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Introduction: The Dynamiker® Fungus (1–3)-β-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)-β-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. © 2022, The Author(s).

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 open‑heart 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 (COVID‑19) infection, concluding that the percentage of neutrophils may be a predictor of the severity of COVID‑19 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 COVID‑19 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 COVID‑19 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 COVID‑19, according to multivariate logistic regression analysis, including age, the male sex and the presence of comorbidities as confounders.

Objective: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. Design: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability. Methods: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-followup (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound. Findings: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980 - 2018). Median time to diagnosis was 3.5 years (IQR: 1.1 - 7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years. Interpretation: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infec-tions/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV‐1 outbreak ten years ago in Athens, Greece. Transmission rate can be consid-ered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hos-pitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupa-tion differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75–12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Objectives: Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals. Methods: Cross-sectional survey. Results: A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values

Objectives Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. Methods Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. Results A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. Conclusions Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission. ©

Healthcare workers (HCWs) have been recognized as a high-risk group for infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study estimated their risk of infection based on hospital characteristics. Factors significantly associated with increased risk for SARS-CoV-2 infection were: working in a non-referral hospital compared with a coronavirus disease 2019 (COVID-19) referral hospital, working in a hospital with a high number of employees, and working in a hospital with an increased number of patients with COVID-19. This study revealed gaps in infection control in the non-referral hospitals. There is an urgent need for continuous training in infection control practices. Compliance of HCWs with the use of personal protective equipment should also be addressed. © 2020 The Healthcare Infection Society

Objectives: To assess the impact of an antifungal stewardship (AFS) program on appropriate use, consumption and acquisition costs of antifungals, and on clinical outcomes (in-hospital-mortality, in-hospital-length-of-stay). Methods: The study was conducted at a 535-bed tertiary-care hospital and had three consecutive periods. A) Observational period (10 months): all antifungal prescriptions were prospectively evaluated. B) Educational intervention to increase the awareness on proper antifungals use. C) Implementation of a non-compulsory AFS program (10 months) based on prospective audit and feedback. Interrupted time series analysis has been used to assess the impact of the intervention. Results: During the pre-interventional period 198 AF prescriptions for 147 patients, have been evaluated compared to 181 prescriptions in 138 patients during the AFS period. Statistical analysis showed a significant immediate drop of inappropriate prescriptions after intervention with a significantly declining trend thereafter, and a significant drop of the total consumption of antifungals immediately after the intervention with a significant declining trend thereafter. All-cause, in-hospital- mortality was stable during the pre-intervention period with a significant declining trend after the AFS program implementation, although no immediate intervention effect could be established. Comparison of pre-and post-interventional periods showed significant reduction in acquisition costs (-26.8%, p

Background: To investigate intention rates to get vaccinated against COVID-19 among healthcare personnel (HCP) in Greece. Methods: Cross-sectional survey. Results: The response rate was 14.5%. Of 1521 HCP with a known profession, 607 (39.9%) were nursing personnel, 480 (31.6%) physicians, 171 (11.2%) paramedical personnel, 72 (4.7%) supportive personnel, and 191 (12.6%) administrative personnel. Overall, 803 of 1571 HCP (51.1%) stated their intention to get vaccinated while 768 (48.9%) stated their intention to decline vaccination. Most HCP (71.3%) who reported intent to get vaccinated noted contributing to the control of the pandemic and protecting their families and themselves as their reasons, while the most common reason for reporting intent to decline vaccination was inadequate information about the vaccines (74.9%), followed by concerns about vaccine safety (36.2%). Logistic regression analysis revealed that the probability of intending to get vaccinated increased with male gender, being a physician, history of complete vaccination against hepatitis B, history of vaccination against pandemic A (H1N1) in 2009–2010, belief that COVID-19 vaccination should be mandatory for HCP, and increased confidence in vaccines in general during the COVID-19 pandemic. The following factors were associated with a lower intention to get vaccinated: no vaccination against influenza the past season, no intention to get vaccinated against influenza in 2020–2021, and no intention to recommend COVID-19 vaccination to high-risk patients. Conclusion: There is an urgent need to built safety perception towards COVID-19 vaccines and raise vaccine uptake rates by HCP, and thus to protect the healthcare workforce and the healthcare services. © 2021 Australasian College for Infection Prevention and Control

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. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

