Combining Clarithromycin with Trimethoprim-Sulfamethoxazole (TMP-SMX)
Clarithromycin can be safely combined with trimethoprim-sulfamethoxazole (TMP-SMX) when clinically indicated, but this combination should be used judiciously due to potential side effects and antimicrobial resistance concerns. 1, 2
Clinical Scenarios Where Combination Is Appropriate
- For disseminated Mycobacterium avium complex (MAC) infection, clarithromycin is recommended in combination with ethambutol with or without rifabutin, while TMP-SMX is not part of the standard regimen 3
- For bacterial respiratory infections in HIV-infected patients, both clarithromycin and TMP-SMX have been used separately for prophylaxis, but not typically in combination 3
- For complex infections requiring broad coverage, the combination may be appropriate in specific clinical scenarios, though this should be based on culture results and antimicrobial susceptibility testing 4
- For treatment of melioidosis (Burkholderia pseudomallei infection), TMP-SMX is used after initial intensive therapy, but not typically with clarithromycin 5
Monitoring and Precautions
- Monitor renal function regularly when using this combination, especially in elderly patients or those with pre-existing renal impairment 4, 2
- Watch for signs of hyperkalemia, particularly in patients with renal impairment or those taking other medications that can increase potassium levels 4
- Monitor complete blood count periodically due to potential hematologic adverse effects, especially thrombocytopenia which occurred in 12.5% of patients in one study of TMP-SMX 6
- Be vigilant for cutaneous reactions, which may indicate hypersensitivity to either medication 4, 2
Dosing Considerations
- Both medications require dose adjustment in renal impairment 4
- TMP-SMX should not be administered to pregnant women, nursing mothers, or infants aged <2 months due to potential risks 4
- High-dose clarithromycin (1,000 mg twice daily) is associated with higher mortality rates than standard dosing (500 mg twice daily) in MAC disease treatment 3
Antimicrobial Stewardship Considerations
- The combination should not be used indiscriminately to prevent bacterial respiratory infections, as this might promote development of resistant organisms 3
- TMP-SMX has limited activity against anaerobic bacteria, so clarithromycin would not significantly enhance anaerobic coverage in this combination 7
- For skin and soft tissue infections, TMP-SMX is often preferred for MRSA coverage, while clarithromycin may be considered for other indications 8
- When treating bacterial respiratory infections in HIV patients, either TMP-SMX or clarithromycin/azithromycin may be effective for prophylaxis, but these drugs should not be prescribed solely for preventing bacterial respiratory infection 3
Conclusion
While clarithromycin and TMP-SMX can be combined when clinically indicated, this combination should be used judiciously with appropriate monitoring for adverse effects and consideration of antimicrobial stewardship principles 1, 2.