COTRIMOXAZOLE

Fixed drug combination of Sulfamethoxazole and Trimethoprim
MOA

PROPERTIES:
  • Individually, both are bacteriostatic, but combination is –bactericidal
  • Both drugs have almost similar half lives (10 Hrs)
  • Maximum synergism if the organism is sensitive to both the agents
  • Optimal synergism is obtained at 20 (S) : 1 (T) concentration (MIC of both is reduced by 3 - 6 times)
  • This ratio is obtained at 5:1 dose ratio ( e.g. 800 mg:160 mg)
  • Because TMP has large Vd and enters many tissues – plasma conc. is low
  • But, TMP crosses BBB and placenta and SMZ not TMP is more rapidly absorbed than SMZ
  • TMP is 45% plasma protein bound but SMZ is 65% bound
ANTIBACTERIAL SPECTRUM:
  • Similar to sulfonamides
  • Additional benefits: Salmonella typhi, Serratia, Klebsiella Enterobacter, Yersinia and Pneumocystis jiroveci
  • Sulfonamides resistance strains of S. aureus, E. coli, gonococci, meningococci and H influenzae
RESISTANCE: Slow to develop
  • By mutational changes or plasmid mediated acquisition of a DHFRase enzyme having lower affinity for the inhibitior.
USES:
  • Uncomplicated infection of the lower urinary tract infection
  • T/t of choice for grade IV vesicoureteric reflux with recurrent UTI Cotrimoxazole
  • Cystitis (5 tablet dose)
  • chronic and recurrent urinary tract infections (including enterobacteriaceae) – 3-10 days
  • Respiratory tract infection – lower and upper, chronic bronchitis, facio-maxillary infections, otitis media due to gm+ve cocci and H influenzae etc
  • Typhoid
  • Bacterial diarrhoeas & dysentery: due to campylobacter, E coli, Shigella etc.
  • Pneumocystis jiroveci: Severe pneumonia - Prophylactic use in AIDS patients(CD4 count is less than 200) with neutropenia. Dose – DS tablet 4-6 times 2-3 weeks
  • Chancroid – H. ducreyi
  • Alternative to penicillin in agranulocytosis patients, scepticaemia etc.
ADVERSE EFFECT:
  • All adverse effects of sulfonamides – nausea, vomiting, stomatitis, rash etc
  • Folate deficiency (megaloblastic anaemia) – patients with marginal folate levels
  • Blood dyscrasias
  • Pregnancy: teratogenic risk, Neonatal haemolysis and methaemoglobinaemia
  • Patients with renal disease may develop uremia
  • Fever, rash and bone marrow hyperplasia
  • Elderly – risk of bone marrow toxicity from cotrimoxazole
  • Diuretics given with cotrimoxazole have produced a higher incidence of thrombocytopenia
  • Bone marrow hypoplasia among AIDS patients with Pneumocystis jiroveci infection
Exam Question
  • Cotrimoxazole is effective against P carinii
  • T/t of choice for grade IV vesicoureteric reflux with recurrent UTI Cotrimoxazole
  • In cotrimoxazole, sulphamethoxazole and trime­thoprim are in the ratio of-5 : 1
  • The drug with definite risk of hemolysis in patients with G6PD deficiency is Cotrimoxazole
  • Cotrimoxazole therapy is to be given in HIV infected patients irrespective of presence of symptoms if CD4 count is less than 200
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