Aim: Healthcare personnel (HCP) are prioritized for coronavirus disease 2019 (COVID-19) vaccination to protect them and non-disruptive provision of healthcare services. We assessed the impact of the Pfizer-BioNTech vaccine on morbidity and absenteeism among HCP. Methods: We studied 7445 HCP in five tertiary-care hospitals in Greece from November 15, 2020 through April 18, 2021. Results: A total of 910 episodes of absenteeism and 9695 days of absence were recorded during the entire study period. Starting from January 4, 2021, 4823/7445 HCP (64.8%) were fully or partially vaccinated. Overall, 535 episodes of absenteeism occurred from January 4, 2021 through April 18, 2021, including 309 (57.76%) episodes among 2622 unvaccinated HCP and 226 (42.24%) episodes among 4823 vaccinated HCP (11.8 versus 4.7 episodes of absenteeism per 100 HCP, respectively; p-value < 0.001). The mean duration of absenteeism was 11.9 days among unvaccinated HCP compared with 6.9 days among vaccinated HCP (p-value < 0.001). Unvaccinated HCP more frequently developed acute respiratory infection, influenza-like illness, and COVID-19 (p-values < 0.001 for all comparisons). Vaccine effectiveness for fully vaccinated HCP was estimated at 94.16% [confidence interval (CI): 88.50%-98.05%) against COVID-19, 83.62% (CI: 73.36%-90.38%) against SARS-CoV-2 infection (asymptomatic or COVID-19), and 66.42% (CI: 56.86%-74.15%) against absenteeism. Conclusion: The COVID-19 pandemic had a considerable impact on healthcare workforce. The Pfizer-BioNTech vaccine significantly reduced morbidity, COVID-19, absenteeism and duration of absenteeism among HCP during a period of high SARS-CoV-2 circulation in the community. It is expected that HCP vaccination will protect them and healthcare services and contain healthcare costs. © 2021 Elsevier Ltd

Introduction: Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for pneumococcal infections and should be vaccinated against Streptococcus pneumoniae. Data on the rates of pneumococcal vaccination among patients with ARDs in Southern Europe are scarce. Here, we estimate the pneumococcal vaccination rate in patients living in Greece with ARDs, explore the patients’ awareness regarding vaccination, and try to recognize factors that influence the vaccine uptake. Methods: Between October 2015 and September 2016, a structured questionnaire was provided to all consecutive patients with ARDs attending one outpatient clinic of our department. The survey included parameters concerning patients’ demographics, underlying ARD and immunosuppressive medications, other comorbidities, vaccine type, knowledge about infection risk and necessity of vaccination. Univariate and multivariate analyses were performed to study any association of these factors with the vaccination uptake. Results: Overall, 395 patients with ARDs (30.13% aged >65 years and 78.99% female) participated in our survey. The most frequent ARD was rheumatoid arthritis (43.04%); 40.51% of patients were receiving biologic agents and 44.56% steroids. Pneumococcal vaccination rate was 49.37%, while 45.06% of patients have been vaccinated during the last five years and only 8.21% of them had a second pneumococcal vaccine, as per national guidelines. The decision of vaccination was significantly influenced by the patient's age (>65 years) (p < 0.001) and the complete awareness of reasons for being vaccinated (p < 0.001), but not by presence of comorbidities, the type of ARD or administration of a biologic agent. The main reason for no vaccination was that it was not suggested by the caring physician (82.50%). Conclusions: In our cohort of patients with ARDs the pneumococcal vaccination was suboptimal. Better understanding of the significance of vaccination by the patient and suggestion for vaccination by the caring physician will improve vaccination uptake and optimize the clinical benefits among patients with ARDs. © 2021 Elsevier Ltd

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. © 2021 The Authors

The incidence of acute coronary events is increased among people living with HIV (PLWH), but there is no risk estimation score, nor a surrogate biomarker able to predict subclinical coronary artery disease (sCAD). We assessed the performance of: (i) Framingham risk score (FRMs), (ii) peripheral (carotid and femoral) artery atheromatosis, and (iii) coronary artery calcium (CACs) score, to detect the presence of sCAD, in PLWH. In a cohort of PLWH free of cardiovascular disease (CVD), we measured sCAD and CACs by computed tomography, calculated FRMs, and assessed carotid/femoral plaques by ultrasound. In 56 participants (age: 49 ± 10 years, men: 88%, FRMs: 7.2 ± 6.9; mean number of carotid/femoral plaques: 1.4 ± 1.5; CACs >0 present in 59%, median CACs 0.9 [IQR 0-22]): (i) minimal sCAD (stenosis 1%-24%; present in 30%) and mild sCAD (25%-49%, 25%) were effectively detected by FRMs, number of plaques, and CACs [area under the curve (AUC) of CACs was better than that of both FRM and plaques, p < .05]; (ii) moderate sCAD (stenosis 50%-69%; present in 8.9%) was detected by number of plaques and CACs, but similar AUC (0.969 vs. 0.867, respectively, p = NS); and (iii) severe sCAD (70%-99%, present in only 3 [5.4%]) was detected only by CACs. A high prevalence of sCAD in asymptomatic PLWH free of CVD was detected; CACs is a highly efficient biomarker to detect all grades of sCAD, however, the number of carotid/femoral plaques combined is also a very promising - lower cost and radiation free - surrogate biomarker. Future, larger studies are needed to verify these results. © 2021 Mary Ann Liebert Inc.

