A 46-year-old woman with newly diagnosed and untreated HIV infection was admitted to the ICU last night with possible pneumocystis pneumonia. Her CD4 count is 42 cells/µL. She is currently intubated and sedated. Since arrival she has had five episodes of bloody loose stools. PCR for C. difficile is negative and stool studies for bacteria and parasites are pending. Colonoscopy performed at bedside reveals areas of friable, erythematous mucosa with submucosal hemorrhage and large, deep ulcerations. Biopsies are sent for definitive diagnosis.
What empiric antimicrobial should you start while awaiting results?
Correct Answer: C
Although increasingly rare with improvements in antiretroviral therapy, cytomegalovirus colitis is still a concern in HIV-positive patients with CD4 counts <100 cells/µL (usually <50 cells/µL). As the colitis progresses through the full thickness of the bowel, there is a risk for perforation, a life-threatening surgical emergency. Other complications include hemorrhage, infection, and toxic megacolon. Thinning of the bowel wall can lead to bacteremia. Patients with suspected CMV colitis with severe symptoms such as this one should be started on empiric antiviral therapy while awaiting definitive pathologic diagnosis. Endoscopic and biopsy findings confirm the diagnosis. Endoscopy findings are variable and can include diffuse or localized areas of friable, erythematous mucosa with submucosal hemorrhage and mucosal ulcerations. Biopsy shows characteristic intranuclear (“owl’s eye”) and cytoplasmic inclusion bodies. Recommended treatment is either ganciclovir or foscarnet for 3 to 6 weeks. Relapse is common and maintenance therapy is often required for those with poorly controlled HIV. Prophylaxis with valganciclovir is indicated until the CD4 count is >100 cells/µL for 6 months, and there is no evidence of active CMV disease. PCR for toxigenic genes is highly specific and sensitive for diagnosis of C. difficile colitis. So, a negative PCR rules out CDI.
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A 56-year-old man with a recent diagnosis of acute myeloid leukemia was admitted 10 days ago for induction chemotherapy with cytarabine and anthracycline. Over the past 24 hours he has developed worsening abdominal pain and distension along with a fever of 38.8°C and watery diarrhea. CT shows bowel wall thickening of >10 mm in both the small and large intestine.
Which of the following statements is true regarding this patient’s likely diagnosis?
Correct Answer: B
Neutropenic enterocolitis (NE), also known as necrotizing enterocolitis or ileocecal syndrome, involves inflammation and necrosis of the gut in a neutropenic patient caused by an invasive infection. Patients with an absolute neutrophil count (ANC) <1,500 cells/µL are at risk, although generally the ANC is much lower. Any segment of the gastrointestinal (GI) tract may be involved. Patients being treated for acute leukemia appear to be at highest risk, but it has been documented in most neutropenic and immunocompromised populations. The lack of neutrophils allows overgrowth of gut organisms, particularly gram-negative bacilli. One proposed mechanism of NE is GI distension and impaired perfusion leading to decreased mucosal integrity, allowing entry of these organisms into the bowel wall. Bowel wall integrity can also be compromised by chemotherapy. This can lead to ischemic necrosis, perforation, and/or peritonitis. Signs include lower abdominal tenderness and distension, watery diarrhea, and occasionally GI bleeding. Bacteremia is common and many patients will present with sepsis. Gram-negative bacteria are the usual culprit, but other bacteria and fungi are not uncommon. Most experts suggest that the combination of abdominal pain and fever in a neutropenic patient warrants treatment for presumptive NE with imaging used to help confirm the diagnosis. CT often shows bowel wall thickening and edema, which is also common in C. diff colitis; pneumatosis intestinalis is more specific for either NE or ischemia. Other CT findings can include nonspecific ileus, phlegmon, pericecal inflammation, mesenteric stranding, free air, and extraluminal fluid collections. Histologic examination is the gold standard for diagnosis, but due to the risk of perforation and bleeding from colonoscopy in neutropenic, thrombocytopenic patients, tissue samples are rarely obtained. Colonoscopy can show thickened, edematous, hemorrhagic bowel with diffuse ischemic colitis present in the majority of cases. Treatment includes broad-spectrum antibiotics, bowel rest, nasogastric suction, parenteral nutrition, and IV fluids. Myeloid growth factors may also improve outcomes. Surgery is reserved for those with evidence of perforation, peritonitis, gangrenous bowel, or refractory GI hemorrhage. In fact, all febrile neutropenic patients should be started on empiric broad-spectrum antibiotics.
A previously healthy 36-year-old woman is brought in by ambulance following a seizure. Her husband reports that she has no history of seizures but had been complaining of diarrhea and vomiting for almost a week. She went out of town to a family reunion 10 days ago and had talked to several other family members who also became ill, some even needed to go to the hospital. On examination the patient is confused with diffuse abdominal tenderness. Vitals are within normal limits. Although in the ED she experiences an episode of grossly bloody diarrhea. Significant laboratory results include:
Peripheral blood smear shows a large number of schistocytes.
Which of the following statements is true regarding this patient’s disease process?
Correct Answer: D
Enterohemorrhagic Escherichia coli (EHEC or Shiga toxin producing E. coli) is a cause of bloody, infectious diarrhea commonly associated with ingestion of contaminated food such as fresh produce, undercooked beef, or various prepackaged products. Although most infections resolve without complications, occasionally patients go on to develop the triad of nonimmune hemolytic anemia, thrombocytopenia, and AKI known as hemolytic-uremic syndrome (HUS). Although HUS is more commonly associated with children, some newer outbreaks have preferentially affected adults. The most common serotype is E. coli O157:H7; however, outbreaks associated with non-O157 serotypes have also been reported. The incubation period is 2 to 12 days. Stool culture is the gold standard for diagnosis, but a presumptive diagnosis can be made based on the presence of bloody diarrhea and the triad of HUS. Central nervous system involvement is common and can include seizures, stroke, coma, hemiparesis, or cortical blindness. Management of the gastroenteritis is generally supportive care including IV fluids. Antimotility agents should not be given and may be associated with increased risk of developing HUS. Antibiotics have not been found to be helpful. For patients who develop HUS, admission with close monitoring is recommended with the use of IV fluids, antihypertensives, renal replacement therapy, and red blood cell transfusions as clinically indicated. Anticoagulation, fresh frozen plasma, steroids, or Shiga toxin binders have not been shown to offer benefit. Unlike with thrombotic thrombocytopenic purpura or nondiarrheal (atypical) HUS, plasmapheresis has also not been shown to improve outcomes. Overall prognosis is good, even for patients that require dialysis. EHEC-associated HUS has a mortality rate of <5%.
A 63-year-old woman with a history of hypertension and dyslipidemia presents to the emergency department with severe right upper quadrant pain. On examination, she is grimacing and agitated with notable jaundice. She is oriented to self only. She has right upper abdominal tenderness, but no peritoneal signs. Vital signs include:
Pertinent laboratory test results include:
Blood cultures are pending. An ultrasound performed at bedside shows biliary dilation.
Appropriate initial management includes which of the following:
Severe acute cholangitis is a life-threatening condition caused by biliary obstruction complicated by infection of the biliary tree. Many patients present with Charcot’s triad of right upper quadrant abdominal pain, fever, and jaundice. In cases of severe (suppurative) cholangitis, patients may also have hypotension and altered mental status, which make up Reynold’s pentad. Any type of biliary obstruction can lead to acute cholangitis, but biliary calculi are the most common cause. Other causes include benign or malignant biliary stricture and biliary stent obstruction. Enteric bacteria are the most common culprit, and 20% to 80% of patients will have bacteremia. Gram-negative rods such as E. coli and Klebsiella are often cultured, but gram-positive cocci and anaerobes are not unusual.
The diagnosis of acute cholangitis can be difficult; many patients have a more subtle presentation than this case. Updated Tokyo guidelines for definitive diagnosis include the presence of three criteria: (1) systemic inflammation (fever, leukocytosis, leukopenia, or elevated C-reactive protein, (2) cholestasis (jaundice or liver function tests >1.5 times upper limit of normal), and (3) imaging findings (biliary dilation or evidence of the cause of biliary obstruction on imaging). There are many imaging choices, but ERCP is the most sensitive and has the added benefit of treating the cholangitis through decompression of the biliary tree. However, given the risk associated with sedation/anesthesia for this procedure, noninvasive imaging is usually performed first. Management is focused on treating the infection and relieving obstruction. First steps include rehydration with IV fluids, correction of electrolyte abnormalities and coagulopathy, and broad spectrum antibiotics. Frequently recommended first-line antibiotic regimens include piperacillin/tazobactam or a third- or fourth-generation cephalosporin.
Patients with severe acute cholangitis such as this one should be monitored in the ICU because they are at risk for rapid clinical deterioration and mortality is high. Patients managed only conservatively have a mortality approaching 100%, so the next step is biliary decompression, with ERCP preferred over surgery. ERCP has a success rate of 98% and a much lower complication rate compared to surgical decompression. Surgical drainage is now rarely performed because of a very high risk of complications (∼66%) and a mortality rate >30%.
A previously healthy 42-year-old man was admitted to the ICU last night with progressive weakness and was intubated early this morning when he became unable to protect his airway. Per his wife, he was in his usual state of health until 2 days ago when he began to complain of weakness, numbness, and pain in his legs. She called an ambulance yesterday when he started having similar symptoms in his arms. On examination he has symmetric weakness in both upper and lower extremities and absence of deep tendon reflexes. CSF studies show a protein level of 110 mg/dL (normal range 15- 45 mg/dL) and a white blood cell count of <5 cells/µL. Further history reveals that the whole family had suffered a diarrheal illness a couple of weeks ago.
What is the most commonly identified infectious precursor to this patient’s syndrome?
Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis. Patients generally present with progressive, symmetric ascending weakness of the limbs, often accompanied by paresthesia and pain. On examination, patients will have hypo- or areflexia. GBS may progress to involve the facial nerves and respiratory muscles. CSF studies often reveal albuminocytologic dissociation with an elevated protein level, but normal cell counts. C. jejuni is the most commonly identified infectious disease preceding the development of GBS, occurring in around 30% of cases. CMV is the second most common and Epstein-Barr virus, varicellazoster virus, and Mycoplasma pneumoniae have also been implicated. C. jejuni appears to cause GBS via an autoimmune mechanism involving carbohydrate mimicry between human ganglioside GM1 and C. jejuni lipooligosaccharide. Another late onset complication of C. jejuni is reactive arthritis, also via an immune mechanism.