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Thiamphenicol in the treatment of chancroid. A study of 1,128 cases

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Thiamphenicol, an aminic derivate of hydrocarbilsulfonil propandiol, was used for the treatment of 1,171 chancroid bearing patients. Each patient was medicated with 5.0 g of granulated thiamphenicol, orally, in a single dose, and was reevaluated 3, 7 and 10 days after the treatment. Ten patients (0.89%) did not respond to the proposed treatment. 133 patients presented healed ulcers after 3 days of treatment, 976 patients healed chancres on the seventh day after the treatment, and 39 patients took 10 days to present healed chancres. The results of this study indicate that the rate of patients that were cured, the low incidence of side effects, and the practicality of administration make of thiamphenicol an excellent choice for the treatment of chancroid.
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Rev. Inst. Med. trop. S. Paulo
42 (3): 133-135, May-June, 2000.
(1) Department of Dermatology, Faculty of Medicine, University of S. Paulo, S. Paulo, SP, Brasil
(2) Faculty of Public Health, University of S. Paulo, S. Paulo, SP, Brasil
Correspondence to: Walter Belda Junior, Av. Acoçe 162, 04075-020 S. Paulo, SP, Brasil
THIAMPHENICOL IN THE TREATMENT OF CHANCROID. A STUDY OF 1,128 CASES
Walter BELDA JUNIOR(1), Luis Fernando de Goes SIQUEIRA(2) & Luiz Jorge FAGUNDES(2)
SUMMARY
Thiamphenicol, an aminic derivate of hydrocarbilsulfonil propandiol, was used for the treatment of 1,171 chancroid bearing
patients. Each patient was medicated with 5.0 g of granulated thiamphenicol, orally, in a single dose, and was reevaluated 3, 7 and 10
days after the treatment. Ten patients (0.89%) did not respond to the proposed treatment. 133 patients presented healed ulcers after 3
days of treatment, 976 patients healed chancres on the seventh day after the treatment, and 39 patients took 10 days to present healed
chancres. The results of this study indicate that the rate of patients that were cured, the low incidence of side effects, and the practicality
of administration make of thiamphenicol an excellent choice for the treatment of chancroid.
KEYWORDS: Thiamphenicol; Chancroid; Therapy
INTRODUCTION
Thiamphenicol (dextrosulfenidol) synthezised in 1951, belongs to
the group of hydrocarbilsulfonil propandiol aminic derivates, obtained
from methylmercapto acetofenona. According to MINGOIA
7
, “The only
antibiotic similar to chloramphenicol that has drawn some attention and
presents some superiority over the natural antibiotic is thiamphenicol,
characterized by the methylsulfonic radical instead of the nitrogroup”.
At a sub-cellular level, thiamphenicol inhibits the protein synthesis,
joining the ribosomes and thus preventing the binding of the amino acid
with the peptiltransferase.
Chloramphenicol’s toxic side effects are attributed to the substances
of reduction caused by the nitrogroup. With thiamphenicol, instead of
this group (0
2
N) there is methylsulfonila (CH
3
SO
2
), thus the inexistence
of such risks. Anemia, found in prolonged treatments, is reversible. There
is no risk of relative overdose in individuals with altered hepatic function.
In vivo studies in which high doses of thiamphenicol have been given
belie any role of this drug in altering the lymphocytic blastogenesis
8
.
Minor reversible side effects, like nausea, headache, diarrhea,
gastralgia and skin prurigo or rash have been reported
1
. Although its
action is basically bacteriostatic, thiamphenicol, in the same
concentration, proved bactericide for members of species of
Streptococcus, Neisseria, Klebsiella and Brucella, being active against
Chlamydia, Mycoplasma and several other anaerobic organisms. It
doesn’t present any activity against Mycobacterium tuberculosis and
Trichomonas vaginalis
2
.
Ulcers of mixed etiology, problems of bacterial identification on
culture or slides, are possibly precluding the real understanding of the
problem. Due to their growing resistance or the need of a long-term
regimen, classical drugs demand continuous research not only on new
but also more simplified therapeutic options, in order to prevent the
patients’ evasion and/or treatment interruption.
Based upon former experiments with thiamphenicol we have
employed the product in a single dose of 5.0 g, taking into account that
a convenient route of administration, short treatment period and a specific
antibacterial spectrum are the most important factors for a optimal
treatment strategy.
Since 1984, thiamphenicol has been used in the treatment of
chancroid, sporadically at the beginning, in the form of capsules and
with a ten day long treatment
3, 6
, and later, in a granulated form in a
single dose
4,5
.
PATIENTS AND METHODS
The study group included male patients bearing chancroid, attended
at the Sexually Transmitted Diseases Service, Dermatology Division,
Hospital das Clínicas, Faculty of Medicine, São Paulo University and
Faculty of Public Health from University of São Paulo, during the period
comprised between 1984 and 1999. The diagnosis was confirmed by the
clinical characterization of genital chancres, necrotic and painful, and
laboratorially, with negative research for Treponema pallidum in darkfield
microscopy; identification through direct bacterioscopy with Gram
134
BELDA JUNIOR, W.; SIQUEIRA, L.F. de G. & FAGUNDES, L.J. - Thiamphenicol in the treatment of chancroid. A study of 1,128 cases. Rev. Inst. Med. trop. S. Paulo, 42(3):133-135, 2000.
staining, negative gram bacillus forming palisades or simple chains and/
or in a typical disposition in the polymorphonuclear cytoplasm, on
material obtained from chancre pus.
