*With the exception of programs from the ACCEL series, each of which qualifies for up to 4 Category 1 CME credits.
NEW Audio-Digest Gastroenterology
Volume 27, Issue 05
March 7, 2013
Clostridium difficile and Intra-abdominal Infections Robert G. Martindale, MD, PhD
Case Studies in Gastrointestinal Infections Thomas G. Fraser, MD
The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.
Gastroenterology Program Info Accreditation InfoCultural & Linguistic Competency Resources
The goal of this program is to improve the management of patients with gastrointestinal (GI) infections. After hearing and assimilating this program, the clinician will be better able to:
1 Manage patients with Clostridium difficile infection of any severity.
2. Assess the various surgical procedures that are used for patients with infection.
3. Differentiate between the types of peritonitis based on clinical features.
4. Assess the merits of nonoperative procedures for acute appendicitis.
5. Determine the causative pathogen in patients with acute diarrheal illness.
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Clostridium difficile and Intra-abdominal Infections
Robert G. Martindale, MD, PhD, Professor and Chief, Division of General Surgery, Oregon Health and Science University School of Medicine, Portland
Case presentation: female patient aged 23 yr who had recently given birth; patient had ruptured membranes but did not progress to labor; given single dose of fluoroquinolone for prophylaxis before cesarean delivery; patient discharged at 3 days postpartum with no complications; emergency visit — patient comes to emergency department (ED) on fifth day postpartum complaining of fever, nausea, and diarrhea; white blood cell (WBC) count 14,700/µL and serum creatinine l1.3 mg/dL; symptoms improved upon administration of fluids; obstetrician recommends discharge of patient from ED and advises against antibiotics; patient returns to ED next day with signs of sepsis (WBC count 36,000/µL, serum creatinine 1.9 mg/dL, heart rate 124 beats/min); patient admitted to intensive care unit (ICU) with presumptive diagnosis of endometritis; computed tomography (CT) revealed dilation of colon; laboratory results revealed Clostridium difficile (CDF) infection; emergency general surgery staff called and patient given broad-spectrum antibiotics, intravenous (IV) metronidazole (Flagyl), vasopressin, and norepinephrine; mean arterial pressure 60 mm Hg; patient taken to operating room (OR), where extensive pseudomembranous colitis discovered; total abdominal colectomy and end ileostomy performed; surgery went well and patient taken off pressors while still in OR; patient discharged 4 days later; pearl — no standard length for postcolectomy antibiotic therapy
Background: 25% of patients who take broad-spectrum antibiotics get antibiotic-associated diarrhea (AAD); CDF responsible for 10% to 15% of cases of AAD; recent changes — epidemics of drug-resistant (metronidazole-resistant) strains of CDF occurring in areas around United States; 3% to 10% of drug-resistant CDF strains threatening and fulminant (usually involves NAP1 or related strains); increased incidence of hypervirulent strains of CDF; increased recurrence rates; increasing associated causative mortality; infection with CDF increasingly requires surgical intervention; poor outcomes even after surgery (surgery not performed soon enough in many cases); surgery for CDF sepsis has mortality rate of 29% to 33%; no guidelines exist that can predict fulminant course of infection
Diagnosis: severity of CDF infection can range from mild diarrhea to toxic megacolon; cytotoxicity assay slower but more accurate than toxin assay; cytotoxicity assay has 6% chance of false negative result while toxin assay has 10% to 20% chance of false negative result; test for fecal leukocytes not helpful; 12% to 24% relapse rate within 2 mo of infection (50% of relapses come from germination of spores and other 50% from new strains); classification of CDF — anaerobe; spore-forming gram-positive rod; transmission via fecal-oral route; vegetative form easily killed (dead within minutes of exposure to air); spores can live for months on dry surfaces and germinate at proper temperature, moisture content, and pH; spores resistant to gastric acid, antibacterial soaps, hand sanitizers, and conventional disinfectants; bleach kills spores if allowed to dry in presence of spores; path of infection — spores ingested germinate in gut and become flagellated, allowing migration into colon, where they produce toxins that injure mucosa and cause exudative phase; colonocytes degenerate and die during exudative phase; macrophages migrate into colon and stick to endothelium of colon due to increased expression of intercellular adhesion molecule (ICAM-1); ICAM-1 allows WBCs to stick to endothelium and form pseudomembrane; pseudomembrane reduces penetration of antibiotic into infected areas; risk factors — advanced age (CDF colitis more common in patients aged >65 yr); multiple comorbidities; immunocompromise; patients with transplanted organs at higher risk; patients with Crohn disease at higher risk (may be misdiagnosed as flare); recently pregnant women at elevated risk; use of antibiotics; fluoroquinolone drugs most strongly associated with CDF-associated diarrhea and should not be used for prophylaxis; medication that alters gastric acid; recent gastrointestinal (GI) surgery; patients with obstruction or ileus; antiperistaltic drugs; contact with spores or contaminated foods; stay in hospital, ICU, or long-term care skilled nursing facility; epidemiology — 500,000 cases estimated in United States during 2011; 61 discharges per 100,000 carried diagnosis of CDF infection in 2011; mortality increasing due to evolution of new strains; 25% of cases of CDF infection in hospital due to perioperative prophylaxis; dental work prophylaxis also significant source of CDF infection; described geographical distribution of new strains of CDF misleading due to skewed reporting
