What is the treatment for Mycobacterium abscessus infection after Total Knee Replacement (TKR)?

Treatment of Mycobacterium abscessus Infection After Total Knee Replacement

M. abscessus periprosthetic joint infection after TKR requires a two-stage revision with complete prosthesis removal, prolonged multidrug antimicrobial therapy (minimum 6 months), and delayed reimplantation only after confirmed infection eradication. 1

Surgical Management: Two-Stage Revision is Mandatory

Complete removal of all prosthetic components, infected cement, and thorough debridement of infected bone and soft tissues is essential for treatment success. 1 Single-stage procedures with debridement and implant retention have much higher infection recurrence rates due to mature biofilm formation by mycobacteria and should not be used. 1

Stage 1: Explantation and Debridement

• Remove all prosthetic components, cement, and infected hardware completely 1
• Perform aggressive excision of all infected bone and soft tissue 1
• Place antibiotic-loaded cement spacer 1
• Collect at least 5-6 tissue specimens from multiple suspicious sites for both routine bacterial culture AND specific mycobacterial culture (hold for 6 weeks) 1
• Send explanted prosthesis for sonication if available 1

Stage 2: Delayed Reimplantation

• Wait minimum 6 months before reimplantation 1
• Confirm infection eradication with multiple preoperative joint aspirations and normalized inflammatory markers (ESR, CRP) before proceeding 1
• Repeat aspirations are critical because recurrence rates remain high and can be devastating 1

Antimicrobial Therapy: Prolonged Multidrug Regimen Required

M. abscessus is a rapidly-growing, multidrug-resistant mycobacterium that requires combination therapy. 2, 3 Standard anti-tubercular drugs are NOT effective due to inherent resistance. 2

Intensive Phase (3-12 weeks depending on severity):

• Intravenous amikacin PLUS 1, 4, 3
• One or more additional IV agents: imipenem (preferred due to better tolerability), cefoxitin, or tigecycline 1, 5
• Oral macrolide: azithromycin preferred over clarithromycin (better tolerability, fewer drug interactions) 1, 4

Critical caveat: Cefoxitin causes neutropenia in 51% and must be discontinued in 60% of patients after median 22 days. 1 Tigecycline causes significant nausea/vomiting limiting prolonged use. 1 Therefore, imipenem is the best companion IV agent. 1

Continuation Phase (to complete 6-12 months total):

• Oral azithromycin (macrolide backbone) 1, 4, 3
• Inhaled amikacin 1
• 2-3 additional oral agents selected from: minocycline, clofazimine, moxifloxacin, linezolid, or doxycycline 1, 3, 6
• Base antibiotic selection on susceptibility testing but do not be dictated solely by it 1

Treatment duration: Minimum 6 months total, with some cases requiring up to 12 months depending on severity and response. 1, 4

Diagnostic Pitfalls to Avoid

M. abscessus PJI presents indolently and mimics aseptic loosening, with negative initial cultures in up to 61.5% of cases. 1 This is a common diagnostic trap.

• ESR/CRP can be normal in early NTM infections—do not exclude infection based on normal inflammatory markers alone 1
• Infections typically lack purulence and erythema despite being aggressive 1
• Withhold antibiotics for at least 2 weeks before obtaining cultures to maximize yield 1
• If initial cultures are negative but clinical suspicion remains high, specifically request mycobacterial cultures and hold for 6 weeks (not standard 5-day incubation) 1
• Send multiple tissue specimens (minimum 5-6), not just fluid, as tissue has higher yield 1
• PCR and next-generation sequencing can identify NTM in culture-negative cases 1

Multidisciplinary Coordination is Non-Negotiable

Coordinate care with infectious disease specialists and clinical pharmacists from the outset to optimize antimicrobial dosing, monitor for drug toxicity (especially amikacin ototoxicity/nephrotoxicity, macrolide QT prolongation, linezolid neuropathy), manage drug-drug interactions, and ensure patient adherence to the prolonged, poorly-tolerated regimen. 1, 3

Prognosis and Monitoring

Despite optimal treatment, recurrence rates remain high and can be detrimental. 1 New skin lesions appearing during active therapy after initial improvement may represent immunologic response to mycobacterial death rather than treatment failure. 1 However, maintain high vigilance and obtain repeat cultures if relapse is suspected. 5

Successful cases have been reported using this two-stage approach with prolonged combination antimicrobials, achieving functional outcomes (90° flexion, ambulation with assistive device). 4, 3