Effect of the Novel Influenza A (H1N1) Virus in the Human Immune System

BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.S

Could Immunophenotype Guide Molecular Analysis in Patients with Myeloid Malignancies?

Objective: Immunophenotype has been correlated with molecular aberrations in several studies. The aim of this study was the discovery of immunophenotypic features related to mutations in AML and MDS patients connected to prognostic factors. Moreover, an effort to evaluate a method for the detection of the most common NPM1 mutations of exon12 and Internal Tandem Duplications (ITD) mutations of FLT3 gene by flow cytometry was performed. Method: Patients with de novo myeloid neoplasms [ AML and MDS (AML-M3 patients were excluded)] were included. FLT3/ITD/TKD and NPM1 mutations were detected by PCR and fragment analysis. The immunophenotypic analysis was performed by multi-dimensional flow cytometry (FC) with a standardized panel of monoclonal antibodies on peripheral blood or bone marrow samples. Nucleophosmin Antibody and CD135 were used for the mutations immunophenotypic detection. Results: NPM1 and/or FLT3 mutations correlated with low or no expression of more immature cells markers such as CD34, CD117, HLADR, as well as higher expression of more mature markers such as CD11b. The higher expression of CD33 should be mentioned as well. The presence of NPM1mut and FLT3/ITD does not seem to be detectable by FC at least using these two monoclonal antibodies. The presence of CD7 aberrant lymphoid marker’s expression was associated with FLT3mut, NPM1wt genotype. CD56 or CD2 positivity was found only in patients’ samples negative for NPM1 and/or FLT3 mutations. Conclusions: Certain immunophenotype findings including the presence of aberrant lymphoid markers may be indicative of the presence of mutations in NPM1 and FLT3 linked to prognosis

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

The impact of an antimicrobial cycling strategy for febrile neutropenia in patients with haematological malignancies

