Ulcerative colitis medical therapy: Difference between revisions

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::***** Note (1): [[Infliximab]] is contraindicated in patients with untreated latent [[Tuberculosis|TB]], pre-existing demyelinating disorder, [[optic neuritis]], moderate to severe [[Congestive heart failure|CHF]], current or recent [[malignancy]]
::***** Note (1): [[Infliximab]] is contraindicated in patients with untreated latent [[Tuberculosis|TB]], pre-existing demyelinating disorder, [[optic neuritis]], moderate to severe [[Congestive heart failure|CHF]], current or recent [[malignancy]]
::***** Note (2): Transdermal [[Nicotine (transdermal)|nicotine]] is effective in achieving remission.
::***** Note (2): Transdermal [[Nicotine (transdermal)|nicotine]] is effective in achieving remission.
::***'''Maintenance of Remission'''
:***'''Maintenance of Remission'''
::****Preferred regimen (1):  [[Sulfasalazine]], [[olsalazine]], [[mesalamine]], and [[balsalazide]]
::****Preferred regimen (1):  [[Sulfasalazine]], [[olsalazine]], [[mesalamine]], and [[balsalazide]]
::**** Alternative regimen (1): [[6-mercaptopurine]] '''OR''' [[azathioprine]]  
::**** Alternative regimen (1): [[6-mercaptopurine]] '''OR''' [[azathioprine]]  

Revision as of 16:08, 21 May 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The first step in the management of an acute ulcerative colitis attack involves determining the anatomical extent of the disease endoscopically, and the severity of the disease, clinically. This classification is important to determine the necessity for topical (in distal disease) or systemic (in extensive disease) pharmacotherapy. Additionally, the severity of the disease may help determine the prognosis and the requirement for more aggressive intervention. Once the disease goes into remission, the goal of maintenance therapy is to prevent any subsequent acute exacerbations.

Medical Therapy

The goal is to induce remission initially with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important. The medications used to induce and maintain a remission somewhat overlap, but the treatments are different. Physicians first direct treatment to inducing a remission which involves relief of symptoms and mucosal healing of the lining of the colon and then longer term treatment to maintain the remission.

Standard treatment for ulcerative colitis depends on extent of involvement (proximal vs. distal) and disease severity (e.g. mild, moderate, severe and fulminant).

