2,925
Views
14
CrossRef citations to date
0
Altmetric
Review

Pharmacologic management of Mycobacterium ulcerans infection

ORCID Icon, , , &
Pages 391-401 | Received 16 Nov 2019, Accepted 31 Mar 2020, Published online: 20 Apr 2020

References

  • van der Werf TS, Stienstra Y, Johnson RC, et al. Mycobacterium ulcerans disease. Bull World Health Organ. 2005;83(10):785–791.
  • Radford AJ. What’s in a name? Ulcerans disease: infections due to Mycobacterium ulcerans. Trans R Soc Trop Med Hyg. 2009;103(10):979–980.
  • Johnson PDR, Stinear T, Small PLC, et al. Buruli ulcer (M. ulcerans Infection): new insights, new hope for disease control. PLoS Med. 2005;2(4):e108.
  • van der Werf TS, van der Graaf WT, Tappero JW, et al. Mycobacterium ulcerans infection. Lancet. 1999;354(9183):1013–1018.
  • de Zeeuw J, Alferink M, Barogui YT, et al. Assessment and treatment of pain during treatment of Buruli ulcer. PLoS Negl Trop Dis. 2015;9(9):e0004076.
  • Woolley RJ, Velink A, Phillips RO, et al. Experiences of pain and expectations for its treatment among former Buruli ulcer patients. Am J Trop Med Hyg. 2016;95(5):1011–1015.
  • Sizaire V, Nackers F, Comte E, et al. Mycobacterium ulcerans infection: control, diagnosis, and treatment. Lancet Infect Dis. 2006;6(5):288–296.
  • Stienstra Y, van Roest MHG, van Wezel MJ, et al. Factors associated with functional limitations and subsequent employment or schooling in Buruli ulcer patients. Trop Med Int Health. 2005;10(12):1251–1257.
  • Stienstra Y, van der Graaf WTA, Asamoa K, et al. Beliefs and attitudes toward Buruli ulcer in Ghana. Am J Trop Med Hyg. 2002;67(2):207–213.
  • Asiedu K, Etuaful S. Socioeconomic implications of Buruli ulcer in Ghana: a three-year review. Am J Trop Med Hyg. 1998;59(6):1015–1022.
  • Simpson H, Deribe K, Tabah EN, et al. Mapping the global distribution of Buruli ulcer: a systematic review with evidence consensus. Lancet Glob Health. 2019;7(7):e912–22.
  • Omansen TF, Erbowor-Becksen A, Yotsu R, et al. Global epidemiology of Buruli Ulcer, 2010–2017, and analysis of 2014 WHO programmatic targets. Emerging Infect Dis. 2019;25(12):2183–2190.
  • Mulder AA, Boerma RP, Barogui Y, et al. Healthcare seeking behaviour for Buruli ulcer in Benin: a model to capture therapy choice of patients and healthy community members. Trans R Soc Trop Med Hyg. 2008;102(9):912–920.
  • Renzaho AMN, Woods PV, Ackumey MM, et al. Community-based study on knowledge, attitude and practice on the mode of transmission, prevention and treatment of the Buruli ulcer in Ga West District, Ghana. Trop Med Int Health. 2007;12(3):445–458.
  • Alferink M, van der Werf TS, Sopoh GE, et al. Perceptions on the effectiveness of treatment and the timeline of Buruli ulcer influence pre-hospital delay reported by healthy individuals. PLoS Negl Trop Dis. 2013;7(1):e2014.
  • Raghunathan PL, Whitney EAS, Asamoa K, et al. Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana. Clin Infect Dis. 2005;40(10):1445–1453.
  • Wallace JR, Mangas KM, Porter JL, et al. Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer. PLoS Negl Trop Dis. 2017;11(4):e0005553.
  • Walsh CM, Gebert MJ, Delgado-Baquerizo M, et al. A global survey of Mycobacterial diversity in soil. Appl Environ Microbiol. 2019;85(17):623.
  • Meyers WM, Shelly WM, Connor DH, et al. Human Mycobacterium ulcerans infections developing at sites of trauma to skin. Am J Trop Med Hyg. 1974;23(5):919–923.
  • Debacker M, Zinsou C, Aguiar J, et al. First case of Mycobacterium ulcerans disease (Buruli ulcer) following a human bite. Clin Infect Dis. 2003;36(5):e67–8.
