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Frontiers in Chemistry 2020In this study, two isomeric impurities were identified in cefotiam hydrochloride injection preparation and were characterized. Column-switching HPLC-MS and NMR...
In this study, two isomeric impurities were identified in cefotiam hydrochloride injection preparation and were characterized. Column-switching HPLC-MS and NMR techniques were used to identify the impurity 1 as the Δ3(4) isomers of cefotiam. Using software-based calculations, it was predicted that neither of the isomeric impurities was embryotoxic. This study provides a reference for the production, storage, and quality control of cefotiam and related cephalosporin antibiotics.
PubMed: 33585401
DOI: 10.3389/fchem.2020.619307 -
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 -
Molecular Informatics Feb 2022In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing...
In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations. Based on these numerical calculations following compounds were found as hit inhibitors for the SARS-CoV-2 main protease: Pinokalant, terlakiren, ritonavir, cefotiam, telinavir, rotigaptide, and cefpiramide. In addition, following 3 compounds were identified as inhibitors for Spike/ACE2: Denopamine, bometolol, and rotigaptide. In order to verify the predictions of in silico analyses, 4 compounds (ritonavir, rotigaptide, cefotiam, and cefpiramide) for the main protease and 2 compounds (rotigaptide and denopamine) for the Spike/ACE2 interactions were tested by in vitro experiments. While the concentration-dependent inhibition of the ritonavir, rotigaptide, and cefotiam was observed for the main protease; denopamine was effective at the inhibition of Spike/ACE2 binding.
Topics: Angiotensin-Converting Enzyme 2; Antiviral Agents; Cefotiam; Coronavirus 3C Proteases; Drug Evaluation, Preclinical; Drug Repositioning; Drugs, Investigational; Humans; Molecular Docking Simulation; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Drug Treatment
PubMed: 34529322
DOI: 10.1002/minf.202100062 -
Medicine Nov 2022Antibiotics can cause central nervous system disturbances, manifesting as dizziness, confusion, headache, and seizures. Seizures due to antibiotic administration are...
RATIONALE
Antibiotics can cause central nervous system disturbances, manifesting as dizziness, confusion, headache, and seizures. Seizures due to antibiotic administration are related to increased excitatory neurotransmission because antibiotics act as competitive antagonists of the γ-aminobutyric acid type A receptor.
PATIENT CONCERNS AND CLINICAL FINDINGS
All 5 patients, comprising 4 females and one male and aged 45 to 72 years, underwent open craniotomy with additional surgical maneuvers according to their specific disease. All patients presented American Society of Anesthesiologists Physical Status grades 1 to 2. There were no specific underlying diseases, except hepatitis C and hypertension. However, seizures developed sequentially in the 5 patients after neurosurgery.
DIAGNOSES, INTERVENTIONS, AND OUTCOMES
Early postcraniotomy seizures (PCS) developed in the patients after neurosurgery. Prophylactic antibiotics were administered in all cases to prevent infection due to open craniotomy. This included the administration of 10 g and 2 g of an antibiotic (cefotiam HCL; Jetiam Intravenous Injection 1g®) an hour before the surgery in the ward and half an hour before the surgery in the operating room, respectively. After surgery, cefotiam HCL 2 g was administered in all patients on the day of surgery. Five patients had myoclonic seizure or generalized tonic-clonic seizure several times at emergence or in the intensive care unit.
LESSONS
Early PCS occurred in every patient when an overdose of the prophylactic antibiotic was administered. This report showed that the preoperative prophylactic antibiotic cefotiam administered in double doses evoked early PCS within a few hours of drug administration. Furthermore, such experiences caution that preoperative intravenous cephalosporins, including cefotiam, should be administered carefully in open craniotomy.
Topics: Female; Humans; Male; Neurosurgery; Cefotiam; Neurosurgical Procedures; Seizures; Anti-Bacterial Agents
PubMed: 36451405
DOI: 10.1097/MD.0000000000031714 -
Pharmaceuticals (Basel, Switzerland) May 2021The objective of this study was to characterize individual case safety reports (ICSRs) and adverse drug reactions (ADRs) related to second-generation cephalosporins and...
BACKGROUND
The objective of this study was to characterize individual case safety reports (ICSRs) and adverse drug reactions (ADRs) related to second-generation cephalosporins and resulting in hepatobiliary disorders, in VigiBase, WHO global database.
