Diverticulitis

Diverticular disease (diverticulosis, diverticulitis) is a general term that references the presence of diverticula, small pouches in the large intestinal (colonic) wall. These outpouchings arise when the inner layers of the colon push through weaknesses in the outer muscular layers.[1] Notably, diverticulosis can occur anywhere in the colon, but it is most common in the left colon (descending or sigmoid colon).

The cause of diverticulosis is unclear, but it has been associated with increased pressure from constipation or increasing abdominal girth in obesity. The classic high-fat and low-fiber diet of the Western culture may be a major contributor to the development of diverticulosis. The low-fiber diet is thought to predispose to diverticulosis owing to a slower fecal transit time and smaller stool weight. The highest prevalence of diverticular disease is in North America, where approximately 50% of the older adult population has diverticulosis, as compared to a 0.5% prevalence in the developing nations of Africa and Asia.[10]

Diverticular disease can be asymptomatic (diverticulosis) or involve acute or chronic, symptomatic inflammation of these pouches (diverticulitis). Although diverticulitis has been generally considered a disease of older adults, as many as 20% of patients with diverticulitis are younger than 50 years. In its chronic form, patients may have recurrent bouts of low-grade or overt diverticulitis.

For patient education resources, see Digestive Disorders Center, as well Diverticulitis (Diverticulosis) Symptoms and Diet and Abdominal Pain (Adults).

A diverticulum is a mucosal protrusion through the intestinal wall that occurs along natural areas of weakness. In the large intestine, there is only one complete muscular layer, the inner circular layer, whereas the small intestine and rectum have two muscular layers. The outer longitudinal muscular layer of the large intestine is arranged in three ribbons, the taeniae coli. Diverticula typically occur at sites where the vasa recta, or nutrient vessels in the wall of the colon, penetrate the circular layer, between the taeniae.[11]

Diverticula typically develop in rows along the mesenteric side of the antimesenteric taeniae coli; rarely, they penetrate through the taeniae. It is presumed that the diverticula occur along the mesentery due to the larger caliber of vessels producing a larger area of weakness in the circular muscle layer. As individuals age, the colonic wall collagen develops more cross-linking, leading to decreased elasticity and an increased risk of mucosal herniation. Thus, the stiffer colonic wall is more prone to submucosal tears, which, in turn, can contribute to herniation.[12]

Because the taeniae are shorter than the length of the colon, the colon develops saclike folds, the haustra.[13] As partially digested food, water, and digestive enzymes enter the large intestine in the form of chyme, colonic movement is triggered in the form of segmentation. Segmentation contractions occur as a result of the circular muscle layer, which results in slow mixing. This contrasts with peristalsis of the intestinal longitudinal muscles, which cause forward (caudal) progression of the luminal contents. It has been thought that the waves of high intestinal pressure during segmentation lead to muscular atrophy and herniation of the colon wall, which, in turn, form diverticula. This process may also explain why diverticulosis is more commonly found in the sigmoid colon, which has the smallest caliber and therefore receives the highest pressures in the large intestine.

Dietary habits may also be a significant contributing factor in the development of diverticulosis,[11] particularly given the global geographic distribution of this condition. Slow colonic transit time, heavy stool weight, and decreasing stool frequency (constipation) may contribute to diverticulum formation.[10] Studies to determine which dietary components have the largest effect on stool habits have shown that the standard Western diet (eg, high red meat content, low fiber, refined sugar) has a strong association with the incidence of diverticulosis. However, causation remains to be proven.

True diverticula contain all the layers of the gastrointestinal wall (mucosa, muscularis propria, and adventitia) (eg, Meckel diverticulum). False diverticula, or pseudo-diverticula do not contain the muscular layers or adventitia, only involving the submucosa and mucosa. Diverticula can occur anywhere in the gastrointestinal tract but are usually observed in the colon. As noted earlier, the sigmoid colon has the highest intraluminal pressures and is the most commonly affected site.

Diverticula found in the left colon (predominantly in the sigmoid) are usually false diverticula, and they are often seen in Western populations. Right-sided and cecal diverticula, however, are more frequently true diverticula; these are usually seen in people of Asian descent. Cecal diverticula are generally rare compared to those found in the left colon.[14]

Diverticulitis is defined as an inflammation of one or more diverticula. Its pathogenesis remains unclear. Fecal material or undigested food particles may collect in a diverticulum, causing obstruction. This obstruction may result in distention of the diverticula secondary to mucous secretion and overgrowth of normal colonic bacteria. Vascular compromise and subsequent microperforation or macroperforation then ensue. Alternatively, some investigators believe that increased intraluminal pressure[15] or inspissated food particles cause erosion of the diverticular wall, resulting in inflammation, focal necrosis, and perforation. Diverticulitis is frequently mild when pericolic fat and mesentery wall off a small perforation. However, larger perforations and more extensive disease lead to abscess formation and, rarely, intestinal rupture or peritonitis.

It has been postulated that diverticulitis may also result from alterations in immune responses and in the intestinal bacteria, or gut microbiome.[16] As small tears develop in the colon and become inflamed/infected, diverticulitis results. The microbiome is a prominent area of focus in current research. Investigators hope to isolate and grow bacteria from stool samples of individuals with asymptomatic diverticulosis and those with acute diverticulitis. Should these bacterial populations statistically differ, it may help clinicians to understand which patients are at a greater risk of developing diverticulitis. It may also allow the treatment of such changes in microbiota and the prevention of complicated disease.

Fistula formation is a complication of diverticulitis. Fistulas to adjacent organs and the skin may develop, especially in the presence of an abscess. In men, colovesicular fistulas are the most common. In women, the uterus is interposed between the colon and the bladder, and this complication of fistula formation is only seen following a hysterectomy. The uterus precludes fistula formation from the sigmoid colon to the urinary bladder. However, colovaginal and colocutaneous fistulas can form, albeit uncommonly.