  • MacCallum P, JC T, Buckle G, et al. A new mycobacterial infection in man. J Pathol Bacteriol. 1948;60(1):93–122.
  • Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet. 2006;367(9525):1849–1858.
  • Clancy JK, Dodge OG, Lunn HF, et al. Mycobacterial skin ulcers in Uganda. Lancet. 1961;2(7209):951–954.
  • Revill WD, Morrow RH, Pike MC, et al. A controlled trial of the treatment of Mycobacterium ulcerans infection with clofazimine. Lancet. 1973;2(7834):873–877.
  • Espey DK, Djomand G, Diomande I, et al. A pilot study of treatment of Buruli ulcer with rifampin and dapsone. Int J Infect Dis. 2002;6(1):60–65.
  • Dhople AM. Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dapsone, against Mycobacterium ulcerans. J Antimicrob Chemother. 2001;47(1):93–96.
  • Dhople AM. In vitro activity of KRM-1648, either singly or in combination with ofloxacin, against Mycobacterium ulcerans. Int J Antimicrob Agents. 2001;17(1):57–61.
  • Dhople AM, Namba K. In vitro activity of sitafloxacin (DU-6859a) alone, or in combination with rifampicin, against Mycobacterium ulcerans. J Antimicrob Chemother. 2002;50(5):727–729.
  • Portaels F, Traore H, De Ridder K, et al. In vitro susceptibility of Mycobacterium ulcerans to clarithromycin. Antimicrob Agents Chemother. 1998;42(8):2070–2073.
  • Thangaraj HS, Adjei O, Allen BW, et al. In vitro activity of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin against Ghanaian isolates of Mycobacterium ulcerans. J Antimicrob Chemother. 2000;45(2):231–233.
  • Bentoucha A, Robert J, Dega H, et al. Activities of new macrolides and fluoroquinolones against Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother. 2001;45(11):3109–3112.
  • Dega H, Bentoucha A, Robert J, et al. Bactericidal activity of rifampin-amikacin against Mycobacterium ulcerans in mice. Antimicrob Agents Chemother. 2002;46(10):3193–3196.
  • Ji B, Lefrançois S, Robert J, et al. In vitro and in vivo activities of rifampin, streptomycin, amikacin, moxifloxacin, R207910, linezolid, and PA-824 against Mycobacterium ulcerans. Antimicrob Agents Chemother. 2006;50(6):1921–1926.
  • Ji B, Chauffour A, Robert J, et al. Orally administered combined regimens for treatment of Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother. 2007;51(10):3737–3739.
  • Ji B, Chauffour A, Robert J, et al. Bactericidal and sterilizing activities of several orally administered combined regimens against Mycobacterium ulcerans in mice. Antimicrob Agents Chemother. 2008;52(6):1912–1916.
  • Etuaful S, Carbonnelle B, Grosset J, et al. Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. Antimicrob Agents Chemother. 2005;49(8):3182–3186.
  • Omansen TF, Stienstra Y, van der Werf TS. Treatment for Buruli ulcer: the long and winding road to antimicrobials-first. Cochrane Database Syst Rev. 2018;12(4):ED000128.
  • Guarner J, Bartlett J, Whitney EAS, et al. Histopathologic features of Mycobacterium ulcerans infection. Emerging Infect Dis. 2003;9(6):651–656.
  • J. G. Buruli Ulcer:review of a neglected skin mycobacterial disease. J Clin Microbiol. 2018;56(4):e01507–17.
  • George KM, Chatterjee D, Gunawardana G, et al., Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. 1999;283(5403):854–857.
  • van der Werf TS, Stinear T, Stienstra Y, et al. Mycolactones and Mycobacterium ulcerans disease. Lancet. 2003;362(9389):1062–1064.
  • Read JK, Heggie CM, Meyers WM, et al. Cytotoxic activity of Mycobacterium ulcerans. Infect Immun. 1974;9(6):1114–1122.
  • Hockmeyer WT, Krieg RE, Reich M, et al. Further characterization of Mycobacterium ulcerans toxin. Infect Immun. 1978;21(1):124–128.
