Antibacterials

Review of General Principles

MIC/MBC – based upon serum concentration; some compartments (e.g., CNS) are harder to penetrate

easiest to penetrate: urinary tract (10-50 fold higher conc. than serum); b -lactams can even overwhelm resistant strains

hardest to penetrate: CNS, bone, biliary tree, prostate – hardest is eye (requires local injections into vitreous)

cidal (kill directly) vs. static (inhibit growth so that immune system can catch up)

must use cidal if immune system is inactive (immunosuppressed, neutropenic, CNS infections)

drug interactions: combinations can be synergistic, additive, or inhibitory

e.g., don’t combine antibiotics that require cell division (b -lactams) with agents that inhibit cell division (tetracycline)

two catagories of drugs:

(1) concentration dependent – concentration is most important (ratio of area under curve to MIC); higher concentrations produce more effect; these drugs work even after the conc. < MIC (post-antibiotic effect)

(2) MIC dependent – time above MIC is most important; maximum effect at about 3 to 5 times MIC – above that, no additional effect no matter how high concentration becomes

Summary of Antibiotics

	dep	static/cidal	mode of action	mode of resistance	CNS penetration
macrolides	MIC	static	50S ribosome	altered ribosomes	(-)
TMP-SMX	conc	static (cidal for some)	folate metabolism	altered folate enzymes	(+) (historically)
tetracyclines	conc	static	30S ribosomal	decreased influx/increased efflux	(+) (historically)
quinilones	conc	cidal	topoisomerases (II and IV)	altered topoisomerase, also decreased influx/increased efflux	probably – still awaiting trials
glycopeptides	conc	cidal	cell wall (like b -lactams)	change peptidoglycan intermediary molecules	(+) when no other choice (MRSA)
chloramphenicol	conc	static (cidal in CNS)	50S ribosome	hydrolytic enzymes (plasmid borne)	(+) b -lactam allergy or non-inflamed meninges
aminoglycocides	conc	cidal	30-50S ribosome interface	hydrolytic enzymes	(-) do get into CNS, but CSF is acidic!
b -lactams	MIC	cidal	cell wall	hydrolysis (beta lactamase) OR alteration of PBPs	(++) very effective if it gets in (3^rd gen cephalo)