Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

both filtration and tubular secretion and probenecid does increase peak concentra-

tion and plasma half-life but to a lesser extent than penicillin.

Use during CVVHDF

Although the same dose should be given, dose interval adjustment is required for

patients on CVVHDF. Cefuroxime should be given 8 hourly, cefotaxime 12 hourly,

and ceftazidime 12–24 hourly. No interval adjustment is required for ceftriaxone.

Side effects


Hypersensitivity – cross-reactivity with otherβ-lactams (see above).


Haematological – a positive Coombs test has been reported with cefuroxime but

without clinical consequences. Platelet abnormalities are much rarer than with

ticarcillin, and ceftazidime has been associated with transient eosinophilia.


Liver function – ceftazidime has been reported to cause abnormal liver function.

First-generation

Cefradineis active againstβ-lactamase producing staphylococcus, streptococ-

cus and anaerobic gram-positive cocci. It has less activity against Neisseria while

H. influenzaeis resistant. It is used commonly when surgical prophylaxis for gram-

positive organisms is required (classically orthopaedic surgery). Cefradine’s lack of

gram-negative cover makes it unsuitable for GI surgery.

Second-generation

This generation is more resistant toβ-lactamase and has greater activity against

H. influenzaeandNeisseria gonorrhoea(N. gonorrhoea).Cefuroximeis active

against Salmonella, Proteus sp.,Esch. coli,Klebsiella, Citrobacter and Enterobacter.

E.faecalis,Acinetobacter, Serratia and Pseudomonas remain resistant. Cefuroxime

is commonly used for surgical prophylaxis during bowel surgery but lacks sufficient

anaerobic cover to be used as a sole agent.

Third-generation

These drugs have improved gram-negative activity but their activity against some

gram-positive bacteria (i.e.Staph. aureus)isless than the second-generation agents.

Cefotaximehas the same gram-negative spectrum as cefuroxime except Acineto-

bacter, Serratia and some Pseudomonas are covered in addition.Ceftazidimeis

highly active against Pseudomonas, including strains resistant to aminoglycosides,

but much less active against staphylococcus.Ceftriaxonehas a long duration of

action due to its long half-life and is administered once daily. These agents all have

avery broad spectrum of activity and may encourage superinfection with resistant

bacteria or fungi. Injudicious use of third-generation agents has been implicated in

the encouragement of MRSA.