  • Bretzel G, Siegmund V, Racz P, et al. Post-surgical assessment of excised tissue from patients with Buruli ulcer disease: progression of infection in macroscopically healthy tissue. Trop Med Int Health. 2005;10(11):1199–1206.
  • Rondini S, Horsfield C, Mensah-Quainoo E, et al. Contiguous spread of Mycobacterium ulcerans in Buruli ulcer lesions analysed by histopathology and real-time PCR quantification of mycobacterial DNA. J Pathol. 2006;208(1):119–128.
  • Sarfo FS, Phillips R, Wansbrough-Jones M, et al. Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease. Cell Microbiol. 2016;18(1):17–29.
  • Kishi Y. Chemistry of mycolactones, the causative toxins of Buruli ulcer. Proc Natl Acad Sci USA. 2011;108(17):6703–6708.
  • Stinear TP, Mve-Obiang A, Small PLC, et al. Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci USA. 2004;101(5):1345–1349.
  • Stinear TP, Pryor MJ, Porter JL, et al. Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology. 2005;151(3):683–692.
  • Porter JL, Tobias NJ, Pidot SJ, et al. The cell wall-associated mycolactone polyketide synthases are necessary but not sufficient for mycolactone biosynthesis. PLoS ONE. 2013;8(7):e70520.
  • Coutanceau E, Decalf J, Martino A, et al. Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med. 2007;204(6):1395–1403.
  • Baron L, Paatero AO, Morel J-D, et al. Mycolactone subverts immunity by selectively blocking the Sec61 translocon. J Exp Med. 2016;7(3):e2101.
  • Sarfo FS, Converse PJ, Almeida DV, et al. Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease. PLoS Negl Trop Dis. 2013;7(3):e2101.
  • Song O-R, Kim H-B, Jouny S, et al. A bacterial toxin with analgesic properties: hyperpolarization of DRG neurons by Mycolactone. Toxins (Basel). 2017;9(7):227.
  • Danser AHJ, Anand P. The angiotensin II type 2 receptor for pain control. Cell. 2014;157(7):1504–1506.
  • Demangel C, High S. Sec61 blockade by mycolactone: A central mechanism in Buruli ulcer disease. Biol Cell. 2018;110(11):237–248.
  • En J, Goto M, Nakanaga K, et al. Mycolactone is responsible for the painlessness of Mycobacterium ulcerans infection (Buruli ulcer) in a murine study. Infect Immun. 2008;76(5):2002–2007.
  • En J, Kitamoto S, Kawashima A, et al. Mycolactone cytotoxicity in Schwann cells could explain nerve damage in Buruli ulcer. PLoS Negl Trop Dis. 2017;11(8):e0005834.
  • Anand U, Sinisi M, Fox M, et al. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: mechanisms underlying hypoalgesia in Buruli ulcer. Mol Pain. 2016;12. doi:10.1177/1744806916654144
  • FS S, Phillips RO, Zhang J, et al., Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease. BMC Infect Dis. 2014;14(1):202–210.
  • Dega H, Robert J, Bonnafous P, et al. Activities of several antimicrobials against Mycobacterium ulcerans infection in mice. Antimicrob Agents Chemother. 2000;44(9):2367–2372.
  • Almeida D, Converse PJ, Ahmad Z, et al. Activities of rifampin, rifapentine and clarithromycin alone and in combination against Mycobacterium ulcerans disease in mice. PLoS Negl Trop Dis. 2011;5(1):e933.
  • Almeida DV, Converse PJ, Li S-Y, et al. Bactericidal activity does not predict sterilizing activity: the case of rifapentine in the murine model of Mycobacterium ulcerans disease. PLoS Negl Trop Dis. 2013;7(2):e2085.
  • Fraga AG, Martins TG, Torrado E, et al. Cellular immunity confers transient protection in experimental Buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination. PLoS ONE. 2012;7(3):e33406.
  • Nakanaga K, Ogura Y, Toyoda A, et al. Naturally occurring a loss of a giant plasmid from Mycobacterium ulcerans subsp. Shinshuense makes it non-pathogenic. Sci Rep. 2018;8(1):1–12.
  • Sarpong-Duah M, Frimpong M, Beer M, et al. Clearance of viable Mycobacterium ulcerans from Buruli ulcer lesions during antibiotic treatment as determined by combined 16S rRNA reverse transcriptase/IS 2404 qPCR assay. PLoS Negl Trop Dis. 2017;11(7):e0005695.
