versão On-line ISSN 1678-9946
Rev. Inst. Med. trop. S. Paulo v.42 n.3 São Paulo maio/jun. 2000
THIAMPHENICOL IN THE TREATMENT OF CHANCROID. A STUDY OF 1,128 CASES
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
Thiamphenicol (dextrosulfenidol) synthezised in 1951, belongs to the group of hydrocarbilsulfonil propandiol aminic derivates, obtained from methylmercapto acetofenona. According to MINGOIA7, "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 (02N) there is methylsulfonila (CH3SO2), 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 blastogenesis8.
Minor reversible side effects, like nausea, headache, diarrhea, gastralgia and skin prurigo or rash have been reported1. 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 vaginalis2.
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 treatment3, 6, and later, in a granulated form in a single dose4,5.
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 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.
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.
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.
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 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.
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Received: 25 November 1999
Accepted: 17 April 2000
Correspondence to: Walter Belda Junior, Av. Acoçe 162, 04075-020 S. Paulo, SP, Brasil