What is trimethoprim-sulfamethoxazole (Bactrim)? How does it work? What are the FDA-approved and non-FDA approved indications for using this antimicrobial drug? Learn about its administration, adverse effects, and monitoring as part of an interprofessional treatment approach.

Understanding Trimethoprim-Sulfamethoxazole (Bactrim)

Trimethoprim-sulfamethoxazole, also known as co-trimoxazole and abbreviated as SXT, TMP-SMX, TMP-SMZ, or TMP-Sulfa, is a widely used antimicrobial agent. It was first prescribed by healthcare professionals in 1974 and is now included in the World Health Organization’s list of essential medicines due to its cost-effectiveness and broad range of applications.

FDA-Approved Indications for Trimethoprim-Sulfamethoxazole

The FDA has approved the use of trimethoprim-sulfamethoxazole for the following indications:

• Acute infective exacerbation of chronic bronchitis
• Otitis media in pediatric patients
• Traveler’s diarrhea (both treatment and prophylaxis)
• Urinary tract infections
• Shigellosis
• Pneumocystis jirovecii pneumonia (PJP/PCP), both for prophylaxis and treatment
• Toxoplasmosis, both for prophylaxis and treatment

Non-FDA Approved Indications for Trimethoprim-Sulfamethoxazole

In addition to the FDA-approved indications, trimethoprim-sulfamethoxazole has also been used for the following non-approved indications:

• Prophylaxis in HIV-infected individuals
• Acne vulgaris
• Listeriosis
• Melioidosis
• Pertussis (whooping cough)
• Staphylococcus aureus infections, including methicillin-resistant Staphylococcus aureus (MRSA)
• Tuberculosis
• Whipple’s disease
• Isosporiasis
• Malaria
• Community-acquired pneumonia

Mechanism of Action of Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole works by inhibiting two different steps in the bacterial synthesis of essential nucleic acids and proteins, creating a synergistic anti-folate effect.

Sulfamethoxazole is a sulfonamide that directly competes with p-aminobenzoic acid (PABA) during the synthesis of dihydrofolate, inhibiting the enzyme dihydropteroate synthase.

Trimethoprim, on the other hand, is a direct competitor of the enzyme dihydrofolate reductase, resulting in the inhibition of the production of tetrahydrofolate, an active form of folate.

When used alone, these drugs only act in a bacteriostatic manner. However, when used in combination, they can be bactericidal, especially in the treatment of urinary tract infections.

Administration of Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole can be administered orally without regard to meals, but it is best to take it with at least 8 ounces of water. It also has an intravenous formulation, and the choice of oral or intravenous administration depends on the type of infection or prophylactic use.

The drug is administered in a 1 to 5 ratio of trimethoprim to sulfamethoxazole, as a tablet formulation, to ensure the desired peak synergistic effect ratio of 1 to 20 in the body.

Patients with impaired renal function must have their dosing regimen calculated based on their renal function, as listed in the prescribing information.

Adverse Effects of Trimethoprim-Sulfamethoxazole

What are the potential adverse events associated with trimethoprim-sulfamethoxazole?

Trimethoprim-sulfamethoxazole can cause a variety of adverse effects, including gastrointestinal issues, skin reactions, hematologic abnormalities, and more. Healthcare providers should be aware of these potential adverse events and monitor patients accordingly.

Interprofessional Strategies for Optimal Use of Trimethoprim-Sulfamethoxazole

How can the interprofessional team work together to improve patient outcomes when using trimethoprim-sulfamethoxazole?

Effective communication and coordination among the interprofessional team, including physicians, pharmacists, nurses, and other healthcare professionals, is key to ensuring the proper use of trimethoprim-sulfamethoxazole and optimizing patient outcomes. This may involve medication review, dose adjustments, adverse event monitoring, and patient education.

Conclusion

In conclusion, trimethoprim-sulfamethoxazole is a widely used antimicrobial agent with a range of approved and off-label indications. Understanding its mechanism of action, administration, adverse effects, and the need for an interprofessional approach to its use is crucial for healthcare providers to effectively manage infections and improve patient outcomes.

Trimethoprim Sulfamethoxazole – StatPearls – NCBI Bookshelf

Continuing Education Activity

Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-Sulfa. It is an antimicrobial used to treat and prevent many bacterial infections. This drug is very cost affordable and used for many types of illnesses. The FDA-Approved indications include acute infective exacerbation of chronic bronchitis, otitis media in pediatrics only, travelers diarrhea for treatment and prophylaxis, urinary tract infections, shigellosis, pneumocystis jirovecii, pneumonia/pneumocystis carinii pneumonia (PJP/PCP), and toxoplasmosis, both as prophylaxis and treatment. There are also non-FDA-approved indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of TMP-SMX, so providers can direct patient therapy where necessary for infections as part of the interprofessional team.

Objectives:

• Identify the antimicrobial mechanism of action of trimethoprim/sulfamethoxazole, focusing on each component individually and the synergism of the combination.

• Summarize the approved indications for initiating antimicrobial therapy with trimethoprim/sulfamethoxazole.

• Outline the potential adverse events associated with trimethoprim/sulfamethoxazole.

• Explain interprofessional team strategies for improving care coordination and communication to properly use trimethoprim/sulfamethoxazole to improve patient outcomes in infectious disease.

Access free multiple choice questions on this topic.