  • O’Brien DP, Ford N, Vitoria M, et al. Management of BU-HIV co-infection. Trop Med Int Health. 2014;19(9):1040–1047.
  • Westenbrink BD, Stienstra Y, Huitema MG, et al. Cytokine responses to stimulation of whole blood from patients with Buruli ulcer disease in Ghana. Clin Diagn Lab Immunol. 2005;12(1):125–129.
  • Sarfo FS, Phillips RO, Rangers B, et al. Detection of Mycolactone A/B in Mycobacterium ulcerans-infected human tissue. PLoS Negl Trop Dis. 2010;4(1):e577.
  • Phillips R, Sarfo FS, Guenin-Macé L, et al., Immunosuppressive signature of cutaneous Mycobacterium ulcerans infection in the peripheral blood of patients with Buruli ulcer disease. J Infect Dis. 2009;200(11):1675–1684.
  • O’Brien DP, Robson ME, Callan PP, et al. “Paradoxical” immune-mediated reactions to Mycobacterium ulcerans during antibiotic treatment: a result of treatment success, not failure. Med J Aust. 2009;191(10):564–566.
  • Nienhuis WA, Stienstra Y, Abass KM, et al., Paradoxical responses after start of antimicrobial treatment in Mycobacterium ulcerans infection. Clin Infect Dis. 2012;54(4):519–526.
  • Frimpong M, Agbavor B, Duah MS, et al. Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: relationship to bacterial load. PLoS Negl Trop Dis. 2019;13(8):e0007689.
  • Yeboah-Manu D, Kpeli GS, Ruf MT, et al. Secondary bacterial infections of Buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin. PLoS Negl Trop Dis. 2013;7(5):e2191.
  • Amissah NA, Glasner C, Ablordey A, et al. Genetic diversity of Staphylococcus aureus in Buruli ulcer. PLoS Negl Trop Dis. 2015;9(2):e0003421.
  • Kpeli G, Darko Otchere I, Lamelas A, et al. Possible healthcare-associated transmission as a cause of secondary infection and population structure of Staphylococcus aureus isolates from two wound treatment centres in Ghana. New Microbes New Infect. 2016;13:92–101.
  • Amissah NA, Chlebowicz MA, Ablordey A, et al. Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients. Int J Med Microbiol. 2017;307(4–5):223–232.
  • Amissah NA, Chlebowicz MA, Ablordey A, et al. Molecular characterization of Staphylococcus aureus isolates transmitted between patients with Buruli ulcer. PLoS Negl Trop Dis. 2015;9(9):e0004049.
  • Barogui YT, Klis S, Bankolé HS, et al. Towards rational use of antibiotics for suspected secondary infections in Buruli ulcer patients. PLoS Negl Trop Dis. 2013;7(1):e2010.
  • Crofton J, Mitchison DA. Streptomycin resistance in pulmonary tuberculosis. Br Med J. 1948;2(4588):1009.
  • Daniels M, Hill AB. Chemotherapy of pulmonary tuberculosis in young adults; an analysis of the combined results of three medical research council trials. Br Med J. 1952;1(4769):1162–1168.
  • Yawalkar SJ, McDougall AC, Languillon J, et al. Once-monthly rifampicin plus daily dapsone in initial treatment of lepromatous leprosy. Lancet. 1982;1(8283):1199–1202.
  • Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416.
  • Sauret J, Hernández-Flix S, Castro E, et al. Treatment of pulmonary disease caused by Mycobacterium kansasii: results of 18 vs 12 months’ chemotherapy. Tuber Lung Dis. 1995;76(2):104–108.
  • Griffith DE, Brown-Elliott BA, Wallace RJ. Thrice-weekly clarithromycin-containing regimen for treatment of Mycobacterium kansasii lung disease: results of a preliminary study. Clin Infect Dis. 2003;37(9):1178–1182.
  • Fujita M, Kajiki A, Tao Y, et al. The clinical efficacy and safety of a fluoroquinolone-containing regimen for pulmonary MAC disease. J Infect Chemother. 2012;18(2):146–151.
  • Miwa S, Shirai M, Toyoshima M, et al. Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study. Ann Am Thorac Soc. 2014;11(1):23–29.
