Management of Clostridioides difficile infection: an Italian Delphi consensus.

BACKGROUND: Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. OBJECTIVES: To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. METHODS: An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. RESULTS: Consensus was reached on 21 of the 25 statements addressing the management of CDI. CONCLUSIONS: Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy.

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Meningococcal Conjunctivitis in a 54-Year-Old Man: Case Report and Review of the Literature.

Neisseria meningitidis represents an uncommon pathogen of acute bacterial conjunctivitis. In this brief report, we describe a case of meningococcal conjunctivitis in an immunocompetent adult male, with a review of the literature. The patient went to the outpatient ophthalmology clinic complaining of severe ocular discomfort, burning, and redness for more than 2 weeks and, at slit lamp examination, he was diagnosed with a mild conjunctivitis. Microbiology cultures of ocular swabs revealed the growth of colonies, as pure culture, identified as N. meningitidis of serogroup B. A diagnosis of primary meningococcal conjunctivitis was made and treatment of patient with intramuscular injections of ceftriaxone in addition to topical moxifloxacin eye drops for 2 weeks led to clinical improvement and, finally, to a complete recovery, in accordance with microbiological findings. Ophthalmologists must be aware of the possibility of primary meningococcal conjunctivitis cases, even uncommon, and the need to treat with systemic antibiotics and their close contacts with adequate antibiotic chemoprophylaxis.

The burden of Clostridioides difficile infection in COVID-19 patients: A systematic review and meta-analysis.

OBJECTIVES: The main aim of this systematic review and meta-analysis was to assess the proportion of confirmed COVID-19 patients with Clostridioides difficile infection (CDI) and to describe risk factors and outcome of these patients. METHODS: MEDLINE and Cochrane Central Register of Controlled Trials databases were searched up to July 15, 2021. We included studies reporting data on CDI occurring in patients with a confirmed diagnosis of COVID-19. We pooled proportion of CDI patients using a random effects model (DerSimonian-Laird method) stabilising the variances using the Freeman-Tukey double arcsine transformation. RESULTS: Thirteen studies were included in the systematic review. All the studies retrospectively collected data between February 2020 and February 2021. The reported CDI incidence rates ranged from 1.4 to 4.4 CDI cases per 10,000 patient-days. Seven studies reported data on the number of COVID-19 patients who developed CDI and the total number of COVID-19 patients in the study period and were included in the meta-analysis, comprising 23,697 COVID-19 patients. The overall pooled proportion of COVID-19 patients who had CDI was 1% [95% confidence interval: 1-2]. Among studies reporting CDI occurrence in patients with and without COVID-19, the majority of them reported reduced or unchanged CDI rates compared to pre-COVID period. CONCLUSIONS: CDI is a relevant issue for COVID-19 patients. Adherence to infection prevention and control measures and to the antimicrobial stewardship principles is crucial even during the COVID-19 pandemic.

Hospitalized patients with diarrhea: Rate of Clostridioides difficile infection underdiagnosis and drivers of clinical suspicion.

OBJECTIVES: Clostridioides difficile infection (CDI) represents a challenging issue, with an evolving epidemiology. Main objectives of our study were: to assess the frequency of diarrhea of overall etiology, including CDI, as a cause of hospital admission or occurring during hospital stay;- to determine the rate of underdiagnosis of community-acquired (CA-), health care associated (HCA)- and hospital onset (HO-) CDI, and explore factors associated with its clinical suspicion by physicians. METHODS: A prospective cohort study included all hospitalized patients with diarrhea at two acute-care hospitals. C. difficile (CD) tests were performed on every stool samples, irrespective of the treating physician request. Factors associated with the likelihood of CD test request by physicians were assessed. RESULTS: We enrolled 871 (6%) patients with diarrhea. CD test performed on all diarrheic stool samples was positive in 228 cases (26%); 37, 106, 85 cases of CA- (14%), HCA- (42%) and HO- diarrhea (24%), respectively. Treating physicians did not request CD test in 207 (24%) diarrhea cases. The rate of CDI underdiagnosis was 11% (24/228); it was higher in CA-CDI (27%, 10/37). Logistic regression analysis identified age >65 years (RR 1.1; 95 CI 1.06-1.2) and hospitalizations in the previous 3 months (RR 1.2; 95% CI 1.1-1.3) as independent factors associated with the likelihood of requesting the CD test by the physician. These risk factors differed by epidemiological classification of diarrhea and by hospital. CONCLUSIONS: Our study confirmed the relevance of CDI underdiagnosis and provided new insights in the factors underlying the lack of CDI clinical suspicion.

Postmortem Findings in Italian Patients With COVID-19: A Descriptive Full Autopsy Study of Cases With and Without Comorbidities.

BACKGROUND: Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse. METHODS: To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy. RESULTS: COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities. CONCLUSIONS: SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.

An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019.

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020.

Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.

Factors affecting reported Clostridioides difficile infection rates; the more you look the more you find, but should you believe what you see?

