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Gastrointestinal

Diverticular disease

Last revised in December 2023

Diverticula are sac-like protrusions of mucosa through the muscular wall of the colon, which occur in the sigmoid colon

Diverticular disease: Summary

  • Diverticula are sac-like protrusions of mucosa through the muscular wall of the colon, which occur in the sigmoid colon in about 80% of people over the age of 85. 
    • The majority of people have symptoms in the left lower abdomen. 
    • In a minority of people and in people of Asian origin, symptoms may be right-sided.
    • Diverticulum formation may be associated with a low-fibre diet.
  • Diverticulosis is a condition where diverticula are present without symptoms.
    • It may present with a large, painless rectal bleed, or be found incidentally during investigation for other symptoms.
  • Diverticular disease is a condition where diverticula cause symptoms, such as intermittent lower abdominal pain, without inflammation and infection.
  • Diverticulitis is a condition where diverticula become inflamed and infected, typically causing severe lower abdominal pain, fever, general malaise, change in bowel habit, and occasionally rectal bleeding.
    • 'Uncomplicated' diverticulitis refers to diverticular inflammation that does not extend to the peritoneum.
    • 'Complicated' diverticulitis refers to diverticulitis associated with complications, such as abscess, peritonitis, fistula, obstruction, or perforation.
  • The presence of diverticula is rare before the age of 40 years, and the risk increases with age.
  • If a person has suspected diverticular disease, assessment should include taking a history, performing an abdominal examination, and referring for imaging or endoscopy to confirm the diagnosis.
  • If a person has confirmed diverticulosis, management includes considering offering bulk-forming laxatives for people with constipation, and providing advice about:
    • Eating a healthy, balanced, including increasing fibre intake for people with a low-fibre diet.
    • Ensuring an adequate fluid intake.
    • Exercise, weight loss if they are obese, and stopping smoking. 
  • If a person has confirmed diverticular disease, management includes:
    • Arranging urgent admission if there is significant rectal bleeding.
    • Advising the person to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesia (such as codeine). 
    • Providing advice on diet and lifestyle, fluid intake, stopping smoking, weight loss and exercise, and when to seek medical advice.  
    • Considering offering bulk-forming laxatives, simple analgesia, or an antispasmodic.
    • Reassessing the person if symptoms are persistent or do not respond to treatment.
  • Urgent hospital admission should be arranged for people with acute diverticulitis and uncontrollable pain with any features of complicated acute diverticulitis. 
  • If a person has suspected uncomplicated diverticulitis, management in primary care includes: 
    • Offering an oral antibiotic if they are systemically unwell, immunosuppressed, or have significant comorbidities. 
    • Considering a no antibiotic strategy for people who are systemically well. 
    • Advising on the use of analgesia, and when to re-present if symptoms persist or worsen. 
    • Reassessing the person if symptoms persist or deteriorate, and considering referral to secondary care for further assessment if necessary. 
    • Considering arranging referral to a specialist in colorectal surgery if a person has frequent or severe recurrent episodes of acute diverticulitis.

Have I got the right topic?

From age 18 years onwards.

This CKS topic is largely based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a].  

This CKS topic covers the management of diverticulosis (asymptomatic diverticula), diverticular disease (symptomatic diverticula), and diverticulitis (inflamed or infected diverticula) in adults.

This CKS topic does not cover the management of complications including fistula, abscess, perforation, obstruction, peritonitis, or haemorrhage.

There are separate CKS topics on Constipation and Gastrointestinal tract (lower) cancers - recognition and referral.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

December 2023 — minor update. Information on possible neurological adverse effects of cefalexin added in line with updated SPC.

Previous changes

July 2023 — minor update. The manufacturer's SPC for metronidazole has been updated to note that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

May 2023 — minor update. Added potential adverse effects of co-amoxiclav to include Kounis syndrome (an allergic reaction which can result in myocardial infarction), aseptic meningitis, linear IgA disease (renal deposition of IgA), and drug-induced enterocolitis syndrome (all of unknown frequency). These adverse effects were noted in an update to the manufacturer’s summary of product characteristics.

September 2022 — minor update. The dosage frequency of metronidazole when taken with trimethoprim has been amended.  

December 2021 — reviewed. A literature search was conducted in December 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. 

January 2021 — minor update. The duration of antibiotic treatment for uncomplicated acute diverticulitis has been updated in line with the NICE guideline Diverticular disease: diagnosis and management.

December 2019 — minor update. Topic updated in line with NICE NG147 Diverticular disease: diagnosis and management, 2019.

March 2019 — minor update. Prescribing information for quinolones updated in line with MHRA, 2019, Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects.

January 2019 — minor update. Aortic aneurysm and dissection is now listed as an adverse effect of ciprofloxacin. 

December 2017 — minor update. Advice on intake of fruits containing sorbitol removed. 

September 2017 — minor update. SPC update on quinolones to align all CKS topics prescribing advice. Prostatitis – chronic, Gonorrhoea, Pyelonephritis, Diarrhoea – prevention and advice for travellers, Dyspepsia – unidentified cause, Dyspepsia – proven functional, Dyspepsia – proven peptic ulcer, Diverticular disease, Gastroenteritis and Scrotal pain and swellings. 

July 2017 — reviewed. A literature search was conducted in June 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. Sections on risk factors and prognosis have been added to Background information. The recommendations on assessment and management of suspected acute diverticulitis have been amended in line with current evidence. The Prescribing information section has been updated and expanded.

June 2014 — minor update. Recommendations in prescribing information have been clarified and links amended.

March 2013 — reviewed. A literature search was conducted in November 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to clinical recommendations have been made.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

June 2012 — minor update. Broken link to table fixed.

June 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic. 

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

December 2007 to March 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.

July 2005 — updated to incorporate the Referral guidelines for suspected cancer published by the National Institute for Health and Care Excellence (NICE). Issued in July 2005.

November 2004 — reviewed. Validated in March 2005 and issued in April 2005.

September 2001 — reviewed. Validated in November 2001 and issued in April 2002.

February 1999 — written, replacing guidance on Diverticular disease and Diverticulitis. Validated in April and August 1999.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 December 2021.

HTAs (Health Technology Assessments)

No new HTAs since 1 December 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 December 2021.

Systematic reviews and meta-analyses

No new systematic reviews published since 1 December 2021.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 December 2021.

New policies

No new national policies or guidelines since 1 December 2021.

New safety alerts

No new safety alerts since 1 December 2021.

