Gastrointestinal and Hepatobiliary Infections PDF

Access Provided by: Infectious Diseases: A Clinical Short Course, 4e Chapter 8: Gastrointestinal and Hepatobiliary Infections Frederick S. Southwick INTRODUCTION GUIDING QUESTIONS 1. What are the three most common bacterial causes of infectious diarrhea, and how are these infections contra...

Access Provided by: Infectious Diseases: A Clinical Short Course, 4e Chapter 8: Gastrointestinal and Hepatobiliary Infections Frederick S. Southwick INTRODUCTION GUIDING QUESTIONS 1. What are the three most common bacterial causes of infectious diarrhea, and how are these infections contracted? 2. Which test is useful for differentiating viral from bacterial diarrhea? 3. How does Clostridium difficile cause diarrhea, and how is pseudomembranous colitis diagnosed? 4. What are the findings that suggest the development of spontaneous peritonitis? 5. How do abdominal abscesses usually form, and how are they best managed? 6. Which pathogen most commonly causes peptic ulcer disease? 7. How do hepatic abscesses usually develop, and which bacteria are most commonly cultured? 8. What are the three most common forms of viral hepatitis, and how are they contracted? 9. What are the major complications of viral hepatitis? INFECTIOUS DIARRHEA POTENTIAL SEVERITY Can be life­threatening in infants, young children, and elderly people. Most individuals with this illness can be managed as outpatients. Diarrheal illness is one of the leading causes of death among children 15,000 and creatinine >1.5. The most feared complications of pseudomembranous colitis are toxic megacolon and bowel perforation. These complications arise in a small proportion of patients (0.4–4%), but are associated with a high mortality (30–50%). Persistent fever, marked elevation of the peripheral WBC count, lack of response to antibiotics, and marked bowel thickening on CT scan are worrisome findings. For severe disease oral vancomycin should be increased to 500 mg q6h and combined with intravenous metronidazole (500 mg IV q8h). If ileus is severe vancomycin enemas should also be administered. In patients with WBC >25,000 and rising serum lactate surgical intervention is often required. Subtotal colectomy with rectal sparing is recommended. Diverting ileostomy with saline wash out and vancomycin flushes is another possible approach, but evidence as to the benefit of this procedure is limited. Downloaded 2024­11­2 Recurrent disease 10:50asAa Your is common IP is consequence of residual spores in the stool that are not killed by the antibiotic. First­time recurrences should be Chapter 8: Gastrointestinal and Hepatobiliary Infections, treated with either oral vancomycin or fidaxomicin Frederick at the same dosesS. Southwick and Page 20 / 66is duration as initial treatment. For subsequent recurrences oral vancomycin ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility recommended for 14 days followed by tapering of the dose to 125 mg two times per day for a week, then 125 mg once per day for a week, and finally 125 mg every 2 or 3 days for 2–8 weeks. For refractory cases repopulation of the bowel with normal flora (fecal microbiota transplant) is highly (0.4–4%), but are associated with a high mortality (30–50%). Persistent fever, marked elevation of the peripheral WBC count, lack of response to antibiotics, and marked bowel thickening on CT scan are worrisome findings. For severe disease oral vancomycin should be increased to 500 mg Access q6h by: Provided and combined with intravenous metronidazole (500 mg IV q8h). If ileus is severe vancomycin enemas should also be administered. In patients with WBC >25,000 and rising serum lactate surgical intervention is often required. Subtotal colectomy with rectal sparing is recommended. Diverting ileostomy with saline wash out and vancomycin flushes is another possible approach, but evidence as to the benefit of this procedure is limited. Recurrent disease is common as a consequence of residual spores in the stool that are not killed by the antibiotic. First­time recurrences should be treated with either oral vancomycin or fidaxomicin at the same doses and duration as initial treatment. For subsequent recurrences oral vancomycin is recommended for 14 days followed by tapering of the dose to 125 mg two times per day for a week, then 125 mg once per day for a week, and finally 125 mg every 2 or 3 days for 2–8 weeks. For refractory cases repopulation of the bowel with normal flora (fecal microbiota transplant) is highly effective. Donor selection is critical to lower the risk of transmission of other diseases and this procedure awaits approval by the FDA. KEY POINTS About the Diagnosis, Treatment, and Prevention of Clostridium Difficile Diarrhea 1. Diagnosis: a. Patients should have 3 loose bowel movements per day and not be on parenteral feeding or taking laxatives. b. A two­step testing algorithm is recommended beginning with stool PCR or glutaminedehydrogenase. If this test is positive ELISA for toxin A and B should be performed. If positive treatment should be initiated. c. The cytotoxicity assay remains the definitive test, but it is expensive and takes several days. d. Endoscopy is usually not required, and risks perforation. 2. Treatment: a. Drugs must be orally administered (except for metronidazole). b. Vancomycin and fidaxomicin are the treatments of choice. Metronidazole is inferior and repeated treatment is associated with neurotoxicity. c. For severe disease the vancomycin dose should be increased and if ileus is present vancomycin should also be given by enema. d. Severe disease may require bowel resection; mortality is 30–50%. e. Relapse is common because of residual spores. Re­treat with vancomycin or fidaxomicin for first relapse. If further relapses, oral vancomycin with a dosage taper is preferred. 