Challenges in assessing the immunization status of adults in Germany-lessons from a population-based VACCELERATE survey on polio vaccination.

PURPOSE: Considering the re-emergence of poliomyelitis (PM) in non-endemic regions, it becomes apparent that vaccine preventable diseases can rapidly develop epi- or even pandemic potential. Evaluation of the current vaccination status is required to inform patients, health care providers and policy makers about vaccination gaps. METHODS: Between October 28 2022 and November 23 2022, 5,989 adults from the VACCELEREATE Volunteer Registry completed an electronic case report form on their previous PM vaccine doses including number, types/-valencies and the time of administration based on their vaccination records. A uni-/multivariable regression analysis was performed to assess associations in participant characteristics and immunization status. RESULTS: Among German volunteers (n = 5,449), complete PM immunization schedule was found in 1,981 (36%) participants. Uncertain immunization, due to unknown previous PM vaccination (n = 313, 6%), number of doses (n = 497, 9%), types/-valencies (n = 1,233, 23%) or incoherent immunization schedule (n = 149, 3%) was found in 40% (n = 2,192). Out of 1,276 (23%) participants who reported an incomplete immunization schedule, 62 (1%) never received any PM vaccine. A total of 5,074 (93%) volunteers reported having been vaccinated at least once and 2,087 (38%) indicated that they received vaccination within the last ten years. Female sex, younger age, as well as availability of first vaccination record were characteristics significantly associated with complete immunization (p < 0.001). CONCLUSION: Full PM immunization schedule was low and status frequently classified as uncertain due to lack of details on administered doses. There is an obviousneed for improved recording to enable long-term access to detailed vaccination history in the absence of a centralized immunization register.

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Staphylococcus epidermidis induced toxic shock syndrome (TSS) secondary to influenza infection.

BACKGROUND: To date, few cases of TSS caused by coagulase negative (CoN) staphylococci have been reported in the literature. Recent data show that CoN staphylococci are capable of secreting a number of enterotoxins and cytotoxins, normally produced by S. aureus. Herewith, we describe a case of TSS caused by Staphylococcus epidermidis with a favorable outcome. CASE PRESENTATION: We report a case of a 46-year-old man who developed TSS from S. epidermidis. The patient was admitted for a 7-day history of general malaise and headache following a recent influenza infection and a 3-day history of vomiting, diarrhea, diffuse erythroderma, and fever. The main laboratory findings on admission were leukopenia (WBC 800/mm3), thrombocytopenia (Plt count 78.000/mm3), elevated urea, creatine levels and increased inflammatory markers (CRP 368 mg/ml). The patient had clinical and radiological evidence of pneumonia with chest computed tomography (CT) showing diffuse bilateral airspace opacifications with air bronchogram. On the second day, a methicillin resistant S. epidermidis (MRSE) strain was detected in both sets of blood cultures, but the organism was unavailable for toxin testing. All other cultures and diagnostic PCR tests were negative. His clinical signs and symptoms fulfilled at that stage four out of five clinical criteria of TSS with a fever of 39 °C, diffuse erythroderma, multisystem involvement and hypotension. On the same day the patient was admitted to the ICU due to acute respiratory failure. The initial treatment was meropenem, vancomycin, levofloxacin, clindamycin, IVIG and steroids. Finger desquamation appeared on the 9th day of hospitalization, fulfilling all five clinical criteria for TSS. CONCLUSIONS: To our knowledge, this is the first adult case with TSS induced by CoNS (MRSE) secondary to an influenza type B infection, who had favorable progression and outcome. Further research is warranted to determine how TSS is induced by the CoNS infections.

An update on asthma diagnosis.

OBJECTIVE: Asthma imposes a significant health and socioeconomic burden with an average prevalence impacting 5-10% of the global population. The aim of this narrative review is to update the current literature on topics related to asthma diagnosis. DATA SOURCES: Original research articles were identified from PubMed using the search terms "asthma diagnosis" and "asthma misdiagnosis". STUDY SELECTIONS: Recently published articles (n = 51) detailing the diagnosis, misdiagnosis of asthma, and the updated recommendations of the European and international asthma guidelines. RESULTS: Emerging evidence revealed that asthma might represent a rather heterogenous clinical entity with varying underlying molecular mechanisms. Attempts have been made to unravel these traits to better provide accurate diagnosis and a more efficient patient-based management approach. The lack of a gold standard test for asthma diagnosis has contributed to its over- and underdiagnosis. This is problematic, given that overdiagnosis might lead to delay of both diagnosis and prompt treatment of other diseases, while underdiagnosis might substantially impact quality of life due to progression of asthma by increased rate of exacerbations and airway remodeling. In addition to poor asthma control and potential patient harm, asthma misdiagnosis is also associated with excessive costs. As a result, current international guidelines emphasize the need for a standardized approach to diagnosis, including objective measurements prior to treatment. CONCLUSION: Future research is warranted to define the optimal diagnostic and treatable traits approach especially for patients with severe asthma, as they may benefit from the advent of newly targeted asthma management.

