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Nov./Dec. 2009
Vol. 19 No. 11
Patient Care and Science
EIN Update: Intestinal Complications, Oseltamivir, and H1N1

The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of EIN, IDSA (EIN’s sponsor), or the Centers for Disease Control and Prevention (CDC), which funds the EIN. The reader assumes all risks in using this information. 

As this challenging influenza season continues, EIN members are asking about intestinal complications possibly related to novel H1N1 influenza and the effects of oseltamivir. Starting a recent discussion, a member from Ohio shared the case of a 5-year-old child who recently died after being hospitalized with a PCR-confirmed case of H1N1.

“My understanding is the child had improved to the point that discharge was considered,” the member wrote. “He then rapidly deteriorated and died. [A] post-mortem exam found 700 mL of dark brown fluid in the abdominal cavity. It seems difficult to believe the processes are unrelated, but I find nothing in the literature about an association.” Other details from the autopsy were not yet available, the member reported.

A respondent from Texas described a 4-year-old who tested positive for influenza at an outside hospital using a rapid test, was started on oseltamivir, and “presented to us with very severe colitis on day four of [oseltamivir]. He was in DIC [disseminated intravascular coagulation]  and ultimately required surgery and colostomy due to necrosis of [the] bowel. We did a full workup and never isolated any bacterial or viral pathogen.”

Other EIN members shared related cases, including a respondent from Washington state, who described a 55-year-old man who tested positive for H1N1 but had no prior medical problems. The patient had sudden onset of malaise, diarrhea, and confusion. On admission, “he had a severe lactic acidosis and was found to have a severely ischemic colon requiring partial colectomy,” the member wrote.

A respondent from New York told of a 32-week-old infant born to a mother with fulminant and lethal H1N1. The infant developed a perforation requiring colostomy. “The mother was treated with oseltamivir, the infant was not,” the member wrote. “Despite the presumed high level viremia in the mother at the time of the infant's emergent birth, we never detected influenza from the newborn. The perforation was thought to be secondary to the intrauterine hypoxemia during the time the mother could not be effectively oxygenated/ventilated.”

A final case was shared by a member from San Diego: a 55-year-old women with confirmed H1N1 who died after three weeks. While on extracorporeal membrane oxygenation (ECMO), the patient deteriorated suddenly “with abdominal distention and elevated lactic acid of 6.3. The patient was on oseltamivir and had just received one dose of peramivir.” A chest X-ray at that time did not show air under the diaphragm, but did show pneumopericardium and pneumomediastinum. A postmortem analysis was not done.

The reports of intestinal perforation in children with H1N1 who had received oseltamivir suggest a need for more investigation, a California respondent wrote. The member suggested submitting a report to MedWatch, the Food and Drug Administration’s (FDA) safety information and adverse event reporting program. (To report an adverse event to MedWatch, visit this website or call 1-800-332-1088.)

Distinguishing between hemorrhagic colitis and ischemic colitis is important, a member from Maryland responded, noting the possibility that H1N1 “may be associated with ischemic colitis—it seems to be associated with pulmonary embolism.” The member cited a July 2009 MMWR Dispatch reporting that five out of 10 H1N1 patients in a Michigan intensive care unit had pulmonary embolism.

Oseltamivir, meanwhile, may be associated with hemorrhagic colitis and a mild coagulopathy, the member continued, citing a 2009 article in Cardiology on the influence of the antiviral on the risk of stroke after influenza infection. A member from Texas posted another reference, a 2007 Journal of Infection and Chemotherapy article describing acute hemorrhagic colitis associated with oral administration of oseltamivir for influenza.

In a separate discussion, an EIN member from Pennsylvania raised a question about the expanded use of oseltamivir: “Now that we are using unprecedented quantities of this drug, has anyone noted any associations between oseltamivir and hepatocellular injury?”

The member was aware of two adults in the past few months with unexplained increases in aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) that began after hospitalization with influenza-like illness (ILI), although neither was confirmed via rapid testing to have influenza. “In both cases, enzymes increased after admission/initiation of oseltamivir and improved after medication stopped/illness subsided,” the member wrote. “One patient had a history of liver transplantation; however, her lab abnormalities resolved too quickly to prompt a liver biopsy.”

A respondent from Washington state noted a similar association of ILI with abnormal liver enzymes in his area. “I am not sure if it relates to [oseltamivir] or the underlying ILI/H1N1 influenza,” he wrote. A 2006 commentary from the American Journal of Pathology discusses systemic viral infections and collateral liver damage, the member added.

In light of the current H1N1 pandemic, IDSA convened a group of influenza experts to address a number of clinical questions about the clinical management and antiviral treatment of patients with H1N1 influenza. This group is developing a Frequently Asked Questions document that will be available soon on the IDSA website.


E-mail the Emerging Infections Network.

The Emerging Infections Network (EIN) is a provider-based sentinel network designed to help the public-health community detect trends in emerging infectious diseases.

A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) with funding from the Centers for Disease Control and Prevention (CDC), EIN tracks emerging infectious diseases and keeps the public-health community up to date with new disease trends, difficult cases, and other issues affecting members’ clinical practices. The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. Click here for more information or to join EIN.
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