Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report
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Aeromonas species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate.
A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect) presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was negative for A. hydrophila. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events.
We present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.
KeywordsLaparoscopic Cholecystectomy Gall Bladder Cholelithiasis Tocilizumab Choledocholithiasis
Aeromonas hydrophila is distributed widely in fresh and salt water, and is also found in food, treated drinking water, domestic water supplies and hospital water supply systems [1, 2]. Typically, patients acquire Aeromonas species by oral consumption or direct contact with contaminated water or seafood. Thus, gastroenteritis and mild-to-moderate soft-tissue infections are the most common presentations. In immunocompromised individuals, such as patients with cirrhosis, malignant diseases, chronic renal failure, diabetes mellitus or steroid use, Aeromonas spp. cause substantial mortality from a wide spectrum of infections. These include hepatobiliary infection, invasive skin and soft-tissue infections, primary bacteremia, burn infections, pleuropulmonary infection, meningitis and endocarditis [1, 2]. The species A. hydrophila, A. caviae, and A. veronii biovar sobria account for more than 85% of human infections [1, 2]. Aeromonas infection is often polymicrobial and fatality rates range from 28% to 46% in cases of bacteremia, mostly caused by A. hydrophila and A. veronii biovar sobria[1, 2, 3]. Tocilizumab, developed as a treatment of rheumatoid arthritis, is a humanized anti-interleukin-6 receptor monoclonal antibody, and can cause infections as adverse events. We report here a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with rheumatoid arthritis using tocilizumab.
Aeromonas spp. are ubiquitous mobile Gram-negative rods found in water sources. They cause a wide range of human illness; possible routes of transmission include contaminated food and exposure of wounds to environments that contain the pathogen [1, 4]. Severe A. hydrophila infections usually involve immunocompromised people with chronic illness [1, 2]. Aeromonas spp. produce a beta-lactamase, which makes them resistant to ampicillin and first-generation cephalosporins. The antimicrobial agents most active against Aeromonas are the third-generation cephalosporins, imipenem and fluoroquinolones [5, 6].
The frequency of acute suppurative cholangitis due to Aeromonas is low (less than 3%) [1, 3]. Aeromonas hepatobiliary infections are commonly associated with cholelithiasis, choledocholithiasis, malignancy, other immunocompromised conditions and recent surgical procedures [1, 2, 3].
Tocilizumab, used for the treatment of rheumatoid arthritis, is a humanized monoclonal antibody against interleukin-6, a cytokine that plays a multifunctional and important role in the immune response . Infection was the most common adverse event associated with tocilizumab in clinical trials [7, 8]. Serious bacterial, viral or fungal infections can occur when using tocilizumab, such as tuberculosis . The rate of serious infections was 3.6 events per 100 patient-years, but the overall rate of fatal infections was low (0.13 events per 100 patient-years) .
In this immunocompromised patient receiving treatment with tocilizumab and with known cholelithiasis, sepsis with A. hydrophila and Klebsiella pneumoniae developed secondary to pyogenic cholangitis due to choledocholothiasis. No gastrointestinal symptoms preceded or were concurrent with sepsis, and a stool culture was negative for A. hydrophila. There were no signs of soft tissue infection and no previous episodes of treating infections with antibiotics during the past year. Only A. hydrophila was detected in the gall bladder after the cholangitis had improved. These results may suggest that A. hydrophila was carried in the biliary tract and that stone obstruction of the biliary tract caused sepsis with ascending infection of Klebsiella pneumoniae. No other infectious pathway seems likely.
In healthy individuals, bacteria are not found in the gall bladder, but in patients with gallstones the percentage of positive cultures depends upon the severity of the disease and age . Thus, preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.
We present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in a patient with gallstones and rheumatoid arthritis using tocilizumab.
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