Trimoxazole

Traveller s diarrhoea may be eaused by one of many gastrointestinal pathogens (Table 6.4). However, enterotoxigenic Escherichia coli is the most common pathogen. Whilst it is generally short-lived, traveller s diarrhoea can seriously mar a brief period abroad, be it for holiday or business purposes. Although not universally accepted, the use of short-course co-trimoxazole or quinolone such as norfloxacin can abbreviate an attack in patients with severe disease. 

Q85 The combination of antibacterial agents in co-trimoxazole presents a synergistic activity. Co-trimoxazole is associated with rare but serious side-effects. 

Co-trimoxazole refers to the combination of sulfamethoxazole and trimethoprim, which offers synergistic activity. Co-trimoxazole is associated... 

Co-trimoxazole is a folate antagonist and should be avoided in the first and the third trimesters of pregnancy. In the third trimester there is an increased risk of neonatal haemolysis and methaemoglobinaemia, whereas in the first trimester there is a teratogenic risk caused by the trimethoprim (folate antagonist) component. 

Co-trimoxazole consists of trimethoprim and sulphamethoxazole combined because of their synergistic antimicrobial effects. Trimethoprim is a folate antagonist that poses a teratogenic risk. 

Pneumocystis carinii pneumonia occurs in immunocompromised patients and it hence is a common cause of pneumonia in AIDS. High doses of co-trimoxazole are indicated for treatment of mild-to-moderate pneumocystis pneumonia. This condition should be treated by those experienced in its management as it can be fatal. 

Trimethoprim inhibits bacterial DHF reductase, the human enzyme being significantly less sensitive than the bacterial one (rarely bone marrow depression). A 2,4-diaminopyrimidine, trimethoprim, has bacteriostatic activity against a broad spectrum of pathogens. It is used mostly as a component of co-trimoxazole. 

Co-trimoxazole is a combination of trimethoprim and the sulfonamide sulfamethoxazole. Since THF synthesis is inhibited at two successive steps, the antibacterial effect of co-trimoxazole is better than that of the individual components. Resistant pathogens are infrequent a bactericidal effect may occur. Adverse effects correspond to those of the components. 

Trimethoprim (TMP)-Sulfamethmazole (SMX) [Co-Trimoxazole] (Bactrim, Septra) [Antibiotic/Folate Antagonist] Uses un Rx prophylaxis, otitis media, sinusitis, bronchitis Action SMX T synth of dihydro-folic acid TMP T dihydrofolate reductase to impair protein synth Dose Adul. 1 DS tab PO bid or 5-20 mg/kg/24 h (based on TMP) IV in 3-4 doses P. jiroveci ... 

NSAID and warfarin ACE inhibitors and K-sparing dinretic Verapamil and beta-adrenergic antagonists Nenromnscnlar (NM) blockers and aminoglycosides Alcohol and benzodiazpines Thioridazine and halofantrine Clozapine and co-trimoxazole Increased risk of bleeding Increased risk of hyperkalaemia Bradycardia and asystole Increased NM blockade Increased sedation Increased risk of QT interval prolongation Increased risk of bone marrow suppression... 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

Trimethoprim is a competitive inhibitor of the enzyme dihydrofolate reductase and can thus prevent the formation of tetrahydrofolate thereby blocking the synthesis of purines. The affinity of trimethoprim for the enzyme in microorganisms is 10,000 times higher than for the human enzyme which explains the selective toxicity. Used alone its main indication is acute uncomplicated urinary tract infections. It is then as effective as co-trimoxazole but has the advantage of fewer adverse reactions. 

Note that in addition to the adverse events due to trimethoprim the combination trimethoprim-sulfamethoxazole may cause all of the untoward reactions associated with sulfonamides. In HIV positive patients the incidence of rashes can increase to 50%. Desensibilisation with increasing doses of co-trimoxazole has been successful. 

Alternative to amoxicillin or co-trimoxazole for resistant upper respiratory pathogens expensive, but bid dosing... 

Inferior5 to 1 l-daypost-therapyrnicrobiologiceradicationratescomparedtocip rofloxacin and co-trimoxazole for acute cystitis eradication rates comparable to nitrofurantoin... 

Reserve for women unable to tolerate or unlikely to comply with 3-day courses of co-trimoxazole or trimethoprim... 

Rx with sulfamethoxazole (see co-trimoxazole monograph) with polymixin B sulfate (Polytrim Ophthalmic)... 

Good alternative to co-trimoxazole in patients taking warfarin... 

Antibacterials ciprofloxacin hydrochloride co-trimoxazole (sulfamethoxazole/ trimethoprim) doxycycline hyclate mentronidazole vancomycin hydrochloride... 

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