Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria

Pfaeffle, Herman; Alameer, Reem; Marshall, Mary H.; Houpt, Eric R.; Albon, Dana; Heysell, Scott K

doi:10.1016/j.pupt.2021.102058

Cited by 20 publications

(9 citation statements)

References 22 publications

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“…[5] Clofazimine has shown excellent in vitro susceptibility results to nontuberculosis mycobacteria. [15,16] It is a well-tolerated drug and could be an alternative to rifamycins. [17] The IDSA guidelines and a recent consensus guideline recommend multidrug therapies with at least 3 drugs, including macrolides plus rifampicin, ethambutol, moxifloxacin, clofazimine or amikacin.…”

Section: Discussionmentioning

confidence: 99%

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report

et al. 2022

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Rationale: Since its first identification in the early 1990s, Mycobacterium genavense has been considered and opportunistic pathogen. It mainly causes gastrointestinal symptoms, but also disseminated infections in severely immunosuppressed patients. Sclerosing mesenteritis is a long-term complication with high morbidity and mortality. As it is a rare condition, there are no specific guidelines for its management. We report a challenging case of persistent M. genavense infection, and propose surgery as an alternative treatment strategy.Patient concerns: A 38-year-old Caucasian man presented to the emergency room with fever, abdominal pain, and night sweats for 3 months. HIV screening revealed a previously unknown HIV-1 infection, with a CD4 cell count of 216 cell/µL and viral load of 361.000 copies/mL at diagnosis. A body CT-scan showed mild splenomegaly as well as mesenteric and retroperitoneal enlarged lymph nodes. Fine needle aspiration revealed the presence of acid-fast bacilli, but mycobacterial cultures were negative. In the second sample, 16S RNA sequencing yielded a diagnosis of M. genavense infection. Despite 2 years of corticosteroids and antimycobacterial treatment excluding rifampicin due to a severe cutaneous reaction, there was no clinical improvement and an increase in the mesenteric lymph node size was observed, with a sclerosing transformation of the mesentery. A surgical approach was proposed to release small bowel loops and to remove fibrin. A second surgery was required due to an acute peritonitis ought to yeyunal segmental isquemia and perforation. Finally, the patient evolved favorably, and antimycobacterial drugs were suspended without relapse.Lessons.Despite a prolonged multidrug strategy, some patients develop persistent M. genavense infection. Once sclerosing mesenteritis is established, clinicians have few treatment options. Surgery should be considered in patients with sclerosing mesenteritis or bowel obstruction. The combination of medical and surgical treatment could be a potential cure for these patients.Abbreviations: AIDS = acquired immunodeficiency syndrome, ART = antiretroviral therapy, FDG = fluorodeoxyglucose, HIV = human immunodeficiency virus, IGRA = interferon-gamma release assay, MAC = Mycobacterium avium complex, PCR = polymerase chain reaction, PET/CT = positron emission tomography/computed tomography.

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Section: Discussionmentioning

confidence: 99%

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report

et al. 2022

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“…Clofazimine has been historically used for the treatment of leprosy, but its use has been increasing in the treatment of NTM-PD, despite limited data to support efficacy. Recently, data from various retrospective observational studies have suggested efficacy, supported by a recent meta-analysis which demonstrated a treatment success rate of 56.8% when clofazimine was part of the treatment regimen [ 91 – 94 ]. However, regimens containing clofazimine demonstrated lower rates of treatment success compared with non-clofazimine containing regimens [ 93 ].…”

Section: Methodsmentioning

confidence: 99%

Meeting the challenges of NTM-PD from the perspective of the organism and the disease process: innovations in drug development and delivery

Laan¹,

Snabilié²,

Obradović³

2022

Respir Res

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Non-tuberculous mycobacterial pulmonary disease (NTM-PD) poses a substantial patient, healthcare, and economic burden. Managing NTM-PD remains challenging, and factors contributing to this include morphological, species, and patient characteristics as well as the treatment itself. This narrative review focusses on the challenges of NTM-PD from the perspective of the organism and the disease process. Morphological characteristics of non-tuberculous mycobacteria (NTM), antimicrobial resistance mechanisms, and an ability to evade host defences reduce NTM susceptibility to many antibiotics. Resistance to antibiotics, particularly macrolides, is of concern, and is associated with high mortality rates in patients with NTM-PD. New therapies are desperately needed to overcome these hurdles and improve treatment outcomes in NTM-PD. Amikacin liposome inhalation suspension (ALIS) is the first therapy specifically developed to treat refractory NTM-PD caused by Mycobacterium avium complex (MAC) and is approved in the US, EU and Japan. It provides targeted delivery to the lung and effective penetration of macrophages and biofilms and has demonstrated efficacy in treating refractory MAC pulmonary disease (MAC-PD) in the Phase III CONVERT study. Several other therapies are currently being developed including vaccination, bacteriophage therapy, and optimising host defences. Newly developed antibiotics have shown potential activity against NTM-PD and include benzimidazole, delamanid, and pretomanid. Antibiotics commonly used to treat other infections have also been repurposed for NTM-PD, including clofazimine and bedaquiline. Data from larger-scale studies are needed to determine the potential of many of these therapies for treating NTM-PD.

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“…Clofazimine has been prescribed in drug regimens for MAC and M. abscessus infections since the 1990s [ 77 ]. The oral administration of clofazimine is well tolerated in almost all species of NTM [ 78 ]. Moreover, the real action of clofazimine is not well described; nevertheless, available evidence has suggested that it inhibits bacterial proliferation by binding to its DNA strand and blocking the function of template strands of DNA and intracellular redox cycling [ 77 ].…”

Section: Importance Of Antimicrobial Resistance Mechanisms Of Ntm Spe...mentioning

confidence: 99%

Nontuberculous Mycobacterial Resistance to Antibiotics and Disinfectants: Challenges Still Ahead

Tarashi

Siadat

Fateh

2022

BioMed Research International

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The mortality incidence from nontuberculous mycobacteria (NTM) infections has been steadily developing globally. These bacterial agents were once thought to be innocent environmental saprophytic that are only dangerous to patients with defective lungs or the immunosuppressed. Nevertheless, the emergence of highly resistant NTM to different antibiotics and disinfectants increased the importance of these agents in the health system. Currently, NTM frequently infect seemingly immunocompetent individuals at rising rates. This is of concern as the resistant NTM are difficult to control and treat. The details behind this NTM development are only beginning to be clarified. The current study will provide an overview of the most important NTM resistance mechanisms to not only antibiotics but also the most commonly used disinfectants. Such evaluations can open new doors to improving control strategies and reducing the risk of NTM infection. Moreover, further studies are crucial to uncover this association.

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Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria

Cited by 20 publications

References 22 publications

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report

Meeting the challenges of NTM-PD from the perspective of the organism and the disease process: innovations in drug development and delivery

Nontuberculous Mycobacterial Resistance to Antibiotics and Disinfectants: Challenges Still Ahead

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