Frequent detection of CMV and EBV in the intestine of patients with inflammatory bowel disease

Background: Although a growing number of reports have described inflammatory bowel disease (IBD) complicated with cytomegalovirus (CMV) and Ebstein Barr (EBV) infection, there are limited molecular studies that investigate CMV and EBV genome in intestinal sections of patients with IBD. Methods: A cross-sectional prospective study was conducted between September 2000 and June 2003 in a cohort of 85 patients diagnosed with IBD (58 with ulcerative colitis and 27 with Crohn’s disease) in 2 adult gastrointestinal referral centers in Athens, Greece. Prevalence of CMV and EBV infection was estimated by pathologic studies in intestinal sections and by molecular assays in blood and intestinal tissue samples of IBD patients and compared with those from a control group of 45 individuals with noninflammatory diseases. Results: Immunohistochemical staining showed CMV antigen in 18 IBD patients (13 with ulcerative colitis, 16 with severe disease), whereas CMV antigen was not detected in any of the controls. CMV genome in both the intestinal tissue [29 (34,1%) of the 85 patients] and blood [23 (28%) of the 82 patients] was found by polymerase chain reaction. 21 (36,2%) out of 29 CMV positive patients had ulcerative colitis and the remaining 8 (29,6%) had Crohn’s disease. In addition, five (5,9%) IBD patients (2 with ulcerative colitis and 3 with Crohn’s disease) had detectable CMV genome in their intestinal samples but not in their blood. In the control group, five (11,6%) individuals had detectable CMV genome in their blood, but only one (2,6%) in his intestine. EBV detection in the intestinal tissue by PCR revealed 43/75 (57%) positive patients; 31/53 (58%) had ulcerative colitis and 12/22 (54%) had Crohn’s disease. EBV detection in blood by PCR revealed 24/88 (27%) positive patients. In addition 26 (68%) patients with clinically severe ulcerative colitis more often had detectable EBV genome in their intestinal tissue as well as the 11(73%) patients with severe Crohn’s disease. In the control group, 20 (44%) individuals had detectable EBV genome in their blood but only 6 (15%) in their intestine. Conclusion: Patients with ulcerative colitis had more often detectable CMV genome in their blood as well as in their intestinal tissue samples compared with controls (p= 0.036 and p<0,0001, respectively). However, patients with Crohn’s disease had more often detectable CMV genome only in their intestinal tissue samples compared with controls (p=0,0005). Detection of CMV genome in blood or intestinal tissue was significantly associated with short duration of IBD (p=0,0088 and 0,04, respectively) but not with age, sex, severity of the disease, activity at colonoscopy, pancolitis, administration of a specific treatment, and surgery. In this cross-sectional prospective study, detection of CMV genome or antigen in the intestine was commonly associated with IBD. Patients with ulcerative colitis compared with control subjects more often had detectable EBV genome only in their intestinal tissue (p=0,00001). The same was noticed with Crohn’s disease not only in the intestinal tissue but also in the blood (p=0,0013 and p=0,016 respectively). In addition patients with clinically severe IBD (ulcerative colitis and Crohn disease) more often had detectable EBV genome in their intestinal tissue (p=0,0195 and p=0,096 respectively).