Sections

Buruli Ulcer

Medication

Medication Summary

The goal of therapy is to reduce morbidity and prevent complications.

Rifampin (Rifadin, Rimactane)

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Rifampin inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur.

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. It has no activity against anaerobes. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

Moxifloxacin (Avelox, Vigamox)

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Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in the inhibition of bacterial DNA replication and transcription.

Streptomycin sulfate (G-Mycin, Garamycin)

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Streptomycin sulfate is for the treatment of susceptible mycobacterial infections. Use it in combination with rifampin. Streptomycin sulfate may be used in patients with severe liver dysfunction (transaminase levels >3- to 5-fold normal).

Amikacin (Amikin)

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Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes; it blocks the recognition step in protein synthesis and causes growth inhibition. Use the patient's ideal body weight for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

Clarithromycin (Biaxin)

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Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

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N'krumah RT, Koné B, Tiembre I, Cissé G, Pluschke G, Tanner M, et al. Socio-Environmental Factors Associated with the Risk of Contracting Buruli Ulcer in Tiassalé, South Côte d'Ivoire: A Case-Control Study. PLoS Negl Trop Dis. 2016 Jan. 10 (1):e0004327. [QxMD MEDLINE Link].
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Landier J, Boisier P, Fotso Piam F, Noumen-Djeunga B, Simé J, Wantong FG, et al. Adequate wound care and use of bed nets as protective factors against Buruli Ulcer: results from a case control study in Cameroon. PLoS Negl Trop Dis. 2011 Nov. 5(11):e1392. [QxMD MEDLINE Link]. [Full Text].
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Chany AC, Tresse C, Casarotto V, Blanchard N. History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease). Nat Prod Rep. 2013 Dec. 30(12):1527-67. [QxMD MEDLINE Link].
Klis S, Ranchor A, Phillips RO, Abass KM, Tuah W, Loth S, et al. Good quality of life in former Buruli ulcer patients with small lesions: long-term follow-up of the BURULICO trial. PLoS Negl Trop Dis. 2014 Jul. 8 (7):e2964. [QxMD MEDLINE Link].
Trubiano JA, Lavender CJ, Fyfe JA, Bittmann S, Johnson PD. The incubation period of Buruli ulcer (Mycobacterium ulcerans infection). PLoS Negl Trop Dis. 2013. 7(10):e2463. [QxMD MEDLINE Link]. [Full Text].
Landier J, Constantin de Magny G, Garchitorena A, Guégan JF, Gaudart J, Marsollier L, et al. Seasonal Patterns of Buruli Ulcer Incidence, Central Africa, 2002-2012. Emerg Infect Dis. 2015 Aug. 21 (8):1414-7. [QxMD MEDLINE Link].
[Guideline] Guidance on sampling techniques for laboratory-confirmation of Mycobacterium ulcerans infection (Buruli ulcer disease). Available at http://www.who.int/buruli/Guidance_sampling_techniques_MU_infection.pdf?ua=1.
O'Brien DP, Walton A, Hughes AJ, Friedman ND, McDonald A, Callan P, et al. Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort. Med J Aust. 2013 May 6. 198(8):436-9. [QxMD MEDLINE Link].
Mueller YK, Bastard M, Nkemenang P, Comte E, Ehounou G, Eyangoh S, et al. The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon. PLoS Negl Trop Dis. 2016 Apr. 10 (4):e0004593. [QxMD MEDLINE Link].
Pommelet V, Vincent QB, Ardant MF, Adeye A, Tanase A, Tondeur L, et al. Findings in patients from Benin with osteomyelitis and polymerase chain reaction-confirmed Mycobacterium ulcerans infection. Clin Infect Dis. 2014 Nov 1. 59 (9):1256-64. [QxMD MEDLINE Link].
Ruf MT, Bolz M, Vogel M, Bayi PF, Bratschi MW, Sopho GE, et al. Spatial Distribution of Mycobacterium ulcerans in Buruli Ulcer Lesions: Implications for Laboratory Diagnosis. PLoS Negl Trop Dis. 2016 Jun. 10 (6):e0004767. [QxMD MEDLINE Link].
Walsh DS, Portaels F, Meyers WM. Buruli ulcer: Advances in understanding Mycobacterium ulcerans infection. Dermatol Clin. 2011 Jan. 29(1):1-8. [QxMD MEDLINE Link].
Herbinger KH, Adjei O, Awua-Boateng NY, Nienhuis WA, Kunaa L, Siegmund V, et al. Comparative study of the sensitivity of different diagnostic methods for the laboratory diagnosis of Buruli ulcer disease. Clin Infect Dis. 2009 Apr 15. 48(8):1055-64. [QxMD MEDLINE Link].
Herbinger KH, Beissner M, Huber K, Awua-Boateng NY, Nitschke J, Thompson W, et al. Efficiency of fine-needle aspiration compared with other sampling techniques for laboratory diagnosis of Buruli ulcer disease. J Clin Microbiol. 2010 Oct. 48(10):3732-4. [QxMD MEDLINE Link]. [Full Text].
Phillips R, Horsfield C, Kuijper S, et al. Sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium ulcerans in an Assay using punch biopsy specimens for diagnosis of Buruli ulcer. J Clin Microbiol. 2005 Aug. 43(8):3650-6. [QxMD MEDLINE Link].