  • Caminero JA, Scardigli A, van der Werf TS, et al. Treatment of drug-susceptible and drug resistant TB. In: Migliori GB, Bothamley G, Duarte R, et al., editors. Tuberculosis. Sheffield (UK): ERS Monograph; 2018. p. 152–178.
  • Scollard DM, Adams LB, Gillis TP, et al. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19(2):338–381.
  • Gröschel MI, Walker TM, van der Werf TS, et al. Pathogen-based precision medicine for drug-resistant tuberculosis. PLoS Pathog. 2018;14(10):e1007297.
  • Marsollier L, Stinear T, Aubry J, et al. Aquatic plants stimulate the growth of and biofilm formation by Mycobacterium ulcerans in axenic culture and harbor these bacteria in the environment. Appl Environ Microbiol. 2004;70(2):1097–1103.
  • Herbinger K-H, Adjei O, Awua-Boateng N-Y, et al. Comparative study of the sensitivity of different diagnostic methods for the laboratory diagnosis of Buruli ulcer disease. Clin Infect Dis. 2009;48(8):1055–1064.
  • Marsollier L, Honoré N, Legras P, et al. Isolation of three Mycobacterium ulcerans strains resistant to rifampin after experimental chemotherapy of mice. Antimicrob Agents Chemother. 2003;47(4):1228–1232.
  • Beer M, Awua-Boateng N-Y, Thompson W, et al. A genotypic approach for detection, identification, and characterization of drug resistance in Mycobacterium ulcerans in clinical samples and isolates from Ghana. Am J Trop Med Hyg. 2010;83(5):1059–1065.
  • Owusu E, Newman MJ, Addo KK, et al. In vitro susceptibility of Mycobacterium ulcerans isolates to selected antimicrobials. Can J Infect Dis Med Microbiol. 2017;2017(4):5180984–5180986.
  • Converse PJ, Almeida DV, Tyagi S, et al. Shortening Buruli ulcer treatment with combination therapy targeting the respiratory chain and exploiting Mycobacterium ulcerans gene decay. Antimicrob Agents Chemother. 2019;63(7):e00426–19.
  • Liu Y, Gao Y, Liu J, et al. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model. Nat Commun. 2019;10(1):524–529.
  • Omansen TF, van der Werf TS, Phillips RO. Antimicrobial treatment of Mycobacterium ulcerans infection. In: Pluschke G, Röltgen K, editors. Buruli ulcer. Cham (Switzerland): Springer; 2019. p. 203–220.
  • Converse PJ, Xing Y, Kim KH, et al. Accelerated detection of mycolactone production and response to antibiotic treatment in a mouse model of Mycobacterium ulcerans disease. PLoS Negl Trop Dis. 2014;8(1):e2618.
  • Gumbo T, Pasipanodya JG, Nuermberger E, et al. Correlations between the hollow fiber model of tuberculosis and therapeutic events in tuberculosis patients: learn and confirm. Clin Infect Dis. 2015;61(suppl 1):S18–24.
  • Pasipanodya JG, Nuermberger E, Romero K, et al. Systematic analysis of hollow fiber model of tuberculosis experiments. Clin Infect Dis. 2015;61(suppl 1):S10–7.
  • Srivastava S, van Rijn SP, Wessels AMA, et al. Susceptibility testing of antibiotics that degrade faster than the doubling time of slow-growing mycobacteria: ertapenem sterilizing effect versus Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2016;60(5):3193–3195.
  • van Rijn SP, Srivastava S, Wessels MA, et al. Sterilizing effect of ertapenem-clavulanate in a hollow-fiber model of tuberculosis and implications on clinical dosing. Antimicrob Agents Chemother. 2017;61(9):e02039–16.
  • Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005–1015.
  • Boehme CC, Nicol MP, Nabeta P, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011;377(9776):1495–1505.
  • CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I, Bi L, et al. Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing. N Engl J Med 2018;379(15):1403–1415.
  • Lunn HF, Ree RJ. Treatment of mycobacterial skin ulcers in Uganda with a riminophenazine derivative (B.663). Lancet. 1964;1(7327):247–249.