Changes in product availability

No changes in product availability since 1 December 2021.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a working diagnosis of diverticular disease and diverticulitis.
  • Arrange referral to confirm the diagnosis of diverticular disease if needed.
  • Manage symptoms of diverticular disease and diverticulitis in primary care, where possible and appropriate.
  • Arrange urgent admission for people with acute diverticulitis, if appropriate.
  • Advise on self-management strategies for diverticulosis to reduce the risk of developing diverticular disease and the complications of diverticulitis.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

Antibiotic prescribing

  • Review and, if appropriate, revise local policies that relate to antimicrobial stewardship to ensure these are in line with NICE guidelines on Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use and Antimicrobial stewardship: changing risk-related behaviours in the general population.
  • Optimise current prescribing practice and use implementation techniques to ensure prescribing is in line with NICE antimicrobial prescribing guidelines or the NICE/PHE summary of antimicrobial prescribing guidance – managing common infections, PHE guidance Start smart − then focus, local trust antimicrobial guidelines and the Antimicrobial Stewardship in Primary Care collaboration TARGET antibiotics toolkit.  
  • Promote the Antibiotic Guardian call to action and the Keep Antibiotics Working campaign.

[NICE, 2019b]

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

What is it?

  • Diverticula are sac-like protrusions of mucosa through the muscular wall of the colon. They occur in the sigmoid and descending colons in about 85% of people.
    • About 15% of diverticula are found in the right (ascending) colon, and this is more common in people of Asian origin.
    • The exact cause of diverticulosis and diverticulitis is not known, but diverticulum formation may be associated with a low-fibre diet. This lowers stool bulk, slows transit times, and increases intraluminal pressure. This is theorized to promote herniation of the mucosa through relatively weak areas where the vasa recti penetrate the colonic wall. 
  • Diverticulosis is a condition where diverticula are present without symptoms.
  • Diverticular disease is a condition where diverticula cause symptoms, such as intermittent lower abdominal pain, without inflammation and infection.
  • Diverticulitis is a condition where diverticula become inflamed and may be caused by infection, typically causing severe lower abdominal pain, fever, general malaise, and occasionally rectal bleeding.
    • 'Uncomplicated' diverticulitis refers to diverticular inflammation without symptoms of acute abdomen, or signs of perforation or abscess formation. 
    • 'Complicated' diverticulitis refers to diverticulitis associated with complications, such as abscess, peritonitis, fistula, obstruction, or perforation. 

[Wilkins, 2013; Swanson, 2018; Buchs, 2020; Schultz, 2020; BMJ, 2021; Peery, 2021a; Peery, 2021b]

What are the risk factors?

The exact cause for the development of diverticular disease and diverticulitis is not known, but the following risk factors may be involved:

  • Older age — incidence of diverticulitis increases with age and is most common in people aged over 50-60 years.
  • Genetic —  genes contribute 40-50% of diverticulitis risk. 
    • Monozygotic twins are twice as likely as dizygotic twins to develop diverticulosis [Wilkins, 2013].
  • Low-fibre diet — a lifelong diet deficient in fibre is associated with development of diverticula, and studies indicate that dietary fibre has a protective effect against development of diverticulosis and diverticulitis. However, the role of diet is unclear as there is some evidence that vegetarians with high fibre diets have increased hospital admissions with acute diverticulitis.  
    • A systematic review and meta-analysis found that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake [Aune, 2020].
  • Diet rich in red meat — higher consumption of red meat is associated with an increased risk of diverticulitis, and compared with meat-eaters, a vegetarian diet is associated with reduced risk of hospital admission or death due to diverticular disease. 
  • Smoking — this has been linked to the development of diverticular disease, and is associated with an increased risk of complications.
  • Obesity — in prospective cohort studies, obesity was associated with an increased risk of diverticulitis, complications, recurrence and diverticular bleeding.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), opioids — there is a strong association between NSAIDs and opioid analgesic use and perforation of colonic diverticula. NSAIDs are also associated with diverticular bleeding. 
  • Immunosuppression — people who are immunosuppressed have an increased risk of acute diverticulitis, complicated diverticulitis, and mortality from diverticulitis compared with patients who are immunocompetent.

[Wilkins, 2013; Swanson, 2018; Strate, 2019; Aune, 2020; Buchs, 2020; Schultz, 2020; BMJ, 2021; Miller, 2021; Peery, 2021a] 

How common is it?

  • The precise prevalence of diverticulosis is unknown, as most people are asymptomatic — about 80-85% of people with diverticula remain asymptomatic, about 10-15% develop symptomatic diverticular disease, and the remainder develop diverticulitis [Bugiantella, 2015].
  • The prevalence of diverticulosis and acute diverticulitis is increasing in developed countries [Bugiantella, 2015; Sartelli, 2020], resulting in an increase in hospital admissions for complications — in England, between 1996 and 2006 the incidence of hospital admission for diverticular disease increased from 0.56 to 1.2 per 1000 population per year [Miller, 2021]. 
  • The prevalence of diverticulosis increases with age — 85% of people are aged over 50 years [Miller, 2021].  
    • Diverticulosis occurs in 5–10% of people aged over 45 years, and about 80% of people aged over 85 years [Wilkins, 2013]. 
  • For people with diverticulosis, the lifetime risk of developing acute diverticulitis is about 4% [Sartelli, 2020; Miller, 2021].
    • In people aged over 50 years with diverticulitis, most are women, while in those aged under 50 they are mostly men.
    • The proportion of younger people presenting with acute diverticulitis requiring surgery is increasing — up to 20% of people with acute diverticulitis are aged under 50 years.
  • Around 12% of people with diverticulitis present with complicated disease [Peery, 2021b].

What are the complications?

  • Diverticular haemorrhage occurs in about 15% of people with diverticulosis, diverticular disease, or diverticulitis.
    • Bleeding occurs where the penetrating blood vessels responsible for the bowel wall weakness run over the diverticulum, making them vulnerable to injury. Bleeding is usually abrupt and painless.
    • One-third of bleeds are massive, requiring emergency transfusion; bleeding stops spontaneously in 70–80% of cases.
  • Diverticulitis may also be associated with serious or life-threatening complications, such as:
    • Intra-abdominal abscess formation — for example, pericolic or pelvic abscess.
      • Signs include abdominal mass on examination or peri-rectal fullness on digital rectal examination. 
    • Perforation and peritonitis — perforation of the colonic wall may occur at the site of inflammation, and perforation into the intra-abdominal cavity may cause purulent or faecal peritonitis, leading to sepsis. People with perforation had a 4.5-fold increase in 1-year mortality compared with the general population, in a population-based cohort study.
      • Signs include abdominal rigidity and guarding on examination. 
    • Stricture and fistula formation — most commonly fistulae occur to the bladder, but may be to the vagina, uterus, skin, or another part of the bowel. People with stricture or fistula had a 2.5-fold increase in 1-year mortality compared with the general population, in a population-based cohort study.
      • Signs include faecaluria, pneumaturia, pyuria or the passage of faeces through the vagina. 
    • Intestinal obstruction — from fibrosis and stricture formation following recurrent inflammatory episodes.
      • Signs and symptoms include colicky abdominal pain, absolute constipation (passage of no flatus or stool), vomiting or abdominal distention. 
    • Sepsis — signs and symptoms include altered mental state, raised respiratory rate, low systolic blood pressure, raised heart rate, low tympanic temperature, no urine output or skin discolouration. For more information see the CKS topic on Sepsis. 

