Lung function at three months after hospitalization due to COVID­19 pneumonia: Comparison of alpha, delta and omicron variant predominance periods.

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant.

Early 3­day course of remdesivir for the prevention of the progression to severe COVID­19 in the elderly: A single­centre, real­life cohort study.

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes.

Bone Marrow Iron Stores Are Not Associated with Increased Risk for Invasive Fungal Infections in Patients with Newly Diagnosed Acute Leukemia or Myelodysplastic Syndrome in Transformation: Is There a Relationship?

Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation to determine whether baseline iron overload as measured using the bone marrow iron store (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow-up period (invasive aspergillosis n = 16, candidemia n = 5, mucormycosis n = 1). A baseline BMIS score ≥ 3 indicated that iron overload was relatively common (38/98 patients, 38%), and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05-325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation.

The Use of Low-Dose Chest Computed Tomography for the Diagnosis and Monitoring of Pulmonary Infections in Patients with Hematologic Malignancies.

The study aimed to assess the image quality and diagnostic performance of low-dose Chest Computed Tomography (LDCCT) in detecting pulmonary infections in patients with hematologic malignancies. A total of 164 neutropenic patients underwent 256 consecutive CT examinations, comparing 149 LDCCT and 107 Standard-Dose Chest CT (SDCCT) between May 2015 and June 2019. LDCCT demonstrated a 47% reduction in radiation dose while maintaining acceptable image noise and quality compared to SDCCT. However, LDCCT exhibited lower sensitivity in detecting consolidation (27.5%) and ground glass opacity (64.4%) compared to SDCCT (45.8% and 82.2%, respectively) with all the respective p-values from unadjusted and adjusted for sex, age, and BMI analyses being lower than 0.006 and the corresponding Odds Ratios of detection ranging from 0.30 to 0.34. Similar trends were observed for nodules ≥3 mm and ground glass halo in nodules but were not affected by sex, age and BMI. No significant differences were found for cavitation in nodules, diffuse interlobular septal thickening, pleural effusion, pericardial effusion, and lymphadenopathy. In conclusion, LDCCT achieved substantial dose reduction with satisfactory image quality but showed limitations in detecting specific radiologic findings associated with pulmonary infections in neutropenic patients compared to SDCCT.

Biomarkers predicting the 30­day mortality of patients who underwent elective surgery and were infected with SARS­CoV­2 during the post­operative period: A retrospective study.

The coronavirus disease 2019 (COVID-19) pandemic is a significant global concern that has had major implications for the healthcare system. Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoing elective or emergency surgical procedures have a substantial risk of mortality and peri-operative complications. The present study aimed to describe the characteristics of patients who underwent elective surgery and developed nosocomial SARS-CoV-2 infection post-surgery. Patients who underwent thoracic, upper and lower abdominal or peripheral elective surgery with a polymerase chain reaction diagnosis of COVID-19, at 3-7 days after the surgery, were enrolled in the present retrospective study. Demographics, vaccination status against SARS-CoV-2, Charlson comorbidity index (CCI) and laboratory data were recorded upon admission to the hospital unit. In total, 116 subjects (80 males, 36 females; mean age, 67.31±16.83 years) fulfilling the inclusion criteria were identified. Among the 116 participants, 14 (12.1%) were intubated. From the 116 individuals analyzed, 84 were alive after 30 days (survivors), and 32 had succumbed to the disease (non-survivors). The mortality rate was 27.6% (32/116). The non-survivors had an older age and a higher CCI score. At the evaluation upon admission to the hospital unit, the survivors presented with higher serum albumin levels and a higher number of blood lymphocytes. In addition, the survivors exhibited lower levels of lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase (ALP) and C-reactive protein (CRP), as well as a higher neutrophil to lymphocyte ratio (NLR) and CRP to albumin ratio (CAR) (P<0.05). The patients that were intubated had higher levels of gamma glutamyl-transferase (GGT), ALP and ferritin, as well as a higher NLR and platelet to lymphocyte ratio upon admission to the hospital unit (P<0.05). According to the Cox proportional hazards multivariate regression analysis, the only independent predictors of mortality and intubation were ALP and GGT upon admission, respectively (P<0.05). On the whole, the findings of the present study suggest that more stringent guidelines are required in order to prevent infection during the post-operative period.

Immature granulocytes: Innovative biomarker for SARS­CoV­2 infection.