  • Pettit JH, Marchette NJ, Rees RJ. Mycobacterium ulcerans infection. Clinical and bacteriological study of the first cases recognized in South East Asia. Br J Dermatol. 1966;78(4):187–197.
  • Converse PJ, Tyagi S, Xing Y, et al. Efficacy of rifampin plus clofazimine in a murine model of Mycobacterium ulcerans disease. PLoS Negl Trop Dis. 2015;9(6):e0003823.
  • Converse PJ, Almeida DV, Tasneen R, et al. Shorter-course treatment for Mycobacterium ulcerans disease with high-dose rifamycins and clofazimine in a mouse model of Buruli ulcer. PLoS Negl Trop Dis. 2018;12(8):e0006728.
  • Chauffour A, Robert J, Veziris N, et al. Sterilizing activity of fully oral intermittent regimens against Mycobacterium ulcerans infection in mice. PLoS Negl Trop Dis. 2016;10(10):e0005066.
  • Scherr N, Bieri R, Thomas SS, et al. Targeting the Mycobacterium ulcerans cytochrome bc1: aa3for the treatment of Buruli ulcer. Nat Commun. 2018;9(1):5370–5379.
  • Bolz M, Ruggli N, Ruf M-T, et al. Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease. PLoS Negl Trop Dis. 2014;8(7):e2968.
  • Williamson HR, Mosi L, Donnell R, et al. Mycobacterium ulcerans fails to infect through skin abrasions in a guinea pig infection model: implications for transmission. PLoS Negl Trop Dis. 2014;8(4):e2770.
  • Fenner F. The pathogenic behavior of Mycobacterium ulcerans and Mycobacterium balnei in the mouse and the developing chick embryo. Am Rev Tuberc. 1956;73(5):650–673.
  • Shepard CC. Acid-fast bacilli in nasal excretions in leprosy, and results of inoculation of mice. Am J Hyg. 1960;71(2):147–157.
  • Lefrançois S, Robert J, Chauffour A, et al. Curing Mycobacterium ulcerans infection in mice with a combination of rifampin-streptomycin or rifampin-amikacin. Antimicrob Agents Chemother. 2007;51(2):645–650.
  • Yotsu RR, Richardson M, Ishii N. Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease). Cochrane Database Syst Rev. 2018;8(8):CD012118.
  • Jansson M, Beer M, Phillips RO, et al. Comparison of two assays for molecular determination of rifampin resistance in clinical samples from patients with Buruli ulcer disease. J Clin Microbiol. 2014;52(4):1246–1249.
  • Goldstein BP. Resistance to rifampicin: a review. J Antibiot. 2014;67(9):625–630.
  • Kapetas AJ, Sorich MJ, Rodrigues AD, et al. Guidance for rifampin and midazolam dosing protocols to study intestinal and hepatic cytochrome P450 (CYP) 3A4 induction and de-induction. Aaps J. 2019;21(5):78.
  • Svensson RJ, Aarnoutse RE, Diacon AH, et al. A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses. Clin Pharmacol Ther. 2018;103(4):674–683.
  • Boeree MJ, Diacon AH, Dawson R, et al. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Am J Respir Crit Care Med. 2015;191(9):1058–1065.
  • Boeree MJ, Heinrich N, Aarnoutse R, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017;17(1):39–49.
  • Omansen TF, Almeida D, Converse PJ, et al. High-dose rifamycins enable shorter oral treatment in a murine model of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2019;63(2):e01478–18.
  • Marsollier L, Prévot G, Honoré N, et al. Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin. Int J Antimicrob Agents. 2003;22(6):562–566.
  • Zhang T, Li S-Y, Converse PJ, et al. Rapid, serial, non-invasive assessment of drug efficacy in mice with autoluminescent Mycobacterium ulcerans infection. PLoS Negl Trop Dis. 2013;7(12):e2598.
  • Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999;74(5):519–528.
  • Feldman WH, Karlson AG. Mycobacterium ulcerans infections; response to chemotherapy in mice. Am Rev Tuberc. 1957;75(2):266–279.
  • Pattyn SR, Royackers J. Treatment of experimental infection with Mycobacterium leprae in mice. Ann Soc Belges Med Trop Parasitol Mycol. 1965;45:27–30.
