TeacherOfMedicine: Cephalosporins and carbapenems

Oral cephalosporins are second- and third-line treatment options for urinary and respiratory tract infections.
Intravenous cephalosporins and carbapenems are reserved for the treatment of infections that are very severe or complicated, or caused by antibiotic-resistant organisms. Due to their broad antimicrobial spectrum they can be used for most indications (with these caveats).

Cephalosporins and carbapenems are derived from naturally occurring antimicrobials produced by fungi and bacteria. Like penicillins, their antimicrobial effect is due to their β-lactam ring. During bacterial cell growth, cephalosporins and 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 and death. Both types of antibiotic have a broad spectrum of action.
For cephalosporins, progressive structural modification has led to successive ‘generations’ (first to fifth), with increasing activity against Gram-negative bacteria and less oral activity.
Cephalosporins and 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).

Gastrointestinal upset, such as nausea and diarrhoea, are common.
Less frequently, antibiotic-associated colitis occurs when broad-spectrum antibiotics kill normal gut flora, allowing overgrowth of toxin-producing Clostridium difficile. This is debilitating and can be complicated by colonic perforation and death.
Hypersensitivity, including immediate and delayed reactions may occur (see Penicillins).
As cephalosporins and carbapenem share structural similarities to penicillins, cross-reactivity may occur with some penicillin-allergic patients.
There is a risk of central nervous system toxicity including seizures, particularly where carbapenems are prescribed in high dose or to patients with renal impairment.

Cephalosporins and carbapenems should be used with caution in people at risk of C. difficile infection, particularly those in hospital and the elderly.
The main contraindication is history of allergy to a penicillin, cephalosporin or carbapenem, particularly if there was an anaphylactic reaction.
Carbapenems should be used with caution in patients with epilepsy.
A dose reduction is required for both drug classes in renal impairment.

As broad-spectrum antibiotics, cephalosporins and carbapenems can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K.
Cephalosporins may increase nephrotoxicity of aminoglycosides.
Carbapenems reduce plasma concentration and efficacy of valproate.

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