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Liposomal amikacin for treatment of M. avium infections in clinically relevant experimental settings
1Institut für Medizinische Mikrobiologie und Infektionsimmunologie, Klinikum Benjamin Franklin, FU Berlin, Germany.
Abstract:
In an effort to optimize rational chemotherapy against M. avium infections in a clinically meaningful context, we tested whether liposome-encapsulated amikacin would effectively reduce the bacterial load in (i) intravenously infected immunodeficient SCID mice, (ii) immunocompetent mice in both early and late stages of intravenous infection, and (iii) immunocompetent mice with pulmonary M. avium infection. Although complete eradication of M. avium was never achieved following intravenous infection, mycobacterial CFUs decreased by 3 to 4 logs in the spleens and livers of mice treated for three weeks with twice-weekly intravenous injections of liposomal amikacin and continued to stay low in the liver, even in the absence of specific immunity. Mice treated in the chronic stage of infection equally benefited from therapy and showed signs of attenuated granulomatous inflammation in the liver. Even moribund mice responded to liposomal amikacin by significantly gaining weight and survived their infected untreated littermates by at least 4 months. In contrast, during pulmonary M. avium infection, treatment with liposome-encapsulated amikacin only resulted in a transient plateau of bacterial proliferation in the lungs, and the infection exacerbated immediately after cessation of therapy.
Insights
Liposome-encapsulated amikacin significantly reduced Mycobacterium avium bacterial load in mice with systemic infection, improving survival. However, it only temporarily controlled pulmonary infections, highlighting its limitations for certain M. avium disease types.
Area of Science:
- Microbiology
- Pharmacology
- Immunology
Background:
- Mycobacterium avium infections pose significant challenges, particularly in immunocompromised individuals.
- Optimizing chemotherapy for M. avium requires effective drug delivery and sustained efficacy.
- Liposomal drug formulations offer potential for improved therapeutic outcomes.
Purpose of the Study:
- To evaluate the efficacy of liposome-encapsulated amikacin against Mycobacterium avium infections in various mouse models.
- To assess the impact of liposomal amikacin on bacterial load, inflammation, and survival.
- To determine the effectiveness of this formulation in both systemic and pulmonary M. avium infections.
Main Methods:
- Testing liposomal amikacin in immunodeficient and immunocompetent mice with intravenous M. avium infection.
- Evaluating treatment in early and late stages of chronic infection.
- Assessing efficacy in a pulmonary M. avium infection model.
- Measuring bacterial colony-forming units (CFUs), host weight, survival, and liver inflammation.
Main Results:
- Liposomal amikacin reduced M. avium CFUs by 3-4 logs in spleen and liver following intravenous infection.
- Therapy improved survival and reduced liver inflammation in chronically infected mice, even in moribund individuals.
- Pulmonary M. avium infection showed only transient bacterial control, with relapse upon treatment cessation.
Conclusions:
- Liposome-encapsulated amikacin demonstrates significant efficacy against systemic M. avium infections, reducing bacterial burden and improving host outcomes.
- The formulation shows promise for treating disseminated M. avium disease, offering therapeutic benefits even in severe cases.
- Efficacy is limited in pulmonary M. avium infections, suggesting formulation or delivery challenges for lung-specific targeting.