  • Klis S, Stienstra Y, Phillips RO, et al. Long term streptomycin toxicity in the treatment of Buruli ulcer: follow-up of participants in the BURULICO drug trial. PLoS Negl Trop Dis. 2014;8(3):e2739.
  • Nienhuis WA, Stienstra Y, Thompson WA, et al., Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet. 2010;375(9715):664–672.
  • Phillips RO, Sarfo FS, Abass MK, et al. Clinical and bacteriological efficacy of rifampin-streptomycin combination for two weeks followed by rifampin and clarithromycin for six weeks for treatment of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2014;58(2):1161–1166.
  • Phillips RO, Robert J, Abass KM, et al. Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for early, limited Buruli ulcer lesions: a randomised, open label, non-inferiority phase 3 trial. Lancet. 2020. doi:10.1016/S0140-6736(20)30047-7
  • Dinos GP. The macrolide antibiotic renaissance. Br J Pharmacol. 2017;174(18):2967–2983.
  • Rodvold KA. Clinical pharmacokinetics of clarithromycin. Clin Pharmacokinet. 1999;37(5):385–398.
  • Alffenaar JWC, Nienhuis WA, de Velde F, et al. Pharmacokinetics of rifampin and clarithromycin in patients treated for Mycobacterium ulcerans infection. Antimicrob Agents Chemother. 2010;54(9):3878–3883.
  • O’Brien DP, Hughes AJ, Cheng AC, et al. Outcomes for Mycobacterium ulcerans infection with combined surgery and antibiotic therapy: findings from a south-eastern Australian case series. Med J Aust. 2007;186(2):58–61.
  • O’Brien DP, McDonald A, Callan P, et al. Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study. PLoS Negl Trop Dis. 2012;6(1):e1473.
  • Friedman ND, Athan E, Walton AL, et al. Increasing experience with primary oral medical therapy for Mycobacterium ulcerans disease in an Australian cohort. Antimicrob Agents Chemother. 2016;60(5):2692–2695.
  • O’Brien DP, Friedman D, Hughes A, et al. Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients. Intern Med J. 2017;47(9):1011–1019.
  • Pranger AD, van der Werf TS, Kosterink JGW, et al. The role of fluoroquinolones in the treatment of tuberculosis in 2019. Drugs. 2019;79(2):161–171.
  • Alffenaar J-W, Gumbo T, Aarnoutse R. Shorter moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2015;372(6):576.
  • Alsaad N, van der Laan T, Van Altena R, et al. Trimethoprim/sulfamethoxazole susceptibility of Mycobacterium tuberculosis. Int J Antimicrob Agents. 2013;42(5):472–474.
  • Alsaad N, Van Altena R, Pranger AD, et al. Evaluation of co-trimoxazole in treatment of multidrug-resistant tuberculosis. Eur Respir J. 2012;42(2):504–512.
  • Demoulin L, Médard M, Kellens J. Antibiogram of mycobacteria for erythromycin, tetracycline and cotrimoxazole. Pathol Biol. 1983;31(3):195–197.
  • Fehr H, Egger M, Senn I. Cotrimoxazol in the treatment of Mycobacterium ulcerans infection (Buruli ulcer) in west Africa. Trop Doct. 1994;4(2):61–63.
  • Portaels F, Van den Breen L, Pattyn SR. Sensitivity of mycobacteria to dapsone. Arzneimittelforschung. 1982;32(9):1124–1125.
  • Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017, Ahmad N, Ahuja SD, Akkerman OW, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet. 2018;392(10150):821–834.
  • Bolhuis MS, Tiberi S, Sotgiu G, et al. Linezolid tolerability in multidrug-resistant tuberculosis: a retrospective study. Eur Respir J. 2015;46(4):1205–1207.
  • Bolhuis MS, van der Werf TS, Kerstjens HAM, et al. Treatment of MDR-TB using therapeutic drug monitoring: first experiences with sub-300 mg linezolid dosages using in-house made capsules. Eur Respir J. 2019;54(6):1900580.
  • Arenaz-Callao MP, González Del Río R, Lucía Quintana A, et al. Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening. PLoS Negl Trop Dis. 2019;13(1):e0007126.
  • Klis S, Kingma RA, Tuah W, et al. Clinical outcomes of Ghanaian Buruli ulcer patients who defaulted from antimicrobial therapy. Trop Med Int Health. 2016;21(9):1191–1196.
