Treatment for Buruli ulcer: the long and winding road to antimicrobials-first

Omansen, Till F.; Stienstra, Ymkje; Werf, Tjip S van der

doi:10.1002/14651858.ed000128

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…Meanwhile, several studies had demonstrated the in vitro susceptibility of M. ulcerans to an array of antimicrobial agents, both in vitro [26][27][28][29][30][31][32] as well as in experimental animal studies [31][32][33][34][35]. Eventually, the landmark study by Etuaful et al [36] changed the thinking about the potential role of antimicrobial treatment for Buruli ulcer [37]. In that study, for the first time, the killing of M. ulcerans was demonstrated in early lesions of humans with cultureor PCR confirmed Buruli ulcer.…”

Section: From Bench To Bedand Back Againmentioning

confidence: 99%

Pharmacologic management ofMycobacterium ulceransinfection

Werf

Barogui²,

Converse

et al. 2020

Expert Review of Clinical Pharmacology

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Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa. Areas covered: We review BU drug treatmentin vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested. Expert opinion: A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.

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Section: From Bench To Bedand Back Againmentioning

confidence: 99%

Pharmacologic management ofMycobacterium ulceransinfection

Werf

Barogui²,

Converse

et al. 2020

Expert Review of Clinical Pharmacology

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“…Treatment of Buruli ulcer (BU), a disease primarily endemic to regions of sub-Saharan Africa and parts of Australia (1), has evolved from extensive surgical excision to the first effective combination chemotherapy regimen of rifampin (RIF, R) and streptomycin given daily for 8 weeks to the currently recommended oral regimen of RIF and clarithromycin (CLR, C) for 8 weeks (2,3). Though clinical studies have shown good efficacy of the RIF+CLR regimen ( 4), shortening the duration of treatment and reducing the potential for adverse effects and drug-drug interactions would make it easier to implement.…”

Section: Introductionmentioning

confidence: 99%

Impact of dose, duration and host immune status on ultrashort telacebec treatment in a mouse model of Buruli ulcer

Nuermberger

2021

Preprint

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Telacebec (Q203) is a new anti-tuberculosis drug in clinical development with extremely potent activity againstMycobacterium ulcerans, the causative agent of Buruli ulcer (BU). The potency of Q203 has prompted investigation of its potential role in ultra-short, even single-dose, treatment regimens for BU in mouse models. However, the relationships of Q203 dose and duration and host immune status to treatment outcomes remain unclear, as does the risk of emergence of drug resistance with Q203 monotherapy. In the present study, immunocompetent BALB/c and immunocompromised SCID-beige mice were infected in both hind footpads and treated eight weeks later. In both mouse strains, controls received rifampin-clarithromycin; others received Q203 at 0.5 or 2 mg/kg/d for 5 or 10 days. Additionally, BALB/c mice received a single dose of 2.5 or 10 mg/kg or 3.3 mg/kg/d for 3 days. Treatment response was based on changes in footpad swelling and CFU counts at the end of treatment as well as 4 and 13 weeks after stopping treatment. Efficacy depended on total dose more than duration. Total doses of 5-20 mg/kg rendered nearly all BALB/c mice culture-negative 13 weeks post-treatment without selection of Q203-resistant bacteria. Although less potent in SCID-beige mice, Q203 still rendered the majority of footpads culture-negative at total doses of 10-20 mg/kg. However, Q203 resistance was identified in relapse isolates from some SCID-beige mice. Overall, these results support the potential of Q203 monotherapy for single-dose or other ultra-short therapy for BU, although highly immunocompromised hosts may require higher doses or durations and/or combination therapy.

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Neue Empfehlung für Standardmedikation

Omansen¹,

Kreuels²

2020

Flugmedizin · Tropenmedizin · Reisemedizin - FTR

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Das Buruli-Ulkus ist eine vernachlässigte Tropenkrankheit, welche durch das Mycobacterium ulcerans verursacht wird. Die Krankheit kommt in Westafrika sowie in Australien und Japan vor. Der Übertragungsweg ist nicht endgültig geklärt, M. ulcerans ist jedoch ein Umweltpathogen und die Übertragung am ehesten multifaktoriell. Die Infektion verursacht teils entstellende und in einigen Teilen der Welt stigmatisierte Hautläsionen, welche auch die Bewegungsfreiheit einschränken können 1.

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Treatment for Buruli ulcer: the long and winding road to antimicrobials-first

Cited by 5 publications

References 20 publications

Pharmacologic management ofMycobacterium ulceransinfection

Pharmacologic management ofMycobacterium ulceransinfection

Impact of dose, duration and host immune status on ultrashort telacebec treatment in a mouse model of Buruli ulcer

Neue Empfehlung für Standardmedikation

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