Rondini S, Mensah-Quainoo E, Junghanss T, Pluschke G. What does detection of Mycobacterium ulcerans DNA in the margin of an excised Buruli ulcer lesion tell us?. J Clin Microbiol. 2006 Nov. 44(11):4273-5. [QxMD MEDLINE Link].
Yeboah-Manu D, Asante-Poku A, Asan-Ampah K, Ampadu ED, Pluschke G. Combining PCR with microscopy to reduce costs of laboratory diagnosis of Buruli ulcer. Am J Trop Med Hyg. 2011 Nov. 85(5):900-4. [QxMD MEDLINE Link]. [Full Text].
de Souza DK, Quaye C, Mosi L, Addo P, Boakye DA. A quick and cost effective method for the diagnosis of Mycobacterium ulcerans infection. BMC Infect Dis. Jan 2012. 12:Jan 18. [QxMD MEDLINE Link]. [Full Text].
Siegmund V, Adjei O, Nitschke J, et al. Dry reagent-based polymerase chain reaction compared with other laboratory methods available for the diagnosis of Buruli ulcer disease. Clin Infect Dis. 2007 Jul 1. 45(1):68-75. [QxMD MEDLINE Link].
Gordon CL, Buntine JA, Hayman JA, Lavender CJ, Fyfe JA, Hosking P, et al. All-oral antibiotic treatment for buruli ulcer: a report of four patients. PLoS Negl Trop Dis. 2010 Nov 30. 4(11):e770. [QxMD MEDLINE Link]. [Full Text].
Eddyani M, Vandelannoote K, Meehan CJ, Bhuju S, Porter JL, Aguiar J, et al. A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer. PLoS Negl Trop Dis. 2015 Nov. 9 (11):e0004158. [QxMD MEDLINE Link].
Leigheb G, Cammarota T, Zavattaro E, et al. Ultrasonography for the monitoring of subcutaneous damage in Mycobacterium ulcerans infection (Buruli ulcer). Ultrasound Med Biol. 2008 Oct. 34(10):1554-63. [QxMD MEDLINE Link].
Guarner J, Bartlett J, Whitney EA, Raghunathan PL, Stienstra Y, Asamoa K, et al. Histopathologic features of Mycobacterium ulcerans infection. Emerg Infect Dis. 2003 Jun. 9 (6):651-656. [QxMD MEDLINE Link].
Converse PJ, Nuermberger EL, Almeida DV, Grosset JH. Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?. Future Microbiol. 2011 Oct. 6(10):1185-98. [QxMD MEDLINE Link]. [Full Text].
Converse PJ, Almeida DV, Nuermberger EL. Drug Efficacy Testing in the Mouse Footpad Model of Buruli Ulcer. Methods Mol Biol. 2022. 2387:195-207. [QxMD MEDLINE Link].
[Guideline] World Health Organization. Treatment of mycobaterium ulcerans disease (Buruli ulcer): guidance for health workers:. World Health Organization. Available at http://ttp://www.who.int/iris/bitstream/10665/77771/1/9789241503402_eng.pdf. Accessed: March 2013.
Chauty A, Ardant MF, Adeye A, et al. Promising clinical efficacy of streptomycin-rifampin combination for treatment of buruli ulcer (Mycobacterium ulcerans disease). Antimicrob Agents Chemother. 2007 Nov. 51(11):4029-35. [QxMD MEDLINE Link].
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 Aug. 49(8):3182-6. [QxMD MEDLINE Link].
Sarfo FS, Phillips R, Asiedu K, Ampadu E, Bobi N, Adentwe E, et al. Clinical efficacy of combination of rifampin and streptomycin for treatment of Mycobacterium ulcerans disease. Antimicrob Agents Chemother. 2010 Sep. 54(9):3678-85. [QxMD MEDLINE Link]. [Full Text].
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Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet. 2010 Feb 20. 375(9715):664-72. [QxMD MEDLINE Link].
Johnson PD, Hayman JA, Quek TY, et al. Consensus recommendations for the diagnosis, treatment and control of Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer) in Victoria, Australia. Med J Aust. 2007 Jan 15. 186(2):64-8. [QxMD MEDLINE Link].
Friedman ND, Athan E, Hughes AJ, Khajehnoori M, McDonald A, Callan P, et al. Mycobacterium ulcerans disease: experience with primary oral medical therapy in an Australian cohort. PLoS Negl Trop Dis. 2013. 7(7):e2315. [QxMD MEDLINE Link]. [Full Text].
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Junghanss T, Um Boock A, Vogel M, Schuette D, Weinlaeder H, Pluschke G. Phase change material for thermotherapy of Buruli ulcer: a prospective observational single centre proof-of-principle trial. PLoS Negl Trop Dis. 2009. 3(2):e380. [QxMD MEDLINE Link]. [Full Text].
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Bertolotti A, Izzo A, Grigolato PG, Iabichella ML. The use of ozone therapy in Buruli ulcer had an excellent outcome. BMJ Case Rep. 2013 Jan 31. 2013:[QxMD MEDLINE Link].
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Adu E, Ampadu E, Acheampong D. Surgical management of buruli ulcer disease: a four-year experience from four endemic districts in ghana. Ghana Med J. 2011 Mar. 45(1):4-9. [QxMD MEDLINE Link]. [Full Text].
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Beissner M, Arens N, Wiedemann F, Piten E, Kobara B, Bauer M, et al. Treatment Outcome of Patients with Buruli Ulcer Disease in Togo. PLoS Negl Trop Dis. 2015. 9 (10):e0004170. [QxMD MEDLINE Link].
Pommelet V, Vincent QB, Ardant MF, Adeye A, Tanase A, Tondeur L, et al. Findings in patients from Benin with osteomyelitis and polymerase chain reaction-confirmed Mycobacterium ulcerans infection. Clin Infect Dis. 2014 Nov 1. 59 (9):1256-64. [QxMD MEDLINE Link].
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Media Gallery