Στη βιβλιογραφία υπάρχουν πολλές αναφορές σχετικά με ασθενείς με ΙΦΝΕ στους οποίους εμπλέκεται λοίμωξη κυρίως από CMV, αλλά και EBV στην πορεία της νόσου. Δεν υπάρχουν όμως ικανές μελέτες σχετικά με την μοριακή ανίχνευση του γονιδιώματος τόσο του CMV όσο και του EBV σε εντερικά τεμάχια ασθενών με ΙΦΝΕ. Μέθοδοι: Η προοπτική μελέτη πραγματοποιήθηκε από τον Σεπτέμβριο 2000 μέχρι και τον Ιούνιο 2003 σε 85 ασθενείς στους οποίους υπήρχε διαγνωσμένη ΙΦΝΕ (58 με ελκώδη κολίτιδα και 27 με νόσο Crohn) σε δύο γαστρεντερολογικές κλινικές μεγάλων νοσοκομείων της Αθήνας. Έγινε εκτίμηση της επίπτωσης της λοίμωξης από CMV και EBV με παθολογοανατομικές τεχνικές σε εντερικά τεμάχια καθώς και μοριακές τεχνικές τόσο στο αίμα όσο και στον εντερικό ιστό των ασθενών με ΙΦΝΕ και σύγκριση με ομάδα μαρτύρων που αποτελούσαν 45 άτομα που δεν παρουσίαζαν φλεγμονή στο έντερο. Αποτελέσματα: Η ανοσοϊστοχημική μελέτη παρουσίασε CMV αντιγόνο σε 18 ασθενείς με ΙΦΝΕ (13 με ελκώδη κολίτιδα, 16 με έξαρση) ενώ δεν ανιχνεύτηκε σε κανένα από την ομάδα των μαρτύρων. Το CMV γονιδίωμα τόσο στο αίμα σε 23 από 82 ασθενείς (28%)όσο και στους ιστούς ανιχνεύτηκε με PCR σε 29 (34,1%) από τους 85 ασθενείς με ΙΦΝΕ, οι 21 (36,2%) απ΄αυτούς με ελκώδη κολίτιδα και οι 8 (29,6%) με ν. Crohn. Επίσης σε 5 (6%) ασθενείς με ΙΦΝΕ (2 με ελκώδη κολίτιδα και 3 με νόσο Crohn) ανιχνεύτηκε CMV γονιδίωμα στον εντερικό ιστό χωρίς να ανιχνευτεί στο αίμα τους. Στην ομάδα των μαρτύρων σε 5 (11,6%) άτομα ανιχνεύτηκε CMV γονιδίωμα στο αίμα τους αλλά μόνο σε ένα (2,6%) στον εντερικό ιστό. Στον EBV δεν πραγματοποιήθηκε ανοσοϊστοχημική μελέτη των ιστών. Το EBV γονιδίωμα ανιχνεύτηκε με PCR στον ιστό σε 43 (57%) από τους 75 ασθενείς με ΙΦΝΕ από τους οποίους οι 31 (58%) με ελκώδη κολίτιδα και οι 12 (54%) με ν. Crohn, ενώ στο αίμα σε 24 (27%) από τους 88. Ενδιαφέρον παρουσιάζουν τα αποτελέσματα με PCR στον ιστό στους ασθενείς με ΙΦΝΕ σε έξαρση τόσο σε ελκώδη κολίτιδα σε 26 ασθενείς (68%) όσο και σε ν. Crohn σε 11 από τους 15 ασθενείς (73%). Στην ομάδα των μαρτύρων σε 20 (44%) άτομα ανιχνεύτηκε EBV γονιδίωμα στο αίμα τους αλλά μόνο σε 6 (15%) από τα 39 στον εντερικό ιστό. Συμπέρασμα: Στους ασθενείς με ελκώδη κολίτιδα ανιχνεύεται συχνότερα το CMV γονιδίωμα στο αίμα τους όπως και στο ιστό σε σύγκριση με την ομάδα μαρτύρων (p=0,036 και p<0,0001 αντίστοιχα). Οι ασθενείς όμως με ν. Crohn έχουν πιο συχνά CMV γονιδίωμα μόνο στον εντερικό ιστό σε σχέση με την ομάδα μαρτύρων (p=0,0005) και όχι στο αίμα. Η ανίχνευση του CMV γονιδιώματος στο αίμα ή τον εντερικό ιστό έχει σχέση με τη μικρή διάρκεια της νόσου (p=0,0088 και 0,04 αντίστοιχα) αλλά όχι με την ηλικία, το φύλο, την σοβαρότητα της νόσου, την ενεργότητα κατά την εξέταση της κολονοσκόπησης, το τοξικό μεγάκολο, τη θεραπεία ή τη χειρουργική αντιμετώπιση. Επίσης στους ασθενείς με ελκώδη κολίτιδα ανιχνεύεται συχνότερα το EBV γονιδίωμα μόνο στον ιστό (p<0,0001) σε σχέση με την ομάδα μαρτύρων. Οι ασθενείς όμως με ν. Crohn έχουν πιο συχνά ΕBV γονιδίωμα τόσο στον εντερικό ιστό όσο και στο αίμα (p=0,0013 και p=0,016 αντίστοιχα). Τέλος υπάρχει στατιστικά σημαντική διαφορά στην παρουσία EBV γονιδιώματος στην έξαρση της νόσου και στις δύο οντότητες δηλαδή στην ελκώδη κολίτιδα και στη ν. Crohn αλλά μόνο στον εντερικό ιστό σε σχέση με τους ασθενείς που βρίσκονται σε ύφεση τόσο ενδοσκοπικά όσο και κλινικά (p=0,0195 και p=0,096 αντίστοιχα)