Indications

Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-sulfa.[1][2] It is an antimicrobial used to treat and prevent many bacterial infections. In 1974, TMP/SMX healthcare professionals began prescribing the medication, and the drug is now on the list of the World Health Organization’s (WHO) essential medicines. [3] This drug is very cost affordable and used for many types of illnesses.[4]

The FDA-Approved Indications

• Acute infective exacerbation of chronic bronchitis

• Otitis media in pediatrics only

• Travelers diarrhea for treatment and prophylaxis

• Urinary tract infections

• Shigellosis

• Pneumocystis jirovecii pneumonia/Pneumocystis carinii pneumonia (PJP/PCP) both prophylactic and treatment

• Toxoplasmosis both prophylactic and treatment

The Non-FDA Approved Indications

• Prophylaxis in HIV-infected individuals

• Acne vulgaris

• Listeria

• Melioidosis

• Pertussis (whooping cough)

• Staphylococcus aureus infections, including methicillin-resistant Staphylococcus aureus (MRSA)

• Tuberculosis

• Whipple disease

• Isosporiasis

• Malaria

• Community-acquired pneumonia

Mechanism of Action

Sulfamethoxazole is a sulfonamide (antimicrobial drug class) that works directly on the synthesis of folate inside microbial organisms, e. g., bacteria. Sulfamethoxazole achieves this directly as a competitor of p-aminobenzoic acid (PABA) during the synthesis of dihydrofolate via inhibition of the enzyme dihydropteroate synthase. Trimethoprim is a direct competitor of the enzyme dihydrofolate reductase, resulting in its inhibition, which halts the production of tetrahydrofolate to its active form of folate. The combination of these two agents is meant to create a synergistic anti-folate effect; tetrahydrofolate is a necessary component for synthesizing purines required for DNA and protein production. When used alone, these drugs only act in a bacteriostatic manner. However, when used in the combination of sulfamethoxazole-trimethoprim, they block two steps in the bacterial biosynthesis of essential nucleic acids and proteins, thus can be bactericidal, e.g., urine.[5]

Sulfamethoxazole is hepatically metabolized by the CYP450 system; it is a CYP2C9 inhibitor. Its half-life is 6 to 12 hours, increasing to between 20 and 50 hours in renal failure.  Trimethoprim has a half-life of 8 to 10 hours, is minimally metabolized in the liver, and is primarily excreted in the urine, essentially unchanged.

Administration

Sulfamethoxazole/trimethoprim may be administered orally without regard to meals. However, it is best to take it with at least 8 ounces of water. It also has an intravenous formulation. The choice of oral or intravenously varies both on the type of infection/or type of prophylactic use. It should not be administered intramuscularly. Patients with impaired renal function must have calculated dosing regimens based on renal function, as listed below. Administration of the two drugs is in a 1 to 5 ratio (trimethoprim:sulfamethoxazole) as a tablet formulation; this is so when they enter the body, their concentration throughout the blood/tissues is 1 to 20, which is the peak synergistic desired effect ratio of the two drugs in combination.[6]

Bacterial Infections

Oral dosage in adults and children weighing 40 kg (88 pounds) or more should have a single tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days. Children 2 months and older must have a weight-adjusted dosage.

Treatment of Pneumocystis jirovecii Pneumonia/Pneumocystis carinii Pneumonia

Adults/children, two months of age and older: The dose is also weight adjusted. Usually 75 to 100 mg per kilogram of body weight for sulfamethoxazole and 15 to 20 mg per kilogram of body weight for trimethoprim each day for 14 to 21 days.[6]

Prevention of Pneumocystis jirovecii pneumonia/ pneumocystis carinii pneumonia

In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim is given once a day. In children two months of age and older, dosages are determined by body size.[6]

Traveler’s Diarrhea

In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days. For children two months and older, use and dosage vary.

Chronic Bronchitis

For acute exacerbations due to strains of Streptococcus pneumoniae or Haemophilus influenzae, one tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days. [7]

Shigellosis

Enteritis caused by Shigella flexneri and Shigella sonnei: 1 tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days; antimicrobial resistance is an increasing concern in this infection.[8]

Urinary Tract Infections

Pyelonephritis

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days

Prostatitis

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days or 2 to 3 months if a chronic infection.[9]

Acne Vulgaris (Non-FDA Approved)

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 18 days

Community-Acquired Pneumonia (Non-FDA Approved)

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days

Renal impairment guidelines are as follows:

• CrCl greater than 30 mL per minute no dose change

• CrCl 15 to 30 mL per minute decrease dose by 50%

• CrCl less than 15 do no use

Use is not recommended in children younger than two months of age.

Adverse Effects

The primary adverse effects of trimethoprim/sulfamethoxazole include rash, photosensitivity, as well as folate deficiency.[10][11] 

A list of the more common side effects includes:

• Loss of appetite

• Nausea/vomiting/dyspepsia

• Painful or swollen tongue

• Dizziness

• Tinnitus

• Fatigue

• Insomnia

• Rash/urticaria

• Anorexia

• Photosensitivity

More serious reactions can include Stevens-Johnson syndrome, various anemias, agranulocytosis, C. diff.-associated diarrhea, myelosuppression, renal failure/interstitial nephritis, pancreatitis, and hepatotoxicity. Hemolytic anemia can occur with sulfa drugs like sulfamethoxazole in patients with a glucose-6-phosphate-dehydrogenase (G6PD) deficiency.

A patient with an unknown sulfa allergy and treated with trimethoprim/sulfamethoxazole may experience anaphylaxis or less serious yet severe symptoms such as hives, itchy eyes, swelling of the mouth and/or throat, and abdominal cramping. [12]

Contraindications

Trimethoprim/Sulfamethoxazole Contraindications

• Known hypersensitivity to either drug or a past sulfa allergy

• Pregnancy (FDA pregnancy category D) – due to the inhibition of folate synthesis, which can lead to congenital abnormalities.

• Liver parenchymal damage, jaundice, and hepatic failure

• Hematological disorders

• Renal insufficiency 

• Neonate less than six weeks of age

Trimethoprim/sulfamethoxazole is an American pregnancy category D medication. Use during early pregnancy has been related to congenital malformations and maternal folic acid deficiency; this may cause neural tube defects (spina bifida), urinary tract defects, oral clefts, and clubbed feet. Use during late pregnancy has been related to preterm labor. The drug also gets excreted in breast milk, and breastfeeding patients should not use trimethoprim/sulfamethoxazole during this time.  

Administration of trimethoprim/sulfamethoxazole should not occur concomitantly with any of the following:

• ACE inhibitors: Risk of hyperkalemia 

• Prilocaine: Risk of methemoglobinemia

• Antiarrhythmics: Risk of QTc prolongation 

• Dapsone: Increases plasma levels of both drugs

• Methenamine: Risk of crystalluria

• Rifampin: Risk of reducing trimethoprim plasma concentrations

• Sulfonylureas 

• Phenytoin: Increase in the half-life of phenytoin

• Antifolates: Risk of megaloblastic anemia

• Lamivudine, zalcitabine, and zidovudine

• Procainamide and/or amantadine 

• Clozapine

• Digoxin: Increase in digoxin levels

• Diuretics: Risk of thrombocytopenia

• Ciclosporin: Risk of kidney function decline

• Spironolactone: Risk of hyperkalemia

Monitoring

When initiating therapy with trimethoprim/sulfamethoxazole, some patients may require a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if the patient has renal impairment or if they are taking a drug that has interactions with potassium.

Toxicity

Overdosing on trimethoprim/sulfamethoxazole is possible, and potential signs of toxicity include:

If there is suspicion of a patient having trimethoprim/sulfamethazine toxicity, a treatment plan includes the administration of activated charcoal (if ingested), gastric lavage, and supportive intravenous (IV) and oral fluids. More severe treatment measures may consist of hemodialysis and alkalizing the patient’s urine.[5]

Enhancing Healthcare Team Outcomes

Prescribing clinicians, including nurse practitioners, primary care providers, physician assistants, and internists who prescribe trimethoprim/sulfamethoxazole (TMP-SMX), should be familiar with ints indications and adverse effects. Also, when a patient receives a prescription of trimethoprim/sulfamethoxazole, some patients may need a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if renal impairment is a known issue or if taking a drug that has interactions with potassium.

Pharmacists should be consulted to verify coverage in conjunction with an infectious disease specialist, verify dosing, perform medication reconciliation, and report any concerns to the rest of the healthcare team. Nurses will administer the drug inpatient and can also confirm that there are no adverse events resulting from therapy with TMP-SMX, reporting any concerns immediately to the prescriber.  In instances of pediatric use or cases of renal impairment, the pharmacist, nurse, and prescriber should coordinate to ensure proper dosing. As with any medication therapy, antimicrobial treatment with TMP-SMX requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient outcomes. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

García-Solache M, Rice LB. The Enterococcus: a Model of Adaptability to Its Environment. Clin Microbiol Rev. 2019 Mar 20;32(2) [PMC free article: PMC6431128] [PubMed: 30700430]

2.

Huang L, Chen X, Xu H, Sun L, Li C, Guo W, Xiang L, Luo G, Cui Y, Lu B. Clinical features, identification, antimicrobial resistance patterns of Nocardia species in China: 2009-2017. Diagn Microbiol Infect Dis. 2019 Jun;94(2):165-172. [PubMed: 30679058]

3.

Krooks J, Weatherall A, Markowitz S. Complete Resolution of Mycobacterium marinum Infection with Clarithromycin and Ethambutol: A Case Report and a Review of the Literature. J Clin Aesthet Dermatol. 2018 Dec;11(12):48-51. [PMC free article: PMC6334835] [PubMed: 30666280]

4.

She WH, Chok KSH, Li IWS, Ma KW, Sin SL, Dai WC, Fung JYY, Lo CM. Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report. BMC Infect Dis. 2019 Jan 18;19(1):66. [PMC free article: PMC6339407] [PubMed: 30658592]

5.

Eyler RF, Shvets K. Clinical Pharmacology of Antibiotics. Clin J Am Soc Nephrol. 2019 Jul 05;14(7):1080-1090. [PMC free article: PMC6625637] [PubMed: 30862698]

6.

Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. [PubMed: 33870843]

7.

Falcon M, Iberico C, Guerra F, Reyes I, Felix E, Flores M, de Los Ríos J, Diaz ME, Casas A, Sanchez-Gambetta S, Carrasco R. A pilot study of safety of sulfamethoxazole, trimethoprim and guaifenesin in pediatric and adult patients with acute bronchitis. BMC Res Notes. 2019 Mar 04;12(1):119. [PMC free article: PMC6399863] [PubMed: 30832720]

8.

Hosseini Nave H, Mansouri S, Sadeghi A, Moradi M. Molecular diagnosis and anti-microbial resistance patterns among Shigella spp. isolated from patients with diarrhea. Gastroenterol Hepatol Bed Bench. 2016 Summer;9(3):205-10. [PMC free article: PMC4947135] [PubMed: 27458513]

9.

Wan CD, Zhou JB, Song YP, Zou XJ, Ma YQ. [Pathogens of prostatitis and their drug resistance: an epidemiological survey]. Zhonghua Nan Ke Xue. 2013 Oct;19(10):912-7. [PubMed: 24218946]

10.

McGee M, Brienesse S, Chong B, Levendel A, Lai K. Tropheryma whipplei Endocarditis: Case Presentation and Review of the Literature. Open Forum Infect Dis. 2019 Jan;6(1):ofy330. [PMC free article: PMC6329903] [PubMed: 30648125]

11.

Hanlon JT, Perera S, Drinka PJ, Crnich CJ, Schweon SJ, Klein-Fedyshin M, Wessel CB, Saracco S, Anderson G, Mulligan M, Nace DA. The IOU Consensus Recommendations for Empirical Therapy of Cystitis in Nursing Home Residents. J Am Geriatr Soc. 2019 Mar;67(3):539-545. [PMC free article: PMC7980083] [PubMed: 30584657]

12.

Gallardo-Cartagena JA, Chiappe-Gonzalez AJ, Astocondor-Salazar LM, Salazar-Mesones BN, Narcizo Susanibar JA, Cucho-Espinoza C, Huaroto-Valdivia LM, Ticona-Chávez ER. [Vibrio cholerae NO-O1/NO-O139 bacteremia in a cirrhotic patient. First case report in Peru and literatura review]. Rev Gastroenterol Peru. 2018 Jul-Sep;38(3):301-305. [PubMed: 30540737]

Disclosure: Tyler Kemnic declares no relevant financial relationships with ineligible companies.

Disclosure: Meghan Coleman declares no relevant financial relationships with ineligible companies.

Trimethoprim Sulfamethoxazole – StatPearls – NCBI Bookshelf

Continuing Education Activity

Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-Sulfa. It is an antimicrobial used to treat and prevent many bacterial infections. This drug is very cost affordable and used for many types of illnesses. The FDA-Approved indications include acute infective exacerbation of chronic bronchitis, otitis media in pediatrics only, travelers diarrhea for treatment and prophylaxis, urinary tract infections, shigellosis, pneumocystis jirovecii, pneumonia/pneumocystis carinii pneumonia (PJP/PCP), and toxoplasmosis, both as prophylaxis and treatment. There are also non-FDA-approved indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of TMP-SMX, so providers can direct patient therapy where necessary for infections as part of the interprofessional team.

Objectives:

• Identify the antimicrobial mechanism of action of trimethoprim/sulfamethoxazole, focusing on each component individually and the synergism of the combination.

• Summarize the approved indications for initiating antimicrobial therapy with trimethoprim/sulfamethoxazole.

• Outline the potential adverse events associated with trimethoprim/sulfamethoxazole.

• Explain interprofessional team strategies for improving care coordination and communication to properly use trimethoprim/sulfamethoxazole to improve patient outcomes in infectious disease.

Access free multiple choice questions on this topic.

Indications

Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-sulfa.[1][2] It is an antimicrobial used to treat and prevent many bacterial infections. In 1974, TMP/SMX healthcare professionals began prescribing the medication, and the drug is now on the list of the World Health Organization’s (WHO) essential medicines.[3] This drug is very cost affordable and used for many types of illnesses.[4]

The FDA-Approved Indications

• Acute infective exacerbation of chronic bronchitis

• Otitis media in pediatrics only

• Travelers diarrhea for treatment and prophylaxis

• Urinary tract infections

• Shigellosis

• Pneumocystis jirovecii pneumonia/Pneumocystis carinii pneumonia (PJP/PCP) both prophylactic and treatment

• Toxoplasmosis both prophylactic and treatment

The Non-FDA Approved Indications

• Prophylaxis in HIV-infected individuals

• Acne vulgaris

• Listeria

• Melioidosis

• Pertussis (whooping cough)

• Staphylococcus aureus infections, including methicillin-resistant Staphylococcus aureus (MRSA)

• Tuberculosis

• Whipple disease

• Isosporiasis

• Malaria

• Community-acquired pneumonia

Mechanism of Action

Sulfamethoxazole is a sulfonamide (antimicrobial drug class) that works directly on the synthesis of folate inside microbial organisms, e. g., bacteria. Sulfamethoxazole achieves this directly as a competitor of p-aminobenzoic acid (PABA) during the synthesis of dihydrofolate via inhibition of the enzyme dihydropteroate synthase. Trimethoprim is a direct competitor of the enzyme dihydrofolate reductase, resulting in its inhibition, which halts the production of tetrahydrofolate to its active form of folate. The combination of these two agents is meant to create a synergistic anti-folate effect; tetrahydrofolate is a necessary component for synthesizing purines required for DNA and protein production. When used alone, these drugs only act in a bacteriostatic manner. However, when used in the combination of sulfamethoxazole-trimethoprim, they block two steps in the bacterial biosynthesis of essential nucleic acids and proteins, thus can be bactericidal, e.g., urine.[5]

Sulfamethoxazole is hepatically metabolized by the CYP450 system; it is a CYP2C9 inhibitor. Its half-life is 6 to 12 hours, increasing to between 20 and 50 hours in renal failure.  Trimethoprim has a half-life of 8 to 10 hours, is minimally metabolized in the liver, and is primarily excreted in the urine, essentially unchanged.

Administration

Sulfamethoxazole/trimethoprim may be administered orally without regard to meals. However, it is best to take it with at least 8 ounces of water. It also has an intravenous formulation. The choice of oral or intravenously varies both on the type of infection/or type of prophylactic use. It should not be administered intramuscularly. Patients with impaired renal function must have calculated dosing regimens based on renal function, as listed below. Administration of the two drugs is in a 1 to 5 ratio (trimethoprim:sulfamethoxazole) as a tablet formulation; this is so when they enter the body, their concentration throughout the blood/tissues is 1 to 20, which is the peak synergistic desired effect ratio of the two drugs in combination.[6]

Bacterial Infections

Oral dosage in adults and children weighing 40 kg (88 pounds) or more should have a single tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days. Children 2 months and older must have a weight-adjusted dosage.

Treatment of Pneumocystis jirovecii Pneumonia/Pneumocystis carinii Pneumonia

Adults/children, two months of age and older: The dose is also weight adjusted. Usually 75 to 100 mg per kilogram of body weight for sulfamethoxazole and 15 to 20 mg per kilogram of body weight for trimethoprim each day for 14 to 21 days.[6]

Prevention of Pneumocystis jirovecii pneumonia/ pneumocystis carinii pneumonia

In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim is given once a day. In children two months of age and older, dosages are determined by body size.[6]

Traveler’s Diarrhea

In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days. For children two months and older, use and dosage vary.

Chronic Bronchitis

For acute exacerbations due to strains of Streptococcus pneumoniae or Haemophilus influenzae, one tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days. [7]

Shigellosis

Enteritis caused by Shigella flexneri and Shigella sonnei: 1 tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days; antimicrobial resistance is an increasing concern in this infection.[8]

Urinary Tract Infections

Pyelonephritis

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days

Prostatitis

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days or 2 to 3 months if a chronic infection.[9]

Acne Vulgaris (Non-FDA Approved)

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 18 days

Community-Acquired Pneumonia (Non-FDA Approved)

One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days

Renal impairment guidelines are as follows:

• CrCl greater than 30 mL per minute no dose change

• CrCl 15 to 30 mL per minute decrease dose by 50%

• CrCl less than 15 do no use

Use is not recommended in children younger than two months of age.

Adverse Effects

The primary adverse effects of trimethoprim/sulfamethoxazole include rash, photosensitivity, as well as folate deficiency.[10][11] 

A list of the more common side effects includes:

• Loss of appetite

• Nausea/vomiting/dyspepsia

• Painful or swollen tongue

• Dizziness

• Tinnitus

• Fatigue

• Insomnia

• Rash/urticaria

• Anorexia

• Photosensitivity

More serious reactions can include Stevens-Johnson syndrome, various anemias, agranulocytosis, C. diff.-associated diarrhea, myelosuppression, renal failure/interstitial nephritis, pancreatitis, and hepatotoxicity. Hemolytic anemia can occur with sulfa drugs like sulfamethoxazole in patients with a glucose-6-phosphate-dehydrogenase (G6PD) deficiency.

A patient with an unknown sulfa allergy and treated with trimethoprim/sulfamethoxazole may experience anaphylaxis or less serious yet severe symptoms such as hives, itchy eyes, swelling of the mouth and/or throat, and abdominal cramping. [12]

Contraindications

Trimethoprim/Sulfamethoxazole Contraindications

• Known hypersensitivity to either drug or a past sulfa allergy

• Pregnancy (FDA pregnancy category D) – due to the inhibition of folate synthesis, which can lead to congenital abnormalities.

• Liver parenchymal damage, jaundice, and hepatic failure

• Hematological disorders

• Renal insufficiency 

• Neonate less than six weeks of age

Trimethoprim/sulfamethoxazole is an American pregnancy category D medication. Use during early pregnancy has been related to congenital malformations and maternal folic acid deficiency; this may cause neural tube defects (spina bifida), urinary tract defects, oral clefts, and clubbed feet. Use during late pregnancy has been related to preterm labor. The drug also gets excreted in breast milk, and breastfeeding patients should not use trimethoprim/sulfamethoxazole during this time.  

Administration of trimethoprim/sulfamethoxazole should not occur concomitantly with any of the following:

• ACE inhibitors: Risk of hyperkalemia 

• Prilocaine: Risk of methemoglobinemia

• Antiarrhythmics: Risk of QTc prolongation 

• Dapsone: Increases plasma levels of both drugs

• Methenamine: Risk of crystalluria

• Rifampin: Risk of reducing trimethoprim plasma concentrations

• Sulfonylureas 

• Phenytoin: Increase in the half-life of phenytoin

• Antifolates: Risk of megaloblastic anemia

• Lamivudine, zalcitabine, and zidovudine

• Procainamide and/or amantadine 

• Clozapine

• Digoxin: Increase in digoxin levels

• Diuretics: Risk of thrombocytopenia

• Ciclosporin: Risk of kidney function decline

• Spironolactone: Risk of hyperkalemia

Monitoring

When initiating therapy with trimethoprim/sulfamethoxazole, some patients may require a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if the patient has renal impairment or if they are taking a drug that has interactions with potassium.

Toxicity

Overdosing on trimethoprim/sulfamethoxazole is possible, and potential signs of toxicity include:

If there is suspicion of a patient having trimethoprim/sulfamethazine toxicity, a treatment plan includes the administration of activated charcoal (if ingested), gastric lavage, and supportive intravenous (IV) and oral fluids. More severe treatment measures may consist of hemodialysis and alkalizing the patient’s urine.[5]

Enhancing Healthcare Team Outcomes

Prescribing clinicians, including nurse practitioners, primary care providers, physician assistants, and internists who prescribe trimethoprim/sulfamethoxazole (TMP-SMX), should be familiar with ints indications and adverse effects. Also, when a patient receives a prescription of trimethoprim/sulfamethoxazole, some patients may need a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if renal impairment is a known issue or if taking a drug that has interactions with potassium.