[World Gastroenterology Organisation, 2007; Humes, 2012; Bugiantella, 2015; NICE, 2019a; Buchs, 2020; BMJ, 2021; Hanna, 2021]

What is the prognosis?

  • The majority of people with diverticulosis are asymptomatic, however, fewer than 5% will develop diverticulitis [Strate, 2019; Sartelli, 2020]. 
  • Diverticulitis may resolve, become chronic, or progress to complications [Morris, 2014].
  • Most people with uncomplicated diverticulitis recover following medical treatment and do not require surgical intervention [BMJ, 2021].
    • In a trial of people with acute uncomplicated diverticulitis confirmed by computed tomography, the median time to recovery was 14 days [Peery, 2021a]. 
    • Approximately 5% of people will experience smouldering diverticulitis, characterized by abdominal pain and continued evidence of inflammation on computed tomography (CT) scan [Peery, 2021b]. 
  • Diverticulitis recurs in around one third of people following response to medical treatment [BMJ, 2021] — about 50% of recurrences occur within one year of the initial episode, and 90% occur within 5 years [Humes, 2016]. Recurrence is:
    • More common in younger people, in those with an abscess at diagnosis, and after an episode of complicated diverticulitis [Peery, 2021a].
    • Associated with high mortality and a less favourable response to therapy. 
  • After an index episode of diverticulitis, the risk of a second episode is [Peery, 2021a]: 
    • 8% at one year.
    • 17% at five years.
    • 22% at 10 years.
  • About 5% of people with diverticular disease have complications when followed up for 10–30 years [Humes, 2016].
    • The risk of complications, such as peritonitis or perforation, is greater during the first episode of diverticulitis, and the risk reduces with each recurrence [Morris, 2014].
    • People who are immunocompromised have a 5-fold increased risk of recurrence with complications, such as bowel perforation, compared to immunocompetent people [Morris, 2014].
  • Following surgical treatment, approximately 25% of people remain symptomatic [BMJ, 2021]. 

Diagnosis of diverticular disease

When should I suspect diverticular disease?

Consider an alternative cause for symptoms before making a working diagnosis of diverticular disease or diverticulitis.

  • Diverticulosis is asymptomatic and in most people remains undiagnosed.
    • It may present with a large, painless rectal bleed, or be found incidentally during investigation for other symptoms.
  • Suspect diverticular disease if a person presents with one or both of:
    • Intermittent abdominal pain in the left lower quadrant (pain may be triggered by eating and may be relieved by the passage of stool or flatus).
    • Tenderness in the left lower quadrant on abdominal examination.
      • In a minority of people and in people of Asian origin, pain and tenderness may be localized in the right lower quadrant.
  • Other signs and symptoms of diverticular disease include:
    • Bloating, constipation, diarrhoea, nausea.
    • Rectal bleeding.
    • Fever.
    • Dysuria.
  • Suspect acute diverticulitis if a person presents with: 
    • Constant abdominal pain (which is usually severe and starts in the hypogastrium before localizing in the left lower quadrant) with any of the following: 
      • Fever.
      • Sudden change in bowel habit and significant rectal bleeding or passage of mucus from the rectum.
      • Tenderness in the left lower quadrant, a palpable abdominal mass or distention on abdominal examination, with a previous history of diverticulosis or diverticulitis. 
  • Suspect a complication of diverticulitis if the person has uncontrolled abdominal pain and any of the following features:  
    • Abdominal mass on examination or peri-rectal fullness on digital rectal examination — possible intra-abdominal abscess. 
    • Abdominal rigidity, guarding, and rebound tenderness on examination — possible perforation and peritonitis.  
    • Altered mental state, raised respiratory rate, low systolic blood pressure, raised heart rate, low tympanic temperature, no urine output or skin discolouration — possible sepsis. 
    • Faecaluria, pneumaturia, pyuria or passage of faeces through the vagina — possible colovesical fistula.
    • Colicky abdominal pain, absolute constipation (passage of no flatus or stool), vomiting or abdominal distention — intestinal obstruction.

 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a], the British Medical Journal (BMJ) Best Practice guide Diverticular disease [BMJ, 2021], the World Gastroenterology Organisation (WGO) guideline Diverticular disease [World Gastroenterology Organisation, 2007], and expert opinion in narrative reviews Left colon acute diverticulitis: an update on diagnosis, treatment and prevention [Bugiantella, 2015], and Diagnosis and management of acute diverticulitis [Wilkins, 2013].

Bleeding in people with diverticulosis

  • It is estimated that 15% of people with diverticulosis will bleed at some time in their lives. The bleeding is usually abrupt, painless, and large in volume, with 33% being massive, requiring emergency transfusion [World Gastroenterology Organisation, 2007]. 

How should I assess a person with suspected diverticular disease?