3. Prevention: a. Spread by hospital personnel; hand washing is critical. b. Limiting clindamycin use may reduce the attack rate. Standard infection control measures must be scrupulously followed to prevent hospital personnel from spreading C. difficile spores from patient to patient. Thorough physical hand washing is critical to remove spores from the hands. Prolonged broad­spectrum antibiotics should be avoided whenever possible. Limiting the use of clindamycin has proved effective in reducing the attack rate in several hospital outbreaks. Viral Diarrhea POTENTIAL SEVERITY A self­limiting disease that can cause dehydration. Viruses cause most cases of acute diarrhea. This form of diarrhea is usually watery, mild, and self­limited. The viruses most commonly associated with viral diarrhea are noroviruses, rotaviruses, enteric adenoviruses, and astroviruses. Downloaded 2024­11­2 10:50 A Your IP is Virology, Pathogenesis, and Epidemiology Chapter 8: Gastrointestinal and Hepatobiliary Infections, Frederick S. Southwick Page 21 / 66 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Norovirus  A self­limiting disease that can cause dehydration. Access Provided by: Viruses cause most cases of acute diarrhea. This form of diarrhea is usually watery, mild, and self­limited. The viruses most commonly associated with viral diarrhea are noroviruses, rotaviruses, enteric adenoviruses, and astroviruses. Virology, Pathogenesis, and Epidemiology Norovirus The single­stranded RNA norovirus belongs to the calicivirus family, a group that derives its name from the distinct cup­ or chalice­like indentations of the viral capsid seen on electron microscopy. There are three genogroups GI, GII, and GIV that cause disease in humans. Because no convenient method is known for propagating the virus, and no animal model of norovirus gastroenteritis exists, little is known about its pathogenesis. The recent development of a human intestinal stem­cell­derived culture system called human intestinal enteroids promises to advance our understanding of this infection. Histopathology from infected human volunteers has revealed that the virus causes blunting of villi and PMN infiltration of the lamina propria in the jejunum. Patients often present with the acute onset of nausea, vomiting, and watery diarrhea. The virus is shed in the stool in high concentrations (1010 viral particles) for 24–48 hours after the onset of illness, and it is also present in high concentrations in vomitus. Ingestion of as few as 18 viral particles can cause disease. Infection is transmitted by contaminated water, surfaces, and food, as well as by person­to­person spread. In addition to contaminated drinking water, swimming pools and lakes can transmit the disease. Norovirus is relatively resistant to chlorine and alcohol. Shellfish is a leading food source, and because the virus is relatively heat resistant, cooking contaminated shellfish does not completely eliminate the risk of infection. Infected food handlers can contaminate food, resulting in large outbreaks and should not handle food for a minimum of 48 hours after symptoms have resolved. Hand hygiene is critical for preventing spread, and food handlers and health care personnel should be encouraged to physically scrub their hands with soap and water to remove viral particles. Large outbreaks have also been reported in closed environments such as ships, military installations, hospitals, and nursing homes. Norovirus is more commonly associated with outbreaks in adults, but infants and children may also be infected by this virus as well as by other members of the calicivirus group. Noravirus can be fatal in patients over age 65 accounting for approximately 800 deaths per year in the United States and immunocompromised patients can become chronically infected. KEY POINTS About Viral Diarrhea 1. Viral diarrhea is the most common form of infectious diarrhea. 2. The disease is caused primarily by four viral groups: a. Norovirus (“Norwalk”): This calicivirus blunts intestinal villi, causes mild malabsorption, is resistant to chlorine, is spread by contaminated water (including swimming pools), contaminated foods, or from person to person. Primarily infects adults. b. Rotavirus: Causes lactase deficiency, and primarily infects infants. Resists hand washing. Peaks in winter. c. Enteric adenovirus 40, 41: Infects infants and young children; peaks in the summer months. d. Astrovirus: Infects children in pediatric wards and elderly people in nursing homes. 3. Clinical spectrum varies from mild, watery diarrhea to severe nausea, vomiting, and fever. No PMNs are found in the stool. Commercial enzyme­ linked immunoabsorbent assays for rotavirus are available. 4. Self­limiting diseases; use supportive care with hydration. Rotavirus The name rotavirus (from the Latin rota, meaning wheel) for this double­stranded RNA virus is derived from the wheel­like appearance of the viral capsid on electron micrographs. It is a member of the reovirus family. Rotaviruses are able to replicate in mature villous epithelial cells in the small intestine. The viral capsid attaches to and penetrates the peripheral membrane of the host cell and enters the cytoplasm. Diarrhea is thought to be caused by loss of absorption by epithelial villi, lactase deficiency, and a decrease in the intestinal concentrations of other disaccharidases. The virus may also increase chloride secretion. Downloaded 2024­11­2 10:50 A Your IP is Rotavirus8:isGastrointestinal Chapter the most common and Hepatobiliary cause Infections, of infant diarrhea, andFrederick by age 3 S. Southwick years, Page more than 90% of children have acquired antibodies. Repeated 22 / 66 infections ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility may occur, indicating minimal cross­protection between strains. Adults may also contract the infection, most commonly from infected children as a consequence of fecal–oral transmission. The virus is resistant to hand washing and to many commonly used disinfectants, but it is inactivated by chlorine. It is able to survive on surfaces, in water, and on the hands for prolonged periods. In developed countries, infections most commonly occur  Access Provided by: The name rotavirus (from the Latin rota, meaning wheel) for this double­stranded RNA virus is derived from the wheel­like appearance of the viral capsid on electron micrographs. It is a member of the reovirus family. Rotaviruses are able to replicate in mature villous epithelial cells in the small intestine. The viral capsid attaches to and penetrates the peripheral membrane of the host cell and enters the cytoplasm. Diarrhea is thought to be caused by loss of absorption by epithelial villi, lactase deficiency, and a decrease in the intestinal concentrations of other disaccharidases. The virus may also increase chloride secretion. Rotavirus is the most common cause of infant diarrhea, and by age 3 years, more than 90% of children have acquired antibodies. Repeated infections may occur, indicating minimal cross­protection between strains. Adults may also contract the infection, most commonly from infected children as a consequence of fecal–oral transmission. The virus is resistant to hand washing and to many commonly used disinfectants, but it is inactivated by chlorine. It is able to survive on surfaces, in water, and on the hands for prolonged periods. In developed countries, infections most commonly occur during the winter months. Enteric