Probiotics and Infective Endocarditis in Patients with Hereditary
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Boumis et al. BMC Infectious Diseases (2018) 18:65 DOI 10.1186/s12879-018-2956-5 CASE REPORT Open Access Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: a clinical case and a review of the literature Evangelo Boumis* , Alessandro Capone, Vincenzo Galati, Carolina Venditti and Nicola Petrosillo Abstract Background: In the last decades, probiotics have been widely used as food supplements because of their putative beneficial health effects. They are generally considered safe but rare reports of serious infections caused by bacteria included in the definition of probiotics raise concerns on their potential pathogenic role in patients with particular predisposing factors. Patients with hereditary hemorrhagic telangiectasia (HHT) are exposed to infections because of telangiectasias and arteriovenous malformations (AVMs). We describe what is, to our knowledge, the first case of infective endocarditis (IE) caused by Lactobacillus rhamnosus in a patient with HHT. A systematic review of the relevant medical literature is presented. Case presentation: A patient with HHT and an aortic bioprosthesis was admitted because of prolonged fever not responding to antibiotics. The patient had a history of repeated serious infections with hospitalizations and prolonged use of antibiotics, and used to assume large amounts of different commercial products containing probiotics. Weeks before the onset of symptoms the patient had been treated with nasal packings and with surgical closure of a nasal bleeding site because of recurrent epistaxis. A diagnosis of IE of the aortic bioprosthesis was made. All blood coltures were positive for L. rhamnosus. The patients responded to a cycle of 6 weeks of amoxicillin/clavulanate plus gentamicin. A systematic review of IE linked to consumption of probiotics, and of infective endocarditis in patients with HHT was conducted. 10 cases of IE linked to probiotics consumption and 6 cases of IE in patients with HHT were found. Conclusions: Consumption of probiotics can pose a risk of serious infections in patients with particular predisposing factors. Patients with HHT can be considered at risk because of their predisposition to infections. Prophylaxis with antibiotics before nasal packings in patients with HHT can be considered. Keywords: Probiotics, Lactobacillus rhamnosus, Infective endocarditis, Hereditary hemorrhagic telangiectasia Background Lactobacilli for example are normally present in the oral Probiotics are described as live microbial feed supple- cavity, ileum and colon and are the dominant microor- ments that beneficially affect the host animal by improv- ganisms in the vagina [2]; these are also the most widely ing its microbial balance [1]. Many microorganisms are represented microorganisms in probiotics. considered probiotics, among these bacterial species of The use of probiotics is widespread. Traditionally, Bifidobacterium, Lactobacillus, Streptococcus, Entero- in many countries they are consumed as fermented coccus and yeasts like Saccharomyces. Many of these mi- dairy food products like yogurt. Moreover, in the last croorganisms constitute part of the normal human flora. two decades their use as food supplements has greatly increased because of their putative beneficial health effects (https://www.naturalproductsinsider.com/ * Correspondence: [email protected] National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, articles/2016/09/the-new-market-profile-of-probiotics- Italy © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Boumis et al. BMC Infectious Diseases (2018) 18:65 Page 2 of 8 consumption.aspx) [3]. Their use has also increased in bacteria and yeasts; three of these contained Lactobacil- the healthcare setting, especially among patients with im- lus rhamnosus, which was also the last probiotic used by paired intestinal integrity and chronic conditions or im- the patient before the recent admission to our hospital. munosuppression, like diabetes mellitus, chronic renal In November, 2016 the patient was transferred from the failure, HIV infection, cirrhosis, neoplasia and organ long term care facility to a medical ward because of transplant [4–7]. bacteremia caused by Streptococcus mutans, which Probiotics are generally considered safe. Rare infec- responded to a cycle of four weeks of IV antibiotics. tions involving lactobacilli or bifidobacteria have been During this hospitalization the patient continued