  • Take a medical history and ask about: 
    • Symptoms, including:
      • Pain — onset, location, severity, duration, frequency (intermittent, or constant).
      • Any exacerbating factors (for example, eating) or relieving factors (for example, passing a stool or flatus). 
      • Other symptoms — diarrhoea, constipation, bloating, fever, rectal bleeding, nausea, dysuria.
    • Risk factors, including:
      • Age.
      • A history or family history of diverticulosis or diverticulitis. 
      • Lifestyle factors — smoking, diet, exercise. 
      • Medication — for example, nonsteroidal anti-inflammatory drugs (NSAIDs), or corticosteroids. 
    • Previous surgical procedures or colon evaluations. 
    • Comorbidities. 
  • Perform an abdominal examination and check for: 
    • Tenderness on palpation, or an abdominal mass, and observe for guarding in the lower left quadrant.  
  • Other examinations to consider include:
    • A pelvic examination in women — to evaluate possible gynaecological causes of pain. 
    • A digital rectal examination — there may be pelvic tenderness.
  • Arrange referral for imaging or endoscopy, where appropriate, to confirm the diagnosis and exclude other causes. 
    • Specialist investigations may include endoscopy, colonoscopy, or computed tomography (CT) colonography to confirm the presence of diverticula. 
  • Other investigations to consider, depending on the history and examination findings, include:
    • Full blood count. 
    • Faecal occult blood test. 
    • Urea and electrolytes. 
    • Kidney function test. 
    • Urinalysis. 
    • C-reactive protein (CRP). 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a], the British Medical Journal (BMJ) Best Practice guide Diverticular disease [BMJ, 2021], the American Society of Colon and Rectal Surgeons (ASCRS) Clinical practice guidelines for the treatment of left-sided colonic diverticulitis [Hall, 2020], the World Society of Emergency Surgery (WSES) 2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting [Sartelli, 2020], the European Association for Endoscopic Surgery (EAES) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGE) 2018 consensus conference on acute diverticulitis management: evidence‑based recommendations for clinical practice [Francis, 2019], and expert opinion in narrative reviews Diagnosis and management of acute diverticulitis [Wilkins, 2013], In the clinic: acute colonic diverticulitis [Swanson, 2018], Update on the management of sigmoid diverticulitis [Hanna, 2021], and Management of colonic diverticulitis [Peery, 2021a]. 

  • NICE advises that for people in whom diverticular disease is suspected current practice is to confirm the presence of diverticula or exclude other causes (such as cancer) using imaging or endoscopy, and recommends referral if this cannot be arranged from primary care [NICE, 2019a].
Assessment of suspected diverticulitis 
  • NICE recommends that people with complicated acute diverticulitis should be referred for same-day hospital assessment and that they should be offered a full blood count, urea and electrolytes test and C-reactive protein (CRP) test in secondary care. People with raised inflammatory markers, should then be offered a contrast CT scan within 24 hours of hospital admission to confirm diagnosis and help plan management. However, there was insufficient evidence available on diagnostic tests for people who are not referred for same-day hospital assessment to make a recommendation [NICE, 2019a].
  • The WSES guideline advises against a diagnosis of acute left-sided diverticulitis based on clinical examination alone as clinical diagnosis usually lacks accuracy [Sartelli, 2020]. It suggests a complete assessment using clinical history, signs, laboratory inflammation markers, and radiological findings.
  • The BMJ best practice guide recommends that for people with suspected acute diverticulitis investigations should include a full blood count, urea and electrolytes, and CRP, and that a CT scan should be performed in people with raised inflammatory markers, and advises that pelvic tenderness on digital rectal examination is also a helpful sign in people with acute diverticulitis [BMJ, 2021].
  • The European Association for Endoscopic Surgery (EAES) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) 2018 consensus conference on acute diverticulitis management recommendation is that selective imaging should be carried out based on CRP levels (over 50 mg/L) and a prior history of acute diverticulitis [Francis, 2019]. 
  • The Association of Coloproctology of Great Britain and Ireland (ACPGBI) recommends that laboratory tests for people with suspected acute diverticulitis should include a full blood count, renal function, amylase and CRP, as CRP can be used as an indicator of the presence of complications [Miller, 2021].
    • People with CRP >150 mg/L have an increased risk of complicated acute diverticulitis, a CRP >200 mg/L is a strong indicator of perforation.
    • CRP has both diagnostic and prognostic value for people with acute diverticulitis, and a CRP value higher than 150 mg/L is associated with an increased risk of postoperative mortality if surgery is undertaken. 
  • ACPGBI recommends that contrast-enhanced CT imaging should be undertaken in all suspected cases of acute diverticulitis in order to confirm the diagnosis, assess severity, and plan therapy.
    • This is supported by expert opinion in a medical textbook, which states that clinical assessment alone for the diagnosis of diverticulitis (or its complications) is not precise enough and that CT imaging is highly accurate and should be performed [Buchs, 2020].

What else might it be?

Alternative causes of symptoms of diverticular disease and diverticulitis include:

Basis for recommendation

This information is based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a], the British Medical Journal (BMJ) Best Practice guide Diverticular disease [BMJ, 2021], the American Society of Colon and Rectal Surgeons (ASCRS) Clinical practice guidelines for the treatment of left-sided colonic diverticulitis [Hall, 2020], and expert opinion in a chapter on Colonic diverticular disease in a medical textbook [Buchs, 2020], narrative reviews Diagnosis and management of acute diverticulitis [Wilkins, 2013], Update on the management of sigmoid diverticulitis [Hanna, 2021], and Practice parameters for the treatment of sigmoid diverticulitis [Feingold, 2014]. 

Management

Scenario: Diverticulosis

From age 18 years onwards.

How should I manage a person with diverticulosis?

  • Advise people with diverticulosis: 
    • That the condition is asymptomatic and no specific treatments are needed.
    • To eat a healthy balanced diet including whole grains, fruit and vegetables. 
      • There is no need to avoid seeds, nuts, popcorn or fruit skins.
      • If they have constipation and a low-fibre diet, increasing their fibre intake gradually may minimise flatulence and bloating.
      • Public Health England's booklet The Eatwell Guide has patient information on eating a healthy, balanced diet, and The Association of UK Dietitians has useful Food Fact Sheets on Fibre and Fruit and vegetables - how to get five-a-day.
    • To drink adequate fluid if they are increasing their fibre intake, especially if there is a risk of dehydration.
      • The Association of UK Dietitians has a useful Food Fact Sheet on Fluid
    • About the benefits of exercise, and weight loss if they are overweight or obese, and stopping smoking, in reducing the risk of developing acute diverticulitis and symptomatic disease.
    • That routine follow-up is not necessary if there is no progression to symptomatic diverticular disease or diverticulitis.
      • Provide information on symptoms that indicate complications or progression to diverticular disease.
  • Consider offering bulk-forming laxatives for people with constipation.  

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a].

  • NICE recommends that people with diverticulosis should increase their fibre intake if they have a low-fibre diet and constipation, but does not recommend a specific target due to a lack of evidence and because people would not know how to reach this target [NICE, 2019c]. 
    • However, a recent systematic review and meta-analysis found that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake [Aune, 2020].

Scenario: Diverticular disease

From age 18 years onwards.

How should I manage a person with diverticular disease?