Pharmacotherapy

  • 1. Mild to Moderate Distal Colitis
    • Acute Management
      • Preferred regimen (1): Topical Mesalamine
      • Preferred regimen (2): Topical corticosteroids
      • Preferred regimen (3):Oral aminosalicylates
      • Alternative regimen (1): Mesalamine enemas or suppositories (in patients refractory to topical corticosteroids or oral aminosalicylates.
      • Alternate regimen (2): Oral prednisone up to 40-60 mg/day AND infliximab 5mg/kg at weeks 0, 2, 6 of treatment
        • Note: Effective dose of Sulfasalazine is 4-6g/day in 4 doses; mesalamine is 2-4.6g/day in 3 doses; balasalazine 6.75g/day in 3 doses; mesalamine multimatrix formulation is 2.4 to 4.8 g/day. These drugs are effective within 2.4 weeks.
    • Maintenance of Remission
    • 2. Mild to Moderate Extensive Colitis
      • Acute Management
        • Preferred regimen (1): oral sulfasalazine titrated up to 4-6g/day OR oral aminosalicylate in doses of up to 4.8g/day of active 5-ASA moiety
        • Alternate regimen (1): Oral steroids (in patients refractory to aminosalicylates in combination with topical therapy)
        • Alternate regimen (2): 6-mercaptopurine AND azathioprine (in patients refractory to oral steroids)
        • Alternative regimen (3): infliximab 5mg/kg I.V. at weeks 0,2, and 6 (steroid refractory or steroid dependent despite adequate 6-MP dosing or intolerant to other regimens)
          • Note (1): Infliximab is contraindicated in patients with untreated latent TB, pre-existing demyelinating disorder, optic neuritis, moderate to severe CHF, current or recent malignancy
          • Note (2): Transdermal nicotine is effective in achieving remission.
      • Maintenance of Remission
  • 1.1.1.2 Presence of comorbidities, use of immunosuppressing drugs, or use of antimicrobials within the previous 3 months
  • 1.1.2 Inpatient treatment
  • 1.1.2.1 Non-ICU treatment
  • 1.1.2.2 ICU treatment
  • 1.1.3 Special considerations
  • 1.1.3.1 Suspected Pseudomonas
  • 1.1.3.2 Suspected methicillin resistant Staphylococcus aureus (add the following)
  • Preferred regimen: Vancomycin 45-60 mg/kg/day divided q8-12h OR Linezolid 600 mg PO/IV q12h for 10-14 days
  • 1.1.3.3 Neutropenic patient [1]
  • 1.1.3.3.1 No risk for multi-drug resistance
  • 1.1.3.3.2 Risk for multi drug resistance
  • 1.2 Pathogen-directed antimicrobial therapy
  • 1.2.1 Bacterial pathogens
  • 1.2.1.1 Streptococcus pneumoniae
  • 1.2.1.1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mg/mL)
  • 1.2.1.1.2 Penicillin resistant (minimum inhibitory concentration > 2 mg/mL)
  • Preferred regimen (Agents chosen on the basis of susceptibililty) : Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
  • Alternative regimen: Vancomycin 45-60 mg/kg/day divided q8-12h (maximum: 2000 mg/dose) for 7-21 days depending on severity OR Linezolid 600 mg PO/IV q12h for 10-14 days OR Amoxicillin 875 mg PO q12h or 500 mg q8 ( 3 g/day with penicillin ,minimum inhibitory concentration 4 ≤ microgram / mL)
  • 1.2.1.2 Haemophilus influenzae
  • 1.2.1.2.1 Non-beta lactamase producing
  • 1.2.1.2.2 Beta lactamase producing
  • 1.2.1.2 Bacillus anthracis (inhalational)
  • 1.2.1.3 Enterobacteriaceae
  • 1.2.1.4 Pseudomonas aeruginosa
  • 1.2.1.5 Staphylococcus aureus
  • 1.2.1.5.1 Methicillin sensitive
  • 1.2.1.5.2 Methicillin resistant
  • Preferred Regimen : Vancomycin 45-60 mg/kg/day divided q8-12h (max: 2000 mg/dose) for 7-21 days OR Linezolid 600 mg PO/IV q12h for 10-14 days
  • Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
  • 1.2.1.6 Klebsiella pneumonia[2]
  • 1.2.1.6.1 Resistant to third generation cephalosporins and aztreonam
  • 1.2.1.6.2 Klebsiella pneumoniae Carbapenemase producers
  • Preferred regimen (1): Colistin (=Polymyxin E).In USA : Colymycin-M 2.5-5 mg/kg per day of base divided into 2-4 doses 6.7-13.3 mg/kg per day of colistimethate sodium (max 800 mg/day). Elsewhere: Colomycin and Promixin ≤60 kg, 50,000-75,000 IU/kg per day IV in 3 divided doses (=4-6 mg/kg per day of colistimethate sodium). >60 kg, 1-2 mill IU IV tid (= 80-160 mg IV tid) OR Polymyxin B (Poly-Rx) 15,000–25,000 units/kg/day divided q12h
  • Note (1): some strains which hyperproduce extended spectrum beta-lactamase are primarily resistant to Ticarcillin-Clavulanate, Piperacillin-Tazobactam
  • Note (2): Extended spectrum beta-lactamases inactivates all Cephalosporins, beta-lactam/beta-lactamase inhibitor drug activation not predictable; co-resistance to all Fluoroquinolones & often Aminoglycosides.
  • Note (3): Can give IM, but need to combine with “caine” anesthetic due to pain.
  • 1.2.1.7 Moraxella catarrhalis
  • 1.2.1.8 Stenotrophomonas maltophilia
  • 1.2.1.9 Bordetella pertussis
  • 1.2.1.10 Anaerobes (aspiration pneumonia)
  • 1.2.1.11 Mycobacterium tuberculosis
  • 1.2.1.11.1 Intensive phase
  • Preferred Regimen: Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
  • Alternative regimen (1): Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
  • Alternative regimen (2): Isoniazid 5 mg/kg/day q24h 3 times per week for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day 3 times per week for 2 months (maximum: 600 mg / day) s AND Ethambutol 5-25 mg/kg (maximum dose: 1.6 g) 3 times per week for 2 months AND Pyrazinamide 1000 - 2000 mg / day 3 times per week for 2 months.
  • 1.2.1.11.2 Continuation phase
  • Preferred Regimen:Isoniazid 300 mg/day PO daily for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO daily for 4 months (10 mg/kg/day)
  • Alternative regimen (1): Isoniazid 300 mg/day PO 3 times per week for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO 3 times per week for 4 months (10 mg/kg/day)
  • 1.2.1.12 Yersinisa pestis
  • 1.2.1.13 Atypical bacteria
  • 1.2.1.13.1 Mycoplasma pneumoniae
  • 1.2.1.13.2 Chlamydophila pneumoniae
  • 1.2.1.13.3 Legionella spp.
  • 1.2.1.13.4 Chlamydophila psittaci
  • Preferred Regimen: Tetracycline 250-500 mg PO q6h
  • Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
  • 1.2.1.13.5 Coxiella burnetii
  • Preferred Regimen: Tetracycline 250-500 mg PO q6h
  • Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
  • 1.2.1.13.6 Francisella tularensis
  • 1.2.1.13.7 Burkholderia pseudomallei
  • 1.2.1.13.8 Acinetobacter species
  • 1.2.1.14 Gram-positive filamentous bacteria
  • 1.2.1.14.1 Actinomyces spp.[3][4]
  • 1.2.1.14.2.1 Initial intravenous therapy (induction therapy)
  • Preferred regimen: Trimethoprim-Sulfamethoxazole (15 mg/kg/day IV of the trimethoprim component in 2 to 4 divided doses) for at least three to six weeks AND Amikacin (7.5 mg/kg IV q12h) for at least three to six weeks
  • Alternative regimen: Imipenem (500 mg IV q6h) AND Amikacin (7.5 mg/kg IV q12h)
  • Note (1): If the patient is allergic to Sulfonamides, desensitization should be performed when possible.
  • Note (2): If the isolate is susceptible to the third-generation cephalosporins (Ceftriaxone, Cefotaxime), Imipenem can be switched to one of these agents.
  • Note (3): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
  • 1.2.1.14.2.2 Oral maintenence therapy
  • Preferred regimen: A sulfonamide (eg,Trimethoprim-Sulfamethoxazole 10 mg/kg/day of the trimethoprim component in 2 or 3 divided doses) AND / OR Minocycline (100 mg bd) AND / OR Amoxicillin-Clavulanate (875 mg bd)
  • Note (1): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
  • Note (2): The duration of intravenous therapy varies with the patient's immune status. In immunocompromised patients, maximal tolerated doses should be given intravenously for at least six weeks and until clinical improvement has occurred; in contrast, immunocompetent patients may be successfully treated with a shorter duration of intravenous therapy. Following the intravenous induction phase, patients may be stepped down to oral antibiotics based upon susceptibility studies
  • Note (3): Serious pulmonary infection is treated for 6 to 12 months or longer.
  • 1.2.2 Viral pathogens
  • 1.2.2.1 Influenza virus
  • Preferred Regimen: Oseltamivir 75 mg PO q12h for 5 days (initiated within 48 hours of onset of symptoms) OR Zanamivir Two inhalations (10 mg total) q12h for 5 days (Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours)
  • 1.2.2.2 Cytomegalovirus[8]
  • Preferred regimen (1): Ganciclovir Induction therapy 5 mg/ kg IV every 12 h for normal GFR; maintenance therapy 5 mg/kg IV daily; 1 g orally every 8 h with food.
  • Preferred regimen (2): Valganciclovir Induction therapy 900 mg orally every 12 h; maintenance therapy 900 mg daily.
  • Alternative regimen (1): Foscarnet Induction therapy 60 mg/ kg every 8 h for 14–21 days or 90 mg/kg every 12 h for 14–21 days; maintenance therapy 90–120 mg/kg per day as a single infusion.
  • Alternative regimen (2): Cidofovir Induction therapy 5 mg/ kg per week for 2 weeks, followed by maintenance therapy every 2 weeks.
  • 1.2.3 Fungal pathogens
  • 1.2.3.1 Coccidioides species
  • Preferred Regimen: Itraconazole 200 mg q12h OR Fluconazole 200-400 mg daily for 3-6 month
  • Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day
  • Note: No therapy is indicated for uncomplicated infection, treat only if complicated infection
  • 1.2.3.2 Histoplasmosis
  • 1.2.3.3 Blastomycosis

