Is teicoplanin and amikacin (antibiotics) a suitable choice for a post-operative total knee replacement (TKR) patient with leukocytosis (elevated white blood cell count)?

Teicoplanin and Amikacin for Post-Operative TKR with WBC 15,000

Teicoplanin combined with amikacin is a reasonable empiric antibiotic choice for suspected periprosthetic joint infection after total knee replacement, but this regimen should only be initiated after obtaining joint aspiration for culture and sensitivity, and the elevated WBC alone (15,000) is insufficient to diagnose infection since peripheral leukocyte counts are often normal in prosthetic joint infections. 1, 2

Critical First Steps Before Antibiotic Administration

Do not start antibiotics until diagnostic workup is complete:

• Obtain ESR, CRP, and serum interleukin-6 immediately to evaluate for occult periprosthetic joint infection, as strongly recommended by the American Academy of Orthopaedic Surgeons 1
• Perform knee joint aspiration for synovial fluid analysis before initiating antibiotics, as this is critical for identifying causative organisms 3
• Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible to avoid false-negative cultures, per the Infectious Diseases Society of America 3, 1
• Obtain knee radiographs as initial imaging to evaluate for signs of loosening, osteolysis, or component migration 1

Why Peripheral WBC Count is Misleading

• Peripheral WBC counts are not elevated in most patients with infected prostheses, making a normal or mildly elevated WBC (like 15,000) meaningless for excluding or confirming infection 1
• CRP has 73-91% sensitivity and 81-86% specificity for prosthetic knee infection when using a cutoff of 13.5 mg/L, making it far more reliable than WBC count 3, 1
• Do not rely on absence of fever, erythema, or warmth around the knee to exclude periprosthetic joint infection—chronic infections frequently present with pain alone 1

Rationale for Teicoplanin and Amikacin Combination

Teicoplanin provides appropriate Gram-positive coverage:

• Teicoplanin is effective against methicillin-resistant and methicillin-susceptible staphylococci, which are the most common pathogens in periprosthetic joint infections 4, 5
• A single pre-operative dose of teicoplanin and gentamicin (an aminoglycoside like amikacin) has demonstrated similar efficacy to other prophylaxis regimens in a study of 4,500 total knee replacements with no significant difference in deep infection rates 6
• Teicoplanin has lower nephrotoxicity potential than vancomycin, especially when administered in combination with an aminoglycoside 4
• Regional prophylaxis with teicoplanin in total knee replacement has shown excellent safety and efficacy, with only one superficial infection out of 205 prostheses implanted 7

Amikacin provides Gram-negative coverage:

• Amikacin is indicated for serious infections due to susceptible Gram-negative bacteria, including Pseudomonas, E. coli, Proteus, Klebsiella, Enterobacter, Serratia, and Acinetobacter species 8
• Amikacin is potentially nephrotoxic and ototoxic, and concurrent use with other nephrotoxic agents (including cephalosporins) should be avoided due to potential additive effects 8
• Patients should be well-hydrated to minimize chemical irritation of renal tubules, and kidney function should be assessed daily during treatment 8

Important Caveats and Monitoring

Glycopeptide-specific considerations:

• Glycopeptides should be administered with a β-lactam to avoid an increase in postoperative methicillin-susceptible Staphylococcus aureus (MSSA) infections, per European Society of Clinical Microbiology and Infectious Diseases guidelines 9
• Teicoplanin-based prophylaxis was associated with increased postoperative infections in two RCTs involving cardiac surgery, though one study showed lower surgical site infections in hip/knee arthroplasty (1% vs 4%) 9

Aminoglycoside-specific considerations:

• Monitor renal function closely during treatment, as elderly patients may have reduced renal function not evident in routine screening 8
• In vitro mixing of aminoglycosides with β-lactam antibiotics may result in significant mutual inactivation, so administer by separate routes 8
• Aminoglycosides should be used with caution in patients with muscular disorders like myasthenia gravis due to potential neuromuscular blockade 8

Monitoring During Treatment

• Monitor CRP and ESR serially to assess treatment response, as CRP is the most sensitive marker with 73-91% sensitivity for prosthetic joint infection 3
• If values plateau or increase after initial improvement, consider repeat joint aspiration and culture to evaluate for persistent infection 3
• Combination testing using CRP, ESR, and fibrinogen provides 93% sensitivity and 100% specificity when at least 2 of 3 tests are abnormal 3