  • Arrange urgent admission if a person with confirmed diverticular disease has significant rectal bleeding (for example, if the person is haemodynamically unstable), as urgent blood transfusion may be required. 
  • If a person is symptomatic but does not need admission: 
    • Advise the person to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesia (such as codeine) if possible, due to the potential increased risk of diverticular perforation. 
    • Provide advice on diet and lifestyle, fluid intake, stopping smoking, weight loss and exercise as for people with diverticulosis.  
      • Advise people that the benefits of increasing dietary fibre may take several weeks to achieve, and if tolerated, a high-fibre diet should be maintained for life. 
    • Provide advice on when they should seek medical advice. 
    • Consider offering:
      • Bulk-forming laxatives if a high-fibre diet is unacceptable to the person or it is not tolerated, or if symptoms of constipation or diarrhoea persist. See the section on Bulk-forming laxatives in Prescribing information for more information and the CKS topic on Constipation for more information on the management of constipation in adults.
      • Simple analgesia (for example paracetamol), as needed if the person has ongoing abdominal pain. 
      • An antispasmodic (for example, mebeverine) if the person has abdominal cramping.
    • Do not offer antibiotics. 
  • Reassess the person if symptoms are persistent or do not respond to treatment, consider alternative causes, investigate and manage appropriately. 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a], the Royal College of Surgeons (RCS) commissioning guide Colonic diverticular disease [RCS, 2014], the British Medical Journal (BMJ) Best Practice guide Diverticular disease [BMJ, 2021], the European Society of Coloproctology: guidelines for the management of diverticular disease of the colon [Schultz, 2020], and expert opinion in a chapter on Colonic diverticular disease in a medical textbook [Buchs, 2020].

Increasing dietary fibre
  • NICE and the BMJ Best Practice guide recommend advising people with diverticular disease and low dietary fibre intake to increase dietary fibre as well as fluid intake, that the benefits of increasing dietary fibre may take several weeks to achieve, and if tolerated, a high-fibre diet should be maintained for life [NICE, 2019a; BMJ, 2021]. 
  • The European Society of Coloproctology states that although a high-fibre diet can be recommended for general health purposes, there is little evidence that it can prevent recurrent episodes or persistent symptoms in people with acute diverticulitis [Schultz, 2020].

Scenario: Acute diverticulitis

From age 18 years onwards.

How should I manage a person with acute diverticulitis?

  • Arrange same-day hospital assessment if the person:
    • Has uncontrollable abdominal pain and any features that suggest complicated acute diverticulitis.
    • Is dehydrated or at risk of dehydration and is unable to take or tolerate oral fluids at home. 
    • Is unable to take or tolerate oral antibiotics (if needed) at home. 
    • Is aged over 65 years.
    • Has significant comorbidity or immunosuppression. 
  • Offer an oral antibiotic if the person with acute diverticulitis is systemically unwell, but does not meet the criteria for referral for suspected complicated acute diverticulitis. 
    • Prescribe co-amoxiclav 500/125 mg three times daily for 5 days — if the person is allergic to penicillin, or this is unsuitable, alternatives include cefalexin (500 mg twice or three times daily for 5 days [up to 1 to 1.5 g three or four times daily for severe infection]) plus metronidazole (400 mg three times daily for 5 days), or trimethoprim (200 mg twice daily for 5 days) plus metronidazole (400 mg three times daily for 5 days).
    • See the Prescribing information section for more information.
  • For people with acute diverticulitis who are systemically well: 
    • Consider a no antibiotic prescribing strategy.
    • Offer simple analgesia (for example, paracetamol) — advise the person to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesia (such as codeine) if possible, due to the potential increased risk of diverticular perforation.
    • Advise the person to re-present if symptoms persist or worsen.
  • Provide all people with acute diverticulitis managed in primary care with verbal and written information on: 
    • Diet and lifestyle as for people with diverticulosis and diverticular disease.
    • The course of acute diverticulitis and the likelihood of complicated disease or recurrent episodes — complicated diverticulitis is most often the first presentation of diverticulitis. The risk of complicated diverticulitis decreases with recurrences.
    • Symptoms. 
    • When and how to seek further medical advice. 
    • Possible investigations and treatments. 
    • Risks of interventions and treatments, including antibiotic resistance, and how invasive these are. 
    • The role of surgery and outcomes (postoperative bowel function and symptoms). 
  • Reassess people managed in primary care if symptoms persist or deteriorate, and consider referral to secondary care for further assessment if necessary. 
  • Do not offer an aminosalicylate or antibiotics to prevent recurrent acute diverticulitis. 
  • Consider arranging referral to a specialist in colorectal surgery if a person is managed in primary care and has frequent or severe recurrent episodes of acute diverticulitis.

Specialist investigations and management

Specialist investigations may include:

  • Contrast computed tomography (CT) scan (or non-contrast CT scan) of the abdomen and pelvis to establish the diagnosis, determine the extent and severity of disease, and exclude any complications.
  • Magnetic resonance imaging (MRI) scan. 
  • Ultrasound scan of the abdomen and pelvis.
  • Urgent colonoscopy to establish the diagnosis and treat the source of bleeding if there is diverticular haemorrhage. 
  • Planned colonoscopy or CT colonography in selected patients after resolution of acute complicated diverticulitis symptoms, to exclude alternative diagnoses such as inflammatory bowel disease, ischaemic colitis, or colorectal cancer. 

Specialist management may include:

  • Intravenous antibiotics, fluid replacement, and analgesia.
  • Urgent surgery for people with acute complicated diverticulitis (for example with peritonitis and sepsis), and for people who do not improve with medical treatment. Surgical options include:
    • Percutaneous drainage of large abscesses. 
    • Laparoscopic lavage. 
    • Simple colostomy formation.
    • Sigmoid resection with colostomy (Hartmann's procedure). 
    • Sigmoid resection with primary anastomosis with or without a diverting stoma. 
  • Elective surgery may be considered for people with recurrent complicated diverticulitis (for example stricture or fistula formation) or immunocompromised people at high risk of complications.

[Wilkins, 2013; Strate, 2015; NICE, 2019a; Sartelli, 2020; BMJ, 2021; Peery, 2021a]

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a], the Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery [Miller, 2021], the American Gastroenterological Association (AGA) Clinical practice update on medical management of colonic diverticulitis: expert review [Peery, 2021b], the World Society of Emergency Surgery (WSES) guideline 2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting [Sartelli, 2020], and the European Society of Coloproctology: guidelines for the management of diverticular disease of the colon [Schultz, 2020].

Admission
  • The recommendations on when to consider admission are based on national guidelines [NICE, 2019a; Miller, 2021; Peery, 2021a; Sartelli, 2020] and what CKS considers good medical practice. 
    • The NICE guideline does not provide a specific recommendation on admission of people who are immunosuppressed or who have significant comorbidity, but recommends offering an antibiotic prescribing strategy to these people and people with acute diverticulitis who are systemically unwell. It also recommends offering oral antibiotics if the person with acute diverticulitis is systemically unwell but does not meet the criteria for referral for suspected complicated acute diverticulitis [NICE, 2019a]. 
    • The AGA advises that people who are immunocompromised are more likely to present with severe or complicated disease, and that there should be a low threshold for cross-sectional imaging, antibiotic treatment, and consultation with a colorectal surgeon [Peery, 2021b]. 
    • The ACPGBI recommends that people with risk factors for failure of outpatient management of acute diverticulitis should be admitted to hospital, including people aged over 65 years, and those with significant comorbidities or immunosuppression [Miller, 2021]. 
    • The WSES guideline also recommends that people who are immunocompromised should be considered at high risk for failure of standard non-operative treatment, and advises that most will require urgent surgical intervention [Sartelli, 2020].
Antibiotic choice
  • The recommendations for antibiotic treatment are based on the NICE guideline. NICE advises that oral ciprofloxacin may also be used as a first-line option in combination with metronidazole, but only if switching from IV ciprofloxacin with specialist advice and if safety issues are considered [NICE, 2019a].
Clear liquid diet 
  • Some experts advise a clear liquid diet until symptoms begin to improve and then introducing a low fibre diet until symptoms resolve [Swanson, 2018], however, NICE found no evidence to support the intervention of bowel rest (clear fluids only) [NICE, 2019a; NICE, 2019d].
    • The European Society of Coloproctology also advises that there is no evidence to support dietary restrictions for people with acute diverticulitis and an unrestricted diet (when tolerated) is preferable [Schultz, 2020].
  • The AGA recommends advising people to consume a clear liquid diet during the acute phase of uncomplicated diverticulitis, as while a small study suggested that a liquid diet is not necessary in the acute phase of diverticulitis, many patients report greater comfort on a clear liquid diet [Peery, 2021b].
  • BMJ best practice guide recommends advising people to consume a low-residue diet consisting of foodstuffs that leave a minimal residue after digestion and absorption in the gut (such as refined bread, cereals, white rice, vegetable and fruit juice without pulp, dairy products) [BMJ, 2021].
Investigations 
  • NICE recommends that people with complicated acute diverticulitis should be referred for same-day hospital assessment and that they should be offered a full blood count, urea and electrolytes test and C-reactive protein (CRP) test in secondary care. People with raised inflammatory markers should then be offered a contrast CT scan within 24 hours of hospital admission to confirm diagnosis and help plan management [NICE, 2019a].
    • However, there was insufficient evidence available on diagnostic tests for people who are not referred for same-day hospital assessment to make a recommendation. 
  • The BMJ best practice guide recommends that for people with suspected acute diverticulitis investigations should include a full blood count, urea and electrolytes, and CRP, and that a CT scan should be performed in people with raised inflammatory markers [BMJ, 2021].
  • Expert opinion from the European Association for Endoscopic Surgery (EAES) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) 2018 consensus conference on acute diverticulitis management is that selective imaging should be carried out based on CRP levels (over 50 mg/L) and a prior history of acute diverticulitis [Francis, 2019]. 
  • The Association of Coloproctology of Great Britain and Ireland (ACPGBI) recommends that laboratory tests for people with suspected acute diverticulitis should include a full blood count, renal function, amylase and CRP, as CRP can be used as an indicator of the presence of complications [Miller, 2021].
    • People with CRP >150 mg/L have an increased risk of complicated acute diverticulitis, a CRP >200 mg/L is a strong indicator of perforation.
    • CRP has both diagnostic and prognostic value for people with acute diverticulitis, and a CRP value higher than 150 mg/L is associated with an increased risk of postoperative mortality if surgery is undertaken. 
  • ACPGBI also recommends that contrast-enhanced CT imaging should be undertaken in all suspected cases of acute diverticulitis in order to confirm the diagnosis, assess severity, and plan therapy.
    • This is supported by expert opinion in a medical textbook, which states that clinical assessment alone for the diagnosis of diverticulitis (or its complications) is not precise enough and that CT imaging is highly accurate and should be performed [Buchs, 2020].
  • The European Society of Coloproctology states that imaging is required to confirm the diagnosis of acute diverticulitis if there is no prior diagnostic information, and that successive presentations may require CT scan to confirm the diagnosis, but as the course of acute uncomplicated diverticulitis even with small abscesses is benign, and severe complications are rare with low C-reactive protein levels, an observational strategy without imaging may be adequate in mild cases, especially in frequent recurrent disease. It advises that if no imaging is obtained, elective endoscopic examination, if not recently done, may be helpful for differential diagnosis [Schultz, 2020]. 
Reassessment
  • NICE advises that people with uncomplicated diverticulitis who are managed in primary care should be reassessed if their symptoms persist or worsen, but does not recommend routine review [NICE, 2019a].
  • The WSES guideline recommends that people with uncomplicated acute diverticulitis managed in an outpatient setting should be reassessed within 7 days, or earlier if symptoms deteriorate [Sartelli, 2020], and some experts advise follow-up in 2 to 3 days [Wilkins, 2013]. 
  • The BMJ best practice guide recommends that people with uncomplicated diverticulitis treated with antibiotics should be reviewed after 5 days [BMJ, 2021].  
  • CKS considers that the decision on when to reassess people with acute diverticulitis managed in primary care should be based on clinical judgement.   
Recurrence
  • There was insufficient evidence for NICE to make a recommendation on management of people with recurrent diverticular disease [NICE, 2019a].
  • The recommendation to consider referring people with recurrent diverticulitis is based on the RCS commissioning guide [RCS, 2014], and is pragmatic, based on what CKS considers to be good medical practice.
    • The decision as to when to offer elective resection for a patient with recurrent (two or more) episodes of diverticulitis is dependent on a number of factors. A single blanket recommendation is not appropriate and the decision as to whether or not to offer surgery in this group of patients should be made on an individual patient basis.
  • Expert opinion in a narrative review is that people with recurrent diverticulitis presenting with mild, typical manifestations can be managed conservatively [Swanson, 2018].

 

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF).

Bulk-forming laxatives

For detailed information on prescribing bulk-forming laxatives, see the Prescribing information section in the CKS topic on Constipation.

Cefalexin

Cautions and contraindications

  • Do not prescribe cefalexin in people with:
    • A known allergy to the cephalosporin group of antibiotics or a history of immediate hypersensitivity to penicillin and other beta-lactams.
  • Prescribe cefalexin with caution in people with:
    • Sensitivity to penicillin and other beta-lactams — up to 10% of penicillin-sensitive people will also be allergic to first and early second-generation cephalosporins and 2-3% for third-generation cephalosporins. 

[ABPI, 2021a; Joint Formulary Committee, 2021]

Adverse effects

  • Gastrointestinal — diarrhoea (most common), nausea, vomiting, abdominal discomfort.
  • Nervous system — headache, dizziness.
    • Tremor, myoclonia, convulsions, encephalopathy have also been reported — most cases occurred in patients with renal impairment on doses above the recommended maximum and resolved following discontinuation. 
  • Psychiatric — hallucinations, confusion, agitation.
  • Skin – rash urticaria, angioedema.
    • Rarely: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (exanthematic necrolysis)
  • Other adverse effects include: 
    • Anaphylaxis.
    • Arthralgia and myalgia.
    • Eosinophilia, neutropenia, thrombocytopenia, haemolytic anaemia. 
    • Genital and anal pruritus.
    • Hepatitis, cholestatic jaundice.
    • Interstitial nephritis (rarely).
    • Pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated.

[ABPI, 2021a; Joint Formulary Committee, 2021]

Drug interactions

  • Aminoglycosides (for example, gentamicin) — possible increased risk of nephrotoxicity. Routine renal monitoring for the aminoglycoside is usually adequate.
  • Oral anticoagulants (warfarin and phenindione) — cefalexin may enhance the anticoagulant effect. Monitor the international normalized ratio (INR) closely during concomitant use. 
  • Probenecid — renal excretion of cefalexin is inhibited. However, no dose adjustment is normally required.

[Preston, 2021]

Pregnancy and breastfeeding

Pregnancy

  • Cefalexin is not known to be harmful in pregnancy, however the manufacturer advises caution.

Breastfeeding

  • Cefalexin is present in small amounts in breastmilk, but may be appropriate to use.
  • The manufacturer advises caution should be exercised, since the neonate is presented with the risk of candidiasis and CNS toxicity due to immaturity of the blood-brain barrier.

[ABPI, 2021a; Joint Formulary Committee, 2021]

Co-amoxiclav

Contraindications and cautions

  • Do not prescribe co-amoxiclav to people with:
    • A true penicillin allergy — gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
    • A history of co-amoxiclav- or penicillin-associated jaundice or hepatic dysfunction.
  • Prescribe co-amoxiclav with caution to people with:
    • A hypersensitivity to cephalosporins.
    • Hepatic impairment.
    • Chronic kidney disease (CKD) — reduce the dose if the estimated glomerular filtration rate (eGFR) is 30 mL/minute/1.73 m2 or less.
    • Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection — increased risk of erythematous rashes.

[EMC, 2024; Joint Formulary Committee, 2021]

Adverse effects

  • Gastrointestinal — diarrhoea (very common), nausea and vomiting (common), drug-induced enterocolitis syndrome (unknown frequency).
    • Very rarely: antibiotic-associated colitis.
  • Nervous system — headache, dizziness (uncommon), aseptic meningitis (unknown frequency).
  • Skin — skin rash, urticaria, pruritus (uncommon), drug reaction with eosinophilia and systemic symptoms (DRESS) (unknown frequency).
    • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalized exanthematous pustulosis.
  • Other rare, or very rare adverse effects include:
    • Hepatitis, cholestatic jaundice.
    • Hyperactivity, convulsions.
    • Hypersensitivity reactions (serious and occasionally fatal).  
    • Interstitial nephritis.
    • Linear IgA disease (renal deposition of IgA).  
    • Leucopenia, thrombocytopenia, haemolytic anaemia.
    • Kounis syndrome (an allergic reaction which can cause myocardial infarction). 

[BNF, 2023; ABPI, 2023]

Drug interactions

Possible drug interactions with co-amoxiclav include:

  • Allopurinol — be aware that concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes. However, concurrent use does not need to be avoided.
  • Aminoglycosides — levels may be reduced with concurrent use in people with severe renal impairment. Monitor levels closely.
  • Anticoagulants (for example warfarin) — isolated cases of increased prothrombin time. Monitor coagulation status within 3 days of starting or stopping co-amoxiclav.
  • Methotrexate — penicillins may reduce the excretion of methotrexate. Serious interactions are uncommon (people on low doses of methotrexate have been affected). For people on high doses, routine monitoring (in line with local protocols) will identify any decreases in elimination. For people on low does, consult national guidelines and protocols.
  •  

[Preston, 2021]

Pregnancy and breastfeeding

Pregnancy

  • Co-amoxiclav is not known to be harmful in pregnancy, but the manufacturer advises that it should be avoided unless considered essential.

Breastfeeding

  • Trace amounts of co-amoxiclav are found in breastmilk, but it is appropriate to use.
    • Monitor infant for gastrointestinal disturbances and oral candida infection, especially if used for prolonged periods or in high doses, although these effects are unlikely to occur.
  • The manufacturer advises that co-amoxiclav should only be used during breastfeeding after a benefit/risk assessment.

[SPS, 2020; EMC, 2024; Joint Formulary Committee, 2021] 

Metronidazole

Contraindications and cautions

  • Prescribe metronidazole with caution to people with:
    • Active or chronic severe peripheral and central nervous system disease, as there is a risk of neurological aggravation.
    • Cockayne syndrome — cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use (oral and suppositories).
      • It should only be used after careful benefit/risk assessment and only if no alternative treatment is available. Specialist advice should therefore be sought before prescribing metronidazole. 
    • Hepatic encephalopathy, due to substantial impairment of metronidazole clearance, which may contribute to symptoms of encephalopathy. Prescribe one-third of the daily dosage once daily.
    • Alcohol dependency — there may be a disulfiram-like reaction (flushing, increased respiratory rate, increased pulse rate, nausea, headache, and dizziness) if taken with alcohol.

[ABPI, 2021b; Joint Formulary Committee, 2021]

Adverse effects

Adverse effects of metronidazole include:  

  • Blood disorders — agranulocytosis, neutropenia, thrombocytopenia, pancytopenia (very rare).
  • Eye — transient diplopia, or myopia (very rare).
  • Gastrointestinal — nausea, vomiting, diarrhoea, epigastric pain, taste disturbances, furred tongue, oral mucositis (unknown frequency).
  • Nervous system — drowsiness, dizziness, convulsions, headaches, encephalopathy (very rare).
  • Psychiatric — confusion, hallucinations (very rare).
  • Skin — rash, pruritus, flushing, erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, fixed drug eruption (very rare).
  • Other possible adverse effects include: 
    • Anorexia.
    • Myalgia, arthralgia.
    • Darkening of urine.
    • Hearing impairment, tinnitus.
    • Liver enzyme increases, jaundice, pancreatitis.

[ABPI, 2021b; Joint Formulary Committee, 2021]

Drug interactions

Drug interactions associated with metronidazole include:

  • Alcohol — some people taking metronidazole experience a disulfiram-like reaction with alcohol.
    • Warn the person that they might experience this reaction if they drink alcohol whilst on metronidazole and for at least 48 hours afterwards. Reactions of this kind are generally more unpleasant than serious.
  • Anticoagulants — the anticoagulant effects of warfarin can be markedly increased by metronidazole. 
    • Monitor the international normalized ratio (INR) and adjust the warfarin dose accordingly. 
  • Busulfan — plasma levels of busulfan may be increased leading to toxicity. Avoid high doses of busulfan. If conventional doses of busulfan are given, monitor blood count weekly.
  • Ergometrine — metronidazole is predicted to increase the exposure to ergot derivatives, which might lead to ergotism. If concurrent use is unavoidable, be alert for symptoms of ergotism (such as coldness, numbness, or tingling of the hands and feet), and strongly advise patients not to take any further doses and to seek medical advice.
  • 5-fluorouracil — the toxicity of fluorouracil, but not its efficacy, is increased by metronidazole. Monitor the person for increased toxicity. 
  • Lithium — seek specialist advice regarding the use of metronidazole with lithium, as metronidazole increases the risk of lithium toxicity. Lithium dose reduction may be required due to the risk of renal damage with concurrent use. Plasma concentrations of lithium, creatinine, and electrolytes should be monitored if metronidazole and lithium are used simultaneously.
  • Phenobarbital — metabolism of metronidazole is increased significantly. Monitor concurrent use as the dose of metronidazole may need to be increased.
  • Phenytoin — metronidazole possibly inhibits the metabolism of phenytoin, leading to increased plasma concentrations. Monitor concurrent use.The manufacturers SPC also notes that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

[Preston, 2021; EMC, 2023]

 

Pregnancy and breastfeeding

Pregnancy

  • There is inadequate evidence of the safety of metronidazole in pregnancy but it has been in wide use for many years without apparent ill consequence.
  • The manufacturer advises that it should only be used if the benefit outweighs the risks and advises against short, high dose regimens.

Breastfeeding

  • Significant amounts of metronidazole are excreted in breast milk, however breastfed infants receive metronidazole in doses that are less than those used to treat infections in infants, although the active metabolite adds to the total infant exposure.
  • The manufacturer advises against the use of short, high-dose regimens.

[ABPI, 2021b; Joint Formulary Committee, 2021; LactMed, 2021]

Trimethoprim

Cautions and contraindications

  • Do not prescribe trimethoprim in:
    • People with severe hepatic insufficiency, or severe renal insufficiency.
    • People with megaloblastic anaemia or other blood dyscrasias.
  • Prescribe trimethoprim with caution in the elderly and people:
    • With impaired renal function.
    • At risk of hyperkalaemia — monitor serum electrolytes closely.
    • With acute porphyria.
    • Predisposed to folate deficiency.

[ABPI, 2020; Joint Formulary Committee, 2021]

Adverse effects

  • Blood disorders — leucopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, hyperkalaemia (particularly in the elderly and in HIV patients), methaemoglobinaemia.
  • Gastrointestinal — nausea, diarrhoea, vomiting (common).
  • Nervous system — headache (common), tremor, ataxia, lethargy, aseptic meningitis (very rare).
  • Psychiatric — depression, hallucinations, confusional states, agitation, anxiety (very rare).
  • Skin — skin rashes, urticaria (common).
    • Rarely: photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodusum, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura, angioedema.
  • Other adverse effects include:
    • Anaphylaxis.
    • Cough.
    • Liver enzyme disturbances, cholestatic jaundice.
    • Myalgia.
    • Impaired renal function. 
    • Uveitis.

[ABPI, 2020; Joint Formulary Committee, 2021]

Drug interactions

  • Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists (AIIRAs) — there may be an increased risk of hyperkalaemia with the concurrent use of these drugs and trimethoprim. Monitor potassium concentrations.  Avoid, where possible, in elderly people with or without chronic renal impairment.
  • Azathioprine and mercaptopurine — increased risk of haematological toxicity in people who have had a renal transplant. However, the combination is commonly used in practice. Monitor the full blood count routinely.
  • Ciclosporin — serum creatinine levels may be increased. Possible increased risk of nephrotoxicity. Monitor ciclosporin concentrations more closely if trimethoprim started.
  • Clozapine — both drugs can cause blood dyscrasias. Concurrent use is contraindicated. 
  • Coumarins (warfarin) — the anticoagulant effect of coumarins may be potentiated. Monitor international normalised ratio (INR) and adjust dose accordingly.
  • Digoxin — digoxin levels may be increased, particularly in the elderly. Monitor for digoxin adverse effects, and adjust dose if necessary.
  • Diuretics — hyperkalaemia may be exacerbated by concomitant administration of diuretics, particularly potassium-sparing diuretics and/or thiazide diuretics and eplerenone.
  • Methotrexate (a folate antagonist) — there is an increased risk of haematologic adverse effects. Several cases of bone marrow suppression have been reported (some fatal). Full blood count should be monitored routinely.
  • Phenytoin — phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust dose accordingly.

[Preston, 2021]

Pregnancy and breastfeeding

  • Pregnancy
    • There is a teratogenic risk in the first trimester of pregnancy. The manufacturer advises that it is contraindicated in women who are pregnant.
    • Where possible first-trimester use of trimethoprim should be avoided, particularly in people at risk of folic acid deficiency or those taking other folate antagonists [UKTIS, 2019].
      • If trimethoprim is indicated during the first trimester, concomitant folate supplementation (folic acid 5 mg) is recommended. 
  • Breastfeeding
    • Trimethoprim is excreted in breastmilk, but is not known to be harmful.

[ABPI, 2020; Joint Formulary Committee, 2021] 

Supporting evidence

This CKS topic is largely based on the National Institute for Health and Care Excellence (NICE) guideline Diverticular disease: diagnosis and management [NICE, 2019a]. The rationale for the individual recommendations is discussed in the relevant basis for recommendation sections.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of diverticular disease.

Search dates

July 2017 - December 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

  • exp Diverticular diseases/

  • (diverticular disease or (diverticulosis or diverticulitis or diverticula)).ti,ab.

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

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Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

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