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Section IVOther important drugsMechanism of action
Clindamycin is a bacteriostatic antimicrobial that inhibits bacterial protein synthesis
bydisrupting the function of the 50S ribosomal subunit. Resistance is inducible in
gram-positive organisms that are normally sensitive and when present often imparts
resistance to macrolides. Clindamycin has also been shown to inhibit the action of
gentamicin on Enterobacter andStaph. aureus.Kinetics
Clindamycin is widely distributed and highly protein bound (94%). It is hydrolyzed
to four different forms (clindamycin base, clindamycose, demethyl and sulphoxide
derivatives) with the sulphoxide derivative being the least active. CSF penetration
is poor and clindamycin is not recommended for CNS infections. Bone and joint
penetration, however, is very good and clindamycin is commonly employed to treat
staphylococcal osteomyelitis. Drug metabolism is not fully elucidated but less than
10% of the drug is cleared in the urine. Although levels rise in renal failure, patients
on CVVHDF should receive the same dose.Side effects
Clindamycin is generally well tolerated although up to 30% of patients may suffer
with diarrhoea. Pseudomembranous colitis (C. difficile)has been associated with
clindamycin use but the incidence is less than 2%. Fever, rash and eosinophilia are
more common (10%) and transient drop in neutrophil and platelet counts have also
being described.Rifamycins
Rifampicin
Rifampicin is a semi-synthetic antimicrobial with potent activity against gram-
positive bacteria. It demonstrates marked activity against staphylococci and strep-
tococci butE.faecalisis more resistant. Legionella sp., Neisseria andH. Influenzae
are susceptible but other gram-negative organisms remain resistant. Most mycobac-
teria (includingM. tuberculosis)aresensitive to rifampicin; howeverM. aviumtends
to be resistant.Mechanism of action
Rifampicin is bactericidal and binds to theβ-subunit of DNA-dependant RNA poly-
merase. This prevents bacterial DNA being transcribed into RNA and thus prevents
protein synthesis. Resistance is readily inducible with rifampicin and this antimi-
crobial should not be used as a single agent. Combination therapy needs careful
consideration as some antimicrobials (ciprofloxacin) are antagonized by rifampicin.