Pharmacists should be consulted to verify coverage in conjunction with an infectious disease specialist, verify dosing, perform medication reconciliation, and report any concerns to the rest of the healthcare team. Nurses will administer the drug inpatient and can also confirm that there are no adverse events resulting from therapy with TMP-SMX, reporting any concerns immediately to the prescriber.  In instances of pediatric use or cases of renal impairment, the pharmacist, nurse, and prescriber should coordinate to ensure proper dosing. As with any medication therapy, antimicrobial treatment with TMP-SMX requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient outcomes. [Level 5]

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References

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García-Solache M, Rice LB. The Enterococcus: a Model of Adaptability to Its Environment. Clin Microbiol Rev. 2019 Mar 20;32(2) [PMC free article: PMC6431128] [PubMed: 30700430]

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Huang L, Chen X, Xu H, Sun L, Li C, Guo W, Xiang L, Luo G, Cui Y, Lu B. Clinical features, identification, antimicrobial resistance patterns of Nocardia species in China: 2009-2017. Diagn Microbiol Infect Dis. 2019 Jun;94(2):165-172. [PubMed: 30679058]

3.

Krooks J, Weatherall A, Markowitz S. Complete Resolution of Mycobacterium marinum Infection with Clarithromycin and Ethambutol: A Case Report and a Review of the Literature. J Clin Aesthet Dermatol. 2018 Dec;11(12):48-51. [PMC free article: PMC6334835] [PubMed: 30666280]

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She WH, Chok KSH, Li IWS, Ma KW, Sin SL, Dai WC, Fung JYY, Lo CM. Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report. BMC Infect Dis. 2019 Jan 18;19(1):66. [PMC free article: PMC6339407] [PubMed: 30658592]

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Eyler RF, Shvets K. Clinical Pharmacology of Antibiotics. Clin J Am Soc Nephrol. 2019 Jul 05;14(7):1080-1090. [PMC free article: PMC6625637] [PubMed: 30862698]

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Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. [PubMed: 33870843]

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Falcon M, Iberico C, Guerra F, Reyes I, Felix E, Flores M, de Los Ríos J, Diaz ME, Casas A, Sanchez-Gambetta S, Carrasco R. A pilot study of safety of sulfamethoxazole, trimethoprim and guaifenesin in pediatric and adult patients with acute bronchitis. BMC Res Notes. 2019 Mar 04;12(1):119. [PMC free article: PMC6399863] [PubMed: 30832720]

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Hosseini Nave H, Mansouri S, Sadeghi A, Moradi M. Molecular diagnosis and anti-microbial resistance patterns among Shigella spp. isolated from patients with diarrhea. Gastroenterol Hepatol Bed Bench. 2016 Summer;9(3):205-10. [PMC free article: PMC4947135] [PubMed: 27458513]

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Wan CD, Zhou JB, Song YP, Zou XJ, Ma YQ. [Pathogens of prostatitis and their drug resistance: an epidemiological survey]. Zhonghua Nan Ke Xue. 2013 Oct;19(10):912-7. [PubMed: 24218946]

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McGee M, Brienesse S, Chong B, Levendel A, Lai K. Tropheryma whipplei Endocarditis: Case Presentation and Review of the Literature. Open Forum Infect Dis. 2019 Jan;6(1):ofy330. [PMC free article: PMC6329903] [PubMed: 30648125]

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Hanlon JT, Perera S, Drinka PJ, Crnich CJ, Schweon SJ, Klein-Fedyshin M, Wessel CB, Saracco S, Anderson G, Mulligan M, Nace DA. The IOU Consensus Recommendations for Empirical Therapy of Cystitis in Nursing Home Residents. J Am Geriatr Soc. 2019 Mar;67(3):539-545. [PMC free article: PMC7980083] [PubMed: 30584657]

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Gallardo-Cartagena JA, Chiappe-Gonzalez AJ, Astocondor-Salazar LM, Salazar-Mesones BN, Narcizo Susanibar JA, Cucho-Espinoza C, Huaroto-Valdivia LM, Ticona-Chávez ER. [Vibrio cholerae NO-O1/NO-O139 bacteremia in a cirrhotic patient. First case report in Peru and literatura review]. Rev Gastroenterol Peru. 2018 Jul-Sep;38(3):301-305. [PubMed: 30540737]

Disclosure: Tyler Kemnic declares no relevant financial relationships with ineligible companies.

Disclosure: Meghan Coleman declares no relevant financial relationships with ineligible companies.

instructions for use, description, reviews of patients and doctors, analogues

Some facts about the product:

Instructions for use

Presentation, composition and packaging

Bactrim is made as a liquid mixture for internal administration. The active ingredients are sulfamethoxazole and trimethoprim. Excipients:

• methylparaben;
• parahydroxybenzoic acid propyl ester;
• flavoring agent;
• fragrances;
• distilled water.

According to the description, the solution is a homogeneous suspension of yellow-white or orange color with a fruity odor.
Packing – 50- and 100-mm glass containers in a set with a measuring spoon. The price of Bactrim is regulated by the legislation of the Russian Federation.

