Whipple's disease medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]
Overview
Antimicrobial therapy is the mainstay of therapy for Whipple's disease. Without antibiotic therapy Whipple's disease is fatal. Intravenous Ceftriaxone or Penicillin G is indicated in the acute phase of Whipple's therapy. For maintenance therapy, patients are typically treated with Trimethoprim-sulfamethoxazole for at least 1 year. Patients who experience either Whipple's disease or allergy to Trimethoprim-sulfamethoxazole require a combination of Doxycycline and Hydroxychloroquine.
Medical Therapy
- Pharmacologic medical therapy for Whipple's disease includes long-term antibiotics. Preferred regimens for initial therapy include Ceftriaxone or Penicillin G or Meropenem if allergic. One year of Trimethoprim-sulfamethoxazole is used for maintenance therapy. In case of sulfa allergy, the combination of Doxycycline and Hydroxychloroquine is used.[1][2][3][4][5][6]
- 1 Classic Whipple's disease
- 1.1 Initial therapy
- 1.1.1 Preferred regimen (1): Ceftriaxone 2 g IV qd for 14 days
- 1.1.2 Preferred regimen (2): Penicillin G 2 million units IV q4h for 14 days
- 1.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 14 days
- 1.2 Maintenance therapy
- 1.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 1.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 1.1 Initial therapy
- 2 CNS infection
- 2.1 Initial therapy
- 2.1.1 Preferred regimen (1): Ceftriaxone 2 g IV qd for 14-28 days
- 2.1.2 Preferred regimen (2): Penicillin G 4 million units IV q4h for 14-28 days
- 2.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 14-28 days
- 2.2 Maintenance therapy
- 2.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 2.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 2.3 Anticonvulsant therapy
- 2.3.1 Preferred regimen (1):
- 2.3.2 Preferred regimen (2):
- 2.1 Initial therapy
- 3 Endocarditis
- 3.1 Initial therapy
- 3.1.1 Preferred regimen (1): Penicillin G 2 million units IV q4h for 28 days
- 3.1.2 Preferred regimen (2): Ceftriaxone 2 g IV qd for 28 days
- 3.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 28 days
- 3.1.1 Preferred regimen (1): Penicillin G 2 million units IV q4h for 28 days
- 3.2 Maintenance therapy
- 3.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 3.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 3.1 Initial therapy
- 4 Relapse
- 4.1 Initial therapy
- 4.1.1 Preferred regimen (1): Penicillin G 4 million units IV q4h for 28 days
- 4.1.2 Preferred regimen (2): Ceftriaxone 2 g IV qd for 28 days
- 4.2 Maintenance therapy
- 4.2.1 Preferred regimen (1): Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year
- 4.2.2 Alternative regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 4.1 Initial therapy
Note (1):Immune reconstitution inflammatory syndrome (IRIS) is a side effect that occured following initiation of antibiotic therapy in Whipple's disease. It is characterized as a flare-up of inflammation and considered fatal. Previous immunosuppressive therapy increases the risk of IRIS.[7] [8]
| Indication | Initial therapy | Maintenance therapy | ||
|---|---|---|---|---|
| Prefered | Alternative | Preferred | Alternative | |
| Classic Whipple's disease | Ceftriaxone 2 g IV qd for 14 days
OR Penicillin G 2 million units IV q4h for 14 days |
Meropenem 1 g IV q8h for 14 days | Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year |
| CNS Whippl'es disease | Ceftriaxone 2 g IV qd for 14-28 days
OR Penicillin G 4 million units IV q4h for 14-28 days |
Meropenem 1 g IV q8h for 14-28 days | Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year |
| Endocarditis | Penicillin G 2 million units IV q4h for 28 days
OR Ceftriaxone 2 g IV qd for 28 days |
Meropenem 1 g IV q8h for 28 days | Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year |
| Relapse | Penicillin G 4 million units IV q4h for 28 days
OR Ceftriaxone 2 g IV qd for 28 days |
Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year | Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | |
References
- ↑ Feurle, Gerhard E.; Junga, Natascha S.; Marth, Thomas (2010). "Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease". Gastroenterology. 138 (2): 478–486. doi:10.1053/j.gastro.2009.10.041. ISSN 0016-5085.
- ↑ Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P (1997). "Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne". Medicine (Baltimore). 76 (3): 170–84. PMID 9193452.
- ↑ Schnider, P. J.; Reisinger, E. C.; Berger, T.; Krejs, G. J.; Auff, E. (1997). "Treatment guidelines in central nervous system Whipple's disease". Annals of Neurology. 41 (4): 561–562. doi:10.1002/ana.410410425. ISSN 0364-5134.
- ↑ Boulos A, Rolain JM, Raoult D (2004). "Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells". Antimicrob. Agents Chemother. 48 (3): 747–52. PMC 353111. PMID 14982759.
- ↑ Feurle GE, Marth T (1994). "An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole". Dig. Dis. Sci. 39 (8): 1642–8. PMID 7519538.
- ↑ Keinath RD, Merrell DE, Vlietstra R, Dobbins WO (1985). "Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients". Gastroenterology. 88 (6): 1867–73. PMID 2581843.
- ↑ Biagi, Federico; Trotta, Lucia; Di Stefano, Michele; Balduzzi, Davide; Marchese, Alessandra; Vattiato, Claudia; Bianchi, Paola I.; Fenollar, Florence; Corazza, Gino R. (2012). "Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease". Digestive and Liver Disease. 44 (10): 880–882. doi:10.1016/j.dld.2012.05.008. ISSN 1590-8658.
- ↑ Moos, V.; Feurle, G. E.; Schinnerling, K.; Geelhaar, A.; Friebel, J.; Allers, K.; Moter, A.; Kikhney, J.; Loddenkemper, C.; Kuhl, A. A.; Erben, U.; Fenollar, F.; Raoult, D.; Schneider, T. (2013). "Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple's Disease". The Journal of Immunology. 190 (5): 2354–2361. doi:10.4049/jimmunol.1202171. ISSN 0022-1767.