Case Presentation: A 33-year-old man with recent travel to India presented with fevers, abdominal pain, and bloody stools. He was admitted two weeks prior to a hospital in India for fever and right upper quadrant pain where he was found to have elevated liver enzymes (ALT 569, AST 390, total bilirubin 9.9) in addition to acute Hepatitis B, Dengue, and Salmonella typhi infections. On discharge, he was prescribed and adherent to a course of an oral carbapenem (faropenem). The patient’s symptoms persisted and he presented to our institution. Admission vital signs were significant for a fever to 100.8 °F and heart rate of 125 beats per minute. Physical exam showed right upper quadrant abdominal tenderness to palpation without guarding or rebound, and negative Murphy’s sign. Labs demonstrated leukocytosis to 11,000 with 5% band neutrophils, ALT 92, AST 94, total bilirubin 2. Abdominal ultrasound found a large steatotic liver, and CT abdomen noted ileocolitis. Infectious work-up detected influenza B, Hepatitis B surface antibody and core IgM antibody, and Salmonella typhi on blood and stool cultures. IgM and IgG antibodies to Dengue virus were undetectable. The patient was treated with oseltamivir and ceftriaxone with subsequent resolution of his symptoms.
Discussion: Typhoid fever is an acute febrile illness caused by Salmonella typhi, transmitted via fecal-oral route through contaminated food and water. 11-21 million cases of typhoid fever occur per year globally, with an estimated 110,000 deaths. (1) With increasing antibiotic resistance in endemic countries, it is important to recognize signs in international travelers and avoid delays in treatment. We describe an unusual case of typhoid fever in a traveler from India with multiple concomitant infections with different modes of transmission: Influenza, Dengue, and Hepatitis B viruses. Co-infection with multiple tropical illnesses presenting as an acute hepatitis, although infrequently seen in the United States, is common in Asia. (2) Prior studies suggest that Hepatitis B infection impairs the action of mononuclear phagocytes, predisposing patients to infection by intracellular pathogens such as Salmonella typhi. (3) Interestingly, our patient was prescribed an oral carbapenem, faropenem, which is only approved for use in Japan and India. Clinical trials have demonstrated limited efficacy of faropenem, with the risk of fostering cross-resistance to other carbapenems, resulting in the FDA declining to approve the medication for use in the United States. (4) Hepatitis B may have predisposed our patient to subsequent typhoid fever and bacteremia, and inadequate antimicrobial coverage with faropenem likely contributed to his persistent symptoms. Ultimately, a broad differential diagnosis for this patient’s hepatocellular injury with persistent fevers informed a thorough infectious work-up that led to effective management of his concomitant infections.
Conclusions: We present the case of a patient with recent travel to India found to have persistent Typhoid bacteremia after a course of oral faropenem in the setting of acute Hepatitis B, Dengue, and Influenza infections. Co-infection of Typhoid fever and Hepatitis B is uncommon and infrequently reported in the literature. In the absence of swift diagnosis and effective treatment, typhoid fever can lead to septic shock and death. It remains critical for U.S. hospitalists to have a high index of suspicion for uncommon pathogens in patients with recent international travel.