Antibiotic Therapy

Response of intestinal WD can be achieved with many drugs (Table 53-2), but the real challenge is to prevent late onset cerebral WD. To reach this goal, our first line recommendation is to combine an induction therapy with intravenous application of a bactericidal drug, ceftriaxone (2 times 1 mg/d) for 14 days, and a maintenance treatment with trimethoprim-sulphamethoxazole (2 times 160 mg, 2 times 800 mg/d by mouth) for 12 months.

Ceftriaxone, a third-generation cephalosporin, is commonly used to treat bacterial meningitis. We have 10 years of experience with its use in WD (Von Herbay et al, 1997;

TABLE 53-2. Overview of Antibiotics Used for the Treatment of Whipple's Disease

Drug(s)

Dosage

Comments

Ceftriaxone

3 mg/d IV

Induction therapy (first 14 days), good

CNS penetration

Meropeneme

3 mg/d IV

Induction therapy (first 14 days), good

CNS penetration, limited experience

Penicillin G

6 to 24 million

Induction therapy (first 7 to 14 days),

plus

units/d IV plus

moderate CNS penetration

streptomycin

1 g/d IM

Trimethoprim-

320 mg/d PO,

Maintenance therapy, first line drug, good

sulfamethoxazole

1600 mg/d PO

CNS penetration, but CNS WD may occur

Doxycycline

100 to 200 mg/d

Maintenance therapy; divergent reports

(or tetracycline)

PO

of low and high rate of clinical relapses

Penicillin VK

500 mg 4 times

Alternative for maintenance therapy,

daily PO

limited experience

Cefixime

400 mg twice

Alternative for maintenance therapy,

daily PO

limited experience

Rifampin

600 mg 4 times

Second line drug, good CNS penetration,

daily PO

limited experience in CNS WD

Chloramphenicol

1000 mg 4 times

Second line drug, worrisome side effects

daily PO

Erythromycin

500 mg 4 times

Second line drug, limited experience

daily PO

Adapted from Maiwald et al, 2002.

CNS = central nervous system, IM = intramuscularly, IV = intravenous, PO = by mouth, WD = Whipple's disease.

CNS = central nervous system, IM = intramuscularly, IV = intravenous, PO = by mouth, WD = Whipple's disease.

Von Herbay, 2003). Alternatively, meropeneme (1 mg 3 times a day) may be given, but our experience with this drug in WD is limited to a 4-year experience. The historical "Duke regimen", previously reported to be effective, might be considered as a further alternative, although penicillin and streptomycin are considered to only moderately penetrate the normal blood-brain barrier.

Apart from common practice, our argument in favour of 1 year of maintenance treatment is derived from follow-up studies of patients with PCR analysis. Clearance of bacterial DNA from the intestinal mucosa occurs within a range of 1 to 12 months, but, in our experience, after 1 year stable intestinal remission is virtually always reached (see below). An other argument for prolonged therapy can be derived from experiments to culture T. whippelii, where the growth of the bacteria is very slow. The estimated duplication time of 4 days is fairly different from common enteric bacteria (eg, Escherichia coli has a doubling time of approximately 20 minutes). Surprisingly, there are a few reports of short term antibiotic treatment resulting in long lasting remissions (Fleming et al, 1998; Bai et al, 1991). This paradox is puzzling.

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