Cephalosporins
Examples
1st Generation:
2nd Generation:
3rd Generation:
- Cefotaxime
- Ceftazidime
- Ceftriaxone
Indications
Their range of activity includes Gram negative and Gram Positive organisms but excludes enterococci and anaerobic organisms. Many staphylococci, streptococci, Escherichia coli, Proteus Mirabilis and Klebsiella spp are susceptible. Second generation have greater stability to β-lactamases than first generation, whilst also being active against H. Influenzae. Second and third generation drugs have inferior staphylococcal action to first generation. Note the stability of the cephalosporins to β-lactamases is being eroded by extended spectrum β-lactamases (ESBLs). Ceftazidime is active against Pseudomonas aeruginosa.
Care should be taken to avoid unnecessary prescription, minimising the risk of C.difficile with use of Co-Amoxiclav, ciprofloxacin and clindamycin, as well as 3rd generation cephalosporins.
Where possible, drugs with a narrower spectrum of organisms are preferred.
Contraindications
Contraindications
- Cephalosporin-hypersensitivity
Cautions
- Caution is advised in patients with renal impairment
- Hypersensitivity to penicillin - between 0.5 and 6.5% of penicillin sensitive patients will be allergic to cephalosporins
Mechanism
Is similar to that of penicillin but the β-lactam ring of cephalosporins is more stable. See Penicillin notes for a more detailed explanation.
Administration
1st Generation:
- Cefaclor - Oral
- Cefalexin - Oral
2nd Generation:
- Cefuroxime - Oral, I.M, I.V.
3rd Generation:
- Cefotaxime - I.M, I.V.
- Ceftazidime - I.M, I.V.
- Ceftriaxone - I.M, I.V.
Adverse Reactions
Common problems include:
- Diarrhoea, Nausea and Vomiting and abdominal discomfort
- Allergic rashes and pruritis
- Possible disturbance in liver enzymes and transient hepatitis
- Candidiasis
N.B. Antibiotic associated colitis may occur with the use of broad spectrum cephalosporins, particularly second and third generation drugs.
Interactions
- Anticoagulant therapy (Warfarin and other Vitamin K antagonist coumarin drugs) - Possible enhancement of anticoagulant effect
- Antibacterials inactivate oral typhoid vaccination
Education
Patients should be advised to comply with instructions from the medical practitioner and to complete the prescribed course of antibiotic therapy as instructed. The accompanying information pamphlet should be read.
Pharmacokinetics
Diffuse well into the lung; kidney; urine; synovial, pleural, and pericardial fluids. Penetration into the cerebral spinal fluid (CSF) of some 3rd generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) is sufficient to treat bacterial meningitis.
Elimination is primarily via the kidneys, though a few exceptions include cefoperazone and ceftriaxone which have significant biliary elimination.
