What is the top choice for chronic suppressive antibiotics in a patient undergoing total knee arthroplasty (TKA), considering potential previous infections or antibiotic use, and possible impaired renal function?

Chronic Suppressive Antibiotics for Total Knee Arthroplasty

For chronic suppressive therapy after TKA with prosthetic joint infection, the top choice is cephalexin 500 mg orally three to four times daily for methicillin-susceptible staphylococci, or co-trimoxazole (trimethoprim-sulfamethoxazole) one double-strength tablet orally twice daily for methicillin-resistant staphylococci. 1

Pathogen-Specific Suppressive Regimens

For Methicillin-Susceptible Staphylococci (MSSA)

• Cephalexin 500 mg orally three to four times daily is the preferred agent 1
• Alternative options include:
  • Dicloxacillin 500 mg orally three to four times daily 1
  • Clindamycin 300 mg orally four times daily 1
  • Cefadroxil 500 mg orally twice daily 1
  • Amoxicillin-clavulanate 500 mg orally three times daily 1

For Methicillin-Resistant Staphylococci (MRSA)

• Co-trimoxazole one double-strength tablet orally twice daily is the preferred agent 1
• Alternative option:
  • Minocycline or doxycycline 100 mg orally twice daily 1

For Other Organisms

• β-hemolytic streptococci: Penicillin V 500 mg orally two to four times daily (preferred), or cephalexin 500 mg orally three to four times daily, or amoxicillin 500 mg orally three times daily 1
• Enterococcus species (penicillin-susceptible): Penicillin V 500 mg orally two to four times daily or amoxicillin 500 mg orally three times daily 1
• Pseudomonas aeruginosa: Ciprofloxacin 250-500 mg orally twice daily 1
• Enterobacteriaceae: Co-trimoxazole one double-strength tablet orally twice daily or β-lactam oral therapy based on susceptibilities 1
• Propionibacterium species: Penicillin V 500 mg orally two to four times daily, or alternatives including cephalexin, amoxicillin, or minocycline/doxycycline 1

Clinical Decision Algorithm for Chronic Suppression

When to Consider Chronic Suppression

Chronic suppressive therapy should be considered in the following scenarios 1:

• Patients unsuitable for or refusing further exchange revision, excision arthroplasty, or amputation 1
• Elderly or immunosuppressed patients 1
• Patients with staphylococcal PJI in whom rifampin was not utilized 1
• Patients whose comorbidities would not allow additional surgery 1
• Patients in whom additional surgery may be limb-threatening in case of treatment failure 1

Duration Considerations

• Indefinite chronic suppression is recommended following the initial treatment course 1
• For staphylococcal infections treated with debridement and retention, suppression follows the 3-month (hip) or 6-month (knee) rifampin-based regimen 1
• For non-staphylococcal PJI, suppression follows 4-6 weeks of pathogen-specific intravenous or highly bioavailable oral therapy 1

Critical Monitoring Requirements

Safety Monitoring

• Antimicrobial dosage must be adjusted based on renal and hepatic function 1
• Clinical and laboratory monitoring for efficacy and toxicity is advisable 1
• Monitor for Clostridium difficile colitis with any antimicrobial 1
• When using fluoroquinolones, discuss and monitor for prolonged QTc interval and tendinopathy 1

Efficacy Monitoring

• Regular clinical assessment for signs of infection recurrence 1
• Consider the potential for progressive implant loosening and loss of bone stock 1

Common Pitfalls and Critical Caveats

What NOT to Use

• Rifampin alone is not recommended for chronic suppression due to rapid resistance development 1
• Rifampin combination therapy is not generally recommended for chronic suppression, though one panel member uses it in selected situations 1
• Linezolid should not be used for indefinite chronic suppression 1

Special Considerations for Renal Impairment

Given the context of possible impaired renal function:

• Cephalexin requires dose adjustment: reduce frequency to every 8-12 hours if creatinine clearance is 10-50 mL/min 1
• Co-trimoxazole requires dose reduction in renal insufficiency 1
• Avoid aminoglycosides in antibiotic-impregnated cement in patients with baseline renal insufficiency, as acute renal failure has been reported 2, 3

Antibiotic Selection Based on Susceptibility

• All antimicrobials must be chosen based on in vitro susceptibility testing 1
• Consider patient drug allergies, intolerances, and potential drug interactions 1
• The decision must account for the ability to use rifampin in the initial treatment phase 1

Controversy in the Guidelines

The IDSA panel could not reach unanimous consensus on chronic suppression use 1:

• Some members would never use chronic suppression after rifampin combination therapy 1
• Others would recommend it in all cases of PJI treated with debridement and retention 1
• Others would use it selectively based on patient factors 1
• Chronic suppression after fluoroquinolone treatment of gram-negative bacilli was not unanimously recommended 1