Ceftriaxone the distinguishing feature of this cephalosporin is its longer duration of action of half-life of 8 hours, permitting once, or at the most twice daily dosing. Penetration into CSF is good and elimination occurs equally in urine and bile.
Ceftriaxone has shown high efficacy in a wide range of serious infections including bacterial meningitis (especially in children), multiresistant typhoid fever, complicated urinary tract infections, abdominal sepsis and septicaemias.
A Single dose of 250 mg i.m. has proven curative in gonorrhoea including PPNG, and in chancroid.
Hyporthrombinaemia and bleeding are the specific adverse effects. Haemolysis is reported.
Cephalosporin are group of semisynthetic antibiotics derived from ‘Cephalosporin-C) obtained from fungus Cephalosporium. They are chemically related to Penicillins.
All Cephalosporins are bactericidal and have the same mechanism of action as Penicillin, i.e. inhibition of bacterial cell wall synthesis.
Classification of Cephalosporin:
- First generation Cephalosporin
- Second generation Cephalosporin
- Third generation Cephalosporin
- Fourth generation Cephalosporin
Adverse effects: Cephalosporins are generally well tolerated, but are more toxic than Penicillin.
- Pain afterm. injection occurs with many Cephalosporins, but some can be injected i.m., while others are injected only i.v. Thrombophlebitis of injected vein can occur.
- Diarrhoea due to alteration of gut ecology or irritative effects is more common with orally administered compounds like Cephalexin, Cefixime which is largely excreted in bile.
- Hypersensitivity reactions are the most important adverse effects of Cephalosporins. Manifestations are similar to Penicillin, but incidence is lower. Rashes are the most frequent manifestation, but anaphylaxis, angioedema, asthma and urticaria have also occurred. About 10% of patients allergic to Penicillin show cross reactivity with Cephalosporins. Those with a history of immediate type of reactions to Penicillin should better not be given a Cephalosporin. Skin tests for sensitivity to Cephalosporins are unreliable.
A positive Coulomb’s test occurs in many patients, but haemolysis is rare.
- Nephrotoxicity: Some Cephalosporins have low grade nephrotoxicity which may be accentuated by pre-existing renal disease, concurrent administration of an aminoglycosides or loop diuretic.
- Bleeding occurs with Cephalosporins having a methylthiotetrazone or similar substitution at position 3 (Cefoperazone, Ceftriaxone).This is due to hypoprothrombinaeamia caused by the same mechanism as warfarin and is more common in patients with cancer, intra-abdominal infections or renal failure.
- Neutropenia and thrombocytopenia are rare adverse effects reported with ceftazidime and some others.
- A disulfiram-like interaction with alcohol has been reported with Cefoperazone.
Currently Cephalosporins are one of the most commonly used antibiotics. Among them they cover a wide range of gram-positive and gram-negative bacterial including some anaerobes but not B. fragilis, or MRSA, enterococci, mycobacteria and chlamydia. Their indications are:
- As alternative to penicillin for ENT, upper respiratory and cutaneous infections, one of the first-generation compounds may be used.
- Respiratory, urinary and soft tissue infectious caused by gram-negative organisms, especially Klebsiella, Proteus, Enterobacter, Serratia. Cephalosporins preferred for these infectious are Cefuroxime, Cefotaxime, Ceftriaxone.
- Penicillinase producing staphylococcal infectious.
- Septicaemias caused by gram-negative organisms: an aminoglycoside may be combined with a Cephalosporin.
- Surgical prophylaxis: the first generation cephalosporins is popular drugs. Cefazolin (i.m. or i.v.) is employed for most type of surgeries including those with surgical prosthesis such as artificial heart valves, artificial joints, etc.
- Meningitis: Optimal therapy of pyogenic meningitis requires bactericidal activity in the CSF, preferably with antibiotic concentrations several times higher than the MBC for the infecting organism. For empirical therapy before bacterial diagnosis, i.v. cefotaxime/ceftriaxone is generally combined with ampicillin or vancomycin or both. Ceftazidine +gentamycin is the most effective therapy for Pseudomonas meningitis.
- Gonorrhoea caused by penicillinase producing organisms: Ceftriaxone is a first-choice drug for single dose therapy of gonorrhoea if the penicillinase producing status of the organism is not known. Cefuroxime and Cefotaxime have also been used for this purpose. For chancroid also, a single dose is as effective as erythromycin given for 7 days.
- Typhoid: Currently, Ceftriaxone and Cefoperazone injected i.v. are the fastest acting and most reliable drugs for enteric fever. They are preferred over fluoroquinolones (especially in children) for empirical therapy, since many typhi strains are resistant to chloramphenicol, ampicillin, cotrimoxazole, and FQs.
- Mixed aerobic-anaerobic infectious in cancer patients, those undergoing colorectal surgery, obstetric complications: cefuroxime, cefactor or one of the third-generation compounds is used.
- Hospital acquired infections, especially respiratory and other infections in intensive care units, resistant to commonly used antibiotics: Cefotaxime, Ceftrizoxime or a fourth-generation drug may work.
- Prophylaxis and treatment of infections in neutropenic patients: Ceftazidine or another third-generation compound, alone or in combination with an aminoglycoside.
Comments are closed.