Immature granulocytes (IGs) include metamyelocytes, myelocytes and promyelocytes, and are the precursors of neutrophils. Increased IG counts found in peripheral blood indicate an enhanced bone marrow activity. In addition, IGs have been evaluated in numerous clinical conditions, such as severe acute pancreatitis, systemic inflammatory response syndrome and infectious complications following open­heart surgery under cardiopulmonary bypass. Neutrophils are considered to play a crucial role in the host defense during bacterial and fungal infections, and are involved in the antiviral immune response. Numerous studies have reported the role of neutrophils in coronavirus disease 2019 (COVID­19) infection, concluding that the percentage of neutrophils may be a predictor of the severity of COVID­19 infection. There has been limited research regarding the role of neutrophil precursors in viral infections, including severe acute respiratory syndrome coronavirus 2 infection. The present thus aimed to evaluate the role of the IG count in patients hospitalized due to COVID­19 infection. The patients were predominantly infected with the alpha variant and were all unvaccinated. The IG count was measured and was found to be associated with disease severity, with patient outcomes, with the duration of hospitalization and with the development of complications. The IG count was a significantly associated with the severity of COVID­19 infection, with greater IG count values being detected in severe and critical cases. In addition, greater IG count values were associated with a longer duration of hospitalization. Furthermore, the IG count was found to be an independent prognostic biomarker of intubation and mortality in patients with COVID­19, according to multivariate logistic regression analysis, including age, the male sex and the presence of comorbidities as confounders.

Evaluation of the Dynamiker® Fungus (1-3)-ß-D-Glucan Assay for the Diagnosis of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies.

INTRODUCTION: The Dynamiker® Fungus (1-3)-ß-D-glucan assay (DFA) allows the testing of samples in smaller batches compared to the well-established Fungitell® assay (FA) making the assay cost-effective in centers with small numbers of samples. Evaluations of its performance for the diagnosis of invasive aspergillosis (IA) are limited. Therefore, we compared the two assays and evaluated their clinical performance in diagnosing IA. METHODS: A total of 60 adult hematology patients were screened for IA, 13 with probable IA, 19 with possible IA, and 28 with no IA. Serum specimens (n = 166) were collected twice-weekly and tested for (1-3)-ß-D-glucan (BDG) using FA and DFA which were compared quantitatively with Spearman rank correlation analysis and qualitatively with the Chi-square test. Agreement and error rates were determined using FA as the reference method. Sensitivity, specificity, and positive predictive and negative predictive values in diagnosing IA were calculated. RESULTS: The performance of the DFA was highly consistent with that of the FA, both quantitatively (rs = 0.913) and qualitatively (kappa = 0.725). The agreement was 85% with 8% minor, no major, and 7% very major errors (FA+/DFA-). Using a cut-off value of 20 pg/mL for DFA, very major errors were reduced to 1%, although 5% major errors were detected. BDG levels were lower with DFA than FA (slope 0.653 ± 0.031). Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) was 67%, 53%, 44%, and 74% for FA, and 53%, 67%, 49%, and 71% for DFA, respectively. The optimal BDG positivity threshold calculated did not lead to significant test quality improvement for either assay. However, a higher % of patients with probable IA (62%) had ≥ 2 consecutive positive specimens compared to patients with no IA (FA-BDG 26%, p = 0.10, and DFA-BDG 10%, p = 0.01) leading to improved sensitivity and NPV (71% and 85% for DFA, and 95% and 96% for FA, respectively). CONCLUSION: DFA could be a valuable alternative to the FA, particularly in laboratories with small numbers of samples. The results of the BDG testing should be carefully interpreted in the high-risk setting of patients with hematologic malignancies. Higher NPV was found using as criterion ≥ 2 consecutive positive samples for diagnosing IA.

Lymphogranuloma Venereum Mimicking Lymphoma on FDG PET/CT.

ABSTRACT: A 42-year-old man presented with painless, left inguinal lymphadenopathy, which was suspicious of malignant lymphoma. Multiple left-sided foci of markedly increased metabolic activity were observed on PET/CT (SUVmax up to 22.3), located at the inguinal, iliac, and para-aortic lymph nodes along with small-sized right inguinal lymphadenopathy. Laboratory tests revealed increased inflammation markers and neutrophilic leukocytosis. Pathological examination from dissected inguinal lymph node was consistent with granulomatous disease. Infection by chlamydia trachomatis was made serologically establishing the diagnosis of lymphogranuloma venereum.

Is Carbapenem-resistant Klebsiella pneumoniae Infection in Pediatric Bone Marrow Transplantation Recipients Inevitably Fatal?

Carbapenem resistance, most notably in Klebsiella pneumonia (KPC), results in infections associated with significant morbidity and mortality. Here we report 2 cases of adolescent patients with KPC infection after high-risk bone marrow transplantation, who eventually succumbed from other causes and review the epidemiology and treatment options for KPC infections in this vulnerable population.