Pharmacological action

Bactrim is an antimicrobial agent with a complex spectrum of action. Sulfamethoxazole has a bacteriostatic effect when, as a result of blocking the reactions of PABA removal, the process of formation of dihydrofolic acid in bacterial cells is suppressed. Trimethoprim inhibits the fermentation and breakdown of folic acid, transforming dihydrofolate into tetrahydrofolate. Under the influence of the agent, two successive phases of the formation of imidazo-pyrimidines and biopolymers formed by nucleotide residues, which are responsible for the creation and development of pathogens, are inhibited. A feature of the drug is the formation of a high saturation of the material in various tissues and body fluids – bone fibers, prostate, kidneys, lungs, bile and cerebrospinal secretions, saliva, lacrimal fluid, in breast lactose.
After the introduction of 90% of the initial volume of the substance is absorbed into the tissues, reaching a maximum density after 1-4 hours. It is found in breast lactose. The level of connection with plasma proteins in sulfamethoxazole is 65%, in trimethoprim – 45%.
Cleavage reactions occur with the creation of acetylated metabolites that are not antimicrobially active. They are extracted by 80% through the urinary system within three days. A small part of the drug comes out through the digestive tract. The half-life in adult patients is within 9-12 hours, in newborns – 7-8 hours, from a year to 10 years – 5-6 hours. In patients with kidney pathologies and the older age group, the elimination time increases.

Readings

Bactrim is prescribed for infectious diseases of the urinary system, respiratory system, gastrointestinal tract, ENT organs, skin, bone tissue.

Contraindications

It is forbidden to use the medication for liver parenchyma disease, acute kidney pathologies, in case of severe forms of blood damage, high bilirubin levels. Caution is required for concomitant diseases of the thyroid organ, bronchial asthma. You can buy Bactrim at a pharmacy or in an online store.

Dosage and Administration

Bactrim is prescribed at a dose of 0.4 to 2 g 2 times a day. The portion for small children under 2 years old is set individually. The maximum daily dose cannot exceed 3.6 g. It is allowed to switch to Bactrim analogues only on the recommendation of a doctor.

Side effects

Most often, accidental phenomena against the background of the use of a combined antimicrobial chemical agent occur on the skin and in the digestive tract. There are complications from:

• blood formation and lymphatic system – decrease in the level of leukocytes, granulocytes, platelets, erythrocytes;
• immunity – nettle fever, angioedema, polyarteritis nodosa, infectious-allergic myocarditis, dermatitis, lupus erythematosus;
• metabolism – an increase in the amount of potassium in the blood serum, a decrease in the level of sodium, sugar;
• mentality – hallucinogenic and depressive states, lack of sleep, high fatigue, psychosis, clouding of consciousness, impaired attention, perception, thinking and emotions.

The appearance of complications after the use of Bactrim is possible from:

• central nervous organization – sensory disturbance, neuritis, meningitis-like conditions, convulsions, dizziness, cephalalgia, ringing in the ears;
• respiratory system – pneumonia;
• digestive department – nausea with or without vomiting, diarrhea, inflammation of the intestines, pancreas;
• hepatobiliary structure – activation of enzymes, increased levels of bilirubin, hepatitis, necrosis of hepatocytes, symptoms of the disappearance of the bile ducts;
• renal and urinary systems – kidney dysfunction, tubulointerstitial chronic nephritis, increased levels of urea, creatinine in the blood, the formation of salts in the urine, increased diuresis;
• skin – the appearance of a rash.

In HIV-infected patients during treatment with the introduction of high doses of Bactrim, according to doctors, pneumonia develops. In 20-25% of patients, the drug has to be discontinued due to severe side effects from:

• psychics – acute psychoses;
• nervous organization – hallucinations, aseptic meningitis, convulsive convulsions, trembling of the limbs like Parkinson’s syndrome, impaired motor skills, vestibular apparatus;
• digestive tract – lack of appetite, irritation of the pituitary surface of the oral cavity, neck, chin.

Many drugs containing sulfonamides cause collateral changes in the form of target-like rashes on the pituitary surface, photophobia. As a result of the use of Bactrim in the area of ​​the musculoskeletal structure, pain occurs in muscles, joints, up to destruction and necrosis of muscle tissue.

Overdose

With a strong overdose, nausea with vomiting, diarrhea, cephalgia, dizziness, impaired visual perception and cognitive abilities develop. Severe types of poisoning are characterized by the formation of salts in the urine, the appearance of blood and the impossibility of urination. Long-term use of chemical means suppresses the processes of blood formation, which causes a decrease in the level of platelets, leukocytes against the background of folic acid deficiency.
To prevent the absorption of the substance into the blood, forced diuresis is prescribed by alkalinizing the urine. Extrarenal blood purification is ineffective. The level of electrolytes and the state of the blood are monitored. In the event of the development of severe clinical changes in the blood or the onset of symptoms of jaundice, special therapy is prescribed. To reduce the effects of trimethoprim, calcium folinate is given in an amount of 3 to 6 mg per day. The duration of the course is one week. You can order Bactrim on a specialized pharmacy website.

