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Two patients on antibiotic prophylaxis with cephradine after orthopaedic implant surgery developed pseudomembranous colitis. Routine administration of antibiotics after such surgery is the policy at many centres. Development of diarrhoea in these patients should be viewed seriously lest this condition is overlooked. Despite recent advances, pseudomembranous colitis can still have a fatal outcome.
Twenty-two patients with chronic recurrent bacterial urinary tract infection, most of whom had underlying physical abnormalities of the tract, were treated with 500 mg cephradine 4-times daily for 10 to 15 days. Eight patients remained completely clear of infection after 2 to 3 months of treatment. This was regarded as a satisfactory result in view of the difficulty in treating this type of case and considering previous unsuccessful courses of antibacterial therapy.
11 patients with peripheral arterial circulatory insufficiency with ulcers on the big toe or on the heel were given 1 g of cephradine intravenously (i.v.) and later 1 g of cefazolin i.v., two cephalosporins with different degrees of protein binding. Antibiotic concentrations were followed in serum and wound secretions after the injections. The peripheral circulatory state of the patients and the degree of protein binding of the cephalosporins used seemed to be of minor importance for the concentrations of the antibiotics in the ulcers, i.e. the infectious focus, compared to local factors such as the bacterial flora of the ulcers. In-vitro studies with bacterial strains isolated from the ulcers of 2 of the patients indicated that beta-lactamases from gram-negative bacteria might be at least part of the explanation for the low concentrations in wound secretion of one or other of the agents used in 4 out of the 11 patients.
Two new penicillins and a new cephalosporin have been synthesized by condensing 2-hydroxy-1-naphthaldehyde with epicillin, 6-aminopenicillanic acid and cephradine, and subsequently reducing the SCHIFF bases with NaBH4. The antimicrobial activities of these compounds are also described.
A pharmacokinetic model has been developed, by means of which all possible time courses of the concentrations of antibiotics in the plasma of treated individuals can be exactly simulated in vitro without diluting the test organism and affecting the growth curves. Equieffective concentrations in the system corresponded to the plasma concentrations in man produced by cefroxadine in a single oral dose of 250 mg and cephalexin and cephradine in a single oral dose of 500 mg.
Basic and clinical experiments were performed on intravenous cephradine (CED) in ophthalmological field. The results are summarized as follows. 1. Serum concentration: After intravenous injection of 1.0 g CED, in a single dose, to a healthy adult, the peak of serum level (34.0 mug/ml) was attained at 15 minutes, then decreased quickly to 2.3 mug/ml by 6 hours. 2. Ocular penetration in rabbit eye: (1) Aqueous humor concentrations: The peak level of aqueous humor (13.45 mug/ml) was obtained at 30 minutes after intravenous injection of 50 mg/kg, in a single dose. Aqueous/Serum ratio was 38.07%. After instillation of 5 mg/ml solution of CED, 5 times every 5 minutes, the aqueous level was recognized 30 minutes and 1 hour, and no detectable 4 hours. After 50 mg/0.5 ml CED subconjunctival injection, in a single dose, the high aqueous levels were observed at 30 minutes and 1 hour, and still detectable 4 hours later. (2) Ocular tissue concentrations: The ocular tissue concentrations at 30 minutes after intravenous injection of 50 mg/kg CED were high in both outer and inner parts of the eye. After 4 hours, the tissue levels remained relatively high concentrations. (3) CLINICAL RESULTS: Intravenous administration of 0.5, 1.0 or 2.0 g CED 1 or 2 times daily revealed excellent or good effects in 8 of 12 cases, such as external hordeolum, internal hordeolum, lid abscess, chronic dacryocystitis, orbital abscess and corneal ulcer. (4) Side effects: Three cases out of 12 complained burning sensation by intravenous injection of CED, but in neither case was it found necessary to withdraw the drugs. No severe side effects such as allergic reactions were observed. No abnormal findings in hepatic and renal function tests were observed.
1) The half-life of serum concentration of cephradine (CED) in patients with normal renal function, was 30 minutes and it prolonged to 83 minutes when combined with probenecid. 2) In the patients with severely impaired renal function, mean serum concentration of CED was 33 mcg/ml 24 hours after 1 g intravenous injection. 3) In clinical observations of 17 cases with infections of lung, urinary tract, and bile duct, the treatment with CED showed excellent results in 5 cases, good in 6, undetermined in 1. No remarkable side effect was observed.
Cephradine (CED) was administered intravenously to the patients with respiratory infection or urinary tract infection with the dosage of 1.0 approximately 4.0 g daily and their clinical effects were investigated. Good clinical effects of CED were obtained in 5 of 8 cases with respiratory infections and in 2 of 5 cases with urinary tract infections. Side effects were noted in 2 cases, but they improved rapidly by the cessation of the drug administration. One case developed skin eruption and the other case complained general burning, palpitation after intravenous injection and slight insomnia. CED is seemed to be effective antibiotic for the respiratory as well as urinary tract infections clinically. However it was advisable that careful attention should be paid when CED is administered to the patient having drug allergy or nephropathy.