Performance, Correlation and Kinetic Profile of Circulating Serum Fungal Biomarkers of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies.

As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-ß-D-glucan (BDG) and Aspergillus DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens (n = 240) from 93 adult hematology patients with probable (n = 8), possible (n = 25) and no (n = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0% for GM (X2 = 55, p < 0.001), 62%/46%/35% for BDG (X2 = 2.5, p = 0.29), 62%/33%/27% for PCR (X2 = 3.9, p = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X2 = 31, p < 0.001), 50%/8%/22% for BDG + PCR (X2 = 6.5, p = 0.038) and 38%/4%/0% for GM + BDG + PCR (X2 = 21, p < 0.001). Higher agreement (76%) and negative correlation (rs = -0.47, p = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45-55% and 90-92% when biomarkers assessed alone and increased to 75-90% and 93-97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11-0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA.

Evolution of epidemiological characteristics of infective endocarditis in Greece.

OBJECTIVE: The clinical profile, management and outcome of infective endocarditis (IE) may be influenced by socioeconomic issues. METHODS: A nationwide prospective study evaluated IE during the era of deep economic crisis in Greece. Epidemiological data and factors associated with 60-day mortality were analyzed through descriptive statistics, logistic and Cox-regression models. RESULTS: Among 224 patients (male 72.3%, mean age 62.4 years), Staphylococcus aureus (n = 62; methicillin-resistant S. aureus (MRSA) 33.8%) predominated in the young without impact on mortality (p = 0.593), whilst Enterococci (n = 36) predominated in the elderly. Complications of IE were associated with mortality: heart failure [OR 2.415 (95% CI: 1.159-5.029), p = 0.019], stroke [OR 3.206 (95% CI: 1.190-8.632), p = 0.018] and acute kidney injury [OR 2.283 (95% CI: 1.085-4.805), p = 0.029]. A 60-day survival benefit was solely related to cardiac surgery for IE during hospitalization [HR 0.386 (95% CI: 0.165-0.903), p = 0.028] and compliance with antimicrobial treatment guidelines [HR 0.487 (95% CI: 0.259-0.916), p = 0.026]. Compared with a previous country cohort study, history of rheumatic fever and native valve predisposition had declined, whilst underlying renal disease and right-sided IE had increased (p < 0.0001); HIV infection had emerged (p = 0.002). No difference in rates of surgery and outcome was assessed. CONCLUSIONS: A country-wide survey of IE highlighted emergence of HIV, right-sided IE and predominance of MRSA in the youth during a severe socioeconomic crisis. Compliance with treatment guidelines promoted survival.

A Prospective Multicenter Cohort Surveillance Study of Invasive Aspergillosis in Patients with Hematologic Malignancies in Greece: Impact of the Revised EORTC/MSGERC 2020 Criteria.

Data concerning the incidence of invasive aspergillosis (IA) in high-risk patients in Greece are scarce, while the impact of the revised 2020 EORTC/MSGERC consensus criteria definitions on the reported incidence rate of IA remains unknown. A total of 93 adult hematology patients were screened for IA for six months in four tertiary care Greek hospitals. Serial serum specimens (n = 240) the sample was considered negative by PCR were collected twice-weekly and tested for galactomannan (GM) and Aspergillus DNA (PCR) detection. IA was defined according to both the 2008 EORTC/MSG and the 2020 EORTC/MSGERC consensus criteria. Based on the 2008 EORTC/MSG criteria, the incidence rates of probable and possible IA was 9/93 (10%) and 24/93 (26%), respectively, while no proven IA was documented. Acute myeloid leukemia was the most (67%) common underlying disease with most (82%) patients being on antifungal prophylaxis/treatment. Based on the new 2020 EORTC/MSGERC criteria, 2/9 (22%) of probable and 1/24 (4%) of possible cases should be reclassified as possible and probable, respectively. The episodes of probable IA were reduced by 33% when GM alone and 11% when GM + PCR were used as mycological criterion. The incidence rate of IA in hematology patients was 10%. Application of the 2020 EORTC/MSGERC updated criteria results in a reduction in the classification of probable IA particularly when PCR is not available.

A comparative study of heterogeneous antibiotic resistance of microbial populations in conventional periprosthetic tissue cultures and sonication fluid cultures of orthopaedics explanted prostheses.

