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Antimicrobial Agents and Chemotherapy Feb 1982Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.
Topics: Adult; Cefamandole; Cefonicid; Cephalosporins; Clinical Trials as Topic; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Pneumococcal Infections; Pneumonia; Random Allocation
PubMed: 7041813
DOI: 10.1128/AAC.21.2.231 -
Antibiotics (Basel, Switzerland) Aug 2022Cefonicid is a second-generation cephalosporin sold under the brand name Sintocef™. It is an injectable drug obtained via a freeze-drying process and is also available...
Cefonicid is a second-generation cephalosporin sold under the brand name Sintocef™. It is an injectable drug obtained via a freeze-drying process and is also available for oral preparations. The high-quality standard required is very challenging to satisfy, and current production protocols are characterized by steps that are lengthy and cumbersome, making the product unattractive for the international market. Industrial R&D is constantly working on the process optimization for API synthesis, with the aim of increasing productivity and decreasing production costs and waste. We herein report a new and efficient method for the synthesis of the cefonicid benzathine salt that provides a good yield and high product stability. The double-nucleophilic and lipophilic nature of ',″-dibenzylethylene diacetate enables the deformylation of the OH-protected group on the mandelic moiety and also enables product crystallization to occur. We demonstrate that the formyl group in the peculiar position has high reactivity, promoting an amidation reaction that deprotects a hydroxy group and generates a new C-N bond in the reaction by-product. Several amines and OH-protected groups have been studied, but none were able to replicate the excellent results of benzathine diacetate.
PubMed: 36009964
DOI: 10.3390/antibiotics11081095 -
Antimicrobial Agents and Chemotherapy Jun 1993The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined... (Comparative Study)
Comparative Study
The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of 25 to 3,000 micrograms/ml. Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adult serum at all concentrations. Two classes of binding sites were found: a high-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was independent of drug concentration. Parameters for class 1 binding sites for cefonicid indicated one binding site per albumin molecule in both adult and neonatal sera, with association constants of 7.0 x 10(4) and 1.3 x 10(4) M-1, respectively. These parameters were also derived for cefuroxime in adult serum and were 0.15 and 7.1 x 10(4) M-1, respectively. In neonatal serum, the combined value (number of binding sites per molecule x equilibrium association constant) was similar to combined values calculated for class 2 binding sites for cefuroxime in adult serum and for cefonicid in neonatal serum (287 versus 195 and 261 M-1, respectively). Cephalosporins have been shown to compete with bilirubin for albumin binding sites. Lower levels of protein binding of cefuroxime in the therapeutic range may mean a lower potential for drug displacement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treating neonatal infections.
Topics: Adult; Aging; Blood Proteins; Cefonicid; Cefuroxime; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Kinetics; Protein Binding
PubMed: 8328784
DOI: 10.1128/AAC.37.6.1343 -
Antimicrobial Agents and Chemotherapy Sep 1984The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft... (Comparative Study)
Comparative Study
The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.
Topics: Aged; Cefamandole; Cefazolin; Cefonicid; Coronary Artery Bypass; Female; Humans; Male; Middle Aged; Myocardium; Pericardium; Premedication
PubMed: 6334490
DOI: 10.1128/AAC.26.3.347 -
Frontiers in Pharmacology 2022Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic...
Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding. A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: "protein binding," "beta-lactam antibiotic," and "body fluid." Only studies were included where protein binding was measured in humans . The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding. Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients. PROSPERO, identifier (CRD42021252776).
PubMed: 35837288
DOI: 10.3389/fphar.2022.900551 -
Antimicrobial Agents and Chemotherapy Jul 1991Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome.
Topics: Cefonicid; Clindamycin; Double-Blind Method; Head; Humans; Neck; Protein Binding; Surgical Wound Infection
PubMed: 1929293
DOI: 10.1128/AAC.35.7.1360 -
Antimicrobial Agents and Chemotherapy Sep 1984Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals...
Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.
Topics: Animals; Azlocillin; Bone and Bones; Cefamandole; Cefonicid; Half-Life; Probenecid; Rabbits
PubMed: 6508259
DOI: 10.1128/AAC.26.3.292 -
Antimicrobial Agents and Chemotherapy Jun 1983The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared for the treatment of uncomplicated lower urinary tract infection in women. Of 50 patients with symptoms of lower urinary tract infection randomized to receive either cefonicid or amoxicillin, 39 were infected with greater than or equal to 10(5) bacteria per ml. At early posttherapy follow-up (5 to 18 days), 19 of 21 (90%) cefonicid-treated patients and 16 of 18 (89%) amoxicillin-treated patients were cured. At late posttherapy follow-up (6 to 7 weeks), 16 of 18 (89%) cefonicid-treated patients and 14 of 15 (93%) amoxicillin-treated patients were cured. One patient was lost to follow-up in each late follow-up group. There were fewer side effects in the cefonicid-treated group. There were significantly more organisms resistant to amoxicillin than to cefonicid in the study population. Considering the small size of the series, single-dose therapy with cefonicid for lower urinary tract infection in women appears to be as safe and effective as conventional multidose therapy with amoxicillin.
Topics: Adult; Amoxicillin; Bacteria; Cefamandole; Cefonicid; Cephalosporins; Female; Humans; Middle Aged; Penicillin Resistance; Urinary Tract Infections
PubMed: 6555015
DOI: 10.1128/AAC.23.6.814 -
Veterinaria Italiana Dec 2022Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other...
Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other animals and people. The most commonly used pharmacodynamic parameter to define potency of antimicrobial drugs is minimum inhibitory concentration (MIC). The aim of this study was to evaluate the antibiotic susceptibility of thirty-six strains of Staphylococcus aureus isolated from dairy goats with mastitis and rabbits with chronic staphylococcosis. Four cephalosporins were tested: cephalexin, cephalotin, cefonicid and ceftiofur. MIC tests were performed according to the microdilution broth method. The calculated values of sensitivity in goats and rabbits were 66.67% and 72.22% for cephalexin, 72.22 % and 94.44% for cefonicid, 77.78% and 94.44% for cephalotin and 77.78% and 100% for ceftiofur, respectively. For all antibiotics, MIC90 of S. aureus from rabbits were lower than MIC90 from goats. These data suggest that more antibiotics are used in goat milk production than in rabbit farming. According to MIC values obtained in this study, ceftiofur and cephalotin may be the best option for treating S. aureus infections in lactating goats. For rabbits, ceftiofur showed lowest MIC values, therefore, it could be an alternative to treatment the infections caused by S. aureus in this species.
Topics: Animals; Female; Rabbits; Staphylococcus aureus; Farms; Cefonicid; Goats; Spain; Lactation; Cephalosporins; Monobactams; Staphylococcal Infections; Cephalothin; Cephalexin; Anti-Bacterial Agents; Goat Diseases
PubMed: 37219839
DOI: 10.12834/VetIt.2241.16176.1