IntroductionFebrile neutropenia represents an emergency syndrome for patients with haematologicalmalignancies demanding timely appropriate and adequate therapy. Inappropriate empiricantimicrobial therapy of septic episodes in febrile neutropenia is associated with increasedmorbidity and mortality exactly as it is for critically ill patients. Antibiotic cycling has been proposedas a strategy to combat the emergence of antimicrobial resistance but has been implemented withconflicting results.MethodsA cycling strategy including four broad-spectrum antimicrobial regimens administrated sequentiallyover 3-month cycles in patients with febrile neutropenia was implemented in a hematology unit,during a 31months period (2001–2003). The endpoints of the study included the impact of cyclingon the adequacy of empiric treatment in the management of febrile neutropenia, the effectivenessof cycling in controlling antimicrobial resistance rates and the colonization of patients with MDRpathogens, using rectal surveillance cultures.ResultsDuring the study period, 58 episodes of febrile neutropenia in 30 patients were recorded and 52episodes (90%) were enrolled in the study. Compliance to the strategy ranged between 57 and100% and overall successful clinical response was 83%. Resistance rates of Gram negativesremained either stable or decreased for Pseudomonas aeruginosa witch was the most commonisolated pathogen at the end of the cycling period and no rectal colonization with resistantpathogens was recorded during the study period. The incidence of Gram-negative showed adecreasing trend while Gram-positives and resistance rates remained unaffected and at low rates. ConclusionsStrengths of the present study are the high rates of empiric treatment appropriateness andsuccessful clinical response, the positive effect on Gram-negative resistance rates, Despite the factthat all studies regarding cycling are relatively old, the study presented here confirms along with theothers present in the literature that antibiotic cycling is feasible in hematology units and withoutadverse effects. Using appropriate cycling design and antibiotic choices, it could be tested as a toolagainst the rapidly increasing antimicrobial resistance.ΕισαγωγήΗ εμπύρετη ουδετεροπενία για τους αιματολογικούς ασθενείς αποτελεί ένα κλινικό σύνδρομοεπείγουσας αντιμετώπισης που απαιτεί την άμεση χορήγηση κατάλληλης αντιμικροβιακήςθεραπείας. Η χορήγηση μη επαρκούς αντιμικροβιακής θεραπείας στα σηπτικά επεισόδια τωνουδετεροπενικών ασθενών έχει συσχετισθεί με υψηλή νοσηρότητα και θνητότητα των ασθενώναυτών όπως ακριβώς και των βαρέως πασχόντων ασθενών στις ΜΕΘ. Το cycling παρόλο πουέχει προταθεί ως μέτρο ελέγχου της μικροβιακής αντοχής η εφαρμογή του έχει καταλήξει σεαμφιλεγόμενα αποτελέσματα. Το cycling στην παρούσα μελέτη εφαρμόστηκε σε μία μικρήαιματολογική μονάδα με στόχο να ελέγξει τα επίπεδα της μικροβιακής αντοχής λόγω αύξησης τωννοσηλευομένων ασθενών με εμπύρετα επεισόδια ουδετεροπενίας και άρα αύξησης τηςκατανάλωσης των αντιμικροβιακών ευρέος φάσματος στο συγκεκριμένο κλινικό τμήμα.ΜεθοδολογίαΗ κυκλική εφαρμογή 4 αντιμικροβιακών σχημάτων ευρέος φάσματος εφαρμόστηκε σε μίααιματολογική μονάδα σε ασθενείς με εμπύρετη ουδετεροπενία για 3-5 μήνες το κάθε σχήμαΠραγματοποιήθηκαν δύο κύκλοι συνολικής διάρκειας 31 μηνών (2001-2003). Μελετήθηκε ηεπίδραση του cycling στην καταλληλότητα της αντιμικροβιακής αγωγής που χορηγήθηκε στουςασθενείς με εμπύρετη ουδετεροπενία, στην κλινική ανταπόκριση των ασθενών, στην εξέλιξη τηςμικροβιακής αντοχής και στον αποικισμό των ασθενών από πολυανθεκτικά παθογόνα.ΑποτελέσματαΚατά την διάρκεια της μελέτης νοσηλεύτηκαν στην κλινική αιματολογικοί ασθενείς που εμφάνισαν58 επεισόδια εμπύρετης ουδετεροπενίας εκ των οποίων τα 52 (90%) εισήχθησαν στην μελέτη. Ησυμμόρφωση στην εφαρμογή του πρωτοκόλλου κυμάνθηκε από 57%-100% και η συνολικήεπιτυχή ανταπόκριση των ασθενών στην αρχική χορηγούμενη αντιμικροβιακή θεραπέια ήταν 83%.Τα επίπεδα μικροβιακής αντοχής των Gram αρνητικών παθογόνων παρέμεινε σταθερή ενώ για τηνPseudomonas aeruginosa που αποτέλεσε το συχνότερο απομονωθέν παθογόνο τα επίπεδαμειώθηκαν στο τέλος της περιόδου εφαρμογής του προγράμματος. Κανένας από τους ασθενείς δεναποικίσθηκε (ορθικός αποικισμός) με πολυανθεκτικό στέλεχος. Η επίπτωση των Gram αρνητικών παθογόνων μειώθηκε τόσο στην κλινική όσο και στο υπόλοιπο νοσοκομείο ενώ των Gram θετικώνπαρέμεινε σταθερή στα χαμηλά αρχικά επίπεδα.ΣυμπεράσματαΤα αποτελέσματα της παρούσας μελέτης βασίζονται στα υψηλά επίπεδα χορήγησης κατάλληλήςεμπειρικής αντιμικροβιακής αγωγής και κλινικής ανταπόκρισης των ασθενών καθώς επίσης καιστην θετική επίδραση του cycling στην εξέλιξη της μικροβιακής αντοχής. Παρόλο το γεγονός ότι οιπερισσότερες μελέτες όπως και η παρούσα είναι σχετικά παλιές καταλήγουν στο ότι η εφαρμογήτου cycling σε αιματολογικές μονάδες είναι εφικτή χωρίς ανεπιθύμητες επιπτώσεις. Ο κατάλληλοςσχεδιασμός της εφαρμογής ενός προγράμματος cycling καθώς και η κατάλληλη επιλογή τωναντιβιοτικών που θα χορηγηθούν θα μπορούσε να μετατρέψει το συγκεκριμένο μέτρο σε ένααποτελεσματικό μέτρο κατά της ταχέως αυξανόμενης μικροβιακής αντοχής

Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek university hospital

Background. The dissemination of acquired metallo-beta-lactamases (MBLs) in members of the family Enterobacteriaceae is regarded as an emerging clinical threat. The clinical characteristics and outcomes of 17 cases of infection due to MBL-producing isolates were analyzed. Methods. During a 3-year period, medical records for all patients with confirmed infection due to an MBL-producing strain belonging to the Enterobacteriaceae family were retrospectively analyzed. We screened for MBL production with the imipenem-ethylenediaminetetraacetic acid disk synergy test, and results were confirmed by polymerase chain reaction. Genetic relatedness between isolates was evaluated by repetitive extragenic palindromic polymerase chain reaction. Results. Fourteen cases of bacteremia and 3 cases of ventilator-associated pneumonia due to an MBL-producing isolate were studied. Most of the patients had previously been colonized with an MBL-producing organism, and almost 60% had been exposed to carbapenems before infection. The isolated pathogens (Klebsiella pneumoniae, 14 cases; and Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes, 1 case each) exhibited variable minimum inhibitor concentrations of carbapenems (1 to &gt; 32 mu g/mL) and resistance to most other beta-lactams. Tigecycline was active against all isolates, whereas colistin and gentamicin were active against 88% of them. Molecular studies confirmed the presence of a gene belonging to bla(VIM-1) cluster in all isolates. Among the 12 K. pneumoniae isolates, which were subjected to molecular typing, 11 distinct clones were identified. Five cases (similar to 30%) occurred in patients who were already receiving carbapenem-containing treatment, and carbapenem treatment was considered to have failed. Twelve cases were treated with a colistin-containing regimen. The attributable mortality rate was 18.8%. Conclusions. MBL-producing Enterobacteriaceae can cause severe, often fatal infection in severely ill patients, irrespective of the MIC of carbapenems. Colonization with an MBL-producer is a preceding event, highlighting the importance of surveillance. Both infection control practices and antibiotic policies should be intensified to contain the spread of these problematic bacteria

The impact of an antimicrobial cycling strategy for febrile neutropenia in a haematology unit

Antibiotic cycling has been proposed as a strategy to combat the emergence of antimicrobial resistance but has been implemented with conflicting results. A cycling strategy including four broad-spectrum antimicrobial regimens administrated sequentially over 3-month cycles in patients with febrile neutropenia was implemented in a haematology unit, during a 2-year period (2001-2003). Compliance to the strategy ranged between 57 and 100% and overall successful clinical response was 83%. Resistance rates of Gram negatives remained either stable or decreased (for Pseudomonas aeruginosa) at the end of the cycling period and no rectal colonization with resistant pathogens was recorded during the study period. The incidence of Gram-negative infections showed a decreasing trend while Gram-positive infections and resistance rates remained unaffected and at low rates

Colistin susceptibility testing by Etest and disk diffusion methods

The accuracy of disk susceptibility methods for colistin against 778 bacterial pathogens was evaluated in comparison with Etest using interpretive criteria available from the Clinical and Laboratory Standards Institute (CLSI). Colistin exhibited excellent activity against Acinetobacter baumannii and Escherichia coli isolates (minimum inhibitory concentration for 90% of the organisms (MIC90) = 0.5 mg/L), whilst it was less active both against Enterobacter spp. and Klebsiella pneumoniae (MIC for 50% of the organisms (MIC50) = 0.5 mg/L, MIC90 = 16 mg/L). Colistin also showed good activity against Pseudomonas aeruginosa (MIC90 = 2 mg/L, MIC50 = 1 mg/L) but poor activity against Stenotrophomonas maltophilia (MIC50 = 8 mg/L, MIC90 = 128 mg/L). Only 0.8% of minor errors were observed between the studied methods for P. aeruginosa isolates when the CLSI criteria were applied. All A. baumannii isolates with a zone diameter &lt;= 12mm were resistant and those with a zone diameter &gt;= 14mm were susceptible according to MIC breakpoints established by the CLSI. Among nine isolates exhibiting a zone diameter of 13 mm, one was resistant to colistin (MIC = 8 mg/L) and eight isolates were susceptible (MIC = 0.5 mg/L). Applying a MIC breakpoint of &lt;= 2 mg/L for susceptibility in Enterobacteriaceae, all isolates with a zone diameter &gt;= 14mm were susceptible, whilst all isolates with a zone diameter &lt;= 11mm were resistant. Among isolates with zone diameters of 12-13 mm, 59% were characterised as susceptible. Major errors were observed only in K. pneumoniae isolates at a rate of 0.8%. The poor agar diffusion characteristics of colistin limit the predictive accuracy of the disk diffusion test and consequently values of 12-13mm should be confirmed with MIC determination by Etest or broth dilution method. (C) 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved