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CORRESPONDENCE
Topical Paromomycin/Methylbenzethonium Chloride Plus
Parenteral Meglumine Antimonate as Treatment of
American Cutaneous Leishmaniasis: Controlled Study
SIR—We congratulate Soto and colleagues [1] for their interesting
study, because to our knowledge it is the first controlled trial
assessing the effect of topical paromomycin/methylbenzethonium
chloride (MBCL) in combination with meglumine antimonate as
treatment of New World cutaneous leishmaniasis. This study did
not show any additional therapeutic effect of the ointment in
combination with parenteral meglumine antimonate, which con-
tradicts findings of earlier studies in which high cure rates were
associated with treatment with the ointment alone or in combina-
tion with meglumine antimonate [2, 3]. Soto et al. argue that this
difference may be due to a better controlled study design. Al-
though this point is undoubtedly true, a number of concerns should
be kept in mind.
Our experience is that MBCL causes pain of the lesion so that
even applying placebo ointment would not allow an adequate
blinded control [3, 4]. Paromomycin/MBCL is well known to
initially cause enlargement of the lesion probably due to the
MBCL component [3–5]. Keeping this factor in mind, it seems
problematic to define enlargement of the lesion as a treatment
failure. Unfortunately, Soto et al. do not indicate how many of the
treatment failures were due to this factor and how many were due
to low reepithelialization rates after 1.5 months. Enlargement of
the lesions during and shortly after treatment is not necessarily a
sign of worsening of the disease but a well-known side effect of
the treatment. Furthermore, it seems doubtful to limit the healing
time to 1.5 months, as it has been observed that many lesions will
heal between 6 and 9 weeks after topical treatment [3, 6].
Soto and colleagues claim that their ointment was prepared
under good manufacturing conditions. However, locally prepared
ointments in the first study by Soto et al. [2] as well as in our study
[3] seemed to be very effective.
Finally, it should be discussed if the combination of topical and
parenteral treatment is desirable. Even if this combination were
proven to be effective, the disadvantages of both drugs add up. On
the one hand, there are the potential systemic toxicity, logistic
problems of intramuscular application, and high price of parenteral
antimonates. On the other hand, there is the pain due to application
of the ointment. From a public health perspective, topical treat-
ment of a diseases that is particularly prevalent in remote rural
areas would be highly desirable. Our group (B. Arana and col-
leagues, Universidad del Valle de Guatemala) is presently under-
taking a controlled trial with the same ointment in Guatemala.
Ge´rard Krause and Axel Kroeger
International Health Division, Liverpool School of Tropical Medicine,
Liverpool, United Kingdom
References
1. Soto J, Fuya R, Herrera R, Berman J. Topical paromomycin/methylbenzethonium
chloride plus parenteral meglumine antimonate as treatment for American cu-
taneous leishmaniasis: controlled study. Clin Infect Dis 1998;26:56 – 8.
2. Soto J, Hernandez N, Mejia H, Grogl M, Berman J. Successful treatment of
New World cutaneous leishmaniasis with a combination of topical
paromomycin/methylbenzethonium chloride and injectable meglumine
antimonate. Clin Infect Dis 1995;20:47–51.
3. Krause G, Kroeger A. Topical treatment of American cutaneous leishman-
iasis with paromomycin and methylbenzethonium chloride: a clinical
study under field conditions in Ecuador. Trans R Soc Trop Med Hyg
1994;88:92– 4.
4. Krause G, Ja¨ger K, Jansen M, Kohl PK, Diesfeld HJ. Hautleishmaniase der
“Alten Welt.” Therapie und Erfolg Dermatologie 1997;27:302– 6.
5. El-On J, Livshin R, Even-Paz Z, Hamburger D, Weinrauch L. Topical
treatment of cutaneous leishmaniasis. J Invest Dermatol 1986;87:284 – 8.
6. Navin TR, Arana BA, Arana FE, de Merida AM, Castillo AL, Pozuelos JL.
Placebo-controlled clinical trial of meglumine antimonate (Glucantime)
vs. localized heat in the treatment of cutaneous leishmaniasis in Guate-
mala. Am J Trop Med Hyg 1990;42:43–50.
Reprints or correspondence: Dr. Ge´rard Krause, Centers for Disease Control
and Prevention Department of Health, Bureau of Epidemiology, 2020 Capital
Circle SE, BIN A-12, Tallahassee, Florida 32399-1734 (gck8a@ibm.net).
Clinical Infectious Diseases 1999;29:466
© 1999 by the Infectious Diseases Society of America. All rights reserved.
1058 –4838/99/2902– 0059$03.00
Reply
SIR—We appreciate the comments of Krause and Kroeger. We too
were disappointed that we could not demonstrate the efficacy of
topical paromomycin/methylbenzethonium chloride (MBCL) as
treatment of cutaneous leishmaniasis.
Krause and Kroeger are concerned about several aspects of
our study design. Local side effects of an active topical agent
would obviate blinding. The active topical ointment may indeed
have side effects, but in our previous report [1], 60% of topical
ointment recipients did not report local side effects. Thus,
subjects in our present report [2] who had no side effects would
not know if they had received the active topical ointment or the
placebo topical ointment. At any rate, for cutaneous leishman-
iasis, treatment success or failure is based on the objective
criterion of lesion size.
Lesions may initially enlarge before healing; therefore, by
declaring enlargement of lesions at the end of therapy as treat-
ment failure, we may declare treatment failure prematurely.
Herein, we break down the total of 68 treatment failures into
enlargement of lesions at the end of therapy, lesions that were
not cured by 1.5 months after therapy, and lesions that relapsed
(table 1). In the key experimental group (patients who were
treated with topical paromomycin/MBCL b.i.d. for 10 days plus
injectable meglumine antimonate for 7 days), treatments of only
three patients were declared failures at the end of therapy, and
enlargement of their lesions was huge: from 182, 64, and 64
mm
2
before therapy to 918, 495, and 225 mm
2
after therapy,
respectively.
Lesions may heal beyond 6 weeks after initiation of therapy,
and we should observe patients for longer periods before de-
claring treatment failure. Experimental groups were compared
466
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