Buruli ulcer can extend to 15% of a person's skin surface and may destroy nerves and blood vessels. Metastatic bone lesions may develop.
An edematous Buruli ulcer in a 9-year-old Togolese girl. Courtesy of Wayne M Meyers, MD.
Photo of Togolese girl taken 5 years after the Buruli ulcer had been excised and repaired with autologous split-skin graft by GB Priuli, MD. Courtesy of Wayne M Meyers, MD.
Well-circumscribed ulceration with sharp, undermined borders on the lower leg. Courtesy of Ronald E Grimwood, Jr, MD, Baylor Scott and White Health.

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Table 1. Pros and Cons of Sampling Techniques From the WHO ^[38]

Method	Pros	Cons
Direct smear examination	• Easy to perform at local level • Does not require expensive materials and equipment • Rapid results • Uses swabs, fine-needle aspiration, and biopsy samples	• Low sensitivity (< 60%) • Needs trained personnel • Needs external quality assurance
PCR	• Results fairly rapid • Uses swabs, fine-needle aspiration, and biopsy samples • High sensitivity (>95%)	• Requires a sophisticated laboratory • Expensive to perform • Needs trained personnel • Requires strict quality control
Culture of M ulcerans	• Uses swabs, fine-needle aspiration, and biopsy samples	• Requires a sophisticated laboratory • Needs trained personnel • Results take >8 weeks • Low sensitivity (20-60%) • Not useful for immediate patient management
Histopathology	• Sensitivity is about 90% • Results fairly rapid (if services are available) • Useful in establishing differential diagnosis and monitoring unexpected response to treatment	• Requires a sophisticated laboratory • Expensive to perform • Needs trained personnel • Requires invasive procedure (ie, biopsy)