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 (

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2–1518 subtype A1 sequences and 168 MTCs in the range of 2–218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011–2015 vs. 1999–2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

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, Staphylococcusepidermidis 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. © 2020, Springer-Verlag France SAS, part of Springer Nature.

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. © 2019 Wiley Periodicals, Inc.

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. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Background Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. Settings Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). Methods All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. Results 5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35-1.74]) and dyslipidemic (aOR:1.18; [1.04-1.34]), less likely to be obese (aOR:0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. Conclusions Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention. Copyright: © 2020 Touloumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This review provides an overview of nonclinical in vivo models that can be used to support orphan designation in selected rare infectious diseases in Europe, with the aim to inform and stimulate the planning of nonclinical development in this area of often neglected diseases. © 2019 The Authors

Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and therapeutic interventions of Candida osteomyelitis. We developed a modified version of the Norden rabbit model of tibial osteomyelitis, in which the right tibia was inoculated intraoperatively with different inocula of C. albicans or normal saline as control. On days 7, 14, and 21 after inoculation, the animals underwent bone radiography, 18-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET/CT) scan, and blood sampling for blood cultures, blood counts, erythrocyte sedimentation rate, and Candida mannan antigen serum levels. On day 21, animals were euthanized, and infected tibias harvested for culture and histology. Among eight evaluable animals inoculated with 1 × 106 to 1 × 107 cfu, histology and bone cultures established the presence of Candida osteomyelitis in seven, with a host response of neutrophils, mononuclear cells, multinucleate giant cells, fibrosis, and necrosis. Infected animals demonstrated radiological signs of osteomyelitis with significantly increased tracer uptake in 18FDG-PET/CT scans (P

Combined Antiretroviral therapy (cART) has improved life-expectancy of people living with HIV (PLHIV) but as they age, prevalence of chronic non-AIDS related comorbidities may increase. We study the evolution of HIV-disease markers and comorbidities’ prevalence in PLHIV in Greece. Two cross-sectional analyses (2003 and 2013) on data from the AMACS cohort were performed. Comparisons were based on population average models and were repeated for subjects under follow-up at both 2003 and 2013. 2,403 PLHIV were identified in 2003 and 4,910 in 2013 (1,730 contributing for both cross-sections). Individuals in 2013 were on average older, diagnosed/treated for HIV for longer, more likely to be on cART, viro-logically suppressed, and with higher CD4 counts. Chronic kidney disease, dyslipidemia and hypertension prevalence increased over time. There was an increase in prescription of lipid-lowering treatment (3.5% in 2003 vs. 7.7% 2013, p20%) increased from 18.2% to 22.2% (p = 0.002). Increase in the prevalence of comorbidities was more pronounced in the subset of patients who were followed in both 2003 and 2013. The increased availability and uptake of cART led to significant improvements in the immuno-virological status of PLHIV in Greece, but they aged alongside an increase in prevalence of non-AIDS related comorbidities. These results highlight the need for appropriate monitoring, optimal cART selection and long-term management and prevention strategies for such comorbidities. © 2018 Pantazis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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. © 2018 by Turkish Society of Hematology.

We assessed the value of conventional culture, vial culture, and broad-range PCR of the sonication fluid (SF), individually or in combinations, for the diagnosis of prosthetic joint infection (PJI). We studied 114 consecutive patients (median age:72.5 years, males: 28.07%) undergoing removal of a total knee or hip prosthesis. By non-microbiologic criteria, 87 patients had aseptic failure, and 27 PJI. All patients had periprosthetic tissue culture, sonication of prosthesis, and study of SF by conventional and vial culture, and PCR. Compared to tissue culture, each test was significantly more sensitive and less specific. If only one test was positive, the sensitivity was 88.46% and specificity 64.29%. If all three SF tests were positive, sensitivity, and NPV were decreasing (34.6% and 80.23%), but specificity and PPV were increasing up to 98.57% and 90.9%, respectively, outperforming tissue culture. A triple negative test practically excluded PJI. © 2018 Elsevier Inc.

