cataract extraction with phacoemulsification and intraocular lens implantation. Because endophthalmitis was suspected to be caused by a low-grade pathogen or fungus, an anterior chamber tap was performed. However, both multiplex PCR and culturing were negative. The patient was treated with topical cefmenoxime, oral minocycline, and subconjunctival injection of vancomycin and ceftazidime, but the intraocular inflammation increased. Then, the anterior chamber was tapped again, and the second PCR amplification and direct sequencing which targeted detected , a rare organism.
CONCLUSION
This is the first reported case of an ocular disorder caused by . We recommend that be considered in cases of delayed-onset postcataract endophthalmitis.. We recommend that be considered in cases of delayed-onset postcataract endophthalmitis.
PubMed: 32231828
DOI: 10.1155/2020/1513069 -
Antimicrobial Agents and Chemotherapy Apr 1987To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three... (Comparative Study)
Comparative Study
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.
Topics: Animals; Cefmenoxime; Cefotaxime; Cefotiam; Ceftriaxone; Drug Evaluation, Preclinical; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Kinetics; Rabbits
PubMed: 3300530
DOI: 10.1128/AAC.31.4.518 -
Antimicrobial Agents and Chemotherapy Mar 1981The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and... (Comparative Study)
Comparative Study
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.
Topics: Animals; Bacteria; Bacterial Infections; Cefamandole; Cefazolin; Cefmenoxime; Cefotaxime; Cefoxitin; Cephalosporins; Drug Synergism; Female; Mice
PubMed: 6264846
DOI: 10.1128/AAC.19.3.454 -
Antimicrobial Agents and Chemotherapy Jan 1981The 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...
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.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Bacteriolysis; Carrier Proteins; Cefmenoxime; Cephalosporins; Culture Media; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Escherichia coli Proteins; Hexosyltransferases; Male; Mice; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Peptidoglycan Glycosyltransferase; Peptidyl Transferases
PubMed: 6941742
DOI: 10.1128/AAC.19.1.56 -
The Journal of Antibiotics Dec 1980The 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]...
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.
Topics: Absorption; Animals; Anti-Bacterial Agents; Bile; Cefmenoxime; Cephalosporins; Dogs; Female; Male; Mice; Rabbits; Rats; Tissue Distribution
PubMed: 6941956
DOI: 10.7164/antibiotics.33.1532 -
CMAJ : Canadian Medical Association... Nov 2020
Topics: Anti-Bacterial Agents; Cefmenoxime; Ceftriaxone; Corneal Perforation; Corneal Transplantation; Drug Therapy, Combination; Erythromycin; Gonorrhea; Humans; Keratoconjunctivitis; Male; Young Adult
PubMed: 33139425
DOI: 10.1503/cmaj.200506 -
Auris, Nasus, Larynx Jun 2022Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used...
OBJECTIVE
Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used vary among regions and according to doctors' preferences. In this study, we aimed to investigate the use of nebulizer therapy for rhinosinusitis. Administration of nebulizer therapy has been affected by the coronavirus disease 2019 (COVID-19) pandemic. Thus, we also investigated the difference in the prevalence of nebulizer use before and during the pandemic.
METHODS
Between February and September 2016 and in January 2021, we administered questionnaire surveys on nebulizer treatment for rhinosinusitis to otorhinolaryngologists, who were members of the Oto-Rhino-Laryngological Society of Japan, in Aomori, Saitama, Mie, Fukui, Shiga, Okayama, and Kagoshima prefectures.
RESULTS
More than 90% of the otorhinolaryngologists performed nebulizer treatment for rhinosinusitis in 2016. In April 2020 (the first wave of the COVID-19 pandemic), the use rate decreased to 20%, but in January 2021, the use rate increased to 60%. Jet nebulizers were the most frequently used type. One-third of the otolaryngologists enlarged the natural opening of the paranasal sinuses in more than half of their patients by using vasoconstrictors. Cefmenoxime and betamethasone were the most commonly used antibiotics and steroids, respectively.