Medical management of CDF-associated disease (CDAD): 2010 guidelines from Infectious Disease Society of America and Surgical Infection Society; mild to moderate initial episode — characterized by WBC count <15,000/µL and creatinine level that has decreased by >1.5 g/dL compared to premorbid level; administer 500 mg metronidazole 3 times/day, over course of 10 to 14 days (timing critical); pearl — germination time of CDF 3 to 5 days; antibiotics must be used at full strength for minimum of 3 germination times; do not taper dose; severe initial episode — 125 mg oral vancomycin, 4 times/day, for 10 to 14 days; severe initial episode plus complications — patient sick, hypotensive, in ICU (case 1); administer 500 mg vancomycin 4 times/day into lumen, plus IV metronidazole; addition of IV antibiotic ensures delivery of drugs to leaky capillaries; consider vancomycin enemas if patient has severe dysmotility; recurrent infection — first recurrence of CDF managed same way as initial occurrence; second recurrence managed with tapering doses of antibiotics
Surgical management: decision to perform surgery on patients with CDF infection based purely on clinical judgment; threshold for surgery decreasing; indicated procedures — traditionally, total abdominal colectomy performed due to perceived failure of less invasive techniques; recent resurgence of less invasive techniques; University of Chicago study — study done with sick patients (in ICU) who had CDAD to test effectiveness of ileostomy and colonic lavage as alternative to colectomy; most had laparoscopic surgery; surgeon performed exploratory laparoscopic surgery to confirm that colon not necrotic; surgeon then brings out loop colostomy and performs lavage with antibiotic solution on surgical table; postoperative antegrade colonic enemas of antibiotic solution administered for 10 days; technique safe (only 1 patient in 42 died during study) and spares colon
Ancillary treatments: fidaxomicin (Dificid, Dificlir) — recently approved luminal-acting antibiotic that does not affect normal gut flora; fidaxomicin lasts longer than vancomycin and has different mechanism of action (bactericidal rather than bacteriostatic); cost effective in certain subgroups of patients (especially in patients with chronic renal failure); effectiveness equivalent to vancomycin in clinical trials; may be superior to vancomycin in preventing recurrence of CDF infection; probiotics — used for prevention of CDF infection for patients receiving antibiotic therapy; numerous studies support efficacy of probiotics for prevention of AAD and CDAD; fecal transplantation — promising data for this method but not widely used; fecal enema from healthy person (usually relative of patient) used to restore normal colon flora in patients with AAD; prevention — hand washing, enteric precautions, judicious use of antibiotics, use of probiotics; use of incorrect antibiotic — study found that 45% of patients in ICU received wrong antibiotic for their disease; study in 1999 found 42% mortality rate for ICU patients who received incorrect antibiotic; other studies confirmed this data; de-escalation therapy arose to correct this problem; de-escalation therapy seeks to ensure death of pathogen by treating patient with broad-spectrum antibiotics initially, followed by de-escalation to narrow-spectrum antibiotics once physician identifies causative organism
Intra-abdominal etiologies: bowel perforations — accounted for roughly 58% of intra-abdominal etiologies in 2012, rate was 4% higher in 1982; bowel necrosis — rarely seen in 1982 (only 5% of patients); more common now because physicians can see ischemic appearance on CT; abscesses — accounted for 21% in 1982; abscesses now identified much earlier
Peritonitis: primary peritonitis — usually not surgical diagnosis; spontaneous bacterial peritonitis (SBP) associated with ascites; monomicrobial (commonly Escherichia coli); peritonitis with multiple species of microbes indicates leakage (look for source); secondary peritonitis — treated as routine intestinal perforation; tertiary peritonitis — infection with unusual organisms (fungi, enterococcus, drug-resistant organisms); usually caused by failure of host defense or failure of source control; immune response — humans have 2 competing immune responses to infections, dilution (peritoneal circulation) and abscess formation (“walling off”); diagnosis — take extra precaution in making diagnosis of peritonitis in very old patients, very young patients, patients on psychotropic drugs and/or with mental illness, and patients with spinal cord injury (nausea may be only symptom); treatment — source control primary objective; provide physiologic support; early, aggressive treatment in ED (follow guidelines for surviving sepsis); provide volume resuscitation; administer broad-spectrum antibiotics early, then de-escalate after identification of organism; tigecycline effective against some extended spectrum β-lactamase producing organisms; tigecycline (Tygacil) used only in extreme cases to prevent development of drug-resistant strains
Treatment of appendicitis: studies suggest that patients with appendicitis diagnosed early should be managed with antibiotics rather than surgery; USC study — nonoperative management of acute, uncomplicated appendicitis associated with fewer complications, better pain control, shorter recovery time, and higher recurrence rate when compared with appendectomy (40% recurrence for antibiotics vs 8% for surgery); guidelines and recommendations — 2010 Surgical Infection Society and Infectious Disease Society of America both state that patients with early phlegmon or early treatment of fluid around appendix do not require appendectomy; data support use of negative-pressure wound device (ABThera) during surgery on patient with copious accumulated pus and fluid; guidelines recommend early antibiotic therapy in ED and percutaneous drainage for patients with abscesses; routine reexploration not recommended, except for patients with GI discontinuity or for source control; ampicillin-sulbactam not recommended due to high rates of resistance of E coli
Case Studies in Gastrointestinal Infections
Thomas G. Fraser, MD, Department of Infectious Disease, Cleveland Clinic, Cleveland, OH
Case 1: man aged 43 yr develops abrupt onset of abdominal pain, nausea, and watery diarrhea with no fever; his children had similar symptoms in preceding weeks; his children have resolved their illness and returned to normal activity; patient and family have not traveled; likely cause — infection with norovirus; study identified norovirus as predominant etiologic agent for community-onset gastroenteritis; characteristics of pathogen — highly contagious; low infectious dose; prolifically shed in stool; evokes little immunity and constantly evolves; persists on fomites for ≤2 wk; leading cause of endemic diarrheal and foodborne disease
Case 2: family presents to ED with uncontrollable vomiting; all had eaten potato salad served with metal spoon at picnic; likely cause — Staphylococcus aureus toxin poisoning; toxin-mediated gastroenteritis; enterotoxin directly stimulates emesis center in brain, noninflammatory response
Case 3: man aged 27 yr travels to Mexican resort for vacation; patient developed progressively loose bowel movements and GI upset; patient did not have fever or chills, and none of his traveling companions got sick; likely cause — traveler’s diarrhea from E coli; traveler’s diarrhea — common; symptoms range from watery diarrhea to dysentery, depending on pathogen; enterotoxigenic E coli (ETEC) most common cause of acute watery diarrhea in travelers; ETEC infection usually self-limited and does not require culture; different forms of E coli — enteropathogenic E coli leading cause of infantile diarrhea; ETEC traditionally associated with traveler’s diarrhea but also causes weanling diarrhea in infants; enteroinvasive E coli causes dysentery-like illness; enterohemorrhagic E coli produces Shiga-like toxin and causes bloody diarrhea without fever; enteroaggregative and diffusely adherent E coli cause childhood diarrhea
Case 4: female patient aged 88 yr presents to ED with fever, abdominal pain, nausea, vomiting, and diarrhea for past 3 days; frequently eats takeout food; patient has tenesmus but no hematochezia; patient has history of stroke and coronary disease; patient has not received antibiotics; patient admitted and hydrated; next step — test for routine pathogens and get blood cultures; New England Journal article — determining proper diagnostic work-up for patients with acute GI illness; first, perform initial assessment and treat symptoms (eg, rehydration); stratify further management according to clinical and epidemiologic features; assess patient’s risk for complications and type of diarrheal illness; patient history — age, immune status, comorbidities, location, food eaten and where it came from, work and play environment; cues — Shigella associated with dysentery-like illness in day-care setting; Yersinia associated with consumption of undercooked sausage; enterohemorrhagic E coli infection associated with undercooked hamburger and petting zoos; Vibrio and Plesiomonasshigelloides associated with consumption of shellfish; Cryptosporidium species associated with contaminated water; norovirus associated with winter and cruise ship diarrhea; management — stool culture positive for Salmonella enteritidis; patient should be treated for Salmonella gastroenteritis because of risk for complications of bacteremia (eg, age<12 mo or >50 yr), immunocompromise, heart valve, or hip prostheses); pearl — most patients with community onset gastroenteritis should receive supportive care only; consider antibiotics in patients with severe symptoms of inflammatory diarrhea
Case 5: female patient aged 16 yr with bloody diarrhea, cramping abdominal pain, and no fever; diarrhea persisted for 3 days and became overtly bloody; patient recently visited petting zoo; physician should get stool cultures for routine pathogens and E coli O157, test for Shiga toxin, and perform complete blood count and chemistry panel; community-onset bloody diarrhea — Shigella most common cause in United States; enterohemorrhagic E coli likely in patients with bloody diarrhea without fever
Case 6: patient aged 25 yr developed watery diarrhea, nausea, and bloating; patient had been hiking in mountains during camping trip 3 wk ago; Giardia lamblia — likely cause; stool ova and parasites test indicated; Giardia associated with freshwater exposure, backpacking, well water; presents with syndrome of chronic diarrhea and bloating; Cryptosporidium parvum — causes self-limiting diarrhea that lasts for several weeks; resistant to chlorination
Dr. Martindale spoke at the 17th Annual Medical and Surgical Approaches to GI Disorders, held July 16-20, 2012, in Kiawah Island, SC, and sponsored by the Medical College of Georgia at Georgia Health Sciences University. Dr. Fraser spoke at Intensive Review of Gastroenterology and Hepatology, held August 15-18, 2012, in San Diego, CA, and sponsored by the Cleveland Clinic. For future CME activities by the Medical College of Georgia or the Cleveland Clinic visit georgiahealth.edu/ce/medicalce/2013 or www.clevelandclinicmeded.com. The Audio-Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.
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