Cephalosporins and Carbapenems

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Give eg's of & indications for cephalosporins and carbapenems. egs: cefalexin, cefotaxime, meropenem, ertapenem Indications: • UTI's, RTI's - 2nd & 3rd line Rx (oral cephalosporins) • Very severe, complicated or ABx resistant infxn - IV cephalosporins & carbapenems
MOA of cephalosporins & carbapenems. Cephalosporins & carbapenems are derived from naturally occurring antimicrobials produced by fungi & bacteria. Like penicillins, their antimicrobial effect is due to their β-lactam ring. During bacterial cell growth, cephalosporins & carbapenems inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient, resulting in bacterial cell swelling, lysis & death. Both types of ABx have a broad spectrum of action. For cephalosporins, progressive structural modification has led to successive ‘generations’ (first to fifth), with ^activity against Gram -ve bacteria & less oral activity. Cephalosporins & carbapenems are naturally more resistant to β-lactamases than penicillins due to fusion of the β-lactam ring with a dihydrothiazine ring (cephalosporins) or a unique hydroxyethyl side chain (carbapenems).
SE's of cephalosporins & carbapenems. • GI upset • ABx associated colitis - ABx's kill normal gut flora & allow overgrowth of C. difficile • Hypersensitivity reactions • CNS toxicity inc seizures - in high doses or in renal impairment
CI's, cautions, & important interactions of cephalosporins & carbapenems. CI's: • Hx of allergy - inc to penicillin (due to similar structure) especially if there was an anaphylactic reaction Cautions: • People at risk of C. difficile infxn - elderly & hospitalised • Epilepsy (reduce dose) Important interactions: As broad-spectrum ABx's, cephalosporins & carbapenems can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K. Cephalosporins may ^nephrotoxicity of aminoglycosides. Carbapenems reduce plasma concentration & efficacy of valproate.

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