Recurrent attacks of diverticulitis can result in the formation of scar tissue, leading to narrowing and obstruction of the colonic lumen.

United States data

Acute diverticulitis is the third most common inpatient gastrointestinal diagnosis in the United States, at an annual cost of $2.1 billion, and it is the most frequently listed gastrointestinal diagnosis in outpatient clinics and the emergency department.[5]

The prevalence of diverticulosis has been shown to be age dependent and ranges from less than 20% at age 40 years to 60% by age 60 years.[2] The prevalence of diverticulitis has been rising over the past several decades, affecting an estimated 180/100,000 persons per year.[17] ​

Previously, it was believed that around 15%-20% of patients with diverticulosis would develop diverticulitis; however, more recent findings have shown the numbers to be closer to 1%-4%.[18] Of those with incident disease, approximately 20% have one or more recurrent episodes within 10 years.[2]

Diverticulitis is also a leading indication for elective colectomy. This condition affects patients' quality of life beyond the period of acute illness.

International data

Diverticular disease occurs more frequently in Western countries but continues to increase worldwide. Why diverticular disease is less common in underdeveloped countries is unclear, but it is presumably secondary to lifestyle and dietary factors. For example, the prevalence of diverticulosis increased in Japan after its population adopted a more Western lifestyle.[19]

Diverticulitis involving the left colon typically affects false diverticula, which are also usually found in Western populations. Right-sided and cecal diverticulitis (involving true diverticula) are more prevalent in the Asian population, accounting for up to 75% of cases of diverticulitis in this group.[20]

Age- and sex-related demographics

The incidence of diverticular disease increases with age (>65% in those >85 years). Most patients with diverticulitis are older than 50 years; the mean age at presentation appears to be about 60 years. However, diverticulitis is increasingly being seen in younger persons.

Although a male preponderance was noted in early series, subsequent studies have suggested either an equal sex distribution or a female preponderance.[2]

In those younger than 50 years, diverticulitis is more common in men; a slight female preponderance exists between the ages of 50 and 70 years, and there is a marked female preponderance in those older than 70 years.[21]

The prognosis in patients with diverticulitis depends on the severity of the illness, the presence of complications, and the presence of any coexisting medical problems. Younger patients with diverticulitis may have more severe disease, possibly due to a delay in the diagnosis and treatment. Immunosuppressed patients have significantly higher morbidity and mortality due to sigmoid diverticulitis.[22]

Morbidity/mortality

Of the patients who have diverticulosis, 80%-85% remain asymptomatic. Approximately 5% develop diverticulitis; 15%-25% of those with diverticulitis develop complications that lead to surgical intervention. These complications include abscess formation, intestinal rupture, peritonitis, and fistula formation.

Diverticulitis may be a more severe illness in those who are immunocompromised, who have significant comorbid conditions, and in those taking anti-inflammatory medications. Note the following:

• After a first occurrence of acute diverticulitis, the 5-year recurrence rate is 20%.[23]

• Patients with diverticulitis who are managed conservatively (ie, do not undergo surgery) have a recurrence rate of 20%-35%.

• In a study of 252 patients, a 47% recurrence rate was reported after 7 years.[24] The rate of surgery in these patients was 8% at 7 years and rose to 14% by 13 years. Recurrence after surgical resection ranged from 1% to 3%. The mortality from complications in patients with recurrent disease in the study was 1%.

• Another study of 337 patients hospitalized for complicated diverticulitis revealed an association of perforation and mortality in those without a prior history of diverticulitis.[25] Of those patients with complicated diverticulitis, 53% presented with a first event.

• These morbidity and mortality data, as well as the recurrence rates, are based on a retrospective review of relatively short-term data.

Many studies have demonstrated the significant association between obesity and the risk of developing diverticulitis. In a large prospective study of 47,228 male health professionals, men with a body mass index (BMI) of at least 30 kg/m2 had a higher relative risk of 1.78 for diverticulitis compared to men with a BMI of less than 21 kg/m2, after adjustment for other risk factors.[26]

Complications

Complications of diverticulitis may be more severe in immunocompromised patients (those infected with human immunodeficiency virus (HIV), organ transplant recipients, those on long-term corticosteroids). These patients are more likely to have perforation.[27]

Complications of diverticulitis include the following:

• Abscess: Most common complication of diverticulitis

• Intestinal fistula, perforation, or obstruction

• Generalized peritonitis

• Sepsis

• Stricture disease

Abscess

Abscesses amenable to percutaneous drainage are larger than 4 cm.[28] Abscesses not amenable to percutaneous drainage are either too small (< 3 cm) or they are adjacent to important structures.[28] Patients who do not improve within 24 to 48 hours after drainage should be referred for surgery.

Patients with abscesses successfully treated with antibiotics or are percutaneously drained should also be referred for elective surgery because of a high rate of recurrence in this population.[27]

Perforation

Frank perforation is diagnosed by the presence of free air under the diaphragm, with or without extravasation of contrast medium or fluid, which can be complicated with life-threatening diffuse peritonitis.

Microperforation (or contained perforation) is only evident by the presence of air bubbles outside of the bowel wall on computed tomography (CT) imaging.

Obstruction

Surgical resection of the involved bowel segment is mandatory to rule out cancer.

Fistula

Diverticular fistulas rarely close spontaneously, and a resection of the affected bowel segment is generally required.

The clinical presentation of diverticulitis, in which diverticula become inflamed or infected, depends on the location of the affected diverticulum, the severity of the inflammatory process, and the presence of complications. Left lower quadrant pain is the most common presenting complaint and occurs in 70% of patients. The pain is often described as crampy and may be associated with a change in the bowel habit. Right-sided diverticulitis of the cecum or ascending colon may present with right lower quadrant pain, which may be confused for acute appendicitis. Even in simple, uncomplicated cases, patients may have fever and/or leukocytosis (an elevated white blood cell count). Symptoms of mild diverticulitis may be confused with overlapping symptoms of irritable bowel syndrome.

The usual initial symptoms of diverticulitis include the following:

• Abdominal pain (most commonly in the left lower quadrant)

• Nausea

• Vomiting

• Constipation or obstipation

• Fever

• Flatulence

• Bloating

Other signs and symptoms in diverticulitis may arise due to an increasing severity of inflammation and the development of complications. Feared complications of diverticulitis include, but are not limited to, abscess (infected collection of pus), perforation (full thickness tearing of the colon), and fistula (abnormal connection between two organs).

Note that immunosuppressed individuals, including those taking corticosteroids, and the elderly are more likely to have an atypical presentation, or may not be symptomatic at all.

A microperforation, most likely walled off by adjacent structures, may present with no systemic signs of illness or infection. However, the disease may progress from a localized and walled-off process to one with peridiverticular inflammatory phlegmon and localized abscess. Systemic signs of infection (eg, fever) then develop.

Diverticulitis can mimic other conditions

Because diverticula and, hence, diverticulitis can develop anywhere in the gastrointestinal tract, symptoms may mimic multiple conditions. Note the following:

• Diverticulitis in the right colon or in a redundant sigmoid colon may be mistaken for acute appendicitis. Cecal diverticulitis can also mimic acute appendicitis, but cecal diverticula are generally rare. Diverticulitis in the transverse colon may mimic peptic ulcer disease, pancreatitis, or cholecystitis. Retroperitoneal involvement may present similarly to renal disease. In women, lower quadrant pain may be difficult to distinguish from a gynecologic process.

• More severe diverticulitis is often accompanied by anorexia, nausea, and vomiting. Typically, the pain is localized, severe, and present for several days prior to presentation. An altered bowel habit, especially constipation, is reported by most patients. A small percentage of patients may complain of urinary symptoms, such as dysuria, urgency, and frequency, due to the inflammation adjacent to urinary tract structures.

• Macroperforation with spillage of colonic contents into the peritoneum can lead to generalized abdominal pain and peritonitis, or it may lead to a localized pelvic, left lower quadrant, or right lower quadrant abscess with more localized abdominal pain and peritonitis.

• Leg pain possibly associated with a thigh abscess and leg emphysema secondary to retroperitoneal perforation from diverticulitis have been reported.

Diverticulitis can present with a range of physical findings, mirroring the severity of the inflammation and the presence of complications, including the following:

• Localized abdominal tenderness

• Abdominal distention

• Tympanic abdomen to percussion

• A tender mass (abscess formation)

• Hypo- or hyperactive bowel sounds

• Absent bowel sounds (perforation)

• Generalized abdominal pain with rebound and guarding (perforation)

• Urinary tract findings (colovesicular/colovaginal fistula) include suprapubic, flank, costovertebral tenderness; pneumaturia (air in urine); fecaluria (stool in urine); or purulent vaginal discharge

Simple and complicated diverticulitis

In simple diverticulitis, fever and localized abdominal tenderness in the area of the affected diverticula are common findings. Left lower quadrant tenderness is the most common physical finding, as most diverticula occur in the sigmoid colon.[15] Right lower quadrant tenderness, mimicking acute appendicitis, can occur in right-sided diverticulitis.

In complicated diverticulitis with abscess formation, a tender palpable mass may be noted. In fact, 20% of cases present with a palpable mass on abdominal, pelvic, or rectal examination. Peritonitis due to a free perforation results in generalized tenderness with rebound and guarding on abdominal examination. The abdomen may be distended and tympanic to percussion. Bowel sounds may be diminished or absent.

Elderly and immunocompromised patients

Elderly patients and individuals taking corticosteroids may have unremarkable findings on physical examination even in the presence of severe diverticulitis. Such patients must be evaluated with a high index of suspicion to avoid a delay in establishing the correct diagnosis.

The presence of fistulas

If a fistula forms, physical examination findings vary depending on the type of fistula. Colovesicular fistulas may present with urinary tract symptoms, such as suprapubic, flank, or costovertebral angle tenderness. Fecaluria or pneumaturia can also be observed. Female patients with colovaginal fistulas may present with a purulent vaginal discharge.

The diagnosis of acute diverticulitis can usually be made on the basis of the history and physical examination. Laboratory tests may be helpful when the diagnosis is in question.

A hemogram may reveal leukocytosis and a left shift, indicating infection. However, the absence of leukocytosis does not rule out diverticulitis, as 20%-40% of patients have a normal white blood cell count. This is particularly true in patients who are immunocompromised, who are elderly, and who have less severe disease. A hemoglobin level is important when the patient reports hematochezia.

Measurement of blood chemistries may be helpful in the patient who is vomiting or has diarrhea to assess electrolyte abnormalities. Assess renal function prior to the administration of most intravenous contrast material.

Liver function tests and lipase levels may help to exclude other causes of abdominal pain.

If a colovesical fistula is suspected, a urinalysis may reveal red or white blood cells. However, inflammation and infection due to diverticulitis adjacent to the ureters or the bladder may be the source of these cells. A urine culture may confirm sterile pyuria due to inflammation versus polymicrobial infection in the case of a fistula.

Blood cultures should be obtained prior to the administration of empiric parenteral antimicrobial therapy in patients who are severely ill or in those with complicated disease.

A pregnancy test must be performed in any female of childbearing age who presents with abdominal pain to rule out ectopic pregnancy, as well as prior to radiologic studies and before administering certain antibiotics to protect a viable fetus.

Although the diagnosis of diverticulitis can be made on clinical grounds, a computed tomography (CT) scan of the abdomen is considered the best imaging method to confirm the diagnosis. The American College of Radiology (ACR) appropriateness criteria for left lower quadrant pain support this recommendation because of the specificity and sensitivity of CT scans, which allow for the diagnosis of the causes of left lower quadrant pain that resembles diverticulitis.[29]

Note the following:

• CT scans are preferred over intraluminal examinations (eg, barium enema), because the bulk of the inflammation is extraluminal. CT scans can help clinicians assess disease severity, the presence of complications, and clinical staging. In the acute setting, CT scans are safer than contrast studies. Sensitivity and specificity, especially with helical CT scanning and colonic contrast, can be as high as 97%.

• Possible CT scan findings include the following: pericolic fat stranding due to inflammation, colonic diverticula, bowel wall thickening, soft-tissue inflammatory masses, phlegmon, and abscesses. Peritonitis, fistula formation, and obstruction can also be assessed. In addition, CT scanning can be used to guide percutaneous drainage of an abscess.

Barium contrast enema is not the imaging modality of choice during an acute episode of abdominal pain and should only be considered in mild to moderate uncomplicated cases of diverticulitis when the diagnosis is in doubt, or for follow-up evaluation for suspected fistula.[29] A water-soluble contrast medium should be used, as leakage of barium into the peritoneum would be catastrophic.

Plain radiograph films are not helpful in making the diagnosis of diverticulitis. However, plain abdominal radiograph series with supine and upright films can demonstrate bowel obstruction or ileus. If free air is present, this can indicate bowel perforation.

Endoscopy is not recommended in the acute setting given the risk of worsening diverticulitis and bowel perforation. After the diverticulitis has subsided, colonoscopy can be used to evaluate the extent of diverticulosis or to rule out a malignancy masquerading as a benign postinflammatory stricture.

Similarly, when findings on computed tomography scan demonstrate are suspicious for colonic carcinoma, colonoscopy is the imaging modality of choice.[29]

Several staging schemes have been proposed for diverticulitis based on the clinical findings, disease extent on imaging studies, and the presence of complications. The simplest method may be to differentiate among asymptomatic diverticulosis, uncomplicated diverticulitis, and complicated diverticulitis.

Clinical staging by Hinchey's classification is based on computed tomography findings and directed toward selection of the proper surgical procedure when diverticulitis is complicated, as follows:

• Stage I disease: Phlegmon or localized pericolic or mesenteric abscess

• Stage II disease: Walled-off pelvic, intra-abdominal, or retroperitoneal abscess

• Stage III disease: Perforated diverticulitis causing generalized purulent peritonitis

• Stage IV disease: Rupture of diverticula into the peritoneal cavity, with fecal contamination causing generalized fecal peritonitis

Table. Modified Hinchey Classification Stage and Diverticulitis Category (Open Table in a new window)

The management of patients with diverticulitis depends on their presentation severity, presence of complications, and comorbid conditions. Therefore, there is no standard treatment in the medical management of diverticular disease, including diverticulitis.[4]

The initial approach involves determining whether the patient has complicated or uncomplicated disease.[2] Uncomplicated diverticulitis is defined as localized diverticular inflammation without complication, whereas complicated diverticulitis consists of inflammation associated with a complication such as abscess, fistula, obstruction, bleeding, or perforation.[30] Computed tomography (CT) imaging can confirm the diagnosis of diverticulitis and distinguish between both disease processes.

Uncomplicated diverticulitis can be managed medically and in an ambulatory setting, whereas complicated disease requires a more aggressive approach that can often require urgent or elective surgery, and treatments that are specific to the complication itself (eg, abscess drainage).[2] A gastroenterology consultation may be helpful, as can further assistance with surgical and interventional radiology consultations. The modified Hinchey classification is based on CT scan findings and is used to categorize diverticulitis as well as help to guide appropriate interventions.[3]

Emergency colectomy is performed when severe complications arise or when the patient's condition does not respond to medical treatment. Complications requiring surgical intervention include the following: purulent peritonitis, uncontrolled sepsis, fistula, and obstruction. In a retrospective study of over 3000 patients, about 20% of patients admitted for acute diverticulitis required emergency colectomy.

Elective resection of the involved bowel segment after three episodes of uncomplicated diverticulitis to prevent further attacks is generally recommended by consensus guidelines. In addition, earlier resection for younger patients with diverticulitis as well as for patients who are immunocompromised has been proposed. As most complicated diverticulitis occurs on the first presentation and data for elective resection have come from small retrospective studies, this recommendation remains controversial.

Successful percutaneous drainage of a diverticular abscess has not been associated with greater recurrence or more severe disease and does not necessitate elective colectomy.

Antibiotics are known to be the mainstay of therapy for most patients with acute diverticulitis, but recent studies have questioned their necessity, especially in mild, uncomplicated disease.[4, 31] It appears that antimicrobial use in acute uncomplicated diverticulitis increases patients' stay in the hospital without lowering the overall or individual complication rates.[32]

A 2012 Cochrane review showed no significant benefit of antibiotic therapy in the treatment of uncomplicated diverticulitis, however these data were based mostly on one well-done randomized controlled trial.[33] The 2015 American Gastroenterological Association (AGA) guidelines stated that clinicians must be selective in using antibiotics in patients in this subgroup of patients.[5]

Patients who have been successfully treated for acute diverticulitis should be reassessed in 6-8 weeks. Those who are symptom free at that time should undergo colonoscopy to rule out malignancy, if they have not had a recent, high-quality colonic examination.[5]

The treatment approach for diverticulitis can be broadly classified into either uncomplicated disease or complicated disease, and it takes into account a few other special considerations.[15] Acute uncomplicated diverticulitis is successfully treated in 70%-100% of patients with conservative management.[34, 35, 36] Patients who present to the emergency department with uncomplicated diverticulitis appear to be able to be safely discharged on oral antibiotics, provided computed tomography (CT) scan findings have been evaluated.[37] However, those whose CT scan findings reveal complicated disease should be admitted for inpatient management with surgical consultation.[37]

The American Gastroenterological Association (AGA) suggests selective, rather than routine, use of antibiotics in patients with acute uncomplicated diverticulitis.[5, 38] Some studies indicate that nonantibiotic management of acute uncomplicated diverticulitis is safe and feasible.[31, 39]

Acute diverticulitis tends to be more severe in very elderly people and in patients who are immunocompromised or who have debilitating comorbid conditions, such as diabetes and renal failure.

Outpatient treatment of diverticulitis

Patients with mild diverticulitis, typically with Modified Hinchey stage 0 and Ia disease, can be started on an outpatient treatment regimen. This consists of a clear liquid diet and 7-10 days of an oral (PO) broad-spectrum antimicrobial regimen that covers anaerobic microorganisms, such as Bacteroides fragilis and Peptostreptococcus and Clostridium organisms, as well as aerobic microorganisms, such as Escherichia coli and Klebsiella, Proteus, Streptococcus, and Enterobacter organisms. Single and multiple antibiotic regimens are equally effective as long as both groups of organisms are covered.[6, 7] According to the World Gastroenterology Organisation (WGO) 2007 practice guidelines for diverticular disease, such a regimen should result in improvement within 48-72 hours.[1]

Note the following:

• A typical oral antibiotic regimen is a combination of ciprofloxacin (or trimethoprim-sulfamethoxazole) and metronidazole. Monotherapy with moxifloxacin or amoxicillin/clavulanic acid are appropriate for outpatient treatment of uncomplicated diverticulitis.

• Instruct patients about being on a clear liquid diet only, and that they can slowly advance the diet as tolerated after clinical improvement, which usually occurs within 2-3 days.

Inpatient treatment of diverticulitis

Hospitalization is required in the presence of evidence of severe diverticulitis, such as systemic signs of infection or peritonitis. Patients who are unable to tolerate oral hydration, whose condition is refractory to outpatient therapy (ie, persistent or increasing fever, pain, or leukocytosis after 2-3 days), who are immunocompromised, or who have comorbidities may also require hospitalization. Patients' pain may be severe enough to require parenteral narcotic analgesia.

Consider the following:

• Initiate bowel rest and intravenous (IV) fluid hydration. Start broad-spectrum IV antibiotic coverage until culture results, if obtained, are available.

• Monotherapy with beta-lactamase-inhibiting antibiotics or carbapenems provides broad antibacterial coverage and is appropriate for patients who are moderately ill and require inpatient admission. Such antibiotics include piperacillin/tazobactam, ampicillin/sulbactam, ticarcillin/clavulanic acid, imipenem, or meropenem.

• Multiple drug regimens are also appropriate options in the hospital setting and may consist of metronidazole and a third-generation cephalosporin or a fluoroquinolone. Such antibiotics include ceftriaxone, cefotaxime, ceftolozane/tazobactam, ciprofloxacin, or levofloxacin. Previously, gentamicin was recommended as part of a multidrug regimen; although this agent is still a reasonable choice, substitution with a third-generation cephalosporin or a fluoroquinolone has been advocated to avoid the risk of aminoglycoside nephrotoxicity.

• For immunocompromised patients, imipenem or meropenem may be preferred over ertapenem for better enterococcal and pseudomonal coverage.

• Pain management is important. Morphine is acceptable for analgesia and is preferred over meperidine owing to the adverse effects associated with meperidine. Although early recommendations for pain management favored meperidine based on a theoretical risk of affecting bowel tone and sphincters, randomized prospective studies comparing the narcotic options are not available. Use of nonsteroidal anti-inflammatory drugs and corticosteroids have been associated with a greater risk of colon perforation and should be avoided whenever possible.[5] The AGA suggests against routinely advising avoidance of aspirin in those with a history of acute diverticulitis.[5]

• Within 2-3 days of hospitalization, the patient's fever, pain, and leukocytosis should begin to resolve. The patient can then begin a clear liquid diet and advance as tolerated. If the patient tolerates oral intake and is clinically stable, they can be discharged to complete a 7-10-day course of PO antibiotic therapy.

• If fever and leukocytosis do not resolve after 2-3 days of treatment or if serial examinations reveal worsening clinical signs or new peritoneal findings, a repeat CT scan of the abdomen is advisable to rule out an abdominal abscess or other complications. The WGO guidelines state that a lack of improvement should prompt clinical suspicion and an investigation for a phlegmon or an abscess.[1]

• If a patient has a peridiverticular abscess that measures more than 4 cm in diameter (Hinchey stage II disease), CT scan-guided percutaneous drainage is indicated. This usually leads to a prompt (< 72 hour) reduction in pain, fever, and leukocytosis. Percutaneous drainage is also beneficial in that it may allow for elective surgery rather than emergency surgery, and it increases the likelihood of a successful one-stage procedure.

• For abscess cavities containing gross fecal material or in the presence of a perforation, early surgical intervention is required.

IV tigecycline is no longer recommended for patients with a severe penicillin allergy due to an increased mortality risk relative to other antimicrobials used to treat severe infections.[40] This higher all-cause mortality warranted a US Food and Drug Administration (FDA) Drug Safety Communication in September 2010, and the addition of a Black Box Warning to its prescribing information.[40] In September 2013, an additional warning was added to the Black Box Warning to indicate that the increased risk of death with IV tigecycline occurred both with FDA-approved uses and nonapproved uses.[41] Tigecycline is now reserved for use in situations when alternative treatments are not suitable.[41]

Dietary and activity considerations

Diet

In mild episodes of diverticulitis, a clear liquid diet is advised. Clinical improvement should occur within 2-3 days; the diet can then be advanced as tolerated. In episodes of moderate to severe acute diverticulitis, administer nothing by mouth (NPO).

Once the acute episode of diverticulitis has resolved, the patient may advance their diet as tolerated and then maintain a lifelong high-fiber diet. Colonoscopy or, alternatively, barium enema with flexible sigmoidoscopy should be obtained after resolution of an initial episode (typically 2-6 wk after recovery) to exclude other diagnoses, such as malignancy,[5, 29] ischemia, and inflammatory bowel disease.

An increasing number of studies have reported the efficacy of different regimens of anti-inflammatory agents, including mesalamine; nonabsorbable antibiotics such as rifaximin; and probiotics alone or in combination in the management of diverticulitis.[42, 43] The AGA does not recommend the use of mesalamine, and it suggests against the use of rifaximin or probiotics, following acute uncomplicated diverticulitis.[5]

In the first US double-blind, placebo-controlled trial of the anti-inflammatory agent mesalamine for diverticulitis, 117 patients randomly assigned within 7 days of documented acute diverticulitis to a once-daily regimen of either 2.4 g delayed-release mesalamine or placebo over 12 weeks, followed by a 9-month treatment-free period, demonstrated persistently lower global symptoms scores for 10 gastrointestinal symptoms on a 0-6 Likert scale in patients receiving mesalamine compared with the placebo group.[43] The rate of complete response was significantly higher with the use of mesalamine than placebo at 6 weeks and 52 weeks, whereas probiotics in combination with mesalamine did not provide additional efficacy.[43]

Studies imply a high-fiber diet will prevent progression of diverticulosis. However, after patients have become symptomatic, the benefit of fiber supplementation is less clear. Recommending patients to avoid seeds and nuts is less common, since it is currently thought that they may not play a significant role in the development of diverticulitis, as previously believed.

Long-term management probably includes a high-fiber, low-fat diet.

Activity

Normal activity is possible after resolution of the acute episode. Patients with diverticular disease should consider vigorous physical activity.[5]

An estimated 15%-25% of patients who present with a first episode of acute diverticulitis have complicated disease that requires surgery. According to the World Gastroenterology Organisation (WGO) 2007 guidelines, 15%-30% of patients admitted for the management of diverticulitis will need surgery during their admission, with a surgical mortality of 18%.[1]

Classic surgical indications include some features characteristic of Hinchey stage III or IV disease, as follows:

• Free-air perforation with fecal peritonitis

• Suppurative peritonitis secondary to a ruptured abscess

• Uncontrolled sepsis

• Abdominal or pelvic abscess (unless computed tomography scan-guided aspiration is possible)

• Fistula formation

• Inability to rule out carcinoma

• Intestinal obstruction

• Failing medical therapy

• Immunocompromised status

• Extremes of age

Recurrent episodes of acute diverticulitis

Elective surgery was previously recommended in any patient who had two or more episodes of diverticulitis that were successfully treated medically; other data have since called this practice into question when the patient is otherwise healthy.

Perioperative considerations

Preoperative antibiotics should be administered to all patients. Single- and multiple-drug regimens, as discussed in Medical Care, are appropriate choices. However, for patients with more extensive contamination, a single-drug regimen (with either imipenem/cilastin or piperacillin/tazobactam) or a multiple-drug regimen (with ampicillin, gentamicin, and metronidazole) may be warranted for peritonitis. Bowel preparation is usually possible for nonemergent situations.

Emergent surgical approach

Guidelines from the 2006 American Society of Colon and Rectal Surgeons (ASCRS) recommend emergency surgery for patients with diffuse peritonitis and for those whose condition fails nonoperative management. Also, patients who are immunosuppressed or immunocompromised are at an increased risk of disease refractory to medical therapy or of bowel perforation, and they should be approached with a lower threshold for surgery.[44]

A two-stage surgical approach is generally the most common procedure performed for the emergency treatment of acute diverticulitis. Note the following:

• The preferred surgical approach in patients with fecal peritonitis and in most cases of purulent peritonitis is the traditional Hartmann procedure.[45, 46] It involves resection of the diseased segment of bowel, an end-colostomy, and closure of the rectal stump. Typically, 3 months later, a second procedure may be performed in which the colostomy is reversed and the intestinal continuity is reestablished with the rectal stump; however, this second operation can be technically difficult and is not performed in many patients.

• An alternative to the Hartmann procedure involves resection of the diseased colon, primary anastomosis (with or without intraoperative colonic lavage), and creation of a proximal diverting stoma, either via colostomy or ileostomy. The second procedure in this process would be to close the stoma. This approach is primarily used when there are relative contraindications to the primary anastomosis but no purulent or feculent peritonitis, and there is nonedematous bowel. Its advantage lies in avoiding the technically difficult second stage used in the Hartmann procedure.

• There is no role for extensive and unnecessary dissections, which open up tissue planes to infection and increase blood loss.

• In a study that examined data from patients who had undergone the Hartmann procedure for acute diverticulitis and then (after a median 7-month period) underwent reversal surgery, Fleming and Gillen investigated the rate of, and risk factors for, complications linked to the reversal procedure and found that of 18 of 76 patients (25%) who underwent reversal had postreversal complications.[46] Risk factors for reversal complications included being a current smoker, having a low preoperative albumin level, and allowing a prolonged period to elapse between the Hartmann and reversal procedures. The authors concluded that despite the reversal surgery's significant complication rate, offering the operation to appropriately selected patients is acceptable. They also suggested that preoperative identification of modifiable risk factors may benefit patients.[46]

Elective surgery

The decision to proceed with elective surgery, typically at least 6 weeks after recovery from acute diverticulitis, should be made on a case-by-case basis.[5] The 2015 American Gastroenterological Association (AGA) guidelines suggest against elective colonic resection in patients with an initial episode of acute uncomplicated diverticulitis.[5] As recommended by the 2007 World Gastroenterology Organisation (WGO) guidelines, this decision should include consideration of the age and medical condition of the patient, the frequency and severity of attacks, and the presence of any persistent symptoms after the acute episode.[5] Other appropriate indications for elective colectomy include an inability to exclude carcinoma, following an episode of complicated diverticulitis treated nonoperatively, or after percutaneous drainage of a diverticular abscess.[1]

Note the following:

• Regarding attack frequency, after one attack of acute diverticulitis, about one third of patients will have a second attack. After a second episode, a further one third will have yet another attack. According to the 2007 WGO guidelines, a repeat episode requires immediate surgery if complications occur, such as free perforation, obstruction, abscess that is not resolved by percutaneous drainage, fistulas, and failure to respond to treatment.[1]

• Regarding disease severity, most patients who present with complicated diverticulitis do so at the time of their first episode. Therefore, once a patient's initial presentation has been determined to be uncomplicated or complicated, the patient's future episodes are likely to follow a similar course.

• A one-stage surgical approach with resection and primary anastomosis is often possible in elective settings because the disease is well localized and/or significantly resolved. The bowel must be well vascularized, nonedematous, tension free, and well prepared. The proximal margin should be an area of pliable colon without hypertrophy or inflammation. The distal margin should extend to the upper third of the rectum where the taenia coalesce. Not all of the diverticula-bearing colon needs to be removed, as diverticula proximal to the descending or sigmoid colon are unlikely to result in further symptoms.

• Patients with Hinchey stage I or II disease can usually have preoperative bowel preparation.

Three-stage procedure

The classic three-stage surgical approach is rarely indicated at present because of its high associated morbidity and mortality. This procedure is considered only in critical situations in which resection cannot safely be performed. Consider the following:

• In the three-stage approach, the initial operation is simply drainage of the diseased segment and creation of a proximal diversion colostomy, without resection.

• The second operation is performed 2-8 weeks later to resect the diseased bowel and perform a primary anastomosis.

• A third operation, performed 2-4 weeks after the second operation, closes the stoma.

Laparoscopy

Increasing experience with laparoscopic techniques for colon resection suggests that some of its advantages include less pain, a smaller scar, and shorter recovery time.[47] There is no change in early or late complications, and the cost and outcome are comparable to open procedures. The laparoscopic approach is best suited for patients in whom the episode of acute diverticulitis has resolved and in patients with Hinchey stage I or II disease.

Special considerations

Consider the following for some forms of complicated diverticulitis:

• Diffuse peritonitis: An appropriate initial empiric antibiotic regimen must include either single-agent therapy with imipenem/cilastin or piperacillin/tazobactam or multidrug therapy with ampicillin, gentamicin, and metronidazole.

• Differentiate obstruction from carcinoma. Even if biopsy results are negative, resection may be necessary to exclude carcinoma if there is enough suspicion based upon appearance alone.

• Abscesses without peritonitis may be amenable to percutaneous drainage with an elective single-stage operation after the episode has resolved. Drainage is usually performed through the anterior abdominal wall, but it may be done transgluteally or through the rectum or the vagina, depending on the location of the abscess. Catheter drainage may be helpful in patients who cannot undergo surgery; the catheter should be left in place until the drainage is less than 10 mL in 24 hours. Obtain periodic catheter sinograms to monitor the resolution of the abscess cavity before the catheter is removed.

• Fistulas generally do not close spontaneously, but they may be managed with an elective one-stage procedure in most cases. Also, in the absence of urinary tract obstruction, observation appears to be safe in patients with contraindications to surgery.

• Patients who are immunosuppressed are at an increased risk for perforation. Surgery is necessary in almost all patients who are either already immunosuppressed or are about to start immunosuppressive therapy.

• Elderly patients: Septic, hemodynamically unstable elderly patients with acute complicated diverticulitis should undergo surgical intervention as soon as possible, regardless of their Hinchey stage.[48] Fit and hemodynamically stable geriatric patients have surgical options similar to those of their younger counterparts; those who are frail but hemodynamically stable should undergo a Hartmann procedure.

A lifelong high-fiber diet for those with asymptomatic diverticular disease may reduce the incidence of diverticulitis and its complications. The 2015 American Gastroenterological Association (AGA) guidelines suggest a fiber-rich diet or fiber supplementation in individuals with a history of acute diverticulitis.[5] However, the guidelines are against routinely advising these patients to avoid the consumption of popcorn and nuts.

According to a large study in the United Kingdom, a high-fiber diet and a vegetarian diet were each significantly associated with a lower risk of diverticular disease-related hospital admission or death.[49]

After recovering from acute diverticulitis, patients should have their colons examined to rule out malignancy. Current modalities include colonoscopy, barium enema, and computed tomography (CT) colonography (virtual colonoscopy).

Virtual colonoscopy may be helpful in evaluating diverticulitis in the elective setting. This procedure combines insufflation of the colon in conjunction with a CT scan to provide data that allow computer generation of a three-dimensional image. Although the technology is widely available in many centers, it is limited by the inability to sample suspicious lesions.

Biopsy of suspicious lesions or strictures can be performed during colonoscopy, which is advantageous.

2015 American Gastroenterological Association (AGA) guidelines

The AGA recommendations on the treatment of diverticulitis include the following[5] :

• Antibiotics should be used selectively in uncomplicated diverticulitis.

• Colonoscopy should be performed after resolution of acute diverticulitis if a high-quality examination has not been done recently.

• Prophylactic colonic resection in uncomplicated diverticulitis should be done on a case-by-case basis.

• A fiber-rich diet or fiber supplementation as well as physical activity (ideally, daily rigorous exercise) are recommended after resolution.

• Aspirin use can be continued after resolution, particularly if it is being used for secondary prevention.

• It is not necessary to avoid nuts and popcorn in patients with diverticulosis or diverticulitis.

• Avoid nonaspirin, nonsteroidal anti-inflammatory drugs if possible.

• Mesalamine, rifaximin, and probiotics are not recommended to prevent recurrence.

2006 American Society of Colon and Rectal Surgeons (ASCRS) practice parameters

The ASCRS recommendations on the management of diverticulitis include the following[44] :

• The initial evaluation should include a history and physical examination, complete blood cell count, urinalysis, and abdominal imaging in select cases.

• Computed tomography (CT) scanning of the abdomen and pelvis is the most appropriate initial imaging method.

• Ultrasonography and magnetic resonance imaging (MRI) can be useful imaging alternatives.

• Nonsurgical treatment includes oral or intravenous antibiotics and diet modification.

• Image-guided percutaneous drainage is usually the most appropriate treatment for stable patients with large diverticular abscesses.

• After resolution of the incident diverticulitis, colonoscopy should be performed if it has not been done recently.

• The decision regarding elective sigmoid colectomy should be individualized.

• Elective colectomy should be considered after recovery from complicated diverticulitis.

• Routine elective resection based on young age (< 50 years) is not recommended.

• Urgent sigmoid colectomy is required for diffuse peritonitis or when nonsurgical management fails.

• The decision to restore bowel continuity after resection must incorporate patient factors, intraoperative factors, and surgeon preference.

Diverticulosis is treated with lifelong dietary modification. However, antibiotics have been the mainstay of therapy for most patients with acute diverticulitis, but more recently, their necessity has been questioned, especially in mild, uncomplicated disease.[4, 31] It appears that antimicrobial use in acute uncomplicated diverticulitis increases patients' stay in the hospital without lowering the overall or individual complication rates.[32] Other studies have shown that the effectiveness of single- or multiple-agent antibiotic regimens for outpatient therapy are essentially the same when they provide both anaerobic and aerobic coverage.[6, 7]

Empiric therapy requires broad-spectrum antibiotics effective against known enteric pathogens. For complicated cases of diverticulitis in hospitalized patients, carbapenems are the most effective empiric therapy because of increasing bacterial resistance to other regimens.

Potential regimens include the following:

• Ciprofloxacin plus metronidazole

• Trimethoprim-sulfamethoxazole plus metronidazole

• Amoxicillin-clavulanate

• Moxifloxacin (use in patients intolerant of both metronidazole and beta lactam agents)

Class Summary

Empiric antimicrobial therapy is essential and should cover all pathogens likely to cause diverticulitis.

Metronidazole (Flagyl, Medro)

Active against various anaerobic bacteria. Enters cell, binds DNA, and inhibits protein synthesis, causing cell death.

Ciprofloxacin (Cipro)

Bactericidal antibiotic that inhibits bacterial DNA synthesis. Used for infections due to E coli, K pneumoniae, E cloacae, P mirabilis, P vulgaris, P aeruginosa, H influenzae, M catarrhalis, S pneumoniae, S aureus (methicillin susceptible), S epidermidis, S pyogenes, Campylobacter jejuni, Shigella species, and Salmonella typhi.

Amoxicillin/clavulanate (Augmentin, Amoclan)

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase–producing bacteria.

This agent is a good alternative antibiotic for patients allergic or intolerant to the macrolide class. It is usually well tolerated and provides good coverage to most infectious agents, but it is not effective against Mycoplasma and Legionella species. The half-life of an oral dosage form is 1-1.3 h. It has good tissue penetration but does not enter the cerebrospinal fluid.

For children >3 months, base the dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.

Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra DS)

Inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid.

Antibacterial activity of TMP-SMZ includes the common urinary tract pathogens, except Pseudomonas aeruginosa.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin binding proteins. Exerts antimicrobial effect by interfering with the synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Highly stable in the presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose is excreted unchanged in urine, and the remainder is secreted in bile and ultimately in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding have been reported to decrease from 95% bound at plasma concentrations < 25 mcg/mL to 85% bound at 300 mcg/mL.

Cefotaxime (Claforan)

Third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which, in turn, inhibits bacterial growth. Used for septicemia and the treatment of gynecologic infections caused by susceptible organisms.

Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Ceftolozane/tazobactam (Zerbaxa)

A cephalosporin antibiotic plus a beta-lactamase inhibitor. Indicated for use in combination with metronidazole for complicated intra-abdominal infections caused by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius. Dose must be adjusted for reduced CrCl.

Moxifloxacin (Avelox)

Moxifloxacin is the only fluoroquinolone that is FDA approved as monotherapy for the treatment of complicated intra-abdominal infections. Moxifloxacin, a broad-spectrum antibiotic, exhibits activity against Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species. Moxifloxacin is active against gram-positive organisms and anaerobes but is less active against Enterobacteriaceae and Pseudomonas species.

Levofloxacin (Levaquin)

For pseudomonal infections and infections due to multidrug resistant gram-negative organisms.

Ampicillin/Sulbactam (Unasyn)

Drug combination of beta-lactamase inhibitor with ampicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.

Piperacillin and Tazobactam sodium (Zosyn)

Anti-pseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.

Ticarcillin and clavulanate potassium (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during active replication.

Antipseudomonal penicillin and beta-lactamase inhibitor that provides coverage against most gram-positive and gram-negative bacteria and most anaerobes.

Meropenem (Merrem)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared with imipenem. Drugs of this class are a good choice for empiric therapy of GI-based infections in hospitalized patients with complicated conditions.

Gentamicin

Aminoglycoside antibiotic used to cover gram-negative organisms.

Not the drug of choice (DOC). Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.

Imipenem and cilastatin (Primaxin)

Used for the treatment of multiple organism infections as in peritonitis when other agents are not appropriate.

Ampicillin

Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Tigecycline (Tygacil)

Tetracycline-type antibiotic with broad coverage. NOTE: Tigecycline has a Black Box Warning. This agent was previously used in patients with a severe penicillin allergy, but owing to an increased risk of all-cause mortality, IV tigecycline is now reserved for use in situations when alternative treatments are not suitable. It is FDA approved for complicated intra-abdominal infections, as well as complicated skin and skin structure infections and community-acquired bacterial pneumonia.