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Postantibiotic effect of amikacin and rifapentine against Mycobacterium avium complex
L E Bermudez1, M Wu, L S Young
1Kuzell Institute for Arthritis and Infectious Diseases, Medical Research Institute of San Francisco, California Pacific Medical Center.
Abstract:
Postantibiotic effect (PAE) has received little attention in the therapy of chronic intracellular infections, such as those caused by mycobacteria. Amikacin is active therapeutically against Mycobacterium avium complex, even though serum levels exceed the MIC for only a few hours. To determine the PAE of amikacin and rifapentine for M. avium, bacteria were exposed to concentrations of 1x, 4x, and 10x the MIC of each drug for up to 120 min. Regrowth of M. avium was compared with similarly diluted untreated cultures. No PAE was observed on an inoculum of 10(4) bacteria when rifapentine was used at 5x MIC, although a slight inhibition of growth was obtained at 10x MIC for 2 h. For amikacin, PAE was observed up to 48 h at concentrations of 4x and 8x MIC and exposure times of 30-120 min. A PAE of 22 h was seen with 10(7) cfu of M. avium during incubation for 30 min with amikacin at 4x MIC. These results show that amikacin, unlike rifapentine, has a long PAE against M. avium.
Insights
Amikacin exhibits a significant postantibiotic effect (PAE) against Mycobacterium avium, lasting up to 48 hours. Rifapentine showed minimal PAE, highlighting amikacin
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Postantibiotic effect (PAE) is crucial for treating chronic intracellular infections, particularly mycobacterial diseases.
- Amikacin demonstrates therapeutic activity against Mycobacterium avium complex (MAC), despite short-term serum concentration exceeding the minimum inhibitory concentration (MIC).
Purpose of the Study:
- To investigate and compare the postantibiotic effect (PAE) of amikacin and rifapentine against Mycobacterium avium.
- To evaluate the impact of drug concentration and exposure time on the PAE of these antibiotics against M. avium.
Main Methods:
- Mycobacterium avium cultures were exposed to varying concentrations (1x, 4x, 10x MIC) of amikacin and rifapentine for up to 120 minutes.
- Bacterial regrowth was monitored and compared to untreated control cultures to determine the PAE.
- Different bacterial inoculums (10^4 and 10^7 CFU) were used to assess the influence of bacterial load on PAE.
Main Results:
- Rifapentine demonstrated no significant PAE at 5x MIC and only slight growth inhibition at 10x MIC for 2 hours.
- Amikacin exhibited a notable PAE against M. avium, persisting for up to 48 hours at concentrations of 4x and 8x MIC with exposure times of 30-120 minutes.
- A substantial PAE of 22 hours was observed with amikacin at 4x MIC for 30 minutes against a high inoculum (10^7 CFU) of M. avium.
Conclusions:
- Amikacin possesses a prolonged postantibiotic effect against Mycobacterium avium, suggesting its potential utility in managing MAC infections.
- Rifapentine displayed a negligible PAE against M. avium, indicating a different mechanism of action or limited efficacy in this context.
- The findings underscore the importance of considering PAE in antibiotic selection for chronic intracellular infections caused by mycobacteria.