Infections That Should Be Treated with Added Probenecid
Probenecid should be added to specific antibiotic regimens for treating gonococcal infections and when using cefoxitin for pelvic inflammatory disease (PID). Based on CDC treatment guidelines, probenecid is primarily indicated as an adjunct to certain antimicrobial therapies to elevate and prolong plasma levels of the antibiotics.
Gonococcal Infections
Recommended Regimens with Probenecid
- Uncomplicated Gonococcal Infections
- Cefoxitin 2 g IM with probenecid 1 g orally in a single dose concurrently 1
- Aqueous procaine penicillin G 4.8 million units IM with probenecid 1 g orally for uncomplicated gonococcal infections 2
- Amoxicillin 3 g orally with probenecid 1 g orally 2, 3
- Ampicillin 3.5 g orally with probenecid 1 g orally 2, 3
Clinical Evidence
- The combination of probenecid with penicillins for gonorrhea treatment has demonstrated cure rates of 97.4% in men 4
- Amoxicillin plus probenecid showed a 100% cure rate in one study of uncomplicated gonorrhea 3
- Epicillin 2 g plus probenecid 1 g achieved a 97% cure rate for gonorrhea 5
Pelvic Inflammatory Disease (PID)
Recommended Regimens with Probenecid
- For outpatient treatment of PID: Cefoxitin 2 g IM plus probenecid 1 g orally in a single dose concurrently, followed by doxycycline 100 mg orally twice a day for 14 days 1
Mechanism and Rationale
Probenecid works by:
- Inhibiting renal tubular secretion of antibiotics
- Elevating and prolonging plasma levels of antibiotics
- Allowing for higher tissue concentrations of antibiotics
- Reducing the required frequency of antibiotic administration
Important Considerations
Dosing
- Standard dose for antimicrobial adjunct therapy: 1 g orally as a single dose 1, 2
- For penicillin therapy in general: 2000 mg (4 tablets) daily in divided doses 2
Contraindications
- Probenecid is contraindicated in children under 2 years of age 2
- Should not be used in patients with severe renal impairment, especially when glomerular filtration rate is 30 mL/minute or less 2
- Should not be started during an acute gouty attack (relevant when used for gout treatment) 2
Limitations
- Ciprofloxacin has been shown to be more effective than amoxicillin plus probenecid in some studies, particularly for penicillinase-producing Neisseria gonorrhoeae (PPNG) 6
- Modern guidelines increasingly favor ceftriaxone without probenecid for gonorrhea due to rising antimicrobial resistance 1, 7
Clinical Pearls
- When treating gonorrhea with penicillin derivatives, always add probenecid to enhance efficacy
- For PID treatment with cefoxitin, probenecid is a necessary component of the regimen
- Probenecid is particularly valuable when treating infections in areas with limited resources where newer antibiotics may not be available
- The PSP (phenolsulfonphthalein) excretion test can be used to determine the effectiveness of probenecid in retarding penicillin excretion 2
Remember that current CDC guidelines have moved away from some of these regimens due to antimicrobial resistance concerns, particularly for gonorrhea. However, in specific clinical scenarios or geographic regions where these antibiotics remain effective, probenecid continues to be an important adjunctive therapy.