Antibiotics

In general, antibiotics are only appropriate for septic complications, bacterial overgrowth, post-operative prophylaxis or perianal disease. They are not recommended as a monotherapy to induce or maintain remission in CD.

Active disease

  • Metronidazole can induce a response (fall in CDAI of 66-90 cf. placebo) or even remission (in 25% in one trial) in colonic Crohn’s disease, but not in small bowel disease; although poorly tolerated long term.
  • Ciprofloxacin has similar efficacy in active luminal disease as mesalazine, with response of 40-50% at 6 weeks.
  • Ciprofloxacin with metronidazole can induce remission (in 46% vs. 63% provided steroids; NS).
  • Uncontrolled case series support use of Metronidazole / Ciprofloxacin in perianal disease, though they rarely induce complete healing; exacerbations often occur when discontinued. They are usually used as adjunct to thiopurines and anti-TNF therapy in perianal Crohn’s disease.
  • Peripheral neuropathy limits the long-term use of metronidazole and can persist in some patients. Tendon inflammation and damage can occur due to ciprofloxacin.
  • Anti-mycobacterial therapy is not recommended.
  • National Formulary should be consulted to review adverse drug reactions and drug interactions.
  • There is increasing evidence that rifaximin 800 mg for 12 weeks may be effective in inducing clinical remission in moderately active luminal CD, however it is still not approved for this indication.

Maintaining remission

Evidence for effectiveness of antibiotics, particularly anti-mycobacterial agents, is lacking.

Prevention of post-surgical recurrence

  • Metronidazole 20mg/kg/d for 3 months reduces endoscopic & clinical (NNT = 5.5) recurrence at 12 months, but not at 24 months.
  • Ornidazole 1g/d for 12 months reduces clinical recurrence, at 12 but not 24 months.
  • Poor tolerance of long-term therapy reduces the effectiveness for these therapies to reduce post-operative recurrence.

Stopping therapy

In septic complications and perianal disease, antibiotics can be prolonged up to the resolution of infection. In the post-operative setting, the use of metronidazole can be stopped after 3 months.

Dosing, administration and monitoring

Before treatment

No particular screening is required before administering antibiotics in CD

Dosing

  • Symptomatic perianal fistula:
    • Ciprofloxacin 1000 mg/day (in 2 divided doses)
    • Metronidazole: 750-1500 mg/day (in 2-3 divided doses)
  • For post-operative prophylaxis in CD:
    • Metronidazole 20 mg/kg for 3 months

Follow-up

  • Metronidazole:
    • Warn about alcohol consumption while on metronidazole due to potential disulfiram-like reaction
    • Monitor serum ciclosporin level if administered as concomitant therapy
    • Monitor lithium levels when lithium is prescribed concomitantly
  • Ciprofloxacin:
    • Consider reduced renal tubular transport of methotrexate when co-administered

Red flag interactions

  • Ciprofloxacin should be stopped in case of pain in Achillles tendon
  • Metronidazole should be stopped in case of peripheral neuropathy

Adverse effects

Metronidazole can cause gastrointestinal symptoms such as nausea, vomiting, and stomatitis. In case of prolonged use, reversible leucopenia or peripheral neuropathy may occur.

Ciprofloxacin may cause tendinitis, especially at Achilles tendon, photosensitivity, central or peripheral neuropathy, QT-interval prolongation, and should be carefully used in case of kidney or hepatic failure, or with concomitant drugs metabolized by CYP1A2.

Special situations

Pregnancy

Both ciprofloxacin and metronidazole should be avoided especially in the first trimester, unless absolutely necessary.

Breastfeeding

Both ciprofloxacin and metronidazole should be avoided.

Surgery

No concerns

Paediatrics

No contraindications

Elderly

No contraindications

Metronidazole and ciprofloxacin have been investigated in treating UC. Based on the current evidence, there is no indication to use antibiotics as a therapy for active UC or to maintain remission in UC. The use of antibiotics is the mainstay in acute and chronic pouchitis, although data from large randomized clinical trials are lacking.

Active disease

Antibiotics are used in UC to treat concomitant C. difficile infection, or sepsis in patients with fulminant colitis. They have no role in acute severe UC. Meta-analysis of 9 RCTs in active UC demonstrated benefit for inducing remission (RR not being in remission 0.64; 95% CI=0.43-0.96) but a diverse range of antibiotics were tested with moderate heterogeneity.

Maintaining remission

The role of antibiotics for the treatment of UC flare ups or for maintenance of remission alone or in combination is not well established. One study suggested adjunctive ciprofloxacin 1-1.5 g/d may enhance standard therapy to induce remission, but did not show robust evidence on maintaining remission. Metronidazole 0.6 g/day has been compared to sulfasalazine 2 g/die in a small RCT showing only slight advantage. There is no robust data to support the use of antibiotics for the maintenance of remission in UC.

Acute and chronic pouchitis

Ciprofloxacin and metronidazole may be effective in acute and chronic pouchitis. The combination of ciprofloxacin 1 g/day and tinidazole 15 mg/kg/day for 4 week resulted effective in 87.5% of patients compared to 50% of patients receiving high-dose mesalamine in a small historical cohort.

Stopping therapy

Antibiotics should be stopped as soon as C. difficile infection or sepsis has resolved. In chronic pouchitis, they may be stopped at week 4.

Dosing, administration and monitoring

Before treatment

No particular screening is required before administering antibiotics in UC

Dosing

  • Ciprofloxacin 1000 mg/day (in 2 divided doses)
  • Metronidazole: 750-1500 mg/day (in 2-3 divided doses)

Follow-up

  • Metronidazole:
    • Warn about alcohol consumption while on metronidazole due to potential disulfiram-like reaction
    • Monitor serum ciclosporin level if administered as concomitant therapy
    • Monitor lithium levels when lithium is prescribed concomitantly
  • Ciprofloxacin:
    • Consider reduced renal tubular transport of methotrexate when co-administered

Red flag interactions

  • Ciprofloxacin should be stopped in case of pain in Achillles tendon
  • Metronidazole should be stopped in case of peripheral neuropathy

Adverse effects

Metronidazole can cause gastrointestinal symptoms such as nausea, vomiting, and stomatitis. In case of prolonged use, reversible leucopenia or peripheral neuropathy may occur.

Ciprofloxacin may cause tendinitis, especially at Achilles tendon, photosensitivity, central or peripheral neuropathy, QT-interval prolongation, and should be carefully used in case of kidney or hepatic failure, or with concomitant drugs metabolized by CYP1A2.

Special situations

Pregnancy

Both ciprofloxacin and metronidazole should be avoided especially in the first trimester, unless absolutely necessary.

Breastfeeding

Both ciprofloxacin and metronidazole should be avoided.

Surgery

No concerns

Paediatrics

No contraindications

Elderly

No contraindications

Terms and conditions

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