Background Aiming to eliminate HIV infection, UNAIDS has set a global “90-90-90” target by 2020. We sought to construct a 6-stages HIV Cascade of Care (CoC) in Greece, overall and by risk group, to assess risk-group and stage-specific progress in achieving the UNAIDS target. Patients and methods Combining data from the HIV/AIDS surveillance system and a population-based HIV cohort study, the CoC included: i) number of people living with HIV (PLHIV) by end of 2013; ii) proportion of PLHIV ever diagnosed; iii) proportion of diagnosed linked-to-care iv) proportion of linked-to-care ever initiating antiretroviral therapy (ART); v) proportion of treated who retained-in-care vi) proportion of those retained-in-care who were virally suppressed (200 copies/mL) at their last visit (01/07/2012-31/12/2013). Results In 2013, 14147 PLHIV were in Greece. Overall, proportions of each stage in the cascade were: 78.4% diagnosed; 86% linked-to-care; 78.5% initiated ART; 86.4% retained-in-care, and 87.1% virally suppressed. Totally, 42.6% of all PLHIV were virally suppressed. The percentage diagnosed was lower among heterosexual men and women (heterosexuals) than in MSM (men who have sex with men) or PWID (people who inject drugs). Most MSM were linked to care (97.2% of diagnosed) while a substantial proportion of PWID were not (80.8% of diagnosed). Once treated, PWID remained in care in similar proportions to MSM. Unlike PWID, a high proportion of the retained in care MSM and heterosexuals achieved viral suppression. Conclusions At the end of 2013, we identified gaps in the HIV CoC in Greece, which differed across risk groups. Targeted interventions are critical in optimizing early diagnosis and timely linkage. A 6-stage CoC, stratified by risk group, can inform strategic public health planning in improving HIV treatment outcomes. © 2018 Vourli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved.

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P=0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.

Background The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. Methods HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003–30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. Results The proportion of sequences with SDRMs was 5.98% (n = 205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. Conclusions The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients. © 2017 Elsevier B.V.

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. © 2017 Skoutelis et al.

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range

Data on the epidemiology of serious fungal infections in Greece are scarce. Our aim was to calculate the burden of serious fungal diseases in Greece. A thorough literature search for papers reporting epidemiological data on serious fungal diseases in Greece was performed. Where no Greek data existed, we used a structured set of assumptions to estimate fungal disease burden, based on specific high-risk populations. Of the 10.8 million population, 85.5 % are adults and 27 % are over 60 years of age. The annual fungal disease estimates are as follows: 142,337 Greek women get recurrent vaginal thrush (2,632 cases/100,000 females); there are 889 cases of esophageal candidiasis (8.2 cases/100,000); annual incidence of Pneumocystis pneumonia is 112 cases; chronic pulmonary aspergillosis prevalence is 386 cases; there are 20,843 patients with allergic bronchopulmonary aspergillosis and 27,744 with severe asthma with fungal sensitization; candidaemia incidence is 541 cases (5.0/100,000); there are 81 cases of Candida peritonitis; invasive aspergillosis occurs in 1,125 patients. According to our calculations, 194,067 individuals (1.79 cases/100,000) in Greece suffer from serious fungal diseases each year. This is the first attempt to determine the burden of fungal diseases in Greece, and provides a crude estimate on its impact on public health. © 2016, Springer-Verlag Berlin Heidelberg.

Magnetic resonance imaging is the imaging method of choice for diagnosing infection of the spine in unoperated cases. 2-[18F]-fluoro-2deoxy-d-glucose positron emission tomography/computed tomography study is recommended to distinguish between spinal infection and common Modic change in patients with metallic implants and prosthetic replacements and for differentiating tuberculous from pyogenic spondylitis in ambiguous cases, reflecting the activity of the infection. Also, it seems to have a strong clinical impact in more than half of patients with infectious spondylitis, while it is superior to other imaging techniques in revealing residual disease after treatment and early response to therapy. New tracers as well as new hybrid modalities are under investigation. © 2015 Elsevier Inc.