METHODS
All second-generation cephalosporins hepatobiliary ADRs reported up to July 2019 were included. Characteristic of cephalosporins and ADRs, aside from disproportionality data were evaluated.
RESULTS
A total of 1343 ICSRs containing 1585 ADRs were analyzed. Cefuroxime was suspected to have caused hepatobiliary disorders in most cases-in 38% of adults and in 35% of elderly. Abnormal hepatic function was the most frequent ADR, followed by jaundice and hepatitis. For 49% of the ADRs reported in the elderly and 51% in the adult population, the outcome was favorable, with fatal outcome for 2% of the adults and 10% of the elderly. Higher proportional reporting ration (PRR) values were reported in the elderly for cefotetan-associated jaundice, cefuroxime-associated acute hepatitis and hepatitis cholestatic as well as for cefotiam and cefmetazole-associated liver disorder.
CONCLUSION
Hepatobiliary ADRs were reported for 2nd generation cephalosporins, with over 50% of cases in adults, without gender differences. Cholestatic hepatitis was predominately reported in the elderly and this category was more prone to specific hepatic reactions.
PubMed: 34067178
DOI: 10.3390/ph14050441 -
Translational Pediatrics Oct 2020To investigate the clinical values of the common biomarkers including blood routine (B-Rt), C-reactive protein (CRP), serum amyloid A (SAA) and procalcitonin (PCT) for...
BACKGROUND
To investigate the clinical values of the common biomarkers including blood routine (B-Rt), C-reactive protein (CRP), serum amyloid A (SAA) and procalcitonin (PCT) for efficacy monitoring of antibiotics in early-onset neonatal sepsis (EONS).
METHODS
The clinical and laboratory data of 78 neonates with confirmed EONS in the neonatal intensive care unit (NICU) of our center from July 1, 2019 to June 30, 2020 were retrospectively analyzed. All the subjects were treated with cefotiam (50 mg/kg q12h) and augmentin (30 mg/kg q12h) within 12 hours after birth. Blood samples were collected 0-12 hours after birth for blood culture, measurements of B-Rt, CRP and SAA. Subsequently, blood sampling was performed at intervals of 12-24, 24-48, 48-96, and 96-144 hours for measurements of B-Rt, CRP, SAA and PCT. Statistical analyses were performed in the SPSS 20.0 software package. P value of <0.05 was considered statistically significant.
RESULTS
WBC count showed no significant change among different intervals (12-24, 24-48, 48-96, and 96-144 hours); in contrast, NEU%, CRP, SAA and PCT significantly differed across all intervals. SAA had sensitivities of 75.86%, 93.1%, 44.83%, and 3.45%, respectively; specificities of 100% across all intervals; and AUCs of 0.879 (P<0.0001), 0.966 (P<0.0001), 0.724 (P<0.0001), and 0.500, respectively (P=1). PCT had sensitivities of 100%, 100%, 79.31%, and 51.72%, respectively; specificities of 100% across all intervals; and AUCs of 1 (P<0.0001), 1 (P<0.0001), 0.793 (P<0.0001), and 0.517 (P>0.8551), respectively.
CONCLUSIONS
WBC count, NEU% and CRP showed no clinical significance for any intervals for efficacy monitoring of antibiotic treatment. SAA and PCT had similar monitoring values at 12-24 and 24-48 hours. SAA is thus more valuable than PCT for efficacy monitoring of antibiotics at the 48-96 and even at the 96-144 hours intervals in EONS.
PubMed: 33209730
DOI: 10.21037/tp-20-326 -
Journal of Chromatography Feb 1990
Topics: Blister; Cefotiam; Chromatography, High Pressure Liquid; Exudates and Transudates; Humans; Molecular Structure; Stereoisomerism
PubMed: 2329175
DOI: 10.1016/s0378-4347(00)83428-3 -
Allergy, Asthma & Immunology Research Mar 2012Cephalosporins can induce occupational allergies, such as asthma, urticaria, and anaphylaxis. We investigated the prevalence and risk factors of sensitization to...
PURPOSE
Cephalosporins can induce occupational allergies, such as asthma, urticaria, and anaphylaxis. We investigated the prevalence and risk factors of sensitization to cephalosporin.
