INFECTIONS: CEPHALOSPORINS + CARBAPENEMS

Question 1

C+C: INDICATIONS

Answer 1

• Oral cephalosporins are 2nd + 3rd line for URINARY + 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

Question 2

C+C: MOA

Answer 2

• 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
• 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)

Question 3

C+C: ADVERSE EFFECTS

Answer 3

• 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

Question 4

C+C: WARNINGS

Answer 4

• 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

Question 5

C+C: INTERACTIONS

Answer 5

• 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

Question 6

C+C: EXAMPLES

Answer 6

• cefalexin
• cefotaxime
• meropenem
• ertapenem