Reported rates of C. difficile infection (CDI) have increased in many settings; however, these can be affected by factors including testing density (test-density) and diagnostic methods. We aimed to describe the impact of multiple factors on CDI rates. Hospitals (n = 182) across five countries (France, Germany, Italy, Spain, and UK) provided data on; size and type of institution, CDI testing methodology, number of tests/month and patient-bed-days (pbds)/month over one year. Incidence rates were compared between countries, different sized institutions, types of institutions and testing method. After univariate analyses, the highest CDI rates were observed in Italy (average 11.8/10,000pbds/hospital/month), acute/primary hospitals (12.3/10,000pbds/hospital/month), small hospitals (16.7/10,000pbds/hospital/month), and hospitals using methods that do not detect toxin (NO-TOXIN) (e.g. GDH/NAAT or standalone NAAT) (10.7/10,000pbds/hospital/month). After adjusting for test-density, highest incidence rates were still in Italy, acute/primary hospitals and those using NO-TOXIN. The relative rate in long-term healthcare facilities (LTHCFs) increased, but size of institution no longer influenced the CDI rate. Test-density appears to have the largest effect on reported CDI rates. NO-TOXIN testing still influences CDI rates, even after adjusting for test-density, which is consistent with tests that 'overcall' true CDI. Low test-density can mask the true burden of CDI, e.g. in LTHCFs, highlighting the importance of good quality surveillance.

Extended Infusion of ß-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study.

BACKGROUND: We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). METHODS: The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. RESULTS: Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11-0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9-32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06-0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03-0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08-0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06-2.47]). CONCLUSIONS: C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient.

An unprecedented Ebola virus (EBOV) epidemic occurred in 2013-2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases "Lazzaro Spallanzani" (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract.

Joint EANM/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults.

PURPOSE: Diagnosis of spondylodiscitis (SD) may be challenging due to the nonspecific clinical and laboratory findings and the need to perform various diagnostic tests including serologic, imaging, and microbiological examinations. Homogeneous management of SD diagnosis through international, multidisciplinary guidance would improve the sensitivity of diagnosis and lead to better patient outcome. METHODS: An expert specialist team, comprising nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), neuroradiologists appointed by the European Society of Neuroradiology (ESNR), and infectious diseases specialists appointed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), reviewed the literature from January 2006 to December 2015 and proposed 20 consensus statements in answer to clinical questions regarding SD diagnosis. The statements were graded by level of evidence level according to the 2011 Oxford Centre for Evidence-based Medicine criteria and included in this consensus document for the diagnosis of SD in adults. The consensus statements are the result of literature review according to PICO (P:population/patients, I:intervention/indicator, C:comparator/control, O:outcome) criteria. Evidence-based recommendations on the management of adult patients with SD, with particular attention to radiologic and nuclear medicine diagnosis, were proposed after a systematic review of the literature in the areas of nuclear medicine, radiology, infectious diseases, and microbiology. RESULTS: A diagnostic flow chart was developed based on the 20 consensus statements, scored by level of evidence according to the Oxford Centre for Evidence-based Medicine criteria. CONCLUSIONS: This consensus document was developed with a final diagnostic flow chart for SD diagnosis as an aid for professionals in many fields, especially nuclear medicine physicians, radiologists, and orthopaedic and infectious diseases specialists.

Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

INTRODUCTION: In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking. AIM AND METHODS: To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem - Intervention/indicator - Comparator - Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed.

Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

BACKGROUND: For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking. AIM AND METHODS: To address this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart. RESULTS AND CONCLUSION: The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM).

Correction to: Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

The authors regret to inform the readers that one of the author's name in the original publication of this article was spelled incorrectly as Victor Casar-Pullicino. The correct spelling is Victor N. Cassar-Pullicino and is now presented correctly in this article.

Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement).

OBJECTIVES: Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society (EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement). METHODS AND RESULTS: After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging. CONCLUSIONS: Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics. KEY POINTS: • For peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities. • Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel. • Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Unexpected human cases of cutaneous anthrax in Latium region, Italy, August 2017: integrated human-animal investigation of epidemiological, clinical, microbiological and ecological factors.

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

Human Serum Albumin Is an Essential Component of the Host Defense Mechanism Against Clostridium difficile Intoxication.

Background: The pathogenic effects of Clostridium difficile are primarily attributable to the production of the large protein toxins (C difficile toxins [Tcd]) A (TcdA) and B (TcdB). These toxins monoglucosylate Rho GTPases in the cytosol of host cells, causing destruction of the actin cytoskeleton with cytotoxic effects. Low human serum albumin (HSA) levels indicate a higher risk of acquiring and developing a severe C difficile infection (CDI) and are associated with recurrent and fatal disease. Methods: We used a combined approach based on docking simulation and biochemical analyses that were performed in vitro on purified proteins and in human epithelial colorectal adenocarcinoma cells (Caco-2), and in vivo on stem cell-derived human intestinal organoids and zebrafish embryos. Results: Our results show that HSA specifically binds via its domain II to TcdA and TcdB and thereby induces their autoproteolytic cleavage at physiological concentrations. This process impairs toxin internalization into the host cells and reduces the toxin-dependent glucosylation of Rho proteins. Conclusions: Our data provide evidence for a specific HSA-dependent self-defense mechanism against C difficile toxins and provide an explanation for the clinical correlation between CDI severity and hypoalbuminemia.

Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: a clinical case and a review of the literature.

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.