Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial

Willemien A. Nienhuis; Ymkje Stienstra; William A. Thompson; Peter C. Awuah; K. Mohammed Abass; Wilson Tuah; Nana Yaa Awua-Boateng; Edwin O. Ampadu; Vera Siegmund; Jan P. Schouten; Ohene Adjei; Gisela Bretzel; Tjip S. van der Werf

doi:10.1016/S0140-6736(09)61962-0

Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial

Willemien A. Nienhuis, Ymkje Stienstra, William A. Thompson, Peter C. Awuah, K. Mohammed Abass, Wilson Tuah, Nana Yaa Awua-Boateng, Edwin O. Ampadu, Vera Siegmund, Jan P. Schouten, Ohene Adjei, Gisela Bretzel, Tjip S. van der Werf^*

^*Corresponding author for this work

Faculty of Medical Sciences/UMCG

Research output: Contribution to journal › Article › Academic › peer-review

228 Citations (Scopus)

Abstract

Background Surgical debridement was the standard treatment for Mycobacterium ulcerans infection (Buruli ulcer disease) until WHO issued provisional guidelines in 2004 recommending treatment with antimicrobial drugs (streptomycin and rifampicin) in addition to surgery. These recommendations were based on observational studies and a small pilot study with microbiological endpoints. We investigated the efficacy of two regimens of antimicrobial treatment in early-stage M ulcerans infection.

Methods In this parallel, open-label, randomised trial undertaken in two sites in Ghana, patients were eligible for enrolment if they were aged 5 years or older and had early (duration

Findings Four patients were lost to follow-up (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, three). Since these four participants had healed lesions at their last assessment, they were included in the analysis for the primary endpoint. 73 (96%) participants in the 8-week streptomycin group and 68 (91%) in the 4-week streptomycin plus 4-week clarithromycin group had healed lesions at 1 year (odds ratio 2.49, 95% CI 0.66 to infinity; p=0.16, one-sided Fisher's exact test). No participants had lesion recurrence at I year. Three participants had vestibulotoxic events (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One participant developed an injection abscess and two participants developed an abscess close to the initial lesion, which was incised and drained (all three participants were in the 4-week streptomycin plus 4-week clarithromycin group).

Interpretation Anti mycobacterial treatment for M ulcerans infection is effective in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin; however, the number of injections of streptomycin can be reduced by switching to oral clarithromycin after 4 weeks.

Original language	English
Pages (from-to)	664-672
Number of pages	9
Journal	LANCET
Volume	375
Issue number	9715
DOIs	https://doi.org/10.1016/S0140-6736(09)61962-0
Publication status	Published - 20-Feb-2010

Keywords

BURULI ULCER
RISK-FACTORS
DISEASE
GHANA
PCR
DIAGNOSIS
LESIONS
STREPTOMYCIN
SENSITIVITY
COMBINATION

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Nienhuis, W. A., Stienstra, Y., Thompson, W. A., Awuah, P. C., Abass, K. M., Tuah, W., Awua-Boateng, N. Y., Ampadu, E. O., Siegmund, V., Schouten, J. P., Adjei, O., Bretzel, G., & van der Werf, T. S. (2010). Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. LANCET, 375(9715), 664-672. https://doi.org/10.1016/S0140-6736(09)61962-0

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title = "Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial",

abstract = "Background Surgical debridement was the standard treatment for Mycobacterium ulcerans infection (Buruli ulcer disease) until WHO issued provisional guidelines in 2004 recommending treatment with antimicrobial drugs (streptomycin and rifampicin) in addition to surgery. These recommendations were based on observational studies and a small pilot study with microbiological endpoints. We investigated the efficacy of two regimens of antimicrobial treatment in early-stage M ulcerans infection.Methods In this parallel, open-label, randomised trial undertaken in two sites in Ghana, patients were eligible for enrolment if they were aged 5 years or older and had early (durationFindings Four patients were lost to follow-up (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, three). Since these four participants had healed lesions at their last assessment, they were included in the analysis for the primary endpoint. 73 (96%) participants in the 8-week streptomycin group and 68 (91%) in the 4-week streptomycin plus 4-week clarithromycin group had healed lesions at 1 year (odds ratio 2.49, 95% CI 0.66 to infinity; p=0.16, one-sided Fisher's exact test). No participants had lesion recurrence at I year. Three participants had vestibulotoxic events (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One participant developed an injection abscess and two participants developed an abscess close to the initial lesion, which was incised and drained (all three participants were in the 4-week streptomycin plus 4-week clarithromycin group).Interpretation Anti mycobacterial treatment for M ulcerans infection is effective in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin; however, the number of injections of streptomycin can be reduced by switching to oral clarithromycin after 4 weeks.",

keywords = "BURULI ULCER, RISK-FACTORS, DISEASE, GHANA, PCR, DIAGNOSIS, LESIONS, STREPTOMYCIN, SENSITIVITY, COMBINATION",

author = "Nienhuis, {Willemien A.} and Ymkje Stienstra and Thompson, {William A.} and Awuah, {Peter C.} and Abass, {K. Mohammed} and Wilson Tuah and Awua-Boateng, {Nana Yaa} and Ampadu, {Edwin O.} and Vera Siegmund and Schouten, {Jan P.} and Ohene Adjei and Gisela Bretzel and {van der Werf}, {Tjip S.}",

