In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 2 ( 2022-02-15)
Abstract:
Moxifloxacin is an attractive drug for the treatment of isoniazid-resistant rifampicin-susceptible tuberculosis (TB) or drug-susceptible TB complicated by isoniazid intolerance. However, co-administration with rifampicin decreases moxifloxacin exposure. It remains unclear whether this drug–drug interaction has clinical implications. This retrospective study in a Dutch TB center investigated how rifampicin affected moxifloxacin exposure in patients with isoniazid-resistant or -intolerant TB. Moxifloxacin exposures were measured between 2015 and 2020 in 31 patients with isoniazid-resistant or -intolerant TB receiving rifampicin, and 20 TB patients receiving moxifloxacin without rifampicin. Moxifloxacin exposure, i.e., area under the concentration-time curve (AUC 0-24h ), and attainment of AUC 0-24h /MIC 〉 100 were investigated for 400 mg moxifloxacin and 600 mg rifampicin, and increased doses of moxifloxacin (600 mg) or rifampicin (900 mg). Moxifloxacin AUC 0–24h and peak concentration with a 400 mg dose were decreased when rifampicin was co-administered compared to moxifloxacin alone (ratio of geometric means 0.61 (90% CI (0.53, 0.70) and 0.81 (90% CI (0.70, 0.94), respectively). Among patients receiving rifampicin, 65% attained an AUC 0-24h /MIC 〉 100 for moxifloxacin compared to 78% of patients receiving moxifloxacin alone; this difference was not significant. Seven out of eight patients receiving an increased dose of 600 mg moxifloxacin reached the target AUC 0-24h /MIC 〉 100. This study showed a clinically significant 39% decrease in moxifloxacin exposure when rifampicin was co-administered. Moxifloxacin dose adjustment may compensate for this drug–drug interaction. Further exploring the impact of higher doses of these drugs in patients with isoniazid resistance or intolerance is paramount.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/aac.01829-21
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2022
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
