Abstract
BackgroundThe treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field.Methodology/Principal findingsThe objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7).Conclusions/SignificanceThese results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers.
Highlights
Buruli Ulcer (BU), is an infectious disease caused by Mycobacterium ulcerans that is mostly prevalent in Africa, and found in Australia, Southeast Asia and South America [1]
Oral Intermittent Treatment against Mycobacterium Ulcerans Infection a cutaneous infection leading to skin ulcerations that can cause severe and debilitating scars
A medical treatment based on two antibiotics was found to be active in an experimental infection model and was recommended by WHO in 2004 for humans
Summary
Buruli Ulcer (BU), is an infectious disease caused by Mycobacterium ulcerans that is mostly prevalent in Africa, and found in Australia, Southeast Asia and South America [1]. In 2004, the World Health Organization recommended to treat BU with a combination of rifampin (RIF) and streptomycin (STR) administered daily during 8 weeks [5]. This standard drug regimen appeared to be effective [6], well tolerated, and of low cost. This regimen is not fully satisfactory because it requires daily injection of STR, which is operationally demanding in most countries where BU is endemic, especially in rural areas, and exposes to aminoglycosides toxicity and to the risk of transmission of blood-borne viral infection.
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