Tetrahydrofolate synthesis pathway
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Bactrim

Co-trimoxazole (abbreviated SXT) is a bacteriostatic antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. The name co-trimoxazole is the International Nonproprietary Name, and has been marketed worldwide under many brand names (GlaxoSmithKline under Septrin®, Hoffmann-La Roche as Bactrim®, and by many other generic pharmaceutical manufacturers). more...

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Synergistic action

Co-trimoxazole exhibits a synergistic antibacterial effect when compared to each of its components administered singly. This is because trimethoprim and sulfamethoxazole inhibit successive steps in the folate synthesis pathway (see diagram below).

Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate reductase. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and are competitive inhibitors of the enzyme; inhibiting the production of dihydropteroic acid.

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid.

Folic acid is an essential precursor in the de novo synthesis of the DNA nucleosides thymidine and uridine. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) thus are dependent on their own de novo synthesis - inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication and transcription.

Clinical indications

Co-trimoxazole is more effective than either of its components individually in treating bacterial infections. However the degree of benefit for the additonal of the Sulfonamide, was in most cases marginal, but reponsible for its high association will allergic responses (see below). Its widespread use has been restricted in many countries to very specific circumstances where its improved efficacy is demonstrated. It may be effective in a variety of upper and lower respiratory tract infections, renal and urinary tract infections, gastrointestinal tract infections, skin and wound infections, septicaemias and other infections caused by sensitive organisms.

Specific indications for its use include: (Rossi, 2004)

  • treatment and prophylaxis of pneumonia caused by Pneumocystis jiroveci (P. carinii)
  • infections caused by Listeria monocytogenes, Nocardia spp., Stenotrophomonas maltophilia (Zanthomonas maltophilia)
  • melioidosis
  • shigellosis
  • traveller's diarrhoea
  • prophylaxis of cerebral toxoplasmosis in HIV patients
  • Whipple's disease

Safety

There has been some concern about its use, however, since it has been associated with both frequent mild allergic reactions and rare but serious adverse effects including Stevens-Johnson syndrome, myelosuppression, agranulocytosis, as well as severe liver damage (cholostatic hepatosis, hepatitis, liver necrosis, fulminant liver failure) and renal impairment up to acute renal failure and anuria. These side-effects are seen especially in the elderly and may be fatal. (Joint Formulary Committee, 2004)

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Clinical quiz
From American Family Physician, 10/1/05

Clinical Quiz questions are based on selected articles in this issue of American Family Physician. Answers appear in this issue. AFP has been reviewed by the American Academy of Family Physicians as having content acceptable for Prescribed credit. Term of approval is for one year from the beginning distribution date of January 2005. This issue has been reviewed and is acceptable for up to 3.5 Prescribed credits, of which 0.5 credit conforms to AAFP criteria for evidence-based continuing medical education (EB CME) clinical content. The amount of CME has been doubled to reflect two-for-one credit for the EB CME portion only. When reporting CME credits, AAFP members should report total Prescribed credits earned for this activity. It is not necessary for members to label credits as EB CME for reporting purposes.

The AAFP is accredited by the Accreditation Council for Continuing Medical Education to provide CME for physicians.

The AAFP designates this educational activity for a maximum of 3.5 Category 1 credits toward the American Medical Association Physician's Recognition Award (AMA/PRA). Each physician should claim only those credits that he or she actually spent in the activity.

AAFP Credit

Each copy of AFP contains a Clinical Quiz answer card. AAFP members may use this card to obtain the designated number of Prescribed credit hours for the year in which the card is postmarked.

AMA/PRA Category 1 Credit

AAFP members who satisfy the Academy's CME requirements are automatically eligible for the AMA/PRA.

Physicians who are not members of the AAFP are eligible to receive the designated number of credits in Category 1 of the AMA/PRA on completion and return of the Clinical Quiz answer card. AFP keeps a record of AMA/PRA Category 1 credits for nonmember physicians. This record will be provided on request; however, nonmembers are responsible for reporting their own Category 1 CME credits when applying for the AMA/PRA or other certificates or credentials.

For health care professionals who are not physicians and are AFP subscribers, a record of CME credit is kept by the AAFP and will be provided to you on written request. You are responsible for reporting CME credits to your professional organization.

NOTE: The full text of AFP is available online (http://www.aafp.org/afp), including each issue's Clinical Quiz. The table of contents for each online issue will link you to the Clinical Quiz. Just follow the online directions to take the quiz and, if you are an AAFP member, you can submit your answers for CME credit.

Instructions

(1) Read each article, answer all questions on the quiz pages, and transfer your answers to the Clinical Quiz answer card (bound into your copy of AFP). This will help you avoid errors and permit you to check your answers against the correct answers.

(2) Mail the Clinical Quiz answer card within one year (by October 31, 2006). The bar code on the answer card contains your identification for CME credit hours.

Before beginning the test, please note: Each Clinical Quiz includes two types of questions: Type A and Type X.

Type A questions have only one correct answer and may have four or five choices. Here is a typical Type A question:

Type X questions may have one or more correct answers. They are multiple true-false questions with four options. Here is a typical Type X question:

Clinical Quiz questions are written by the associate and assistant editors of AFP.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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