What is the treatment for Mycobacterium abscessus infection in a patient with a total knee replacement (TKR)?

Treatment of Mycobacterium abscessus Periprosthetic Joint Infection After Total Knee Replacement

M. abscessus infection after TKR requires two-stage revision arthroplasty with complete prosthesis removal, aggressive debridement, and prolonged multidrug antimicrobial therapy for at least 6 months, with reimplantation only after confirmed infection eradication. 1

Surgical Management: The Critical First Step

Complete removal of all prosthetic components is non-negotiable. Medical management alone has failed in documented cases and cannot be recommended. 2 The surgical approach must include:

• Two-stage revision with complete prosthesis removal (not debridement and retention), as this is the only approach with documented success 1, 2
• Removal of all infected cement and thorough debridement of infected bone and soft tissues 1
• Collection of 5-6 tissue specimens from multiple suspicious sites for both routine bacterial culture and specific mycobacterial culture, holding cultures for 6 weeks 1
• Delayed reimplantation only after confirmed infection eradication, which may take many months 1, 2

A critical pitfall: M. abscessus PJI presents indolently and mimics aseptic loosening, with negative initial cultures in up to 61.5% of cases. 1 Withhold antibiotics for at least 2 weeks before obtaining cultures to maximize yield, and specifically request mycobacterial cultures if initial cultures are negative but clinical suspicion remains high. 1

Antimicrobial Therapy: Intensive Multi-Drug Regimen

Initial Intensive Phase (Minimum 4 Weeks)

The intensive phase should include:

• Intravenous amikacin (10-15 mg/kg daily) 3, 1
• Imipenem (500 mg 2-4 times daily) as the preferred companion IV agent due to better tolerability compared to cefoxitin or tigecycline 4, 3, 1
• Oral azithromycin (preferred over clarithromycin as it is a weaker inducer of macrolide resistance) 4, 1

Alternative IV agents if imipenem is not tolerated include tigecycline or high-dose cefoxitin (up to 12 g/day), though both have significant toxicity profiles. 4, 3 Cefoxitin causes neutropenia in 51% of patients and must be discontinued in 60% after a median of only 22 days. 4 Tigecycline causes significant nausea and vomiting requiring antiemetic prophylaxis with ondansetron or aprepitant. 4

Continuation Phase

After the intensive phase, transition to:

• Oral macrolide (azithromycin preferred) 4, 1
• Nebulized amikacin (if not amikacin-resistant) 4
• Two to three additional oral antibiotics selected from: linezolid, clofazimine, minocycline or doxycycline, moxifloxacin or ciprofloxacin, co-trimoxazole 4

Critical consideration for macrolide resistance: If isolates have a functional erm gene (inducible macrolide resistance) or 23S rRNA mutation (constitutive macrolide resistance), continuous or very extended IV therapy may be necessary rather than switching to oral agents, given the poor efficacy of oral antibiotics alone. 4

Treatment Duration

• Minimum 6 months of total antimicrobial therapy for bone/prosthetic joint infections 3, 1
• Some cases require up to 12 months depending on severity and response 1
• Continue for minimum 12 months after culture conversion if culture conversion is achieved 4
• Treatment should continue throughout the interval between prosthesis removal and reimplantation 1, 2

Multidisciplinary Coordination

Coordinate care with infectious disease specialists and clinical pharmacists from the outset to optimize antimicrobial dosing, monitor for drug toxicity (particularly amikacin ototoxicity and nephrotoxicity), and ensure patient adherence to the prolonged regimen. 1 This is not optional given the complexity of multi-drug regimens and high toxicity rates.

Monitoring and Prognosis

Despite optimal treatment, recurrence rates remain high. 1 Maintain high vigilance and obtain repeat mycobacterial cultures if relapse is suspected. 1 The median time from end of treatment to relapse in pulmonary disease is 523 days (range 202-710 days), suggesting prolonged follow-up is necessary. 4

Key pitfall to avoid: Do not use standard anti-tubercular therapy, as M. abscessus is intrinsically resistant to most first-line TB drugs. 5 This organism is one of the most antibiotic-resistant nontuberculous mycobacteria and requires the specific regimens outlined above. 3, 6