Prevalence, incidence burden and clinical impact of healthcare-associated infections and antimicrobial resistance: a national prevalent cohort study in acute care hospitals in Greece

Purpose: Assessing the overall burden of healthcare-associated infections (HAIs) is challenging, but imperative in evaluating the cost-effectiveness of infection control programs. This study aimed to estimate the point prevalence and annual incidence of HAIs in Greece and assess the excess length of stay (LOS) and mortality attributable to HAIs, overall and for main infection sites and tracer antimicrobial resistance (AMR) phenotypes and pathogens. Patients and methods: This prevalent cohort study used a nationally representative cross-section of 8,247 inpatients in 37 acute-care hospitals to record active HAIs of all types at baseline and overall LOS and in-hospital mortality up to 90 days following hospital admission. HAI incidence was estimated using prevalence-to-incidence conversion methods. Excess mortality and LOS were assessed by Cox regression and multistate models correcting for confounding and time-dependent biases. Results: HAIs were encountered with daily prevalence of 9.1% (95% confidence interval [CI] 7.8% – 10.6%). The estimated annual HAI incidence was 5.2% (95%CI 4.4% – 5.3%), corresponding to approximately 121,000 (95%CI 103,500 – 123,700) affected patients each year in the country. 90-day mortality risk was increased by 80% in patients with HAI compared to those without HAI (adjusted hazard ratio 1.8; 95%CI 1.3 – 2.6). Lower respiratory tract infections, bloodstream infections and multiple concurrent HAIs doubled the risk of death, whereas surgical site and urinary-tract infections were are not associated with increased mortality. AMR had significant impact on the daily risk of 90-day mortality, which was increased by 90%-110% in patients infected by carbapenem-resistant gram-negative pathogens (CR-GNBs). HAIs increased LOS for an average of 4.3 (95% CI 2.4– 6.2) additional days. Mean excess LOS exceeded 20 days in infections caused by major CR-GNBs. Conclusion: HAIs, alongside with increasing AMR, pose significant burden to the hospital system. Burden estimates obtained in this study will be valuable in future evaluations of infection prevention programs

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

Infections caused by carbapenem-resistant gram-negative pathogens in hospitalized children

Background: Carbapenem-resistant Gram-negative pathogens (CRPs) are emerging as major causes of nosocomial infections that increase morbidity, mortality and healthcare costs. Little is known about CRP infections in children. Methods: All newly detected infections caused by carbapenem-resistant Klebsiella spp, Pseudomonas spp or Acinetabocater spp in hospitalized patients are prospectively reported to the Hellenic Center for Disease Control and Prevention. All children <15 years old with a CRP infection reported from November 1, 2010, through March 30, 2012, were included in this study. Results: Between November 2010 and March 2012, 71 CRP infections in 65 children (median age: 1 year) were reported. Underlying conditions existed in 50 (76.9%) children. Cases included pneumonia (25 [35.2%], including 20 ventilator-associated pneumonias), bacteremia (32.4%), urinary tract infection (19.7%) and surgical site infection (12.7%). Isolates were Pseudomonas spp (41.1%), Acinetobacter spp (39.7%) and Klebsiella spp (19.2%). The first positive culture occurred a median of 20 days (range: 0-313 days) after admission. Twenty-four (33.8%) infections occurred in patients with a history of hospitalization the previous 6 months; 42 (59.2%) and 36 (50.7%) infections occurred among patients who had received broad-spectrum antibiotics including carbapenems the previous 6 months, respectively. The crude mortality at 28 days after the first positive CRP culture was 21.1%. Conclusions: Infections caused by CRPs among children are associated with significant morbidity and mortality. Copyright © 2013 by Lippincott Williams & Wilkins

Fludarabine monophosphate in refractory B-chronic lymphocytic leukemia: Maintenance may be significant to sustain response

In the present study we report our results on the efficacy of Fludarabine monophosphate in 20 B-chronic lymphocytic leukemia (CLL) patients, refractory to conventional chemotherapy. Of the 20 patients 14 were males and 6 females with a median age of 58 years (44-70). Eight had Binet stage B and 12 stage C. They were previously treated with chlorambucil, prednisone, mini-CHOP or irradiation. Their disease duration prior to fludarabine administration was 49 months (7-180). Fludarabine was given at a dose of 25mg/m(2) daily, for five consecutive days, monthly for six months and if responding for six additional months. Treatment was administered on an outpatient basis. Complete response (CR) was observed in 7 patients (33%) and partial remission (PR) in 5 (25%). Of the complete responders 5 were males and 2 females with a median age of 60 years (range 55-68); three of them had stage B and 4 stage C disease; the median number of fludarabine courses for achieving CR was 3 (range 2-5). In all CR patients a residual monoclonal CD5/CD19 positive lymphocyte population was found in the peripheral blood. All CRs relapsed shortly after discontinuation of therapy within 12 months. The main toxicity observed was upper respiratory tract and/or pulmonary infections in 8 patients, requiring hospitalization. Among the CRs one patient died during the administration of the third course of therapy, due to a severe hypersensitivity reaction with Stevens-Johnson syndrome. The importance of maintenance therapy is also stressed as PR was sustained in some patients using 3 day cycles every 2-4 months. One patient was maintained in this fashion for 60 + months. This study showed that fludarabine is effective in CLL patients refractory to conventional chemotherapy thus it may be given as the treatment of choice if such patients still require treatment

THE SIGNIFICANCE OF PLATELET MICROPARTICLES IN PATIENTS WITH CHRONIC HEPATITIS C AND THEIR ASSOCIATION WITH ANTIVIRAL TREATMENT AND SMOKING

Background Platelet microparticles (PMPs) are platelet-derived membrane vesicles involved in cardiovascular diseases and atherosclerosis. Chronic hepatitis C (CHC) is associated with increased atherosclerosis, but the effect of therapy on its atherogenic potential has not been adequately studied. Methods We evaluated PMP levels before and after treatment with pegylated-interferon-alfa and ribavirin in 28 CHC patients compared with 20 non-alcoholic fatty liver disease (NAFLD) patients and 20 healthy volunteers (HV). Results Twenty-four (86%) CHC patients achieved sustained virological response (SVR). PMP levels were determined at baseline in CHC, NAFLD patients, and HV, and at end-of-treatment (EOT) and 24 weeks post-treatment (SVR24) in CHC patients. PMP levels at baseline were higher in CHC than NAFLD patients (P<0.001) and HV (P=0.007). Higher PMPs at baseline were observed in smokers than non-smokers with CHC (P=0.006). Among smokers from all groups, PMPs at baseline were higher in CHC than NAFLD patients (P=0.001) and HV (P=0.024). In CHC patients, PMPs declined from baseline to both EOT (P=0.035) and SVR24 (P=0.006). Only CHC patients with SVR had a significant decline in PMPs from baseline to SVR24 (P=0.018). PMPs at ΕΟΤ and SVR24 in all CHC patients were similar to PMPs in NAFLD patients and HV. Conclusions PMP levels are increased in CHC patients, particularly smokers, which further supports the atherosclerotic potential of CHC and suggests a potentially synergistic effect of smoking and CHC on the atherosclerotic process. Since PMP levels in CHC patients with SVR were similar to NAFLD patients and HV, the atherosclerotic potential of CHC seems to be abolished by effective antiviral treatment. © 2016 Hellenic Society of Gastroenterology

Prognostic implications of proliferating cell nuclear antigen (PCNA), AgNORs and p53 in non-Hodgkin's lymphomas

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival