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Pseudomembranous Colitis

Pseudomembranous Colitis

Pseudomembranous colitis is a bacterial disease of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy caused by Clostridium difficile Clostridium difficile A common inhabitant of the colon flora in human infants and sometimes in adults. The type species clostridioides difficile is formerly known as Clostridium difficile. It is a causative agent for clostridioides infections and is associated with pseudomembranous enterocolitis in patients receiving antibiotic therapy. Clostridia. Pseudomembranous colitis is characterized by mucosal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease account for the most commonly diagnosed hospital-acquired diarrheal illnesses. C. difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease can range from asymptomatic colonization Colonization Bacteriology to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and progress to fulminant colitis with systemic sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock in severe cases. The diagnosis is established based on stool studies. Management of pseudomembranous colitis is mainly using antibiotics. Fecal transplant is considered in a few cases, whereas surgical intervention is required in severe cases.

Last updated: 9 Feb, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Definition

Pseudomembranous colitis is an inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of colonic mucosa caused by the toxins released by Clostridium (now reclassified as Clostridioides) difficile.

Epidemiology

  • Accounts for up to 3 million cases of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and colitis in the United States every year
  • Approximately 14,000 deaths in the US every year
  • The majority of cases are hospital acquired.
  • Up to 40% of cases of C. difficile colitis are community acquired.

Etiology

  • Caused by toxigenic strains of C. difficile: 
    • Gram-positive Gram-Positive Penicillins bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus, obligate anaerobe
    • C. difficile can exist in 2 forms:
      • Spore form Spore form Pneumocystis jirovecii/Pneumocystis Pneumonia (PCP): outside the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy; resistant to heat Heat Inflammation, acid, and antibiotics
      • Vegetative form: in the intestine
    • Highly contagious
    • Spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax transmitted via fecal-oral route Fecal-oral route Echovirus
  • Recent antibiotic treatment is the main risk factor. Most commonly implicated antibiotics:
    • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides 
    • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
    • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
    • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins
  • Other risk factors:
    • Proton- pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (gastric-acid suppression Suppression Defense Mechanisms)
    • Advanced age > 65
    • Medical comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
    • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
    • Gastrointestinal surgery
    • Enteral feeding
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • Chemotherapy Chemotherapy Osteosarcoma
    • Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation
    • Inflammatory bowel disease
    • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis

Pathophysiology and Clinical Presentation

Pathogenesis

  • 2%–3% of healthy adults are colonized with C. difficile.
  • 8%–10% of hospitalized adults are colonized.
  • Disruption of the normal flora using antibiotics leads to the overgrowth of C. difficile.
  • Most of the clinical infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are observed in newly colonized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Intestinal damage is due to toxin release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology.
  • Toxins released by C. difficile:
    • Enterotoxin A Enterotoxin A Clostridia:
      • Targets brush-border enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
      • Alters fluid secretion Secretion Coagulation Studies
      • Causes watery diarrhea Watery diarrhea Rotavirus
    • Toxin B (10 times more potent):
      • Depolymerizes actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction 
      • Disrupts cytoskeleton Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. The Cell: Cytosol and Cytoskeleton of enterocytes
      • Causes pseudomembranous colitis

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • Foul-smelling non- bloody diarrhea Bloody diarrhea Diarrhea
  • Cramping abdominal pain Abdominal Pain Acute Abdomen
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
  • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus
  • Fulminant colitis: 
    • Acute abdominal distention Abdominal distention Megacolon and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Signs of sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock:
      • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
      • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
      • Change in mental status
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea may be absent at this point because of the developing colonic ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction.
    • Toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon: 
    • Colonic perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis, ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage can develop.
Table: C. difficile infection (CDI) classification based on severity
Characteristics Mild-to-moderate colitis Severe colitis Fulminant colitis
Number of loose stools/day < 6 ≥ 6 ≥ 6
Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever – +/– +/–
WBC count < 20,000/µL > 20,000/µL > 20,000/µL
Severe abdominal pain Abdominal Pain Acute Abdomen – + +
Rising creatinine levels – +/– +/–
Multiorgan dysfunction – – +
Complete ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction or toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon – – +
Radiological signs of colitis, ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction, or toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon – +/– +
Adapted from: Courtney Cassella. (2016). Imaging in Clostridium difficile Clostridium difficile A common inhabitant of the colon flora in human infants and sometimes in adults. The type species clostridioides difficile is formerly known as Clostridium difficile. It is a causative agent for clostridioides infections and is associated with pseudomembranous enterocolitis in patients receiving antibiotic therapy. Clostridia infection. Retrieved February 8, 2021, from https://sinaiem.org/imaging-in-clostridium-difficile-infection/

Diagnosis

History

  • Acute onset of diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea without alternative explanations
  • Treatment using antibiotics in the past 3 months
  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Recent abdominal surgery
  • Chronic medical conditions

Physical exam

  • Findings minimal in mild cases
  • Severe colitis:
    • Diffuse abdominal tenderness/distention
    • Signs of dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration/ sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock: tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, low urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat output

Laboratory studies

  • Stool studies:
    • Polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)) for C. difficile genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure 
    • Enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS ( EIA EIA HIV Infection and AIDS) for C. difficile antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (rapid, widely available)
    • EIA EIA HIV Infection and AIDS for C. difficile toxins A and B
  • Blood tests:
    • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus (often > 20,000/ÎĽL)
    • Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia (due to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
    • Findings in fulminant colitis:
      • Serum creatinine > 1.5 (possible kidney injury caused by dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration)
      • ↑ Lactate levels 
      • Serum albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests < 2.5 g/dL

Imaging

  • Abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: 
    • Can show colonic dilatation 
    • Free air in case of perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
  • Computed tomography (CT) scan:
    • Can detect colitis, ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction, or toxic megacolon Toxic megacolon An acute form of megacolon, severe pathological dilatation of the colon. It is associated with clinical conditions such as ulcerative colitis; Crohn disease; amebic dysentery; or Clostridium enterocolitis. Megacolon
    • Can reveal complications such as perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
    • Findings of pseudomembranous colitis:
      • “Accordion sign” (with orally administered contrast; mucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation)
      • “Target sign,” “double- halo sign Halo sign Aspergillus/Aspergillosis”: signs of mucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Thickening of the colonic wall
      • Pericolonic stranding
      • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
Ct scan of pseudomembranous colitis

Computed tomography scan of severe pseudomembranous colitis: diffuse colonic wall thickening, with areas suggestive of mucosal hemorrhage

Image: “Abdominal computer tomography” by Division of Gastroenterology and Hepatology, Department of Medicine and Geriatrics, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, New Territories, Hong Kong. License: CC BY 4.0

Flexible sigmoidoscopy Sigmoidoscopy Endoscopic examination, therapy or surgery of the sigmoid flexure. Colorectal Cancer Screening

  • Not necessary if diagnosis is confirmed based on stool studies
  • Only needed if alternative diagnosis is considered
  • Full colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening is not recommended because of the risk of perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis.
  • Findings:
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Friable mucosa
    • Bowel-wall edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Pseudomembranes:
  • Fulminant pseudomembranous colitis

    Endoscopic view of fulminant pseudomembranous colitis: multiple polypoid lesions covered with yellow pseudomembranes

    Image: “Endoscopic view of the sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy” by Division of Gastroenterology and Hepatology, Department of Medicine and Geriatrics, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, New Territories, Hong Kong. License: CC BY 4.0
  • Colonic wall covered by thick pseudomembranes

    Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) showing thick pseudomembranes typical of pseudomembranous colitis

    Image: “ Colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening on the 5th postoperative day” by Abe et al AL Amyloidosis. License: CC BY 2.0

Management

Management of cdi

Algorithm for an approach to the management of Clostridium difficile Clostridium difficile A common inhabitant of the colon flora in human infants and sometimes in adults. The type species clostridioides difficile is formerly known as Clostridium difficile. It is a causative agent for clostridioides infections and is associated with pseudomembranous enterocolitis in patients receiving antibiotic therapy. Clostridia infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (CDIs). Cr: creatinine, IV: intravenous

Image by Lecturio.

Medical management

  • Intravenous resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome, electrolyte correction
  • Stop the offending antibiotic if possible.
  • Antibiotic therapy options include:
    • Oral fidaxomicin
    • Oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
    • Rectal vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with pronounced ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction
    • Oral or intravenous metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
  • Fecal transplant:
    • As an alternative to surgery in the case of fulminant colitis
    • For recurrent CDI 
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have not responded to at least 2 appropriate antibiotic regimens

Surgery

Possible indications:

  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 38.5ÂşC (101.3ÂşF)
  • Significant abdominal distension
  • Peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury
  • Altered mental status Altered Mental Status Sepsis in Children
  • Serum lactate > 2.2 mmol/L
  • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus > 20,000 cells/mL
  • Admission to the intensive care unit
  • Failure to improve with medical therapy
  • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis

Surgical interventions:

  • Total abdominal colectomy with end ileostomy Ileostomy Surgical creation of an external opening into the ileum for fecal diversion or drainage. This replacement for the rectum is usually created in patients with severe inflammatory bowel diseases. Loop (continent) or tube (incontinent) procedures are most often employed. Large Bowel Obstruction 
  • Segmental colectomy is usually not recommended.
  • Alternative to colectomy: 
    • Diverting-loop ileostomy Ileostomy Surgical creation of an external opening into the ileum for fecal diversion or drainage. This replacement for the rectum is usually created in patients with severe inflammatory bowel diseases. Loop (continent) or tube (incontinent) procedures are most often employed. Large Bowel Obstruction with colonic lavage
    • Not an option if perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis or necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage is present

Prevention of hospital transmission

  • Gloving of personnel
  • Isolation of the patient with designated bathroom facilities
  • Avoiding the use of contaminated electronic thermometers and stethoscopes
  • Use of hypochlorite (bleach) solution to decontaminate the rooms of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy washing with soap (alcohol-containing hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy gels are not sporicidal) 
  • Restricting the use of specific antibiotics:
    • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
    • 2nd- and 3rd-generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Up to 25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will experience recurrence within 30 days of completing treatment.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experiencing recurrence are at a higher risk of further recurrence.
  • The overall mortality Mortality All deaths reported in a given population. Measures of Health Status from pseudomembranous colitis is 4.9%–6.2%.

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Differential Diagnosis

  • Crohn’s disease ( CD CD Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery): a chronic, recurrent condition that causes patchy transmural inflammation Transmural inflammation Crohn’s Disease in the terminal ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy and proximal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CD CD Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery typically present with intermittent non- bloody diarrhea Bloody diarrhea Diarrhea and crampy abdominal pain Abdominal Pain Acute Abdomen. Management is with corticosteroids Corticosteroids Chorioretinitis, azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants, antibiotics, and anti- tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)) agents. Complications include malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion, intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis or fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula, and an increased risk of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer. 
  • Ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis ( UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis): an idiopathic Idiopathic Dermatomyositis inflammatory condition that involves the mucosal surface of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Diffuse friability, erosions Erosions Corneal Abrasions, Erosion, and Ulcers with bleeding, and loss of haustra Haustra Colon, Cecum, and Appendix: Anatomy are observed in UC UC Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with bloody diarrhea Bloody diarrhea Diarrhea, colicky abdominal pain Abdominal Pain Acute Abdomen, tenesmus, and fecal urgency. Diagnosis is established based on endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management is with topical mesalamine or 6-mercaptopurine 6-Mercaptopurine An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. Antimetabolite Chemotherapy, or colectomy for severe cases.
  • Infectious Infectious Febrile Infant diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea ( Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess, Klebsiella oxytoca Klebsiella Oxytoca Multidrug-resistant Organisms and Nosocomial Infections, Clostridium perfringens Clostridium perfringens The most common etiologic agent of gas gangrene. It is differentiable into several distinct types based on the distribution of twelve different toxins. Gas Gangrene, and Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella): presents with clinical manifestations similar to those of C. difficile infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease. The diagnosis is distinguished based on stool culture. Management is mostly supportive and requires the use of antibiotics in some cases.
  • Diarrheagenic Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli: causes enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance, enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis, and colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with watery/ bloody diarrhea Bloody diarrhea Diarrhea, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Diagnosis is established based on culture and/or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) using stool samples. The treatment consists of supportive therapy (fluids and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes). Although antibiotics are reserved for severe/persistent cases, they are contraindicated in a few cases.

References

  1. Aberra F.N. (2019). Clostridioides (Clostridium) difficile colitis. Retrieved 29 January 2021, from https://emedicine.medscape.com/article/186458-overview#a6 
  2. Ananthakrishnan A.N. Clostridium difficile infection: Epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011 Jan. 8(1):17-26.
  3. Cohen S.H., Gerding D.N., Johnson S., et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May. 31(5):431-55. 
  4. Kelly C.P., Lamont J.T., Bakken J.S. (2021). Clostridioides (formerly Clostridium) difficile infection in adults: Treatment and prevention. Retrieved 29 January 2021, from https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-infection-in-adults-treatment-and-prevention
  5. Lamont J.T., Kelly C.P., Bakken J.S. (2020). Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis. Retrieved 21 January 2021, from https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-infection-in-adults-clinical-manifestations-and-diagnosis
  6. McDonald L.C., Coignard B., Dubberke E., Song X., Horan T., Kutty P.K. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol. 2007 Feb. 28(2):140-5.
  7. Pant C., Sferra T.J., Deshpande A., Minocha A. Clinical approach to severe Clostridium difficile infection: Update for the hospital practitioner. Eur J Intern Med. 2011;22(6):561-8.
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