What is the advantage of using a sulfa drug in combination with trimethoprim?

Drug information provided by: IBM Micromedex

US Brand Name

Bactrim
Bactrim DS
Septra
Septra DS
SMZ-TMP Pediatric
Sulfatrim
Sulfatrim Pediatric

Canadian Brand Name

Apo-Sulfatrim
Novo-Trimel
Nu-Cotrimox
Septa Pediatric
Septra Pediatric Suspension

Descriptions

Sulfamethoxazole and trimethoprim combination is used to treat infections including urinary tract infections, middle ear infections (otitis media), bronchitis, traveler's diarrhea, and shigellosis (bacillary dysentery). This medicine is also used to prevent or treat Pneumocystis jiroveci pneumonia or Pneumocystis carinii pneumonia (PCP), a very serious kind of pneumonia. This type of pneumonia occurs more commonly in patients whose immune systems are not working normally, including cancer patients, transplant patients, and patients with acquired immune deficiency syndrome (AIDS).

Sulfamethoxazole and trimethoprim combination is an antibiotic. It works by eliminating the bacteria that cause many kinds of infections. This medicine will not work for colds, flu, or other virus infections.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

Tablet
Suspension

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Portions of this document last updated: Feb. 01, 2022

Topic Resources

Trimethoprim (TMP) prevents reduction of dihydrofolate to tetrahydrofolate.
Sulfamethoxazole (SMX) inhibits conversion of p-aminobenzoic acid to dihydropteroate.

This synergy results in maximal antibacterial activity, which is often bactericidal.

Trimethoprim/sulfamethoxazole (TMP/SMX) is available as a fixed combination consisting of a 1:5 ratio (80 mg TMP plus 400 mg SMX or a double-strength tablet of 160 mg TMP plus 800 mg SMX).

Both drugs are well absorbed orally and are excreted in the urine. They have a serum half-life of about 11 hours in plasma and penetrate well into tissues and body fluids, including cerebrospinal fluid. TMP is concentrated in prostatic tissue.

TMP and TMP/SMX are active against

The combination is inactive against

Some Indications for TMP/SMX

Indication

Comments

Chronic bacterial prostatitis Prostatitis Prostatitis refers to a disparate group of prostate disorders that manifests with a combination of predominantly irritative or obstructive urinary symptoms and perineal pain. Some cases result... read more

One of the few effective drugs, but cures < 1/2 of patients, even after 12 weeks

Uncomplicated cystitis Cystitis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more in women

As effective as fluoroquinolones for empiric short-course (3-day) therapy if the rate of TMP/SMX resistance is < 15%

Prophylaxis for recurrent urinary tract infections Bacterial Urinary Tract Infections Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more in women and recurrent urinary tract infections in children Urinary Tract Infection (UTI) in Children Urinary tract infection (UTI) is defined by ≥ 5 × 104 colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 105 colonies/mL... read more

Use of 1/2 to 1 double-strength tablet every night or every other night or, for women with previous recurrences after coitus, after coitus

Treatment of Pneumocystis jirovecii pneumonia Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic... read more

and prophylaxis of this infection in patients with AIDS or cancer

Drug of choice

Intestinal infections due to various bacteria (eg, Shigella Cyclosporiasis Cyclosporiasis is infection with the protozoan Cyclospora cayetanensis. Symptoms include watery diarrhea with gastrointestinal and systemic symptoms. Diagnosis is by detection of characteristic... read more

species, Vibrio Cholera Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria... read more species, Escherichia coli Escherichia coli Infections The gram-negative bacterium Escherichia coli is the most numerous aerobic commensal inhabitant of the large intestine. Certain strains cause diarrhea, and all can cause infection when... read more ) and the protozoans Cystoisospora Cystoisosporiasis Cystoisosporiasis is infection with the protozoan Cystoisospora belli (previously known as Isospora belli). Symptoms include watery diarrhea with gastrointestinal and systemic... read more

and Cyclospora Cyclosporiasis Cyclosporiasis is infection with the protozoan Cyclospora cayetanensis. Symptoms include watery diarrhea with gastrointestinal and systemic symptoms. Diagnosis is by detection of characteristic... read more

species

Usefulness limited by increasing prevalence of resistance

Nocardia Nocardiosis Nocardiosis is an acute or chronic, often disseminated, suppurative or granulomatous infection caused by various aerobic soil saprophytes of the gram-positive bacilli genus Nocardia.... read more

and Listeria monocytogenes Listeriosis Listeriosis is bacteremia, meningitis, cerebritis, dermatitis, an oculoglandular syndrome, intrauterine and neonatal infections, or rarely endocarditis caused by Listeria species. Symptoms... read more infections

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Community-associated methicillin-resistant Staphylococcus aureus infections Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more

Drug of choice for oral treatment of uncomplicated infections caused by community-associated methicillin-resistant S. aureus

TMP/SMX = trimethoprim/sulfamethoxazole.

TMP alone is used less often but may be useful for

Prophylaxis and treatment of urinary tract infection in patients allergic to sulfonamides

TMP/SMX is contraindicated in patients who have had an allergic reaction to either drug.

Relative contraindications include folate deficiency, liver dysfunction, and renal insufficiency.

Sulfonamides enter breast milk, and use during breastfeeding is usually discouraged.

Adverse effects of TMP/SMX include

Folate deficiency
Hyperkalemia
Renal insufficiency

Renal failure in patients with underlying renal insufficiency is probably secondary to interstitial nephritis or tubular necrosis. Also, TMP competitively inhibits renal tubular creatinine secretion and may cause an artificial increase in serum creatinine, although glomerular filtration rate remains unchanged. Increases in serum creatinine are more likely in patients with preexisting renal insufficiency and especially in those with diabetes mellitus.

Folate deficiency (resulting in macrocytic anemia) can also occur. Use of folinic acid can prevent or treat macrocytic anemia, leukopenia, and thrombocytopenia, which sometimes occur with prolonged TMP/SMX use.

Rarely, severe hepatic necrosis occurs. The drug may also cause a syndrome resembling aseptic meningitis.

TMP/SMX may increase warfarin activity and levels of phenytoin, methotrexate, and rifampin. SMX can increase the hypoglycemic effects of sulfonylureas.

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Why are trimethoprim and sulfamethoxazole given together?

The drugs act synergistically to block sequential steps in bacterial folate metabolism: Trimethoprim (TMP) prevents reduction of dihydrofolate to tetrahydrofolate. Sulfamethoxazole (SMX) inhibits conversion of p-aminobenzoic acid to dihydropteroate.

What is the advantage of the combination TMP SMZ?

Prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) has been shown to reduce the incidence of fever, parenteral antibiotic usage, and infections with gram-negative bacteria in hospitalized patients with neutropenia.

How does sulfamethoxazole and trimethoprim work?

What is the mechanism of action of sulfonamides and trimethoprim?

Mechanism of Action Sulfonamides competitively inhibit the incorporation of PABA into folic acid, thereby preventing the synthesis of folic acid. Trimethoprim binds reversibly to and inhibits dihyrofolate reductase,an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid,decreasing folic acid synthesis.