Mechanism of effect
Cephalosporins exert bactericidal activity by interfering with the later stages of bacterial cell wall synthesis through inactivation of one or more penicillin-binding proteins and inhibiting cross-linking of the peptidoglycan structure. The cephalosporins are also thought to play a role in the activation of bacterical cell autolysins which may contribute to bacterial cell lysis.
Antibacterial action: Primarily bactericidal; it also may be bacteriostatic. Activity depends on the organism, tissue penetration, dosage, and rate of organism multiplication. It acts by adhering to bacterial penicillin-binding proteins, inhibiting cell wall synthesis.
Like other first-generation cephalosporins, cephradine is active against many gram-positive organisms and some gram-negative organisms. Susceptible organisms include Escherichia coli and other coliform bacteria, group A beta-hemolytic streptococci, Haemophilus influenzae, Klebsiella, Proteus mirabilis,Staphylococcus aureus, Streptococcus pneumoniae, staphylococci, and Streptococcus viridans.
Cefradine has a high degree of stability to many beta-lactamases. It has a low degree of protein binding and a large volume of distribution. Therefore, tissue levels are generally found to be high.
Oral cefradine can be given twice or four times daily and is well absorbed. Cefradine is acid stable and is rapidly absorbed following oral administration in the fasting state.
Following doses of 250mg, 500mg and 1000mg average peak serum levels of approximately 9, 16.5, and 24.2 micrograms/ml, respectively, were obtained at one hour. The presence of food in the gastrointestinal tract delays the absorption but does not affect the total amount of cefradine absorbed. Measurable serum levels are present six hours after administration.
Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak urine concentrations are approximately 1600 micrograms/ml following a 250mg dose, 3200 micrograms/ml following a 500mg dose, and 4000 micrograms/ml following a 1000mg dose. After 48 hours administration of 100mg/kg/day of cefradine for the treatment of otitis media, cefradine has been measured in the middle ear exudate at an average level of 3.6 microgram/ml.
Respiratory tract infections and skin and soft tissue infections - the usual dose is 250mg or 500mg four times daily or 500mg or 1g twice daily depending on the severity and site of infection.
Urinary tract infections - the usual dose is 500mg four times daily or 1g twice daily. This may need to be increased for severe or chronic infections. Prolonged intensive therapy is needed for complications such as prostatitis and epididymitis.
As for adults. Patients with impaired renal or hepatic function should be monitored as modifications of the dosage schedule may be required.
The usual dose is 25 to 50 mg/kg/day total, given in two or four equally divided doses. For otitis media daily doses from 75 to 100mg/kg in divided doses every 6 to 12 hours are recommended. Maximum dose 4g per day.
Hypersensitivity to the active substance or to any or the excipients
Hematologic: Neutropenia, leukopenia, eosinophilia, thrombocytopenia, thrombocytosis, impaired platelet aggregation
Dermatologic: Rash (maculopapular), puritis, urticaria
Hepatic: Abnormal liver function tests
Renal: Interstitial nephitis
Loop diuretics may increase nephrotoxicity of cephalosporins.
Probenecid has been seen to raise serum concentrations of cefradine, by reducing renal clearance of the cephalosporins.
There is evidence of partial allergenicity between the penicillins and the cephalosporins. Therefore, cefradine should be used with caution in those patients with known hypersensitivity to penicillins. There have been instances of patients who have had reactions to both drug classes (including anaphylaxis).
Following administration of cefradine, a false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with reagent tablets such as Clinitest. This does not occur with enzyme based tests such as Clinistix or Diastix.
Prolonged use of antibiotics may result in overgrowth of non-susceptible organisms. Dosage should be reduced in renal failure .
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Points of recommendation
Do not use this medication if you are allergic to cephradine, or to similar antibiotics such as Ceftin, Cefzil, Keflex, Omnicef, and others.
Before using cephradine, tell your doctor if you are allergic to any drugs (especially penicillins), or if you have kidney disease, diabetes, or a history of intestinal problems.
Take this medication for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated. Cephradine is usually given for up to 3 days after lab tests show that the infection has cleared. Very severe infections may need to be treated for several weeks. Cephradine will not treat a viral infection such as the common cold or flu.
Before using cephradine, tell your doctor if you are allergic to any drugs (especially penicillins), or if you have:
If you have any of these conditions, you may need a dose adjustment or special tests to safely take cephradine.
Category B: No evidence of risk in humans but studies inadequate.