Cefalexin

Nature of the antibiotic

  • Semisynthetic first-generation cephalosporin.

  • Oral preparation only (first oral cephalosporin introduced).

  • Introduced in 1969.

  • Molecular weight – 365.41

  • Cefalexin molecule is a zwitterion.

Mechanism of action

Cefalexin, like other beta-lactams, binds to the penicillin-binding protein (PBP) and prevent peptidoglycan synthesis. It prevents the formation of new cell wall and maintenance of the cell wall leading to autolysis of the bacteria due to osmotic pressure.

Mechanism of resistance

  • Beta-lactamase: Secreted beta-lactamase of the gram-positive bacteria or the beta-lactamase in the periplasmic place of the gram-negative bacteria is able to hydrolyse cefalexin.

  • Altered PBP: alteration of PBP may lead to cefalexin resistance e.g. MRSA.

PK/PD and other properties

  • Bioavailability: High, 82% at the fasting stage, 73% with food.

  • Cefalexin absorption is not impaired by heart failure, achlorhydria, partial gastrectomy.

  • Protein binding: 15%

  • Distribution: High in the kidney, Good concentration is inflamed lung, also found in pancreas, liver and adrenals.

  • Important parameter: Time over MIC.

  • Metabolism: Not metabolised in body.

  • Excretion: Mostly kidney, <1% in bile.

  • Dose adjustment: Necessary in renal impairment

  • Pregnancy: Category B

Indication

  • Urinary tract infections,

– including acute pyelonephritis (not as initial therapy but as oral stepdown)

– catheter-associated UTI

– uncomplicated prostatitis

  • Prophylaxis of recurrent urinary tract infection (unlicensed use)

– (not preferred for VUR prophylaxis, Ref – Kucer)

  • Diverticular disease (with metronidazole)

  • Respiratory tract infections (directed therapy)

  • Skin and soft tissue infections (not animal bite)

  • Otitis media (directed therapy)

  • OM and septic arthritis (sequential therapy)

Spectrum

Gram-positive bacteria:

Gram-negative bacteria:

Anaerobes:

Adverse effects

  • Gastrointestinal adverse effects

  • Eosinophilia, neutrophilia, leucopenia, thrombocytopenia

  • Skin reaction (rash, erythema multiforme, SJS), vulvovaginal candidiasis

  • Headache

  • Rare/less common: Anaphylaxis, C difficile diarrhoea, tubointerstitial nephritis