Pharmacology for Anaesthesia and Intensive Care

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22 Antimicrobials

Kinetics

Rifampicin is very lipid-soluble and correspondingly widely distributed. It penetrates

CSF, abscesses and heart valves well and is 80% protein bound. It is metabolized

byliver microsomes and excreted into the bile. Active transport of the drug into

bile can become saturated and remaining drug will be excreted unchanged in

the urine (where it imparts the characteristic red colour). Rifampicin also induces

hepatic microsomes and other drug metabolism may be accelerated as a result

(anticonvulsants, warfarin, steroids). Plasma levels are unaffected by renal failure

and dose alteration for CVVHDF is unnecessary.

Side effects

Rifampicin is well tolerated causing transient gastrointestinal upset and a red dis-

colouration of body fluids. Liver function is rarely impaired (more common with

intermittent use) but should be monitored throughout therapy. It should be used

with caution if liver function is known to be impaired. Rarely haemolytic anaemia

and acute renal failure have also been reported.

Fusidanes

Fusidic acid

Fusidic acid is a naturally occurring bactericidal antibiotic that exhibits activity

against gram-positive bacteria and some gram-negative organisms (bacilli are highly

resistant). It has appreciable activity againstStaph. aureus,MRSA andStaph. epider-

midisbut streptococci and pneumococci are relatively resistant.

Mechanism of action

Fusidic acid does not bind to bacterial ribosome but forms a complex with elon-

gation factor and GTP. This complex is involved in protein translocation and will

allow the incorporation of one amino acid residue before blocking further chain

elongation. Consequently protein synthesis is inhibited and cell death follows. Clin-

ical resistance remains uncommon especially if fusidic acid is administered with

anti-staphylococcal penicillin. Mono-therapy is not recommended for this reason.

Kinetics

Fusidic acid is well distributed and highly protein bound (95%). Although it pene-

trates cerebral abscesses well, it is not active in the cerebral spinal fluid. Bone penetra-

tion is good and fusidic acid is often used to treat staphylococcal bone and joint sep-

sis. The drug is concentrated and excreted unchanged in the bile but little active drug

appears in faeces. Similarly little drug activity is detected in urine and renal failure

has little effect on plasma levels. Dose alteration while on CVVHDF is unnecessary.