to have reported; however, the widespread use of probiotics in alteration in bowel movements; repeated stool examina- the general population did not seem to determine an in- tions for Clostridium difficile, Salmonella, Shigella and crease of infections [8]. other enteric pathogens and a colonoscopy were nega- Hereditary hemorrhagic telangiectasia (HHT) or tive. No obvious infectious foci were detected, and in Rendu-Osler-Weber disease is an autosomal dominant December, 2016 the patient was discharged at home. disorder characterized by cutaneous telangiectasia, re- Soon after discharge the patient was treated for recur- current epistaxis and visceral arteriovenous malforma- rent epistaxis by an ENT specialist who performed laser tions (AVMs) of the lungs, gastrointestinal tract, liver, coagulation of a nasal bleeding site. and brain. Because AVMs allow the direct communica- In March, 2017, before the admission to our hospital, tion between pulmonary and systemic circulation, pa- the patient, who continued to take probiotics, was tients with HHT are at higher risk for severe infections treated at home by his attending physician with oral cip- like cerebral abscesses, septicemia, arthritis and osteo- rofloxacin followed by IM ceftriaxone for a week, be- myelitis; among extracerebral infections, endocarditis is cause of episodes of fever and night sweats, without very seldom reported. [9]. improvement of symptoms. After 6 days of antimicrobial Hereby we report a case of infective endocarditis treatment, fever and night sweats persisted together with caused by Lactobacillus rhamnosus in a patient with generalized fatigue and malaise and the patient was ad- HHT who was also a heavy consumer of probiotics, and mitted to our hospital. a review of the literature on similar cases. To our know- At admission the patient was febrile (37.9 °C) and as- ledge, this was the first case of infective endocarditis thenic; pulse rate was 87 bpm; blood pressure was 110/ caused by a probiotic strain in a patient with HHT. 70 mmHg. Skin examination revealed diffuse telangiecta- sia of the head, trunk and arms but was negative for signs Case presentation of embolic phenomena. Cardiac examination revealed a 3/ A patient aged > 65 years, affected by HHT, was admit- 6 diastolic murmur. C reactive protein was elevated at ted in March, 2017 to our Institute because of prolonged 7.46 mg/dL (normal upper value < 1); erythrocyte fever not responding to antibiotics. The patient was the sedimentation rate was 100 mm/h; white blood cells first of 4 siblings; two of them were also affected by were 4860/μl (neutrophils 72.5%, lymphocytes 16%); HHT. In 2010 after a screening visit in a reference cen- hemoglobin was 9.0 g/dL and platelets were 218,000/μl; ter for HHT a screening for AVMs of the liver, lung and albumin was 3.2 g/dL; blood chemistry, prothrombin time brain was made with negative results. Apart from re- and liver enzymes were within the normal range. Procalci- peated episodes of epistaxis, often requiring specialist tonin was 0.08 ng/mL, within the normal values. Serology ear, nose and throat (ENT) intervention, nasal packings for Salmonella, Brucella, Coxiella burnetii, Mycoplasma, and laser coagulation, the patient’s medical history was Legionella was negative. Urine culture was also negative. remarkable for repeated infections that required After three days of interruption of all antibiotics, three hospitalization during the years. In 2011 the patient had sets of blood cultures were drawn. A transesophageal a spondylodiscitis with bacteremia caused by Streptococ- echocardiogram reported an 11-mm endocarditic vege- cus mutans; in 2012 a febrile enteritis was diagnosed; in tation on the cuspids of the biologic prosthesis. Accord- 2015 an aortic bioprosthesis was implanted because of ing to Duke’s criteria [10], a diagnosis of infective aortic insufficiency. In July, 2016 the patient was hospi- endocarditis was made. Empiric treatment with ceftriax- talized for septic shock caused by Staphylococcus aureus one 2 g/day and gentamicin 3 mg/kg/day, both by IV bacteremia. After this episode the patient was admitted route, was started. Five blood cultures yielded gram to an intensive care unit and, subsequently, had a pro- positive rods, that were identified as Lactobacillus longed stay in a long term care facility; during this stay rhamnosus. This organism was sensitive to amoxicillin/ the patient had prolonged alterations in bowel move- clavulanate and gentamicin but resistant to ceftriaxone; ments