METHODS
A total of 161 health care workers (HCW), including 138 nurses and 23 pharmacists, and 86 unexposed non-atopic healthy controls were recruited from a single tertiary hospital and the general population. A questionnaire regarding work-related symptoms was administered along with skin prick tests (SPT) to the three most commonly used cephalosporins (cefotiam, ceftriaxone, and ceftizoxime). Serum specific IgE antibodies to conjugates of the three cephalosporins and human serum albumin (HSA) were measured by enzyme-linked immunosorbent assay (ELISA). Binding specificities were confirmed by ELISA inhibition tests.
RESULTS
The prevalence of work-related symptoms in association with cephalosporins was 17.4%. The sensitization rate to any cephalosporin was 3.1% by SPT. Sensitization rates determined by measurement of serum specific IgE antibodies were 17.4% for any cephalosporin, 10.4% for cefotiam, 6.8% for ceftriaxone, and 3.7% for ceftizoxime. A personal history of any antibiotic allergy was a risk factor for work-related symptoms (OR, 24.93; 95% CI, 2.61-238), but not for the presence of serum specific IgE antibodies to cephalosporins (OR, 0.9; 95% CI, 0.18-4.53). A personal history of atopic dermatitis was a risk factor for the presence of serum specific IgE antibodies to cefotiam-HSA conjugate (OR, 6.30; 95% CI, 1.23-32.3).
CONCLUSIONS
A high cephalosporin sensitization rate (17.4%) was detected by ELISA in HCW exposed to cephalosporins. Monitoring of serum specific IgEs to cephalosporin-HSA conjugates will be useful for detecting sensitized subjects.
PubMed: 22379603
DOI: 10.4168/aair.2012.4.2.85 -
Antimicrobial Agents and Chemotherapy Aug 1980The therapeutic effect of cefotiam on experimental urinary tract infections with Proteus mirabilis IFO 3849 in mice was compared with that of cefazolin. The minimal... (Comparative Study)
Comparative Study
The therapeutic effect of cefotiam on experimental urinary tract infections with Proteus mirabilis IFO 3849 in mice was compared with that of cefazolin. The minimal inhibitory concentrations of cefotiam and cefazolin against the test organism were 1.56 and 25 micrograms/ml, respectively. Beginning 3 days after infection, various doses of each cephalosporin were given subcutaneously twice a day for 5 days. Doses of 100 mg of cefotiam per kg or more sterilized the urine within 3 days and effected a marked reduction or complete eradication of bacteria in the bladder walls and kidneys of mice sacrificed the day after treatment was terminated. A dose of cefazolin greater than 800 mg/kg was required for equivalent therapeutic results. Clearance of bacteria from urinary tract organs was as rapid or more rapid with 50-mg/kg doses of cefotiam as with 200-mg/kg doses of cefazolin. Much more rapid clearance was attained with 200-mg/kg doses of cefotiam. The concentrations of cefotiam attained in plasma, kidney, and urine were lower than the cefazolin levels achieved at an equivalent dose. The superiority of cefotiam over cefazolin in treatment of experimental urinary tract infections appears to be due to its greater activity against the test organism.
Topics: Animals; Cefazolin; Cefotiam; Cephalosporins; Dose-Response Relationship, Drug; Female; Mice; Microbial Sensitivity Tests; Proteus Infections; Proteus mirabilis; Urinary Tract Infections
PubMed: 7004338
DOI: 10.1128/AAC.18.2.257 -
Antimicrobial Agents and Chemotherapy Oct 1980The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and...
The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and cefazolin of short and long duration and starting at three different times (3, 18, and 30h) after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. With each of the multiday regimens there was a large segment of the day when plasma levels fell below assayable concentrations. In all cases, cefotiam proved about eight times as active as cefazolin, indicating that the potent in vitro antibacterial activity of cefotiam was well reflected in the therapeutic effect in this model infection. As judged by the total dose administered, the regimen of cefotiam producing a low but sustained plasma level gave better therapeutic effects than that exhibiting a high but transient plasma level. The cefotiam levels in the plasma of mice that received the regimen effective when initiated at 18 h after infection were less than the expected levels in humans after intravenous infusion of the usual clinical dose.
Topics: Animals; Cefazolin; Cefotiam; Cephalosporins; Disease Models, Animal; Drug Administration Schedule; Kanamycin; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Pneumonia
PubMed: 7004342
DOI: 10.1128/AAC.18.4.549