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Mavintramycin A is a promising antibiotic for treating Mycobacterium avium complex infectious disease.

ABSTRACT: Mycobacterium avium complex (MAC) is a serious disease that is mainly caused by infection with the non-tuberculous mycobacteria (NTM), Mycobacterium avium and Mycobacterium intracellulare. Seven new compounds, designated mavintramycins A-G (1-7), were isolated along with structurally related compounds, including amicetin (9) and plicacetin (10), from the culture broth of Streptomyces sp. OPMA40551 as anti-MAC compounds that were active against M. avium and M. intracellulare. Among them, mavintramycin A showed the most potent and selective inhibition of M. avium and M. intracellulare. Furthermore, mavintramycin A was active against more than 40 clinically isolated M. avium, including multidrug-resistant strains, and inhibited the growth of M. avium in a persistent infection cell model using THP-1 macrophages. Mavintramycin A also exhibited in vivo efficacy in silkworm and mouse infection assays with NTM. An experiment to elucidate its mechanism of action revealed that mavintramycin A inhibits protein synthesis by binding to 23S ribosomal RNA in NTM. Mavintramycin A, with a different chemical structure from those of clinically used agents, is a promising drug candidate for the treatment of MAC infectious disease.

SUBMITTER: Hosoda K

PROVIDER: S-EPMC10923286 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Mavintramycin A is a promising antibiotic for treating Mycobacterium avium complex infectious disease.

Hosoda Kanji K Koyama Nobuhiro N Shigeno Satoru S Nishimura Tomoyasu T Hasegawa Naoki N Kanamoto Akihiko A Ohshiro Taichi T Tomoda Hiroshi H

Antimicrobial agents and chemotherapy 20240209 3

Mycobacterium avium complex (MAC) is a serious disease that is mainly caused by infection with the non-tuberculous mycobacteria (NTM), Mycobacterium avium and Mycobacterium intracellulare. Seven new compounds, designated mavintramycins A-G (1-7), were isolated along with structurally related compounds, including amicetin (9) and plicacetin (10), from the culture broth of Streptomyces sp. OPMA40551 as anti-MAC compounds that were active agai ...[more]

PMID: 38334410

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Project description:Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of nontuberculous mycobacteria-pulmonary disease (NTM-PD) after microbiological cure of Mycobacterium avium complex (MAC)-PD. This retrospective study included 631 MAC-PD patients who achieved microbiological cure between 1994 and 2021. Data on the antibiotic maintenance period, defined as the time between culture conversion and treatment completion, were collected. Redevelopment, the subsequent diagnosis of NTM-PD regardless of causative organism after microbiological cure, was investigated. Factors associated with redevelopment were analyzed after adjusting for disease severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) scoring system. In total, 205 (33%) patients experienced redevelopment, with a median maintenance period after culture conversion of 15.0 months (interquartile range, 13.0 to 22.0 months). A greater proportion of patients with the nodular bronchiectatic form of MAC-PD (87% versus 80%, P = 0.033) and a longer maintenance period (median 15.0 versus 14.0 months, P < 0.001) were noted in the redevelopment group compared with the nonredevelopment group. The cumulative rate of redevelopment according to the maintenance period did not differ between the >12-month and ≤12-month groups in the total patient population or the subgroups sorted according to BACES severity. No association between a maintenance period >12 months and redevelopment was identified in multivariate models. Extending the antibiotic maintenance period more than 12 months did not reduce the redevelopment rate even with adjustment for disease severity, suggesting the need to further optimize the duration of the antibiotic maintenance period. IMPORTANCE Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of Mycobacterium avium complex-pulmonary (MAC-PD) disease after microbiological cure. To improve treatment outcomes and reduce the recurrence rate, current guidelines recommend maintenance of antibiotics for a minimum of 12 months after achievement of negative culture conversion. However, the optimal duration of antibiotic therapy for MAC-PD is not currently known. Moreover, in real-world clinical practice, total antibiotic duration is mainly impacted by the length of the maintenance period; however, it is unknown whether extending the maintenance period is beneficial for preventing redevelopment of NTM-PD. Our study may help to address concerns regarding the antibiotic maintenance period after achievement of negative culture conversion in patients with MAC-PD.

Project description:BackgroundAlthough combination therapy using clarithromycin, rifampicin, and ethambutol is recommended for patients with pulmonary Mycobacterium avium complex (MAC) disease, some patients do not tolerate it because of adverse effects or underlying diseases. The efficacy and safety of fluoroquinolone-containing combination regimens as an alternative remain uncertain. This study aimed to compare the efficacy and safety of fluoroquinolone-containing regimens with those of the standard regimens for treating pulmonary MAC disease.MethodsWe retrospectively included consecutive MAC patients who were treated in our hospital between January 2011 and May 2019. Patients treated with fluoroquinolone-containing regimens who had relapsed after treatment with standard regimens were excluded. A propensity score analysis was conducted to reduce selection bias, and the proportions of clinical improvement, defined by chest imaging findings and sputum conversion, were compared between the fluoroquinolone-containing regimen and standard regimen groups.ResultsWe analyzed 28 patients who received fluoroquinolone-containing regimens and 46 who received the standard regimen. Fluoroquinolone-containing regimens were more likely selected for patients with cavitary lesions, diabetes mellitus, culture negativity, a low daily physical activity level, a decreased lymphocyte count and an increased CRP level. The propensity score was calculated using these variables (C-statistic of the area under the receiver operating characteristic curve of the propensity score: 0.807, p < 0.0001). The fluoroquinolone-containing regimens were significantly inferior to the standard regimen in clinical improvements (p = 0.002, Log-rank test) in the univariate analysis, but the significance was lost after adjusting for the propensity score (HR 0.553, 95% CI 0.285-1.074, p = 0.080). Six (21%) patients in the fluoroquinolone-containing regimen group and ten (22%) patients in the standard regimen group experienced low-grade adverse effects.ConclusionsThere was no significant difference in clinical improvement between these regimens after propensity score adjustment. A large-scale prospective study is required to validate these results.

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Mavintramycin A is a promising antibiotic for treating Mycobacterium avium complex infectious disease.

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Mavintramycin A is a promising antibiotic for treating <i>Mycobacterium avium</i> complex infectious disease.

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