As soon as the clinical laboratory diagnosis was established, the
patients received 5.0g of granulated thiamphenicol, dissolved in 50 ml
of water, in a single dose, by mouth. The patients were evaluated clinically
and laboratorially 3, 7 and 10 days after medication.
A total of 1,171 patients, all of them male, whose age distribution is
in Table 1, were evaluated.
RESULTS
At the first clinical laboratory reevaluation, which took place 3 days
after the treatment, 133 patients (11.35%) presented totally healed lesions;
10 patients (0.85%) didn’t return for the first check up. The rest presented
ulcerated lesions and, of these, 7.17% (84 patients) still presented purulent
secretion from the lesions, in a lesser quantity, although positive for
Haemophilus ducreyi.
On the second reevaluation, which took place 7 days after application,
1,076 patients (91.88%) presented completely healed chancres; 33
patients didn’t show up to this second check up and 10 patients (0.87%)
still presented open chancres and positive Haemophilus ducreyi research
on a microscopic slide.
At the final evaluation, which took place 10 days after the treatment,
1,115 patients (98.84%) presented healed lesions, 3 patients still presented
open lesions though non-reactive for Haemophilus ducreyi, and 10
patients persisted with ulcerated lesions and positive research on the
microscopic slide for Haemophilus ducreyi.
After 3 weeks of treatment, the 3 patients who still presented open
lesions at the 10th day of the reevaluation were completely healed.
Few patients showed side effects, which included epigastralgia,
headache, nausea and skin rash, all of them light in intensity and of
short duration.
DISCUSSION
The results at the therapeutic evaluation were related to the confirmed
disappearance of Haemophilus ducreyi, the disappearance of clinic
symptoms (pain) and healing of the ulcers. At the evaluation carried out
on the third day of application, 10 patients (0.85%) did not show up;
133 patients (11.35%) had healed lesions, with no possibility of a
bacterioscopic exam, 1,028 patients presented open lesions, ten of which
still presented a positive Haemophilus ducreyi research on the
microscopic slide. At the second evaluation, carried out after seven days
of treatment, 33 more patients failed to show up. Hence, there was a loss
of 43 patients. Of the 1,128 patients who were evaluated on the seventh
day, 1,076 (95.39%) presented healed lesions and 10 (0.89%) remained
with open lesions and with positive research for Haemophilus ducreyi.
On the third and last evaluation carried out 10 days after the treatment,
1,115 patients (98.84%) presented healed lesions; 3 patients retained
open lesions although non-reactive, and 10 patients (0.89%) retained
open lesions and positive reaction on the slide. These ten patients were
then considered as a therapeutic failure and alternative medication was
then introduced.
After 3 weeks, the 3 patients who still presented open lesions at the
third evaluation with negative direct research, were reevaluated, and found
that their ulcers had already healed. Of the 1,128 patients who completed
the study, 133 presented lesions healed in 3 days; 976 patients presented
a healing between 3 and 7 days after medication and, 39 patients presented
a healing between 7 and 10 days after the treatment. Three patients
showed a healing time between 10 days and 3 weeks (Table 2 ).
We thus obtained a clinical laboratoty cure in 99.11% of the patients,
with only 10 patients (8.9%) not responding to the proposed medication,
making it necessary to use an alternative medication. Few patients
presented side effects, and these were of light intensity and short duration.
The high cure rates, the absence of serious side effects, the low cost
and the practical administration make of thiamphenicol an excellent
choice for the treatment of chancroid.
RESUMO
Tianfenicol no tratamento do cancroide. Estudo de 1.128 casos
O tiamfenicol, derivado amínico do hidrocarbilsulfonil propandiol,
foi utilizado para o tratamento de 1.171 pacientes portadores de cancróide.
Cada paciente foi medicado com 5,0 g de tianfenicol granulado, via oral
e em dose única, sendo reavaliados após 3, 7 e 10 dias do tratamento.
Dez pacientes (0,89%) não responderam à terapêutica proposta; 133
pacientes apresentaram úlceras cicatrizadas após 3 dias do tratamento;
976 pacientes apresentaram lesões cicatrizadas no sétimo dia após o
tratamento e, 39 pacientes levaram 10 dias para apresentarem lesões
Table 2
Healing time after therapy with thiamphenicol
DAYS No. PATIENTS
0 - 3 133
3 - 7 976
7 - 10 39
10 - 21 03
Table 1
Age distribution of patients
AGE No. PATIENTS %
15 - 20 275 23.48
21 - 25 550 46.96
26 - 30 220 18.78
31 - 35 36 03.07
36 - 40 55 04.69
41 - 45 18 01.53
46 - 50 17 01.45
TOTAL 1,171 100
BELDA JUNIOR, W.; SIQUEIRA, L.F. de G. & FAGUNDES, L.J. - Thiamphenicol in the treatment of chancroid. A study of 1,128 cases. Rev. Inst. Med. trop. S. Paulo, 42(3):133-135, 2000.
