From the Guidelines
Tigecycline is not a suitable treatment option for a patient with vancomycin-induced nephrotoxicity due to its limited clinical efficacy in certain infections and low serum concentrations, which make it suboptimal for bloodstream infections 1. When considering alternative treatments for patients with vancomycin-induced nephrotoxicity, it is essential to evaluate the causative pathogen's susceptibility and the site of infection. Tigecycline has a broad spectrum of activity against gram-positive, gram-negative, and anaerobic organisms, but lacks reliable activity against Pseudomonas aeruginosa and Proteus species 1.
Key Considerations
- The standard dosing regimen for tigecycline is a 100 mg initial loading dose followed by 50 mg every 12 hours administered intravenously over 30-60 minutes, which does not require dose adjustment in patients with renal impairment, including those on hemodialysis 1.
- Tigecycline achieves low serum concentrations, making it suboptimal for bloodstream infections, with cure rates in patients with VAP treated with tigecycline being lower than those in patients treated with imipenem (47.9 versus 70.1 %) 1.
- Common side effects of tigecycline include nausea, vomiting, and diarrhea, which occur in approximately 20-30% of patients.
Clinical Efficacy
- Data on the clinical efficacy of tigecycline in real life for infections due to A. baumannii in critically ill patients derive mostly from retrospective non-comparative studies, usually with small numbers of patients, different infection localizations, and with diverse endpoints 1.
- A high dose regimen (loading dose 200 mg followed by 100 mg every 12 h) has been successfully and safely used in severe infections due to MDR bacteria (A. baumannii represented approximately one-third of the cases) 1.
Recommendations
- Before initiating tigecycline, clinicians should confirm the causative pathogen's susceptibility and consider the site of infection to ensure appropriate coverage and clinical efficacy.
- Tigecycline should be used with caution and in combination with other antimicrobials, as it is often used in combination with other antibiotics to enhance its clinical efficacy 1.
From the FDA Drug Label
Renal Impairment A single dose study compared 6 subjects with severe renal impairment (creatinine clearance < 30 mL/min), 4 end stage renal disease (ESRD) patients receiving tigecycline 2 hours before hemodialysis, 4 ESRD patients receiving tigecycline 1 hour after hemodialysis, and 6 healthy control subjects The pharmacokinetic profile of tigecycline was not significantly altered in any of the renally impaired patient groups, nor was tigecycline removed by hemodialysis. No dosage adjustment of tigecycline is necessary in patients with renal impairment or in patients undergoing hemodialysis
Tigecycline is a suitable treatment option for a patient with vancomycin-induced nephrotoxicity (impaired renal function) because:
- The pharmacokinetic profile of tigecycline is not significantly altered in patients with severe renal impairment.
- No dosage adjustment of tigecycline is necessary in patients with renal impairment. 2
From the Research
Tigecycline as an Alternative Treatment Option
- Tigecycline (Tygacil) is a broad-spectrum antibiotic that may be considered as an alternative treatment option for patients with vancomycin-induced nephrotoxicity.
- However, there is limited information available on the use of tigecycline in patients with impaired renal function due to vancomycin-induced nephrotoxicity.
Vancomycin-Induced Nephrotoxicity
- Vancomycin-induced nephrotoxicity is a well-documented adverse effect of vancomycin therapy, with a reported incidence of 10-20% and 30-40% in patients receiving conventional and high doses of vancomycin, respectively 3.
- Risk factors for vancomycin-induced nephrotoxicity include high trough vancomycin levels, concomitant treatment with nephrotoxic agents, prolonged therapy, and admission to an intensive care unit 4, 3.
- The mechanism of vancomycin-induced nephrotoxicity is not fully understood, but it is thought to be related to the increased production of reactive oxygen species and oxidative stress 3.
Comparison with Other Antibiotics
- A study comparing vancomycin and daptomycin for the treatment of severe Gram-positive infections found that vancomycin was associated with a higher incidence of nephrotoxicity (23.3% vs 6.3%) 5.
- Another study found that vancomycin trough concentrations >20 μg/mL and concomitant use of renal hypoperfusion medications were associated with an increased risk of nephrotoxicity 6.
Considerations for Tigecycline Use
- While tigecycline may be a suitable alternative treatment option for patients with vancomycin-induced nephrotoxicity, its use should be carefully considered in patients with impaired renal function.
- There is limited information available on the pharmacokinetics and safety of tigecycline in patients with renal impairment, and further studies are needed to fully understand its potential as an alternative treatment option 7.