Adenoviruses Two serotypes (adenovirus 40 and 41) of this double­stranded DNA virus have been associated with diarrhea. They are the second most frequent cause of nonbacterial gastroenteritis in infants and young children. Infections occur most commonly during the summer months. Astrovirus The single­stranded RNA astroviruses have the appearance of a five­ or six­pointed star on electron micrographs. Astroviruses have been associated with outbreaks of gastroenteritis in children in pediatric wards and in elderly patients in nursing homes. The prevalence of this virus is lower than those for the other known causes of viral gastroenteritis. Clinical Manifestations, Diagnosis, and Treatment CASE 8­3 A young physician arrived in Tuba City, Arizona, to work in an Indian health service clinic. Three days later, he became ill with mild mid­abdominal cramps and watery diarrhea, but denied fever. He continued working, added additional salt and fluid to his diet, and was inconvenienced, but not incapacitated by his illness. On the third day of symptoms, a stool was negative for lactoferrin, and a bacterial culture grew no pathogens. Illness script—A young physician presents with the subacute onset of watery diarrhea and mild abdominal discomfort. He continues to work maintaining hydration with oral fluids. He works on an Indian Reservation. The clinical manifestations of viral diarrhea vary. At one end of the clinical spectrum, the patient may experience mild watery diarrhea with minimal symptoms as described in Case 8­2; at the other extreme, the patient may develop severe nausea, vomiting, abdominal cramps, headache, myalgias, and fevers of 39°C. Stool smear reveals no leukocytes, and cultures are negative for bacterial pathogens. Identification of the specific viral agent is now possible with multiplex PCR. These diseases are self­limiting and last 2–6 days depending on the agent. Maintaining hydration is the primary goal of therapy. CHRONIC DIARRHEA As compared with acute diarrhea, which lasts less than 14 days, chronic diarrhea is defined as diarrhea lasting more than 30 days. Persistent diarrhea defines a diarrheal illness that lasts for more than 14 days. Parasitic Diarrhea Amoebiasis can mimic bacterial enterocolitis; other parasites, such as Giardia lamblia, Cryptosporidium, Isospora belli, and Microsporidium, often present with complaints that mimic viral gastroenteritis. However, in most instances, these parasitic infections are not self­limiting; they persist for prolonged periods. Amoebiasis Life Cycle and Epidemiology Downloaded Amoebiasis is2024­11­2 10:50 A Your caused by Entamoeba IP is. Other amoebic species found in the feces of humans, including E. coli, E. dispar, E. moshkovskii, E. histolytica Chapter 8: Gastrointestinal and Hepatobiliary Infections, hartmanni, E. polecki, Endolimax nana, and Iodamoeba Frederick butschlii, do S. notSouthwick Page 23 / 66 cause disease in humans. E. histolytica trophozoites are large (10–60 μm in ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility diameter) and contain lucent cytoplasm, a single nucleus, and multiple intracellular granules (Figure 8­3). They crawl by chemotaxis, using an actin­ based mechanism that is similar to that used by human macrophages and neutrophils. prolonged periods. Access Provided by: Amoebiasis Life Cycle and Epidemiology Amoebiasis is caused by Entamoeba histolytica. Other amoebic species found in the feces of humans, including E. coli, E. dispar, E. moshkovskii, E. hartmanni, E. polecki, Endolimax nana, and Iodamoeba butschlii, do not cause disease in humans. E. histolytica trophozoites are large (10–60 μm in diameter) and contain lucent cytoplasm, a single nucleus, and multiple intracellular granules (Figure 8­3). They crawl by chemotaxis, using an actin­ based mechanism that is similar to that used by human macrophages and neutrophils. Figure 8­3 Parasites that cause diarrhea. Each pathogen is schematically drawn to scale and represent the form most commonly detected on stool smear. Trophozoites attach to specific galactose receptors on host cells, and after contact, rapidly kill the host cells by a calcium­dependent mechanism. The amoeba also releases numerous proteolytic enzymes that break down the cell matrix anchoring host cells. Flask­shaped mucosal ulcers may be found in the colon at sites of trophozoite invasion. Ulcers can extend into the submucosa and result in invasion of the bloodstream. Amoebae can also travel up to the portal vein and form abscesses in the liver. Because E. histolytica can lyse host neutrophils, acute inflammatory cells are rarely seen in regions of active infection. Immunity against amoebae is mediated primarily by generation of immunoglobulin A antibodies and by cell­mediated immune response. Patients with depressed cell­mediated immunity are at greater risk of disseminated disease. KEY POINTS About Life Cycle and Epidemiology of Amoebiasis 1. Caused by E. histolytica, a parasite that contains ingested red blood cells and that is 10–60 μm in diameter. 2. Parasite binds to galactose receptors on host cells and kills them, and causes flask­like ulcers. 3. Able to invade the portal vein and form abscesses in the liver. 4. Able to lyse host PMNs. Acute inflammatory cells are rarely seen in areas of infection. Specific anti­IgA antibodies and cell­mediated immunity provide protection. 5. Dormant cysts can survive for months in moist, warm environments. 6. Cysts can contaminate food and water. 7. Very common in developing countries. 8. In the United States, the parasite is found in institutionalized patients, sexually active homosexuals, and tourists. In addition to its trophozoite form, E. histolytica forms dormant cysts under unfavorable environmental conditions. The cyst has a distinctive morphology, consisting of a rounded structure with three or four distinct nuclei. These hardy cysts can remain viable for months outside the host in moist, warm environments. Trophozoites are very sensitive to the acid pH of the stomach; however, cysts readily survive the gastric environment, and ingestion of single cyst can cause active infection. Cysts can be spread from person to person by the fecal–oral route and by contaminated food and water. In developing countries, a large proportion of the population becomes infected with E. histolytica, and the infected individuals usually carry the parasite in their stool for 12 months. In the United States, institutionalized patients, particularly the mentally challenged, have a high incidence of stool carriage and disease. An increased incidence has also been observed in sexually active homosexual males. The risk of