The challenge of curbing aminoglycoside resistance: can antimicrobial stewardship programs play a critical role?

Introduction: Aminoglycosides are useful antimicrobials, primarily for serious infections involving aerobic gram-negative pathogens. The inevitable increase in aminoglycoside resistance has led to calls for reducing levels of inappropriate aminoglycoside prescribing through the implementation of various antibiotic stewardship programs (ASPs). These programs mainly include restriction policies and aminoglycoside cycling. Although aminoglycoside resistance rates appear essential for measuring effectiveness of these interventions, most studies have focused on economic outcomes or clinical efficacy and toxicities. Areas covered: In the present study we estimated through a systematic literature review, the impact of early cycling studies and ASPs to aminoglycoside resistance rates for gram-negative pathogens. Expert commentary: Most ASPs support a positive association between aminoglycoside control policies and decrease of resistance rates. However, factors associated with aminoglycoside resistance are complex and multifactorial making it difficult to attribute resistance changes to a specific intervention. Optimized, high-dose, extended-interval aminoglycoside dosing and subsequent dosage monitoring by means of area under the curve and Cmax estimation, seem the most important strategies to improve clinical outcome, minimize toxicity and diminish resistance. The role of the clinical laboratory, using rapid and advanced assays and involved in pharmacodynamic target achievements, is also crucial to enable individualized or tailored aminoglycoside therapy. Future ASPs will need to combine high-quality epidemiological tools, novel diagnostic approaches and effective infection control measures. © 2017 Informa UK Limited, trading as Taylor &amp; Francis Group

Escherichia hermannii as the sole isolate from a patient with purulent conjunctivitis

Escherichia hermannii was isolated in pure culture from a patient with acute purulent conjunctivitis after a minor ocular injury. This is the first report of E. hermannii isolated as the sole pathogen from an infected site without prior antibiotic exposure, confirming the pathogenic potential of the microorganism. Copyright © 2008, American Society for Microbiology. All Rights Reserved

Trends in antimicrobial resistance of clinical isolates of Enterococcus faecalis and Enterococcus faecium in Greece between 2002 and 2007

We analysed trends in antimicrobial resistance of Enterococcus faecalis (N=1498) and E. faecium (N=625) recovered from clinical infections during 2002-2007 in a Greek tertiary care hospital. Molecular assays were used to confirm speciation and genotype of vancomycin-resistant enterococci (VRE). The incidence of infections per 1000 admissions caused by E. faecalis and E. faecium increased during the study period (χ2 for trend=25.5 and 13.3, respectively; P&amp;lt;0.0001). Resistance to ampicillin, high level gentamicin and streptomycin, vancomycin, teicoplanin and linezolid was found in E. faecalis/E. faecium at rates of 1.3/82.4%, 45.6/51.2%, 48.9/69.1%, 0.5/9.6%, 0.1/8.2% and 0.3/1.6%, respectively. The vanA gene was identified in 79.1% of the VRE isolates, with vanB found in the remaining 20.1%. Analysis of antimicrobial resistance trends showed consistently high rates of ampicillin resistance among E. faecium isolates. For both enterococcal species, high level resistance to gentamicin and streptomycin were noted to have increased significantly (P&amp;lt;0.0001). Regardless of these alarming trends, strains exhibiting resistance to oxazolidinones seem to be only sporadic in our region and a trend toward increasing resistance rates to glycopeptides was not detected. © 2009 The Hospital Infection Society

Fecal microbiome transplantation as a means of multidrug resistant bacterial decolonization of the intestine

&lt;p&gt;The partial or complete imbalance of the intestinal microbiome, as a consequence of extensive antibiotic use, can establish a number of pathological conditions, including colonization with multidrug resistant bacteria, which can subsequently lead to severe infections. Therefore, the attempt to restore the microbiome to its prior condition is an approach that can be used supplementary to other therapeutic options. This procedure can be performed through fecal microbiome transplantation (FMT), a method that is being used effectively in treating recurrent Clostridium difficile infection. Several studies have indicated that FMT can effectively eliminate the carrier status of ESBL producing Gram-negative bacteria in up to 40% of the patients. Furthermore, fecal transplantation was able to de-colonize patients from vancomycin-resistant Enterococcus as well as methicillin-resistant Staphylococcus aureus. In addition, this method may be a therapeutic option for antibiotic-associated hemorrhagic colitis. However, as the application of this methodology in research protocols is very recent and the reports are scarce, more studies are required in order to establish the actual effectiveness as well as the safety of FMT in multidrug resistant bacterial de-colonization.&lt;/p&gt

Trends in antimicrobial resistance of clinical isolates of Enterococcus faecalis and Enterococcus faecium in Greece between 2002 and 2007

We analysed trends in antimicrobial resistance of Enterococcus faecalis (N = 1498) and E. faecium (N = 625) recovered from clinical infections during 2002-2007 in a Greek tertiary care hospital. Molecular assays were used to confirm speciation and genotype of vancomycin-resistant enterococci (VRE). The incidence of infections per 1000 admissions caused by E. faecalis and E. faecium increased during the study period (chi(2) for trend = 25.5 and 13.3, respectively; P < 0.0001). Resistance to ampicillin, high level gentamicin and streptomycin, vancomycin, teicoplanin and linezolid was found in E. faecalis I E. faecium at rates of 1.3/82.4%, 45.6/51.2%, 48.9/69.1%, 0.5/9.6%, 0.1/8.2% and 0.3/1.6%, respectively. The vanA gene was identified in 79.1% of the VRE isolates, with vanB found in the remaining 20.1%. Analysis of antimicrobial resistance trends showed consistently high rates of ampicillin resistance among E. faecium isolates. For both enterococcal species, high level resistance to gentamicin and streptomycin were noted to have increased significantly (P < 0.0001). Regardless of these alarming trends, strains exhibiting resistance to oxazolidinones seem to be only sporadic in our region and a trend toward increasing resistance rates to glycopeptides was not detected. (C) 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved

Evaluation of a new phenotypic OXA-48 disk test for differentiation of OXA-48 carbapenemase-producing Enterobacteriaceae clinical isolates

The current phenotypic methods for detecting carbapenemase-producing Enterobacteriaceae (CPE) allow differentiation between class A and B carbapenemases, but they cannot confirm in a single test class D OXA-48 carbapenemase producers. In this study, we evaluated a new phenotypic test, the OXA-48 disk test, which is based on an imipenem disk and two blank disks adjacent to the imipenem disk, loaded with the tested strain and impregnated with EDTA and EDTA plus phenyl boronic acid (PBA), respectively. The evaluation of the OXA-48 disk test was performed with 81 genotypically confirmed OXA-48-type-producing Enterobacteriaceae isolates (41 extended-spectrum β-lactamase [ESBL] producers, 3 AmpC producers, and 37 non-ESBL, non-AmpC producers). To measure the specificity of the test, 173 genotypically confirmed OXA-48-negative Enterobacteriaceae isolates (57 Klebsiella pneumoniae carbapenemase [KPC] producers, 34 VIM producers, 23 KPC/VIM producers, 22 NDM producers, and 37 AmpC or ESBL producers and porin deficient) that were nonsusceptible to at least one carbapenem were chosen for testing. Using the imipenem disk and the distortion of the inhibition halo around both blank disks containing EDTA and EDTA/PBA, the test differentiated all but 3 of the 81 OXA-48 producers (sensitivity of 96.3%). The test was negative for OXA-48 production in all but 4 of the 173 carbapenem-nonsusceptible isolates producing other carbapenemases, AmpCs, or ESBLs (specificity of 97.7%). This evaluation shows that the OXA-48 disk test is an accurate phenotypic method for the direct differentiation of OXA-48-producing Enterobacteriaceae. Its use along with combined disk tests employing inhibitor-supplemented carbapenem disks might allow the differentiation of the currently known carbapenemase types in Enterobacteriaceae species and provide important infection control information. Copyright © 2015, American Society for Microbiology. All Rights Reserved

Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay

Antibiotic combinations including tigecycline have not been studied against Klebsiella pneumoniae carbapenemase (KPC)-producing pathogens. Tigecycline alone and combined with colistin and meropenem was tested against eight genetically unrelated KPC-producing clinical strains of Enterobacteriaceae (four K. pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Serratia marcescens) by time-kill assay. Tigecycline displayed a concentration-independent bacteriostatic activity in seven strains and bactericidal activity in one strain. Colistin showed bactericidal activity at 4x the minimum inhibitory concentration (MIC) in three strains and was bacteriostatic for the remaining strains and concentrations. Meropenem was bactericidal in three strains and bacteriostatic in five strains. The tigecycline + meropenem combination was not bactericidal against the four K. pneumoniae strains and was non-synergistic against all eight strains. Tigecycline + colistin was bactericidal against all strains at most time intervals and concentrations and was also synergistic at 1x and 2x MIC against most strains up to 4-8 h and at 4x MIC up to 24 h against all strains. These findings suggest that, at most drug concentrations, tigecycline, colistin and meropenem as single agents do not exhibit efficient bactericidal activity against most of the KPC-producing strains. Tigecycline alone might be a therapeutic option for infections caused by KPC-producers when bacteriostatic activity is adequate or combined with colistin when bactericidal activity is necessary. Additional in vivo tests are warranted to assess better the killing kinetics of tigecycline combinations against KPC-producers. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved