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Challenges in achieving the guideline-recommended amikacin level for Mycobacterium avium complex pulmonary disease
Takuya Akutsu1, Kazuya Tone1, Airi Hasegawa1
1Department of Respiratory Medicine, The Jikei University School of Medicine Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa, Chiba 277-8567 Japan.
Background:
The addition of aminoglycosides to a macrolide-based regimen is recommended for refractory Mycobacterium avium complex pulmonary disease (MAC-PD). For intravenous amikacin (AMK) administration three times a week, the ATS/ERS/ESCMID/IDSA guidelines recommend targeting a peak serum concentration of 65-80 µg/mL. However, the feasibility of achieving the guideline-recommended AMK concentration remains unclear.
Methods:
From 2018 to 2022, we retrospectively analyzed patients with refractory MAC-PD treated with AMK thrice weekly for ≥3 months combined with an oral regimen of ≥2 drugs, including macrolides. The peak serum concentration and therapeutic effects of AMK were evaluated.
Results:
The median age of the 9 patients was 70 years (range: 50-79 years; 2 men and 7 women). The causative organism was M. avium in all cases. All cases demonstrated susceptibility to AMK, which was administered at a median dose of 700 mg/day (15.8 mg/kg/day) for a median duration of 6 months. One patient experienced hearing loss, which led to AMK discontinuation at 4 months. The median AMK peak concentration was 47.1 μg/mL, with a tendency to be higher in the clinical efficacy group compared to the nonefficacy group. None of patient, except one, achieved the target AMK peak concentration.
Conclusions:
In this preliminary study, the guideline-recommended AMK concentration for MAC-PD was not achieved in the majority of patients. Due to the small sample size and retrospective design, robust conclusions regarding the association between AMK concentrations and clinical outcomes could not be drawn. Prospective randomized controlled trials are required to better define the optimal AMK concentration for efficacy and safety.
Trial Registration:
Not applicable.
Insights
This study found that most patients with refractory Mycobacterium avium complex pulmonary disease did not reach the recommended amikacin peak concentration. Further research is needed to confirm amikacin levels for effective treatment.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Pharmacology
Background:
- Refractory Mycobacterium avium complex pulmonary disease (MAC-PD) often requires aminoglycosides in addition to macrolides.
- Current guidelines recommend targeting intravenous amikacin (AMK) peak serum concentrations of 65-80 µg/mL for thrice-weekly administration.
- The feasibility of achieving these target AMK concentrations in clinical practice is uncertain.
Purpose of the Study:
- To evaluate the achievement of guideline-recommended amikacin (AMK) peak serum concentrations in patients with refractory MAC-PD.
- To assess the relationship between AMK concentrations and therapeutic effects in this patient population.
Main Methods:
- Retrospective analysis of 9 patients with refractory MAC-PD treated with thrice-weekly AMK and ≥2 oral drugs (including macrolides) from 2018-2022.
- Evaluation of AMK peak serum concentrations and clinical efficacy.
- Median AMK dose of 700 mg/day (15.8 mg/kg/day) for a median of 6 months.
Main Results:
- The median AMK peak concentration achieved was 47.1 µg/mL, significantly below the recommended 65-80 µg/mL.
- Only one patient achieved the target AMK concentration.
- A trend suggested higher AMK concentrations in patients with clinical efficacy, though one patient experienced hearing loss requiring AMK discontinuation.
Conclusions:
- The guideline-recommended AMK peak concentration was not achieved in most patients with refractory MAC-PD in this preliminary study.
- Small sample size and retrospective design limit definitive conclusions on AMK concentration-outcome relationships.
- Prospective randomized controlled trials are necessary to establish optimal AMK concentrations for efficacy and safety.
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