The early bactericidal activity of a low-clearance liposomal amikacin in pulmonary tuberculosis

Area of Science:

• Pharmacology
• Infectious Diseases
• Tuberculosis Research

Background:

• Tuberculosis remains a major global health challenge, necessitating novel treatment strategies.
• Liposomal drug delivery systems offer potential for improved therapeutic outcomes.
• Amikacin is a potent aminoglycoside antibiotic used against Mycobacterium tuberculosis.

Purpose of the Study:

• To evaluate the early bactericidal activity (EBA) of liposomal amikacin (MiKasome) in patients with newly diagnosed pulmonary tuberculosis.
• To investigate the relationship between plasma amikacin concentrations and EBA.
• To understand the pharmacokinetic and pharmacodynamic profile of liposomal amikacin in tuberculosis treatment.

Main Methods:

• Seven patients with smear-positive pulmonary tuberculosis received liposomal amikacin (30 mg/kg) intravenously over three days.
• Sputum samples were collected for 16 hours before and after each dose to determine colony-forming unit (cfu) counts.
• Early bactericidal activity (EBA) was calculated based on the reduction in cfu counts.

Main Results:

• High plasma concentrations of total amikacin (>1000 mg/L) were achieved.
• No significant early bactericidal activity (EBA) was observed in sputum samples.
• This lack of EBA contrasts with promising results in experimental murine tuberculosis models.

Conclusions:

• Liposomal amikacin's efficacy in tuberculosis may be limited by its release mechanism.
• Amikacin liberation from liposomes appears restricted to intracellular compartments (macrophages).
• Extracellular bacterial aggregates in tuberculous lesions may not be effectively targeted by this formulation.