Pharmacotherapies

Aminosalicylates

Sulfasalazine has been a major agent in the therapy of mild to moderate UC for over 50 years. In 1977 Mastan S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA and mesalazine) was the therapeutically active compound in sulfasalazine. Since then many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.[9]

Corticosteroids

Immunosuppressive drugs

Biological treatment

Contraindicated medications

Ulcerative colitis is considered an absolute contraindication to the use of the following medications:

References

  1. American Thoracic Society. Infectious Diseases Society of America (2005). "Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia". Am J Respir Crit Care Med. 171 (4): 388–416. doi:10.1164/rccm.200405-644ST. PMID 15699079.
  2. Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
  3. Song JU, Park HY, Jeon K, Um SW, Kwon OJ, Koh WJ (2010). "Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients". Ann Thorac Med. 5 (2): 80–5. doi:10.4103/1817-1737.62470. PMC 2883202. PMID 20582172.
  4. Sudhakar SS, Ross JJ (2004). "Short-term treatment of actinomycosis: two cases and a review". Clin Infect Dis. 38 (3): 444–7. doi:10.1086/381099. PMID 14727221 PMID: 14727221 Check |pmid= value (help).
  5. Lerner PI (1996). "Nocardiosis". Clin Infect Dis. 22 (6): 891–903, quiz 904-5. PMID 8783685.
  6. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ (2006). "Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy". Clin Microbiol Rev. 19 (2): 259–82. doi:10.1128/CMR.19.2.259-282.2006. PMC 1471991. PMID 16614249.
  7. Brown-Elliott BA, Biehle J, Conville PS, Cohen S, Saubolle M, Sussland D; et al. (2012). "Sulfonamide resistance in isolates of Nocardia spp. from a US multicenter survey". J Clin Microbiol. 50 (3): 670–2. doi:10.1128/JCM.06243-11. PMC 3295118. PMID 22170936.
  8. Torres-Madriz G, Boucher HW (2008). "Immunocompromised hosts: perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients". Clin Infect Dis. 47 (5): 702–11. doi:10.1086/590934. PMID 18652557.
  9. S. Kane (2006). "Asacol - A Review Focusing on Ulcerative Colitis".


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