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Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)
Natasha F Sabur1, Mantaj S Brar2, Lisa Wu3
1Department of Respirology, St. Michael's Hospital and West Park Healthcare Centre, Rm 6-049, 30 Bond St, Toronto, ON, M5B 1W8, Canada. natasha.sabur@westpark.org.
Background:
The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity.
Methods:
Patients with MDR-TB treated at our institution receive amikacin at 8-10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016.
Results:
Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6-24.8%); 22.2% had subjective hearing loss (95% CI 11.2-37.1%) and 31.9% subjective tinnitus (95% CI 19.1-47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8-38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84-99%).
Conclusions:
Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.
Insights
Lower doses of amikacin (8-10 mg/kg) effectively treat multidrug-resistant tuberculosis (MDR-TB) with fewer adverse events. This approach offers a safer alternative when standard regimens are not feasible.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Medicine
Background:
- The World Health Organization (WHO) recommends intravenous amikacin at 15 mg/kg for multidrug-resistant tuberculosis (MDR-TB).
- Higher amikacin doses are linked to significant toxicity, posing a challenge for MDR-TB treatment.
Purpose of the Study:
- To evaluate the safety and efficacy of a lower-dose amikacin regimen (8-10 mg/kg) for MDR-TB.
- To assess adverse events and treatment outcomes in patients receiving adjusted-dose amikacin therapy.
Main Methods:
- A retrospective cohort study included 49 patients with MDR-TB treated with amikacin between 2010 and 2016.
- Amikacin doses were initiated at 8-10 mg/kg and adjusted based on therapeutic drug monitoring.
- Key outcomes included time to sputum culture conversion, adverse events (hearing loss, renal dysfunction), and treatment success.
Main Results:
- The median starting amikacin dose was 8.9 mg/kg, with target therapeutic levels reached in a median of 12 days.
- Treatment success was achieved in 84% of patients.
- Adverse events included hearing loss in 12.2% (audiometry) and 22.2% (subjective), tinnitus in 31.9%, and elevated creatinine in 23%.
Conclusions:
- Lower-dose amikacin (8-10 mg/kg) demonstrates acceptable safety and efficacy for MDR-TB treatment.
- This regimen is a viable option when standard MDR-TB drugs are insufficient, provided careful adverse event monitoring is in place.
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