Osteoarticular mycoses due to non-Aspergillus moulds are uncommon and challenging infections. A systematic literature review of non-Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013. Among 145 patients were 111 adults (median age 48.5 [16-92 y]) and 34 pediatric patients (median age 7.5 [3-15 y]); 114 (79.7%) were male and 88 (61.9%) were immunocompromised. Osteomyelitis was due to direct inoculation in 54.5%. Trauma and puncture wounds were more frequent in children (73.5% vs 43.5%; P=0.001). Prior surgery was more frequent in adults (27.7% vs 5.9%; P=0.025). Vertebral (23.2%) and craniofacial osteomyelitis (13.1%) with neurological deficits predominated in adults. Lower limb osteomyelitis (47.7%) and knee arthritis (67.8%) were predominantly seen in children. Hyalohyphomycosis represented 64.8% of documented infections with Scedosporium apiospermum (33.1%) and Lomentospora prolificans (15.8%) as the most common causes. Combined antifungal therapy and surgery was used in 69% of cases with overall response in 85.8%. Median duration of therapy was 115 days (range 5-730). When voriconazole was used as single agent for treatment of hyalohyphomycosis and phaeohyphomycosis, an overall response rate was achieved in 94.1% of cases. Non-Aspergillus osteoarticular mycoses occur most frequently in children after injury and in adults after surgery. Accurate early diagnosis and long-course therapy (median 6 mo) with a combined medicalsurgical approach may result in favorable outcome. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Background: Anti-thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo-SCT) for hemoglobinopathies; however, epidemiology data for transplant-related infections in this population are scarce. Method: We retrospectively analyzed the epidemiology of bacterial, fungal, viral, and parasitic infections in a cohort of 105 children and adolescents with β-thalassemia (n = 100) or sickle cell disease (n = 5) who underwent allo-SCT using human leukocyte antigen (HLA)-identical sibling (n = 96) or HLA-compatible unrelated donors (n = 9) in a single institution. All patients received an ATG-based conditioning regimen. Results: The cumulative incidence of cytomegalovirus (CMV) viremia was 45.7% (95% confidence interval [CI] 33-55%), developing at a median of 48 (range 12-142) days without evidence of overt CMV disease. Herpes zoster developed in 8 patients at a median of 12 months post transplant, while 10 patients presented with late onset hemorrhagic cystitis at a median of 35 days post transplant. The cumulative incidence of bacteremia was 17.1% (95% CI 10.6-25%), occurring at a median of 74 (range 24-110) days. No patient developed probable or definite invasive fungal infection. Four deaths were recorded; 2 of them were attributed to infections (toxoplasmosis and Pneumocystis jirovecii pneumonia, respectively). Conclusion: The rate of infections after allo-SCT, using an ATG-containing preparative regimen, in our population of pediatric patients with hemoglobinopathies is comparable to that reported elsewhere with the use of non-ATG containing regimens. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined antiretroviral treatment (cART) modifications are often required due to treatment failure or side effects. We investigate cART regimens' durability, frequency of treatment-limiting adverse events, and potential risk factors and temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). Statistical analyses were based on survival techniques, allowing for multiple contributions per individual. Overall, 2,756 individuals, aged >15 years, initiated cART. cART regimens were grouped by their initiation date into four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95% confidence interval (CI)] time to first treatment modification was 2.11 (1.95-2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and 29.6% for the four periods, respectively. cART modifications were less frequent in more recent years (adjusted HR= 0.96 per year; p < 0.001). Longer treatment duration was associated with lower HIV-RNA, higher CD4 counts, and being previously ART naive. cART modifications due to treatment failure became less frequent in recent years (adjusted HR= 0.91 per year; p < 0.001). Estimated (95% CI) 1 year cumulative probabilities of treatment-limiting side effects were 16.4% (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for the four periods, respectively, with no significant temporal trends. Risk of side effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART regimens. Treatment modifications have become less frequent in more recent years. This could be partly attributed to the lower risk for side effects of NNRTI-based cART regimens and mainly to the improved efficacy of newer drugs. However, the rate of drugs substitutions due to adverse events remains substantially high. © 2017 Mary Ann Liebert, Inc.

Background: 18-Fluoro-2-deoxy-d-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether 18F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop 18F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis. Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when 18F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second 18F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as 18F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of 18F-FDG signal activity in the infected tibia. Results: All successfully infected animals (n=14), with microbiologically and/or histologically confirmed osteomyelitis, had positive 18F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P=0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P

Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia. © 2015 Elsevier Ltd. All rights reserved.