Experimental diabetes mellitus was induced in adult male rats by injecting streptozotocin (STZ; 60 mg/kg iv) for the purpose of surveying changes in the pharmacokinetics of biliary excretion after the intravenous administration of 40 mg/kg of cefoperazone (CPZ) or cephradine (CED). CPZ, CED, and other organic anions share affinity for the organic anion transport system in the bile canalicular membrane. The STZ treatment had a marked influence on the distribution and elimination of both cephalosporins. The blood levels of both cephalosporins at each time point after administration differed significantly between the STZ-treated and control rats. The values of mean residence time (MRT) of CPZ and CED were significantly decreased in the STZ-treated rats. Basal bile flow rates were increased after the administration of CPZ in the control and STZ-treated rats. Biliary clearance (CLbile) of CPZ was more than 60% of the CLtot, whereas CLbile of CED was less than 20% of CLtot in both groups of rats. The mean CLbile value of CPZ in the STZ-treated rats was 1.0 ml/min higher than that of the control rats, whereas the mean CLbile value of CED was almost the same as that of the control rats. The increased CLbile of CPZ suggested that diabetes alters the biliary excretion of CPZ. The changes in MRT of CPZ in the STZ-treated and control rats are mainly caused by an increase in the biliary excretory rate and renal clearance. The changes in MRT of CED in the STZ-treated and control rats are caused by a decrease in the apparent volume of distribution and increased renal clearance.
This paper presents further preliminary results of a trial of the prophylaxis of sepsis in 165 patients undergoing vascular surgery. The efficacy and safety of a single dose of teicoplanin was examined and compared with three doses of cephradine plus metronidazole. No significant differences were detected in the prophylactic efficacy in either group. The first interim report indicated abnormalities in liver function, maximum at 7 days, in both groups. These findings are confirmed in this second interim report. Raised levels of GGT and alkaline phosphatase are more prominent in patients receiving teicoplanin. Liver function improved by 28 days, however, suggesting that any abnormality is transient.
The preliminary results of a trial to examine and compare the safety, tolerability and efficacy of a single dose of teicoplanin with three doses of cephradine combined with metronidazole are presented in a series of 113 patients undergoing elective vascular surgery. There were no obvious differences in the infection rates and sepsis indicators in either group. Neither drug regimen produced any evidence of renal or hepatic damage, though the levels of three hepatocellular enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT), were seen to be transiently elevated, peaking 7 days post-operatively. The trial continues.
We report the case of an unusual generalized pustular drug eruption caused by the cephalosporin cephradine. Previously reported pustular drug reactions are briefly reviewed. We suggest that a reaction to an administered drug should be considered in the differential diagnosis when a patient presents with fever and a diffuse pustular eruption.
The passage of two antibiotics, cephradine and epicillin, into the milk of 12 lactating women and the amniotic fluid of 48 pregnant women was investigated. All women were given a 500-mg capsule every six hours for at least two days prior to our taking multiple biologic samples from them. Constant levels of both antibiotics were reached in the milk of lactating women as well as in the amniotic fluid of mid-term and full-term pregnant women during the sample period. The ratio of drug concentrations in serum to that in milk was about 5.0 for each antibiotic. In the midtrimester women, the ratio of concentrations in serum to amniotic fluid of both antibiotics was approximately 1.0, suggesting the development of an equilibrium between these two compartments. This ratio was 0.2 for both drugs in the full-term women, demonstrating that the antibiotics concentrated in the amniotic fluid compartment.
6-cephalosporins (cephalothin, cephradine, cephacetrile, cefaclor, cefuroxime, cefotaxime) has been tested in vitro against 212 gram negative bacteria and 60 Staphylococci. Cefuroxime and especially Cefotaxime showed the highest activity against the gram negative bacteria, with a very low MIC. Cefotaxime also acted fairly well against several strains of Pseudomonas. Of the six cephalosporins tested, cephalothin gave the best results against the Staphylococci.
Rabbits were injected intramuscularily with antibiotics in mean therapeutic doses (calculated by body weight) for the period of 7 days. Group I received cephradine, group II--cefuroxime, group III--lincomycin and group IV--amikacin. Determination of complement level by CH50 method was performed before application of antibiotics and at 7, 14, 28 and 42 day of the study. Application of the cephalosporin antibiotics did not result in any changes in the complement level. After application of lincomycin, complement level increased at the 17 day and after amikacin treatment it was higher after 7 days of investigation.
100 patients with septic-surgical diseases were treated with the cephalosporine-derivate Cephradine (Sefril). 79 patients were treated by surgical intervention in advance of the antibiotic therapy, 21 by Sefril in combination with conservative therapy only. The continuance of medication amounted to two weeks in 94%. A complete healing of the pyogenic infection was obtained in 86 patients. Complications occured in 6%.
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