CONCLUSION
Because it is important to perform nasal pretreatment and strict disinfection of nebulizer equipment, it is clear that education of otorhinolaryngologists as well as paramedical personnel is required to ensure safe and effective use of nebulizer therapy in Japan.
Topics: COVID-19; Humans; Japan; Nebulizers and Vaporizers; Pandemics; Sinusitis; Surveys and Questionnaires
PubMed: 34865941
DOI: 10.1016/j.anl.2021.11.007 -
Antimicrobial Agents and Chemotherapy Jun 1983In this study, we were concerned with the effect of probenecid on the pharmacokinetics of 1,000 mg of cefmenoxime administered over a 30-min period by intravenous...
In this study, we were concerned with the effect of probenecid on the pharmacokinetics of 1,000 mg of cefmenoxime administered over a 30-min period by intravenous infusion. Each of a total of 10 subjects received cefmenoxime twice, once with and once without adjunctive probenecid. The data were fit by iterative nonlinear regression procedures to a two-compartment open pharmacokinetic model, with elimination from the central compartment. The mean calculated peak concentration, area under the curve from zero to infinity, and half-life without probenecid were 78.1 micrograms/ml, 77.2 micrograms . h/ml, and 1.14 h, respectively. When cefmenoxime was administered with probenecid, these values were 86.7 micrograms/ml, 158.2 micrograms . h/ml, and 1.78 h, respectively. Averages of about 55 and 46% of the administered doses were recovered in urine samples collected at 0 through 24 h for doses administered without and with probenecid, respectively. The mean corrected renal drug clearance was 159 and 66 ml/min without and with probenecid, respectively. Statistical significance (P less than 0.05) was demonstrated for the differences in beta half-life, (K/net), calculated peak concentration, area under the curve from 0 to infinity, and renal clearance, but not for K21, K12, volume of distribution, or alpha-phase distribution rate constant. The results of this study indicate that tubular secretion is the predominant mechanism of clearance for cefmenoxime and that probenecid alters the pharmacokinetics of the compound by competitively inhibiting its tubular secretion without affecting either the rate or the extent of its distribution.
Topics: Adult; Bile; Cefmenoxime; Cefotaxime; Drug Interactions; Humans; Kidney; Kinetics; Male; Probenecid
PubMed: 6311084
DOI: 10.1128/AAC.23.6.803 -
American Journal of Ophthalmology Case... Jun 2024We report a rare case of microbial keratitis caused by .
PURPOSE
We report a rare case of microbial keratitis caused by .
OBSERVATIONS
A 72-year-old Japanese woman was injured by plant debris and developed oval corneal ulcers and hypopyon in the anterior chamber. After 5 days, she complained of pain, redness, and vision loss in her left eye and was treated with antibacterial eye drops and an ointment (1.5 % levofloxacin hydrate, cefmenoxime hydrochloride, and sterilization and disinfection eye drops; SAN-IODE and ofloxacin ophthalmic ointment). Examination revealed a worsening oval corneal ulcer with Descemet's folds and a faint hypopyon. Considering the infection from soil or plants and the poor response to intensive antibacterial eye drops, topical antifungal eye drops, i.e., 1 % voriconazole eye drops, and 1 % natamycin ointment were applied. Direct microscopy of the corneal scraping with Gram staining was performed and the result was negative. Cultures from corneal scrapings showed the growth of dark colonies after several days. The colony was identified as by sequencing of the fungal internal transcribed spacer region. Pain and vision loss improved with improvement in corneal ulcers. The antifungal treatment was administered for 37 days. Discontinuation of the eye drops after 1 month did not result in keratitis recurrence. At the final follow-up at 70 days, the best-corrected visual acuity was 20/25, with persistent small corneal opacity.
CONCLUSIONS AND IMPORTANCE
Here, we report a case of fungal keratitis caused by . Microbiological identification of the causes of rare infections is difficult in clinical laboratories, necessitating the use of advanced molecular techniques based on amplification and sequencing of appropriate phylogenetic markers. responds to topical voriconazole and natamycin.
PubMed: 38665418
DOI: 10.1016/j.ajoc.2024.102062