Co-administration of Amoxicillin and Macrolides with TMP-SMX for MRSA Treatment

Rationale for Co-administration

The Infectious Diseases Society of America recommends TMP-SMX as a treatment option for MRSA infections, particularly for outpatient skin and soft tissue infections, with dosing typically at 160-320/800-1600 mg PO twice daily 2, 3
Amoxicillin is effective against many gram-positive organisms and is specifically recommended for certain conditions like erysipeloid at a dose of 500 mg three times daily 1, 4
Macrolides such as azithromycin are indicated for specific conditions like cat scratch disease with a recommended dosing protocol of 500 mg on day 1 followed by 250 mg for 4 additional days for patients >45 kg 1

When treating polymicrobial infections where both MRSA and beta-hemolytic streptococci are suspected pathogens, the American College of Physicians recommends co-administration of TMP-SMX with amoxicillin or macrolides 2, 5 is not used, instead: co-administration is recommended 2
For patients with MRSA infection who develop a secondary infection requiring coverage for organisms susceptible to amoxicillin or macrolides, co-administration may be indicated 1, 4

TMP-SMX has good activity against MRSA but poor activity against anaerobes, so additional coverage may be necessary depending on the clinical scenario, according to the Clinical Infectious Diseases guidelines 1, 4
When treating MRSA skin infections, incision and drainage remains the primary treatment for abscesses, with antibiotics as adjunctive therapy, as recommended by the Infectious Diseases Society of America 2

While there are no significant pharmacokinetic interactions between these antibiotics, monitor for potential side effects from each medication, as advised by the Journal of Microbiology, Immunology and Infection 2, 3
Caution is advised when using TMP-SMX in elderly patients or those with renal insufficiency due to increased risk of hyperkalemia, according to the Clinical Infectious Diseases guidelines 2
TMP-SMX is not recommended in pregnant women in the third trimester or in infants younger than 2 months of age, as recommended by the American Academy of Pediatrics 2

If concerns exist about using multiple antibiotics simultaneously, consider Clindamycin as an alternative when susceptibility results are available (if treating MRSA), as recommended by the Journal of Microbiology, Immunology and Infection 3
Linezolid may be considered for more severe MRSA infections requiring broader coverage, according to the Journal of Microbiology, Immunology and Infection 3