BACKGROUND: "Heterogeneity" describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. We aim to investigate the frequency of heterogeneity among microbes isolated from infected prostheses, and its possible correlation with microbial resistance. METHODS: Between May 2014 and June 2019, we investigated 234 patients, at our institution, undergoing revision arthroplasty because of loosening of the prostheses or because of periprosthetic joint infection. All patients had periprosthetic tissue culture, sonication of prosthesis and direct inoculation of Sonication fluid into blood culture bottles. We assessed the presence of heterogeneity among all pathogens isolated from infected prostheses. RESULTS: Using standard non-microbiological criteria to determine periprosthetic joint infection, it was found that 143 patient (61.1%) had aseptic loosening while 91 patients (38.9%) had periprosthetic joint infection. Comparing the two methods, the results of our study showed that the method of sonication was significantly more sensitive than tissue culture [91% (83-96) vs. 43% (33-54); p < 0.005]. In this study, heterogeneity was reported in 15 cases, 16.5% of all infections and 6.4% in the total population. In our study, Staphylococcus epidermidis was the most commonly isolated strain followed by Staphylococcus aureus, at a rate of 35.2% and 19.8%, respectively. Antibiotics in which the microorganisms exhibited heterogeneous bacterial behavior most frequently were Gendamicin (5.3%), Vancomycin (4.9%). CONCLUSION: There is increasing evidence that heterogeneity can lead to therapeutic failure and that the detection of this phenotype is a prerequisite for a proper antibiotic choice to have a successful therapeutic effect.

Regulatory T Cell Counts and Development of Malignancy in Patients with HIV Infection.

BACKGROUND: T-regulatory cells (Tregs) play an important role in maintaining homeostasis by attenuating the cytokine response to T-cell receptor (TCR) stimulation and by suppressing the functioning of neighboring immune cells. In Human Immunodeficiency Virus (HIV) infection, Tregs can be either beneficial, by suppressing generalized T-cell activation, or detrimental, by suppressing protective anti-HIV cell-mediated immunity. An imbalance of Tregs and effector T-cells can blunt immune responses to malignant cells or facilitate inflammation-mediated pathologies. OBJECTIVE: The purpose of our study was to explore the possible correlation between Tregs' concentration and HIV infection's parameters as well as the development of hematological and solid malignancies. METHODS: In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline. All patients were then followed up every 3 months and the development of solid or hematological malignancies was noted. RESULTS: A total of 155 patients were included in the study and the median follow-up period was 64 months. Treg counts were significantly higher among males, patients with high viral load (>350 copies/ml) and patients with virological failure to antiretroviral treatment (ART). Linear regression analysis showed a significant negative correlation between Treg levels and CD4 (+) T-cell counts. Patients with neoplasia had lower levels of Tregs while increasing levels showed a negative correlation with the development of neoplasia. CONCLUSION: In our population of HIV-infected patients, high levels of Tregs were associated with disease progression, and low baseline levels were associated with a higher probability of developing neoplasia.

Management of osteoarticular fungal infections in the setting of immunodeficiency.

Introduction: Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendations based on low quality evidence. Furthermore, the differences between the management of immunocompromised and immunocompetent patients are not distinct. This is a narrative review after a literature search in PubMed, up to November 2019.Areas covered: The major fungal groups causing osteomyelitis and/or arthritis are Candida spp., Aspergillus spp., non-Aspergillus filamentous fungi, non-Candida yeasts and endemic dimorphic fungi. Their epidemiology is briefly analyzed with emphasis on immunodeficiency and other risk factors. Management of OAFIs includes appropriate antifungal drug therapy (liposomal amphotericin B, triazoles or echinocandins), local surgery and immunotherapy for primary immunodeficiencies. Cessation of immunosuppressive drugs is also mandated.Expert opinion: Management of OAFIs includes affordable and available options and approaches. However, research on therapeutic practices is urgently required to be further improved, due to the rarity of affected patients. Evolution is expected to translate into novel antifungal drugs, less invasive and precise surgical approaches and targeted enhancement of immunoregulatory pathways in defense of challenging fungal pathogens.

Toxoplasma gondii: How fatal is it in pediatric allogeneic bone marrow transplantation setting?

Toxoplasmosis is a disease of the immunocompetent population. However, cases of toxoplasma infection associated with immunosuppression have been reported, especially the first months after transplantation. Limited data are available about toxoplasma infection, occurring even many months post-transplant in pediatric patients with nonmalignant and malignant diseases. We report the cases of three patients with early and late disseminated toxoplasmosis and review the literature.

Management of Invasive Fungal Infections in Adult Patients with Hematological Malignancies in Greece during the Financial Crisis: Challenges and Recommendations.

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece.

Therapy of Mucormycosis.

Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties.

Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies.

Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance.

Point-prevalence survey of healthcare facility-onset healthcare-associated Clostridium difficile infection in Greek hospitals outside the intensive care unit: The C. DEFINE study.

BACKGROUND: The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS: There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea. RESULTS: 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009). CONCLUSIONS: The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.