amoebiasis is increased by travel to a developing country and is particularly high in individuals who reside in the endemic area for more than 1 month. Downloaded 2024­11­2 10:50 A Your IP is Chapter 8: Gastrointestinal and Hepatobiliary Infections, Frederick S. Southwick Page 24 / 66 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility KEY POINTS About the Clinical Manifestations, Diagnosis, and Treatment of Amoebiasis moist, warm environments. Trophozoites are very sensitive to the acid pH of the stomach; however, cysts readily survive the gastric environment, and Access Provided by: ingestion of single cyst can cause active infection. Cysts can be spread from person to person by the fecal–oral route and by contaminated food and water. In developing countries, a large proportion of the population becomes infected with E. histolytica, and the infected individuals usually carry the parasite in their stool for 12 months. In the United States, institutionalized patients, particularly the mentally challenged, have a high incidence of stool carriage and disease. An increased incidence has also been observed in sexually active homosexual males. The risk of amoebiasis is increased by travel to a developing country and is particularly high in individuals who reside in the endemic area for more than 1 month. KEY POINTS About the Clinical Manifestations, Diagnosis, and Treatment of Amoebiasis 1. Clinical presentation depends on the degree of invasion: a. Watery diarrhea is associated with superficial infection. b. Bloody diarrhea, tenesmus, abdominal pain, and tenderness with more invasive disease. c. Can be misdiagnosed as ulcerative colitis; corticosteroids can lead to toxic megacolon. d. Right upper quadrant, right shoulder pain, hepatomegaly seen with liver abscess. 2. Diagnosis: a. Stool smears show fewer PMNs that are seen with shigellosis (trophozoites destroy PMNs). b. Stools are always heme­positive. c. Alkaline phosphatase elevated in chronic, but not acute hepatic abscess. d. Stool examination is insensitive; fecal antigen demonstrates variable sensitivity and specificity. PCR is preferred having high sensitivity and specificity. e. Serum is anti­amoebic antibody positive in most patients after 1 week of symptoms. f. Aspirate from liver abscess shows brownish, sterile liquid without PMNs; parasite not usually seen, and antigen may not be detected. 3. Treatment: Metronidazole or tinidazole for active disease; followed by paromomycin for luminal parasites. Clinical Manifestations Symptoms depend on the degree of bowel invasion. Superficial bowel infection is associated with watery diarrhea and nonspecific gastrointestinal complaints. Invasive intestinal disease presents with the gradual onset, over 1–3 weeks, of abdominal pain and bloody diarrhea associated with tenesmus and abdominal tenderness. Fever is noted in some patients. Amoebiasis can be mistaken for ulcerative colitis, and administration of corticosteroids can dramatically worsen the disease and lead to toxic megacolon. Amoebic liver abscess can develop in conjunction with colitis. Patients complain of right upper quadrant pain and can also experience pain referred to the right shoulder. Hepatomegaly is noted in half of all cases. Diagnosis and Treatment Stool smears usually demonstrate PMNs. However, because the amoebic trophozoites destroy human PMNs, the numbers are often lower than are seen in patients with shigellosis. In amoebiasis, stools are always heme­positive, reflecting trophozoite invasion and destruction of bowel mucosa. In acute hepatic disease, alkaline phosphatase may not be elevated, but it rises in chronic hepatic infection. Previously, the diagnosis was made by identifying trophozoites or cysts in the stool. However, two nonpathogenic species E. dispar and E. moshkovskii cannot be morphologically distinguished from E. histolytica. Fecal E. histolytica antigen tests have proven to be superior to stool smear; however, antigen tests have variable sensitivity and specificity. The preferred diagnostic approach is now multiplex PCR of stool that detects amoeba with high sensitivity and specificity in addition to identifying viral and bacterial pathogens that cause enteritis. These tests should be ordered in conjunction with a serum anti­amoebic antibody. The latter test is positive in most patients who have had symptomatic disease for more than 1 week. However, antibodies persist for life and therefore are not helpful in detecting reinfection. Abdominal CT scan should be performed in patients with symptoms consistent with hepatic disease. This test readily identifies abscesses. Serum anti­ Downloaded 2024­11­2 10:50 A Your IP is amoebic antibodies are elevated in 99% of patients with hepatic amoebic abscess. Aspiration of the abscess yields sterile, odorless, brownish liquid Chapter 8: Gastrointestinal and Hepatobiliary Infections, Frederick S. Southwick Page 25 / 66 without PMNs. Amoebae ©2024 McGraw are notReserved. Hill. All Rights generally seen andofare Terms only Use rarely cultured Privacy Policy because Notice the parasite concentrates in the walls of the abscess. Antigen is Accessibility detected in hepatic fluid in only 40% of cases. antigen tests have variable sensitivity and specificity. The preferred diagnostic approach is now multiplex PCR of stool that detects amoeba with high Access Provided by: sensitivity and specificity in addition to identifying viral and bacterial pathogens that cause enteritis. These tests should be ordered in conjunction with a serum anti­amoebic antibody. The latter test is positive in most patients who have had symptomatic disease for more than 1 week. However, antibodies persist for life and therefore are not helpful in detecting reinfection. Abdominal CT scan should be performed in patients with symptoms consistent with hepatic disease. This test readily identifies abscesses. Serum anti­ amoebic antibodies are elevated in 99% of patients with hepatic amoebic abscess. Aspiration of the abscess yields sterile, odorless, brownish liquid without PMNs. Amoebae are not generally seen and are only rarely cultured because the parasite concentrates in the walls of the abscess. Antigen is detected in hepatic fluid in only 40% of cases. Invasive enterocolitis and hepatic abscess should be treated with oral metronidazole (750 mg every 8 hours for 10 days) or tinidazole (2 g daily, divided into three doses, for 3–5 days) (see Table 8­3). Tinidazole has cure rates of 90–93% and is better tolerated than metronidazole. Treatment with metronidazole or tinidazole should be followed by PO paromomycin (25–35 mg/kg daily, divided into three doses, for 7 days) to kill intraluminal parasites. Table 8­3 Treatment of Parasites Causing Chronic Diarrhea Cause Treatment Duration Comments Amoeba Metronidazole 750 mg q8h PO 10 days OR Tinidazole 2 g daily divided into 3 doses PO 3–5 days Tinidazole has a cure rate of 90–93% and is better tolerated than metronidazole Both followed by Paromomycin 25–35 mg/kg daily, divided into 3 doses PO 7 days Required to kill intraluminal amoeba Giardia Tinidazole 2 g × 1 PO Single dose OR Nitazoxanide 500 mg q12h 3 days Second­line therapy 5–7 days Metronidazole 500 mg q12h or 250 mg q8h Cryptosporidium Healthy adult: Nitazoxanide 500 mg q12h 3 days HIV infected: Nitazoxanide 500 mg q12h combined with 14 days Ineffective for HIV patients with CD4 50% PMNs suggests bacterial peritonitis. A predominance of by: Access Provided lymphocytes should raise the possibility of fungal or tuberculous infection. Cultures of the peritoneal fluid (two cultures, 10 mL in each blood culture flask) and Gram stain should be obtained. Yield from a Gram stain is low, but properly obtained peritoneal cultures are positive in more than 90% of cases. Blood cultures should be obtained if systemic symptoms are present, but such cultures are rarely positive. After samples for culture have been obtained, antibiotic should be added to the dialysate. Initial empiric therapy should include a first­generation cephalosporin (cefazolin 500 mg/L loading dose, followed by 125 mg/L in each dialysate bag), or vancomycin if MRSA is suspected (1000 mg loading dose, followed by 25 mg in each bag), and third generation (ceftriaxone or cefotaxime), or fourth generation cephalosporin (cefepime) or aztreonam or an aminoglycoside (gentamicin or tobramycin 0.6 mg/kg or amikacin 2 mg/kg per exchange, once daily). Once­daily aminoglycoside therapy rather than constant treatment is recommended to reduce the risk of ototoxicity. If the patient fails to improve within 48 hours, removal of the dialysis catheter should be considered. For coagulase­negative Staphylococcus antibiotics are recommended for 2 weeks and for S. aureus, enterococcus, and gram­negative pathogens to maximize cure rates antibiotics should be continued for 3 weeks. KEY POINTS About Secondary Peritonitis Associated with Peritoneal Dialysis 1. Clinical presentation is similar to primary peritonitis, accompanied by cloudy dialysate. 2. S. epidermidis and S. aureus most common; P. aeruginosa, fungi, and atypical mycobacteria are also found. M. tuberculosis is less common. 3. Diagnosis: a. WBC count in peritoneal fluid exceeds 100/mm3, with a predominance of PMNs or for automated peritoneal dialysis >50% PMNs. b. Inoculate two blood culture flasks with 10 mL peritoneal fluid each. c. Blood cultures are seldom positive. 4. Treat with intraperitoneal antibiotics: Empiric therapy is a first­generation cephalosporin or vancomycin plus a once­daily aminoglycoside. HEPATIC ABSCESS POTENTIAL SEVERITY Usually presents subacutely. With appropriate drainage and antibiotics, prognosis is excellent. Pathogenesis and Microbiology Spread of pyogenic infection to the liver can occur in multiple ways. Biliary tract infection is most common, followed by portal vein bacteremia associated with intra­abdominal infection, primarily appendicitis, diverticulitis, or inflammatory bowel disease. Direct extension into the liver from a contiguous infection can occur after perforation of the gallbladder or duodenal ulcer, or in association with a perinephric, pancreatic, or subphrenic abscess. Penetrating wounds and postoperative complications may result in liver abscess. Bacteremia from any source can seed the liver via the hepatic artery and result in the formation of multiple abscesses. In approximately one­quarter of cases, a cause cannot be determined. KEY POINTS About the Pathogenesis and Microbiology of Liver Abscess 1. Bacteria seed the liver by multiple routes: a. Biliary tract (most common), b. Portal system in association with intra­abdominal infection, c. Direct extension from intra­abdominal infection, Downloaded 2024­11­2 d. Penetrating 10:50 wounds andA postoperative Your IP is complications and Chapter 8: Gastrointestinal and Hepatobiliary Infections, Frederick S. Southwick Page 37 / 66 ©2024 e. McGraw Hill. All Rights Hematogenous spread.Reserved. Terms of Use Privacy Policy Notice Accessibility 2. Bacteriology is usually similar to secondary peritonitis: associated with intra­abdominal infection, primarily appendicitis, diverticulitis, or inflammatory bowel disease. Direct extension into the liver from a Access Provided by: contiguous infection can occur after perforation of the gallbladder or duodenal ulcer, or in association with a perinephric, pancreatic, or subphrenic abscess. Penetrating wounds and postoperative complications may result in liver abscess. Bacteremia from any source can seed the liver via the hepatic artery and result in the formation of multiple abscesses. In approximately one­quarter of cases, a cause cannot be determined. KEY POINTS About the Pathogenesis and Microbiology of Liver Abscess 1. Bacteria seed the liver by multiple routes: a. Biliary tract (most common), b. Portal system in association with intra­abdominal infection, c. Direct extension from intra­abdominal infection, d. Penetrating wounds and postoperative complications and e. Hematogenous spread. 2. Bacteriology is usually similar to secondary peritonitis: a. Klebsiella (increasing in frequency), micro­aerophilic streptococci (mainly S. milleri) and b. Candida in leukemia patients following neutropenia. The bacteriology of this infection reflects the primary site of infection. As in secondary peritonitis, this infection is usually polymicrobial. Anaerobes are commonly cultured, including Bacteroides species. Fusobacterium, Peptostreptococcus, and Actinomyces species, and microaerophilic streptococci (S. milleri being the most common) are frequently found. Enteric gram­negative rods are also important pathogens, K. pneumoniae (particularly the K1 serotype) being the most common. Candida can also invade the liver, candidal abscesses usually occur in leukemia patients following chemotherapy­ induced neutropenia. Amoebic liver abscess is rare, but complicates 3–9% of patients with amoebic colitis. Clinical Manifestations Fever with or without chills is the most common presenting complaint. It may also be the only complaint, hepatic abscess being one of the most common infectious causes of fever of undetermined origin (see Case 3­1). Abdominal pain develops in about half of these patients, often confined to the right upper quadrant. Pain is usually dull and constant. Weight loss (more than 10 pounds in less than 3 months) is another frequent complaint. Physical examination often reveals tenderness over the liver. Jaundice is rare. In patients with abscess in the upper regions of the right hepatic lobe, pulmonary examination may reveal decreased breath sounds on that side because of atelectasis or pleural effusion. KEY POINTS About the Clinical Manifestations, Diagnosis, and Treatment of Liver Abscess 1. May present as fever of unknown origin: a. Dull right upper quadrant pain is associated with right upper quadrant tenderness. b. Leukocytosis and elevated alkaline phosphatase are seen. 2. CT scan is the diagnostic study of choice. 3. With a single abscess, use serology to rule out amoebiasis. 4. Treat with percutaneous drainage and broad­spectrum antibiotic coverage (same regimens as for secondary peritonitis). 5. Use open drainage for the patient with a. biliary obstruction, Downloaded 2024­11­2 10:50 A Your IP is b. multiloculated Chapter abscess 8: Gastrointestinal and(other than Echinococcus Hepatobiliary Infections,),Frederick or S. Southwick Page 38 / 66 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility c. viscous exudate. common infectious causes of fever of undetermined origin (see Case 3­1). Abdominal pain develops in about half of these patients, often confined to Access Provided by: the right upper quadrant. Pain is usually dull and constant. Weight loss (more than 10 pounds in less than 3 months) is another frequent complaint. Physical examination often reveals tenderness over the liver. Jaundice is rare. In patients with abscess in the upper regions of the right hepatic lobe, pulmonary examination may reveal decreased breath sounds on that side because of atelectasis or pleural effusion. KEY POINTS About the Clinical Manifestations, Diagnosis, and Treatment of Liver Abscess 1. May present as fever of unknown origin: a. Dull right upper quadrant pain is associated with right upper quadrant tenderness. b. Leukocytosis and elevated alkaline phosphatase are seen. 2. CT scan is the diagnostic study of choice. 3. With a single abscess, use serology to rule out amoebiasis. 4. Treat with percutaneous drainage and broad­spectrum antibiotic coverage (same regimens as for secondary peritonitis). 5. Use open drainage for the patient with a. biliary obstruction, b. multiloculated abscess (other than Echinococcus), or c. viscous exudate. Diagnosis, Treatment, and Outcome With the exception of amoebic liver abscess, the peripheral WBC count is usually elevated (above 20,000/mm3), with increased numbers of immature neutrophils. Serum alkaline phosphatase is also elevated in most cases. Blood cultures are positive in up to half of patients. Abdominal CT scan is the most sensitive test for identifying liver abscesses; it demonstrates a discrete area of attenuation at the abscess site. Ultrasound is somewhat less sensitive, but also useful. Abscesses are found most commonly in the right lobe of the liver. If a single large abscess is noted, amoeba serology should be ordered. That test is positive in more than 90% of patients with amoebic hepatic abscess. Ultrasound and CT can both be used to guide needle aspiration for culture and drainage. A finding of brownish fluid without a foul odor suggests the possibility of amoebic abscess. Initial empiric antibiotic therapy should be identical to that for secondary peritonitis. The antibiotic regimen can subsequently be tailored to the abscess culture results. Percutaneous drainage in combination with antibiotics is now the treatment of choice. Open surgical drainage should be considered in patients who continue to have fever after 2 weeks of antibiotic treatment and percutaneous drainage. Open surgery may also be required in patients with biliary obstruction, multiloculated abscesses (other than Echinococcus—see Chapter 12), and highly viscous abscesses. Mortality was high in early series (approaching 100%) when abscesses were not drained; however, with modern antibiotics and drainage techniques, nearly 100% of patients are now cured. KEY POINTS About Pancreatic Abscess 1. Necrotic tissue can become infected by contaminated bile or hematogenous spread. 2. Abscesses are polymicrobial. 3. Use CT scan and ultrasound to guide drainage. 4. Open surgical drainage and debridement of necrotic tissue are usually required. 5. The same broad­spectrum coverage used for secondary peritonitis is recommended. 6. Fatal outcome is more likely in elderly patients. Downloaded 2024­11­2 10:50 A Your IP is Chapter 8: Gastrointestinal and Hepatobiliary Infections, Frederick S. Southwick Page 39 / 66 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility PANCREATIC ABSCESS considered in patients who continue to have fever after 2 weeks of antibiotic treatment and percutaneous drainage. Open surgery may also be Access Provided by: required in patients with biliary obstruction, multiloculated abscesses (other than Echinococcus—see Chapter 12), and highly viscous abscesses. Mortality was high in early series (approaching 100%) when abscesses were not drained; however, with modern antibiotics and drainage techniques, nearly 100% of patients are now cured. KEY POINTS About Pancreatic Abscess 1. Necrotic tissue can become infected by contaminated bile or hematogenous spread. 2. Abscesses are polymicrobial. 3. Use CT scan and ultrasound to guide drainage. 4. Open surgical drainage and debridement of necrotic tissue are usually required. 5. The same broad­spectrum coverage used for secondary peritonitis is recommended. 6. Fatal outcome is more likely in elderly patients. PANCREATIC ABSCESS POTENTIAL SEVERITY A serious, but usually not fatal, complication of pancreatitis that presents subacutely. Pancreatic abscesses usually arise as complication of pancreatitis. Release of pancreatic enzymes leads to tissue necrosis. Subsequently, necrotic tissue can become infected by reflux of contaminated bile or by hematogenous spread. Like other intra­abdominal abscesses, pancreatic abscesses are usually polymicrobial. Ultrasound and CT scan are employed for culture and drainage. Because of the significant quantity of necrotic tissue, open drainage and debridement are usually required in combination with broad­spectrum antibiotics. The same antibiotic regimens recommended for secondary peritonitis offer excellent empiric coverage pending cultures and sensitivities. Survival is improved by early surgical drainage. A fatal outcome is more likely in elderly patients, who more often have accompanying biliary tract disease. CHOLECYSTITIS AND CHOLANGITIS POTENTIAL SEVERITY An acute, potentially life­threatening infection that can be complicated by sepsis. Rapid treatment reduces morbidity and mortality. Pathogenesis and Microbiology Biliary obstruction is most frequently caused by gallstones and results in increased pressure in and distension of the gallbladder. These changes compromise blood flow and interfere with lymphatic drainage, leading to tissue necrosis and inflammation, which lead to cholecystitis. Although infection is not the primary cause of acute cholecystitis, obstruction prevents flushing of bacteria from the gallbladder and is associated with infection in more than half of all cases. If treatment is delayed, infection can spread from the gallbladder to the hepatic biliary ducts and common bile duct, causing cholangitis. The organisms associated with cholecystitis and cholangitis reflect the bowel flora and are similar to the organisms encountered in secondary peritonitis. E. coli, Klebsiella species, enterococci, and anaerobes are most frequently cultured from biliary drainage. Clinical Manifestations The acute onset of right upper quadrant pain, high fever, and chills are most common. Jaundice may also be noted, fulfilling Charcot triad (fever, right upper quadrant Downloaded pain, and10:50 2024­11­2 jaundice). On IP A Your physical is examination, marked tenderness over the liver is commonly elicited. Hypotension may be present, Chapter indicating early gram­negative sepsis. Elderly patients mayFrederick 8: Gastrointestinal and Hepatobiliary Infections, S. Southwick not complain Page 40 / 66 of pain, presenting solely with hypotension. Marked peripheral leukocytosis ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility with increased numbers of PMNs and band forms is the rule. Liver function tests are usually consistent with obstruction, demonstrating an elevated serum alkaline phosphatase, gamma­glutamyl transpeptidase, and bilirubin. On rare occasions, serum aminotransferase enzymes, reflecting The organisms associated with cholecystitis and cholangitis reflect the bowel flora and are similar to the organisms encountered in secondary peritonitis. E. coli, Klebsiella species, enterococci, and anaerobes are most frequently cultured from biliary drainage. Access Provided by: Clinical Manifestations The acute onset of right upper quadrant pain, high fever, and chills are most common. Jaundice may also be noted, fulfilling Charcot triad (fever, right upper quadrant pain, and jaundice). On physical examination, marked tenderness over the liver is commonly elicited. Hypotension may be present, indicating early gram­negative sepsis. Elderly patients may not complain of pain, presenting solely with hypotension. Marked peripheral leukocytosis with increased numbers of PMNs and band forms is the rule. Liver function tests are usually consistent with obstruction, demonstrating an elevated serum alkaline phosphatase, gamma­glutamyl transpeptidase, and bilirubin. On rare occasions, serum aminotransferase enzymes, reflecting hepatocellular damage, may also be elevated (up to 1000 IU) as a result of microabscess formation in the liver. Blood cultures are frequently positive. Diagnosis and Treatment Ultrasonography is the preferred diagnostic study, and it can usually detect gallstones, dilatation of the gallbladder, and dilatation of the biliary ducts, including the common bile duct. Other adjunctive tests may include CT scan or magnetic resonance imaging; however, these tests are generally not recommended for initial screening. Magnetic resonance cholangiopancreatography (MRCP) should be considered in patients with elevated liver function tests because this method has greater sensitivity for detecting common duct stones (100% vs. 14% for ultrasound). Endoscopic retrograde cholangiopancreatography (ERCP) is helpful for confirming the diagnosis, dilating the sphincter of Oddi, removing stones, and placing stents to maintain biliary flow in constricted, fibrotic biliary channels. This procedure should be performed under antibiotic coverage and should be avoided in cases of cholangitis because of the risk of precipitating high­level bacteremia. Broad­spectrum antibiotics should be initiated immediately. Regimens similar to those for secondary peritonitis may be used. KEY POINTS About Cholecystitis and Cholangitis 1. Caused by obstruction of the biliary tree, leading to necrosis and inflammation. 2. Polymicrobial infection occurs in more than half of cases. E. coli, Klebsiella species, enterococci, and anaerobes. 3. Charcot triad—fever, right upper quadrant pain, and jaundice—may be noted. Elderly patients may present with hypotension and no abdominal pain. 4. Diagnosis: a. Elevated alkaline phosphatase, gamma­glutamyl transpeptidase, and bilirubin. Transaminases can occasionally reach 1000 IU. b. Abdominal ultrasound is the preferred diagnostic screening tool. c. If elevated liver function tests order MRCP. d. ERCP to confirm the diagnosis and for treatment. 5. Treatment: a. Broad­spectrum antibiotics as described for secondary peritonitis. b. Biliary drainage and stone removal by ERCP is now the treatment of choice. Also used to dilate the sphincter of Oddi and to place stents to maintain flow. c. Percutaneous drainage is an option for urgent decompression. d. Surgery is required for perforated or gangrenous gallbladder. 6. Mortality in severe cholangitis approaches 50%. Prompt surgical intervention is required for patients with a gangrenous gallbladder and gallbladder perforation. In cases of acute cholecystitis, decompression of the gallbladder and stone removal is now most commonly accomplished by ERCP. Percutaneous drainage is another option for Downloaded 2024­11­2 10:50 A Your IP is decompression. Urgent decompression Chapter 8: Gastrointestinal should Infections, and Hepatobiliary be performed in patients Frederick with persistent abdominal pain, hypotension, fever above 39°C, and S. Southwick Pagemental 41 / 66 confusion. Outcome is usually favorable for mild­to­moderate disease, but mortality approaches ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility 50% in those with severe cholangitis. HELICOBACTER PYLORI­ASSOCIATED PEPTIC ULCER DISEASE  Access Provided by: 6. Mortality in severe cholangitis approaches 50%. Prompt surgical intervention is required for patients with a gangrenous gallbladder and gallbladder perforation. In cases of acute cholecystitis, decompression of the gallbladder and stone removal is now most commonly accomplished by ERCP. Percutaneous drainage is another option for decompression. Urgent decompression should be performed in patients with persistent abdominal pain, hypotension, fever above 39°C, and mental confusion. Outcome is usually favorable for mild­to­moderate disease, but mortality approaches 50% in those with severe cholangitis. HELICOBACTER PYLORI­ASSOCIATED PEPTIC ULCER DISEASE POTENTIAL SEVERITY A chronic disease that causes discomfort but is not life threatening. Microbiology and Pathogenesis Helicobacter pylori is a small, curved, microaerophilic gram­negative rod that is closely related to Campylobacter. This organism is able to survive and multiply within the gastric mucosa. Most H. pylori live freely in this environment; however, a small number adheres exclusively to gastric epithelial cells by surface adherence molecules including BabA, OipA, and SabA, forming adherence pedestals similar to those observed with enteropathogenic E. coli. This organism demonstrates corkscrew­like motility, allowing it to migrate within the gastric and duodenal mucosa. All pathogenic strains express high concentrations of urease, allowing them to generate ammonium ions that buffer the gastric acid. Colonization with H. pylori may be associated with accumulation of increased numbers of inflammatory cells in the lamina propria of gastric epithelial cells where they employ a type IV secretion system to inject a number of bacterial proteins into the host cell cytoplasm. Two of these injected bacterial proteins, CagA and CagE, stimulate the production of inflammatory cytokines that reduce somatostatin levels and increase gastrin levels. Chronic inflammation caused by H. pylori is thought to produce aplastic changes in the gastric mucosa that may lead to gastric carcinomas. KEY POINTS A b o u t Helicobacter Pylori­Associated Peptic Ulcer Disease 1. This is small, curved, microaerophilic gram­negative rod a. survives on the mucosal surface of the stomach adhering to gastric cells by BabA, OipA, and SabA, and b. synthesizes high concentrations of urease, which produces ammonium ions to neutralize acid; injects CagA and CagE that increase inflammation 2. Dyspepsia, belching, and heartburn are the most common symptoms. 3. Diagnosis: a. Test only symptomatic patients. b. Endoscopic biopsy with CLO test for urease is preferred. c. Culture only for refractory cases. d. Urease breath test is expensive, but accurate. e. Monoclonal antibody stool antigen test sensitive and specific. f. Enzyme­linked immunoabsorbent antibody test produces false positives in patients over 50 years of age; titer decreases with treatment. 4. Treatment: a. Triple therapy—PPI, plus amoxicillin, plus clarithromycin (for the penicillin­allergic, replace amoxicillin with metronidazole). b. Quadruple therapy—PPI, plus bismuth, plus amoxicillin, plus clarithromycin (or metronidazole or tetracycline). Downloaded 2024­11­2 10:50 A Your IP is Chapter 8: Gastrointestinal c. For and relapse, use a PPI, Hepatobiliary plus Infections, levofloxacin, Frederick S. Southwick plus amoxicillin. Page 42 / 66 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility with accumulation of increased numbers of inflammatory cells in the lamina propria of gastric epithelial cells where they employ a type IV secretion Access Provided by: system to inject a number of bacterial proteins into the host cell cytoplasm. Two of these injected bacterial proteins, CagA and CagE, stimulate the production of inflammatory cytokines that reduce somatostatin levels and increase gastrin levels. Chronic inflammation caused by H. pylori is thought to produce aplastic changes in the gastric mucosa that may lead to gastric carcinomas. KEY POINTS A b o u t Helicobacter Pylori­Associated Peptic Ulcer Disease 1. This is small, curved, microaerophilic gram­negative rod a. survives on the mucosal surface of the stomach adhering to gastric cells by BabA, OipA, and SabA, and b. synthesizes high concentrations of urease, which produces ammonium ions to neutralize acid; injects CagA and CagE that increase inflammation 2. Dyspepsia, belching, and heartburn are the most common symptoms. 3. Diagnosis: a. Test only symptomatic patients. b. Endoscopic biopsy with CLO test for urease is preferred. c. Culture only for refractory cases. d. Urease breath test is expensive, but accurate. e. Monoclonal antibody stool antigen test sensitive and specific. f. Enzyme­linked immunoabsorbent antibody test produces false positives in patients over 50 years of age; titer decreases with treatment. 4. Treatment: a. Triple therapy—PPI, plus amoxicillin, plus clarithromycin (for the penicillin­allergic, replace amoxicillin with metronidazole). b. Quadruple therapy—PPI, plus bismuth, plus amoxicillin, plus clarithromycin (or metronidazole or tetracycline). c. For relapse, use a PPI, plus levofloxacin, plus amoxicillin. Clinical Manifestations and Diagnosis Patients with H. pylori peptic ulcer disease usually have the classic symptom of dyspepsia: burning pain several hours after meals that is relieved by food and antacids. Belching, indigestion, and heartburn are also frequent complaints. Other than mild midepigastric tenderness, the physical examination is usually normal. Testing for H. pylori is recommended only in symptomatic patients. Noninvasive tests include the urease breath test, in which the patient ingests 13C­ or 14C­labeled urea, and their breath is analyzed for 13C or 14C over the next hour. This test requires expensive equipment, but it is sensitive (88–95%) and specific (95–100%). Stool antigen detection using a monoclonal antibody also has high sensitivity (94%) and specificity (97%) in the absence of PPI administration or gastrointestinal bleeding. In low and moderate prevalence areas this is the diagnostic test of choice. Measurement of IgG antibody levels by ELISA can also be performed; however, false negatives may occur in elderly individuals. Diagnosis is most commonly made by endoscopic biopsy. A biopsy specimen should be first tested for urease (CLO test) that has high sensitivity and specificity in patients not taking bismuth, H2 blockers, or PPIs. Biopsy is the most cost­effective diagnostic method. Specimens can also be cultured using selective media and microaerophilic conditions. Culture to obtain antibiotic sensitivities should be performed in patients who have proved refractory to therapy. H. pylori can also be visualized using silver, Gram, or Giemsa stain, and by immunofluorescence. Treatment Multiple regimens have been used to treat H. pylori, and the ideal regimen has not been determined. Triple therapy with oral amoxicillin (1 g twice Downloaded 2024­11­2 10:50 A Your IP is daily), Chapter oral 8: clarithromycin Gastrointestinal(500 andmg twice daily), and Hepatobiliary a PPI (lansoprazole Infections, Frederick S. 30 mg or omeprazole 20 mg twice daily) for 2 weeks is associated with Southwick