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doi = "10.1016/S0140-6736(09)61962-0",

language = "English",

volume = "375",

pages = "664--672",

journal = "LANCET",

issn = "0140-6736",

publisher = "ELSEVIER SCIENCE INC",

number = "9715",

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Nienhuis, WA, Stienstra, Y, Thompson, WA, Awuah, PC, Abass, KM, Tuah, W, Awua-Boateng, NY, Ampadu, EO, Siegmund, V, Schouten, JP, Adjei, O, Bretzel, G & van der Werf, TS 2010, 'Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial', LANCET, vol. 375, no. 9715, pp. 664-672. https://doi.org/10.1016/S0140-6736(09)61962-0

TY - JOUR

T1 - Antimicrobial treatment for early, limited Mycobacterium ulcerans infection

T2 - a randomised controlled trial

AU - Nienhuis, Willemien A.

AU - Stienstra, Ymkje

AU - Thompson, William A.

AU - Awuah, Peter C.

AU - Abass, K. Mohammed

AU - Tuah, Wilson

AU - Awua-Boateng, Nana Yaa

AU - Ampadu, Edwin O.

AU - Siegmund, Vera

AU - Schouten, Jan P.

AU - Adjei, Ohene

AU - Bretzel, Gisela

AU - van der Werf, Tjip S.

PY - 2010/2/20

Y1 - 2010/2/20

N2 - Background Surgical debridement was the standard treatment for Mycobacterium ulcerans infection (Buruli ulcer disease) until WHO issued provisional guidelines in 2004 recommending treatment with antimicrobial drugs (streptomycin and rifampicin) in addition to surgery. These recommendations were based on observational studies and a small pilot study with microbiological endpoints. We investigated the efficacy of two regimens of antimicrobial treatment in early-stage M ulcerans infection.Methods In this parallel, open-label, randomised trial undertaken in two sites in Ghana, patients were eligible for enrolment if they were aged 5 years or older and had early (durationFindings Four patients were lost to follow-up (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, three). Since these four participants had healed lesions at their last assessment, they were included in the analysis for the primary endpoint. 73 (96%) participants in the 8-week streptomycin group and 68 (91%) in the 4-week streptomycin plus 4-week clarithromycin group had healed lesions at 1 year (odds ratio 2.49, 95% CI 0.66 to infinity; p=0.16, one-sided Fisher's exact test). No participants had lesion recurrence at I year. Three participants had vestibulotoxic events (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One participant developed an injection abscess and two participants developed an abscess close to the initial lesion, which was incised and drained (all three participants were in the 4-week streptomycin plus 4-week clarithromycin group).Interpretation Anti mycobacterial treatment for M ulcerans infection is effective in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin; however, the number of injections of streptomycin can be reduced by switching to oral clarithromycin after 4 weeks.

AB - Background Surgical debridement was the standard treatment for Mycobacterium ulcerans infection (Buruli ulcer disease) until WHO issued provisional guidelines in 2004 recommending treatment with antimicrobial drugs (streptomycin and rifampicin) in addition to surgery. These recommendations were based on observational studies and a small pilot study with microbiological endpoints. We investigated the efficacy of two regimens of antimicrobial treatment in early-stage M ulcerans infection.Methods In this parallel, open-label, randomised trial undertaken in two sites in Ghana, patients were eligible for enrolment if they were aged 5 years or older and had early (durationFindings Four patients were lost to follow-up (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, three). Since these four participants had healed lesions at their last assessment, they were included in the analysis for the primary endpoint. 73 (96%) participants in the 8-week streptomycin group and 68 (91%) in the 4-week streptomycin plus 4-week clarithromycin group had healed lesions at 1 year (odds ratio 2.49, 95% CI 0.66 to infinity; p=0.16, one-sided Fisher's exact test). No participants had lesion recurrence at I year. Three participants had vestibulotoxic events (8-week streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One participant developed an injection abscess and two participants developed an abscess close to the initial lesion, which was incised and drained (all three participants were in the 4-week streptomycin plus 4-week clarithromycin group).Interpretation Anti mycobacterial treatment for M ulcerans infection is effective in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4 weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of streptomycin and rifampicin; however, the number of injections of streptomycin can be reduced by switching to oral clarithromycin after 4 weeks.

KW - BURULI ULCER

KW - RISK-FACTORS

KW - DISEASE

KW - GHANA

KW - PCR

KW - DIAGNOSIS

KW - LESIONS

KW - STREPTOMYCIN

KW - SENSITIVITY

KW - COMBINATION

U2 - 10.1016/S0140-6736(09)61962-0

DO - 10.1016/S0140-6736(09)61962-0

M3 - Article

SN - 0140-6736

VL - 375

SP - 664

EP - 672

JO - LANCET

JF - LANCET

IS - 9715

ER -

Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial

Abstract

Keywords

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