Table 2. Categories of Treatment ^[57]

Category	Form of Disease	Treatment	Primary Aim	Secondary Aim	Level of Health Care System	Diagnosis
I	Small, early lesion (eg, nodules, papules, plaques, ulcers < 5 cm in diameter)	Complete antibiotics If at or near a joint, maintain same movement as on unaffected side If surgery is needed in noncritical areas, consider this after 8 weeks of antibiotic treatment	Cure without surgery Cure without movement limitations	Reduce or prevent recurrence	Community health centers and district hospitals	Strong clinical diagnosis (with or without laboratory conﬁrmation)
II	Nonulcerative and ulcerative plaque and edematous forms Single, large ulcerative lesion 5-15 cm in diameter	Complete antibiotics, before surgery (if possible) If at or near a joint, maintain same movement as on unaffected side	Cure without surgery Reduce extent of the surgical debridement when needed Cure without movement limitations	Reduce or prevent recurrence	Health centers, district and tertiary hospitals	Strong clinical diagnosis (with or without laboratory conﬁrmation)
III	Lesions in the head and neck region, particularly the face Disseminated/mixed forms (eg, osteitis, osteomyelitis, joint involvement) Multiple lesions and osteomyelitis Extensive lesion >15 cm	Complete antibiotics, before surgery (if possible) If at or near a joint, maintain same movement as on unaffected side	Cure without surgery Cure without movement limitations	Reduce or prevent recurrence	District and tertiary hospitals	Strong clinical diagnosis (with or without laboratory conﬁrmation)

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Author

Shannon C Brown, MD Resident Physician, Department of Dermatology, Texas A&M Health Science Center, Baylor Scott and White Health

Shannon C Brown, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Gold Humanism Honor Society, Society for Pediatric Dermatology, Texas Dermatological Society, Texas Medical Association, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Kirstin Altman, MD Assistant Professor of Dermatology, Texas A&M Health Science Center College of Medicine

Kirstin Altman, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Texas Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Franklin Flowers, MD Professor Emeritus, Department of Dermatology, Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

Aaron Z Hoover, MD, FAAD Staff Dermatologist/Dermatopathologist, Front Range Dermatology Associates

Aaron Z Hoover, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Christian Medical and Dental Associations, International Society of Dermatopathology

Disclosure: Nothing to disclose.

Acknowledgements

Special thanks to Ms Carmen Urich for helping me obtain articles needed to update this publication.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of the following previous authors, Brian P. Green, DO, MS, PA-C; Sean T. Gunning, MD; and Mary K. Mather, MD, to the development and writing of this article.

The authors and editors of Medscape Reference would also like to thank Wayne M. Meyers, MD, for his clinical images from his article with Douglas S. Walsh, MD, in Transactions of the Royal Society of Tropical Medicine and Hygiene.^[4]

Buruli Ulcer Medication

Medication Summary

Antibiotics

Rifampin (Rifadin, Rimactane)

Rifampin (Rifadin, Rimactane)

Antibiotic, Quinolone

Ciprofloxacin (Cipro)

Ciprofloxacin (Cipro)

Moxifloxacin (Avelox, Vigamox)

Moxifloxacin (Avelox, Vigamox)

Antibiotic, Aminoglycoside

Streptomycin sulfate (G-Mycin, Garamycin)

Streptomycin sulfate (G-Mycin, Garamycin)

Amikacin (Amikin)

Amikacin (Amikin)

Antibiotic, Macrolide

Clarithromycin (Biaxin)

Clarithromycin (Biaxin)

Buruli Ulcer Medication

Medication Summary

Antibiotics

Rifampin (Rifadin, Rimactane)

Rifampin (Rifadin, Rimactane)

Antibiotic, Quinolone

Ciprofloxacin (Cipro)

Ciprofloxacin (Cipro)

Moxifloxacin (Avelox, Vigamox)

Moxifloxacin (Avelox, Vigamox)

Antibiotic, Aminoglycoside

Streptomycin sulfate (G-Mycin, Garamycin)

Streptomycin sulfate (G-Mycin, Garamycin)

Amikacin (Amikin)

Amikacin (Amikin)

Antibiotic, Macrolide

Clarithromycin (Biaxin)

Clarithromycin (Biaxin)

References

Tables

Contributor Information and Disclosures

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