Drug interactions

With the complex use of an antimicrobial syrup with anticoagulants of indirect influence, the effect of anticoagulants is significantly enhanced. Parallel administration with sulfonylurea metabolites causes an even sharper decrease in the sugar-lowering effect.
The combination of Bactrim with methotrexate enhances the toxic effect of the latter and leads to the development of pancytopenia due to a break in its connection with blood plasma proteins.
Under the influence of anti-inflammatory drugs in combination with Bactrim, the effect of both substances is summed up with the occurrence of side effects. With parallel administration with diuretic materials, the likelihood of a decrease in platelet levels increases. This effect is especially characteristic for older patients.
Simultaneous administration with chloridine increases the effect of the antimicrobial agent due to the inhibition of tetrahydroflic acid, which is involved in the formation of nucleic acids and proteins. At the same time, sulfonamides slow down the synthesis of dihydrofolic acid, which precedes the appearance of tetrahydrofolic acid compounds. This combination is used to eliminate parasitic diseases.
The absorption of the active components of Bactrim when combined with cholestyramine is reduced due to a decrease in the density in the blood substance and the synthesis of insoluble compounds.
The complex use of an antimicrobial chemical agent and antiepileptic substances increases the half-life of phenytoin with a simultaneous increase in its effect and toxicity.
The combination with antimalarial chemicals increases the risk of malignant anemia. Sulfamethoxazole and trimethoprim in combination with digoxin increase the concentration of cardiotonic. In aged patients, control over the level of antiarrhythmic substance in the blood serum should be strengthened. An antimicrobial agent reduces the effectiveness of antipsychotic therapy. When combined with cyclosporine after kidney transplantation, dysfunction of the organs of the urinary structure is observed, which is expressed by an increase in the amount of creatinine in the blood medium.
Parallel administration of Bactrim with angiotensin-converting enzyme blockers has been noted to increase the level of potassium in the blood. This is especially true for older patients.
Trimethoprim, blocking the patency of the urinary system, increases the total and maximum density of dofetilide by 103% and 93% respectively. As a result, there is an inconsistency in the processes of depolarization and repolarization of the ventricular myocardium, the occurrence of ventricular arrhythmia. Bactrim delivery in Moscow is carried out around the clock.

Special instructions

Patients in childhood are prescribed only preparations containing sulfamethoxazole with trimethoprim, which are intended for use in pediatric practice. Monitoring of the level of saturation of sulfamethoxazole in blood plasma is performed every 2-3 days before the next use. When the saturation of the active ingredient in the amount of 150 mcg / ml, therapy is stopped until the indicator drops below 120 mcg / ml.
With prolonged treatment for more than 30 days, blood tests are taken due to the risk of formation of changes in it. They are reversible with daily intake of folic acid at a dose of 3-6 mg. This does not cause violations of the antimicrobial efficacy of the drug. In the presence of an initial folate deficiency in elderly patients, the appointment of an antimicrobial agent should be performed with caution.
To prevent the formation of salts in the urine, it is necessary to maintain sufficient urination. The use of Bactrim increases the risk of allergenic or toxic side effects with reduced filtration activity of the kidneys.
During therapy, it is not recommended to eat food containing PABA – green cabbage, spinach, as well as legumes, carrots, tomatoes. It is necessary to be as little as possible under the influence of sunlight, avoid visiting solariums. The likelihood of developing accidental phenomena against the background of the use of antimicrobial syrup is higher in patients with AIDS. It is not advisable to use a chemical agent for inflammation of the larynx, which is caused by streptococcus A due to the resistance of the microorganism to the drug.
The introduction of Bactrim during the period of gestation, lactation is not shown. In renal pathology, the dosage level is determined on the basis of the creatinine clearance.

Terms and conditions of storage

According to the instructions, the shelf life of the material is 5 years when stored at t ° up to 30 ° C.

Prices for Bactrim in Moscow

Pick up the order at the pharmacy
WER (Moscow)

Favorable prices

Certificates and licenses

References

1. State Register
   medicinal
   funds
2. International Classification of Diseases, 10th Revision (ICD-10)
3. Vidal Drug Formulary

Use of sulfamethoxazole/trimethoprim in the treatment of children with cancer

Antibiotic

Brand names:

Bactrim®, Septra®, Sulfatrim®

Other names:

SMX-TMP, Co-trimoxazole

Often used for:

Infections

Sulfamethoxazole/trimethoprim is an antibiotic; its action is aimed at the destruction of bacteria that cause infections. Some patients are given this drug to prevent pneumonia during chemotherapy. This drug may also be used to treat infections. Follow dosage instructions carefully.

You may need to have blood tests while taking this drug.

Oral tablets

Oral liquid form

Administered intravenously (through a drip) in liquid form

• Nausea and vomiting
• Rash
  
• Sun sensitivity
  
• Loss of appetite
• Diarrhea
• Abdominal pain
• Low blood counts

These side effects may not occur in all patients treated with sulfamethoxazole/trimethoprim. The most common side effects are highlighted in bold, but others are not excluded. Report all possible side effects to your doctor or pharmacist.

Be sure to discuss these and other recommendations with your doctor or pharmacist.

• It is important to drink plenty of fluids while taking this medicine. It is necessary to drink the amount of liquid recommended by the doctor.
• The drug may interfere with the results of some laboratory tests.
• Alcoholic beverages should be avoided while taking this drug.
• Patients should protect their skin from the sun while on therapy with this drug.
• Pregnant, planning pregnancy or breastfeeding patients should notify the attending physician.
• The course of taking the drug must be completed completely in accordance with the recommendations of the attending physician or pharmacist.

Home use of sulfamethoxazole/trimethoprim:

• The drug should be taken at the same time every day.
• This drug can be taken with or without food. If the drug causes stomach upset, it must be taken with food.
• It is recommended to take the drug with a full glass of water.
• In liquid form: shake well before use, measure dosage using the measuring device included.