Historical Lessons

The history of antibiotic therapy goes back to 1951, when a family physician, Dr. G. Ander in England, decided to try chloramphenicol, a new drug at the time, in a 56-year-old male with WD presenting with high fever and diarrhea. His patient's symptoms vanished and remission continued. As chroni called in Dobbins classic test, the patient was later reported (by Dr. Paulley) as an example of idiopathic steatorrhea, because the effect of chloramphenicol was considered as a control of secondary infection on the jejunal mucosa. The real implication was realized later when electron microscopy identified rod shaped bacteria in other patients' tissues. Antibiotic therapy of WD started, in fact, in 1961. During the four decades since, several drugs have been used. In retrospect, three time periods may be recognized.

In the first period, various antibiotics were applied which were available in the 1960s; penicillin, streptomycin, and tetracyline (and some additional drugs) were all given with success. A sequential combination of these 3 drugs, lasting for at least 12 months, was recommended in 1963 (ie, "Duke regimen"). To avoid possible malabsorption of antibiotics, treatment was started with parenteral administration of penicillin and streptomycin. Follow-up observations were favorable, but perhaps due to the requirement of parenteral application, this regimen was less frequently applied in the 1970s.

A second period started in 1970, when knowledge accumulated that monotherapy with tetracycline was apparently also effective. This oral regimen was widely preferred until the late 1980s, and a low rate of relapses was observed.

However, Knox and colleagues (1976) reported severe central nervous system (CNS) relapses in their patients treated with tetracycline. Indeed, in 1985 a retrospective analysis on the long term outcome (ie, after a minimum of 2 years after diagnosis) in a cohort of 88 patients by Keinath and colleagues (1985) reported that signs or symptoms attributable to WD frequently recurred; among 49 patients treated with tetracycline alone, 21 (43%) had clinically defined relapses. Seven of the 49 patients (14%) developed neurologic features suggestive of CNS relapse, and two further patients developed their second relapse in the CNS. The outcome of patients with CNS relapse was generally poor, despite new antibiotic therapies.

A third period started in the mid 1980s. To overcome the crucial problem of CNS relapse, trimethoprim-sulphamethoxazole was preferred, because this drug can penetrate the blood-brain barrier, whereas tetracyline does not. The choice of this drug was later supported by a retrospective study by Feurle and colleagues in 1976. However, with increasing usage of trimethoprim-sulphamethoxazole, several patients were observed who developed late onset CNS WD. In parallel, we observed asymptomatic CNS infection with T. whippelii after long term therapy with trimethoprim-sulphamethoxazole. Thus, it was felt that a more active antimicrobial regimen is necessary to prevent CNS WD.

Constipation Prescription

Constipation Prescription

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