From the Guidelines
Cotrimoxazole (trimethoprim/sulfamethoxazole or TMP-SMX) is a highly effective antibiotic combination used to treat various bacterial infections, with a recommended dosing of one double-strength tablet (160mg trimethoprim/800mg sulfamethoxazole) twice daily for 3 days in uncomplicated cystitis, as supported by the most recent guidelines 1.
Mechanism of Action
Cotrimoxazole works through a synergistic mechanism where trimethoprim inhibits dihydrofolate reductase while sulfamethoxazole blocks dihydropteroate synthase, sequentially inhibiting bacterial folate synthesis and ultimately preventing DNA replication.
Indications and Usage
Common indications include:
- Urinary tract infections
- Respiratory infections (particularly Pneumocystis jirovecii pneumonia in immunocompromised patients)
- Skin/soft tissue infections The choice of cotrimoxazole should be based on local resistance rates, with the Infectious Diseases Society of America (IDSA) recommending its use if resistance rates do not exceed 20% 1.
Dosage and Administration
Standard adult dosing is typically one double-strength tablet (160mg trimethoprim/800mg sulfamethoxazole) twice daily, with duration varying by condition:
- Uncomplicated cystitis: 3 days 1
- Uncomplicated pyelonephritis: 14 days 1
- PCP treatment: higher doses (15-20mg/kg/day of the trimethoprim component) for 21 days
- Prophylaxis in immunocompromised patients: one single-strength tablet daily or one double-strength tablet three times weekly
Safety and Contraindications
Patients should take cotrimoxazole with plenty of fluids, and those with renal impairment require dose adjustments. Common side effects include:
- Rash
- Gastrointestinal disturbances
- Photosensitivity Serious adverse reactions can include:
- Stevens-Johnson syndrome
- Bone marrow suppression
- Hyperkalemia The medication is contraindicated in patients with:
- Sulfa allergies
- Severe liver disease
- Late pregnancy due to risk of kernicterus
Resistance and Limitations
Rising rates of trimethoprim-sulfamethoxazole resistance among uropathogens necessitate careful consideration of local resistance patterns before prescribing cotrimoxazole 1.
From the FDA Drug Label
To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris Acute Otitis Media: For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents Acute Exacerbations of Chronic Bronchitis in Adults: For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when a physician deems that sulfamethoxazole and trimethoprim could offer some advantage over the use of a single antimicrobial agent Shigellosis: For the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei when antibacterial therapy is indicated Pneumocystis jiroveci Pneumonia: For the treatment of documented Pneumocystis jiroveci pneumonia and for prophylaxis against P. jiroveci pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing P jiroveci pneumonia Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic E. coli
The pharmacology of Cotrimoxazole (trimethoprim/sulfamethoxazole) involves the use of a combination of two antimicrobial agents to treat various bacterial infections. The usage of Cotrimoxazole includes:
- Urinary Tract Infections: treatment of infections caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
- Acute Otitis Media: treatment of infections caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae in pediatric patients
- Acute Exacerbations of Chronic Bronchitis in Adults: treatment of infections caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
- Shigellosis: treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei
- Pneumocystis jiroveci Pneumonia: treatment and prophylaxis of pneumonia in immunosuppressed individuals
- Traveler’s Diarrhea in Adults: treatment of diarrhea caused by susceptible strains of enterotoxigenic E. coli 2 3
From the Research
Pharmacology of Cotrimoxazole
- Cotrimoxazole, a combination of trimethoprim and sulfamethoxazole, was developed to provide synergy in antimicrobial action and delay the emergence of resistance 4.
- However, studies have shown that the tissue distribution of trimethoprim and sulfamethoxazole does not favor synergy, and resistance to sulfamethoxazole is high among common pathogens 4.
- Trimethoprim has been found to be active against a wide range of Gram-positive and Gram-negative aerobic bacteria, and is readily absorbed by the oral route, with wide distribution in body fluids and tissues 5.
Usage of Cotrimoxazole
- Cotrimoxazole is effective in treating various bacterial infections, including urinary tract infections, respiratory tract infections, and skin and soft-tissue infections 6.
- However, clinical studies have shown that trimethoprim alone is comparable in efficacy to cotrimoxazole for the treatment of acute uncomplicated urinary tract infections 5.
- The use of cotrimoxazole is recommended to be restricted to specific situations, such as Pneumocystis carinii pneumonia, where the combination has been shown to be beneficial 4, 7.
- Other indications where cotrimoxazole may be superior to trimethoprim include toxoplasmosis, brucellosis, nocardiosis, chancroid, and pneumonia caused by Pneumocystis carinii 7.
Adverse Effects and Interactions
- The common adverse effects of cotrimoxazole include gastrointestinal disturbances and skin rashes, which are well-described adverse effects of sulphonamides 4.
- Serious adverse effects, such as liver disorders and Stevens-Johnson syndrome, appear to be more common with cotrimoxazole than with trimethoprim alone 4.
- Cotrimoxazole may also interfere with folate metabolism, although the evidence is not conclusive 8.
- The adverse event profile of cotrimoxazole is a summation of that of sulphonamide and trimethoprim, and using trimethoprim alone may reduce the incidence and potential severity of adverse events 7.