  • O’Brien DP, Friedman ND, Cowan R, et al. Six versus eight weeks of antibiotics for small Mycobacterium ulcerans lesions in Australian patients. Clin Infect Dis. 2019 Jun 20 (ahead of print). doi:10.1093/cid/ciz532
  • Friedman ND, Athan E, Hughes AJ, et al. Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort. PLoS Negl Trop Dis. 2013;7(7):e2315.
  • Amofah G, Asamoah S, Afram-Gyening C. Effectiveness of excision of pre-ulcerative Buruli lesions in field situations in a rural district in Ghana. Trop Doct. 1998;28(2):81–83.
  • Teelken MA, Stienstra Y, Ellen DE, et al. Buruli ulcer: differences in treatment outcome between two centres in Ghana. Acta Trop. 2003;88(1):51–56.
  • Sarfo FS, Phillips R, Asiedu K, et al. Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2010;54(9):3678–3685.
  • Chauty A, Ardant M-F, Marsollier L, et al. Oral treatment for Mycobacterium ulcerans infection: results from a pilot study in Benin. Clin Infect Dis. 2011;52(1):94–96.
  • Wadagni AC, Barogui YT, Johnson RC, et al., Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial. Lancet Infect Dis. 2018;18(6):650–656.
  • Lee JS, Giesler DL, Gellad WF, et al. Antibiotic therapy for adults hospitalized with community-acquired Pneumonia: a systematic review. JAMA. 2016;315(6):593–602.
  • Alffenaar J-WC, Akkerman OW, Anthony RM, et al. Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers. Expert Rev Anti Infect Ther. 2017;15(1):11–21.
  • Wicha SG, Clewe O, Svensson RJ, et al. Forecasting clinical dose-response from preclinical studies in tuberculosis research: translational predictions with rifampicin. Clin Pharmacol Ther. 2018;104(6):1208–1218.
  • Zuur MA, Pasipanodya JG, van Soolingen D, et al. Intermediate susceptibility dose-dependent breakpoints for high dose rifampicin, isoniazid and pyrazinamide treatment in multidrug-resistant tuberculosis programmes. Clin Infect Dis. 2018;29:565.
  • Dheda K, Lenders L, Magombedze G, et al. Drug-penetration gradients associated with acquired drug resistance in patients with tuberculosis. Am J Respir Crit Care Med. 2018;198(9):1208–1219.
  • van Rijn SP, Zuur MA, Anthony R, et al. Evaluation of Carbapenems for treatment of multi- and extensively drug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2019;63(2). doi:10.1128/AAC.00779-19
  • Wadagni A, Frimpong M, Phanzu DM, et al. Simple, rapid mycobacterium ulcerans disease diagnosis from clinical samples by fluorescence of mycolactone on thin layer chromatography. PLoS Negl Trop Dis. 2015;9(11):e0004247.
  • Velding K, Klis S-A, Abass KM, et al. Wound care in Buruli ulcer disease in Ghana and Benin. Am J Trop Med Hyg. 2014;91(2):313–318.
  • Velding K, Klis S-A, Abass KM, et al. The application of modern dressings to Buruli ulcers: results from a pilot implementation project in Ghana. Am J Trop Med Hyg. 2016;95(1):60–62.
  • Wadagni AC, Steinhorst J, Barogui YT, et al. Buruli ulcer treatment: rate of surgical intervention differs highly between treatment centers in West Africa. PLoS Negl Trop Dis. 2019;13(10):e0007866.
  • Phanzu DM, Mahema RL, Suykerbuyk P, et al. Mycobacterium ulcerans infection (Buruli ulcer) on the face: a comparative analysis of 13 clinically suspected cases from the Democratic Republic of Congo. Am J Trop Med Hyg. 2011;85(6):1100–1105.
  • Barogui Y, Johnson RC, van der Werf TS, et al. Functional limitations after surgical or antibiotic treatment for Buruli ulcer in Benin. Am J Trop Med Hyg. 2009;81(1):82–87.
  • Abass KM, van der Werf TS, Phillips RO, et al. Buruli ulcer control in a highly endemic district in Ghana: role of community-based surveillance volunteers. Am J Trop Med Hyg. 2015;92(1):115–117.