135
cicatrizadas. Os resultados deste estudo indicam que o índice de cura, a
baixa incidência de efeitos colaterais, e a praticidade de administração
fazem hoje do tianfenicol uma excelente escolha no tratamento do
cancróide.
REFERENCES
1. BELDA, W. – O tratamento da uretrite gonocócica aguda masculina pelo tianfenicol:
uma revisão. Rev. bras. Clín. Terap., 7: 375-379, 1978.
2. BELDA, W.; SANTOS JR., M.F.Q. & BELDA JR., W. – Thiamphenicol in the treatment
of male gonococal urethritis. Sex. transm. Dis., 11: 418-419, 1984.
3. BELDA, W.; SANTOS JR., M.F.Q.; BELDA JR., W. et al. - Novos rumos no tratamento
do cancro mole. Experimentação clínica com thiamphenicol. An. bras. Derm., 59:
147-149, 1984.
4. BELDA, W.; SANTOS JR., M.F.Q.; SIQUEIRA, L.F.G. et al. - Emprego do tianfenicol
granulado, em dose única de 5 g no tratamento do cancro mole. An. bras. Derm.,
59: 209-212, 1984.
5. BELDA JR.,W.; SANTI, C.G.& MIRANDEZ, A.A.- Tratamento do cancróide com
tianfenicol. Rev. bras. Med., 42: 204-205, 1985.
6. LATIF, A.S.; CROCCHIOLO, P.R. & LENCROW, R. – Thiamphenicol in the treatment
of chancroid in men. Sex. transm. Dis., 11: 454-455, 1984.
7. MINGOIA, Q. – Tianfenicol e cloranfenicol: diferenciação química e farmacológica.
Rev. bras. Clín. Terap., 6: 495-500, 1977.
8. PASTERNAK, J. - Cloranfenicol - tianfenicol. Aspectos conhecidos e desconhecidos
das interações fármaco-hospedeiro. Rev. bras. Clín. Terap., 5: 259-262, 1976.
Received: 25 November 1999
Accepted: 17 April 2000
Rev. Inst. Med. trop. S. Paulo
42 (3): 136, May-June, 2000.
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... Azithromycin is an effective oral therapy for chancroid and other sexually transmitted disease pathogens [11], but its high cost makes it less suitable in financially challenged settings [4,13,14], as compared with thiamphenicol [15,16]. ...
... The fundamental difference between chloramphenicol and thiamphenicol is the presence in the later agent of the methylsulfonic radical in place of the nitro group, and the absence of this group in thiamphenicol probably accounts for the reduced risk associated with its use. At a sub-cellular level, thiamphenicol inhibits protein synthesis, joining the ribosomes and then preventing the binding of aminoacids with peptidyl transferase [15,20]. ...
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... Thiamphenicol (THI) belongs to a class of antibiotics, the amphenicols, characterized by the phenylpropanoid structure and was first introduced in 1951 [1]. Chemically, THI is the (D (+)-threo-2-di-choloroacetamido-1-(4-methylsulphonylphenyl) propane-1, 3-diol) (Fig. 1). ...
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Tianfenicol e cloranfenicol: diferenciação química e farmacológica
  • MINGOIA Q.
MINGOIA, Q. -Tianfenicol e cloranfenicol: diferenciação química e farmacológica. Rev. bras. Clín. Terap., 6: 495-500, 1977.
Aspectos conhecidos e desconhecidos das interações fármaco-hospedeiro. Rev. bras
PASTERNAK, J. -Cloranfenicol -tianfenicol. Aspectos conhecidos e desconhecidos das interações fármaco-hospedeiro. Rev. bras. Clín. Terap., 5: 259-262, 1976. Received: 25 November 1999
O tratamento da uretrite gonocócica aguda masculina pelo tianfenicol: uma revisão
  • BELDA W.
BELDA, W. -O tratamento da uretrite gonocócica aguda masculina pelo tianfenicol: uma revisão. Rev. bras. Clín. Terap., 7: 375-379, 1978.
Emprego do tianfenicol granulado, em dose única de 5 g no tratamento do cancro mole
  • W Belda
  • M F Q Santos Jr
  • L F G Siqueira
BELDA, W.; SANTOS JR., M.F.Q.; SIQUEIRA, L.F.G. et al. -Emprego do tianfenicol granulado, em dose única de 5 g no tratamento do cancro mole. An. bras. Derm., 59: 209-212, 1984.
Cloranfenicol - tianfenicol. Aspectos conhecidos e desconhecidos das interações fármaco-hospedeiro
  • PASTERNAK J.
Novos rumos no tratamento do cancro mole
  • W Belda
  • M F Q Santos Jr
  • W Belda Jr
BELDA, W.; SANTOS JR., M.F.Q.; BELDA JR., W. et al. -Novos rumos no tratamento do cancro mole. Experimentação clínica com thiamphenicol. An. bras. Derm., 59: 147-149, 1984.