Toxoplasmosis in Transplant Recipients, Europe, 2010-2014.

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.

Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study.

BACKGROUND: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. RESULTS: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. CONCLUSIONS: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries.

BACKGROUND: Mucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking. METHODS: Two large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ≤19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12. RESULTS: Sixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp. (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival. CONCLUSION: Paediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

Exserohilum infections: review of 48 cases before the 2012 United States outbreak.

Exserohilum species are soilborne fungi that have been uncommon causes of human disease. The ongoing outbreak in the United States warrants improved understanding of this pathogen. We systematically reviewed all cases of Exserohilum spp. infections published before the outbreak in 2012 in order to provide a better understanding of the organism and its wider spectrum of human disease. Cases of Exserohilum infections were retrieved by searching PubMed. Demographic data, underlying conditions, microbiology, clinical manifestations, therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were identified from 1975 to 2012. The number of reported cases increased more than twofold during the study period (P < 0.01). Most cases occurred in the southern United States, India, and Israel. Median age of patients was 25 years, with a male predominance. Most infections were due to E. rostratum (60.4%), followed by E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified species. The most frequent underlying conditions were immunosuppression (27.2%), trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection. Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined with a triazole. Surgery was used in 48% of cases and was combined with antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95% confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases highlights several aspects of epidemiology, clinical presentation, risk factors, and management of this unusual pathogen.

Community Antibiotic Consumption in Cyprus for the Period 2015 to 2022.

BACKGROUND: Cyprus currently reports to ESAC-Net the total consumption of antimicrobials, without distinguishing between hospital and community-based antibiotic use. As a result, these data can only provide generalized insights into antimicrobial trends in the country. AIM: This study is a first attempt to retrospectively analyze community antibiotic consumption in Cyprus for the period of 2015 to 2022. MATERIAL AND METHODS: Data on community antimicrobial consumption between 2015 and 2022 were extracted from Pharmatrack's database. Orally administered dispensed antibiotics were categorized under the J01 group of the WHO Anatomical Therapeutic Chemical (ATC) classification and by the WHO's AWaRe classification of antibiotics. Antibiotic consumption was calculated in both packages consumed and per 1000 inhabitants, overall, by year of consumption and districts. RESULTS: During the period of 2015-2022, there was variability in the mean outpatient antibiotic consumption per 1000 inhabitants among the five districts in Cyprus. Community consumption increased by 38% throughout the study period. Additionally, a decrease of 3% in the consumption of WHO 'Access' antibiotics was observed, accompanied with a concurrent increase of 3% in the 'Watch' group. Specifically, in 2022 the WHO 'Access' group consumption in the Cypriot community was 48%, significantly lower than the WHO's goal of 60% and the EU's goal of 70% for 'Access' antibiotic consumption. CONCLUSIONS: Antibiotic consumption in the community of Cyprus between 2015 and 2022 demonstrated substantial variability among districts, with higher consumption in less populated areas. There was an increasing trend in community consumption over the years and a decreasing trend in the percentage of 'Access' antibiotics prescribed.

Perspectives of European Patient Advocacy Groups on Volunteer Registries and Vaccine Trials: VACCELERATE Survey Study.

BACKGROUND: The VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. OBJECTIVE: The aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. METHODS: In an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants' perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. RESULTS: In total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were "positive" toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being "very positive." Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. CONCLUSIONS: Factors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients' willingness to participate in clinical studies.

An Update on the Diagnosis and Treatment of Invasive Mold Disease of the Central Nervous System in Children.

Epidemiological data of CNS IMD in pediatrics are limited. Aspergillus is the most frequently identified species, followed by other rare molds. Prompt diagnosis is of importance to define the optimal therapeutic management with respect to antifungal agent, dose, and evaluation of surgical intervention. The mortality rate of CNS IMD remains high. In this mini review we summarize the current knowledge on diagnosis and treatment of CNS IMD in pediatrics.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe.

BACKGROUND: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.

The Challenges of Vaccine Trial Participation among Underserved and Hard-to-Reach Communities: An Internal Expert Consultation of the VACCELERATE Consortium.

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Acinetobacter baumannii Antibiotic Resistance Mechanisms.

Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.

Impact assessment of COVID-19 non-pharmaceutical interventions in long term care facilities in Cyprus: Safety improvement strategy.

The current COVID-19 crisis has changed our everyday lives almost in every aspect. Many people worldwide have died or hospitalised due to the severe impact of COVID-19 on the vulnerable population, and in particular to the elderly residents of long term care facilities (LTCF). The problem is amplified due to the fact that many of those occupants also suffer from comorbidities (e.g. respiratory and cardiovascular diseases, hypertension, etc.) and are therefore regarded as a susceptible host to severe COVID-19 disease. Impacts can be felt in the wider societal safety level. The aim of the present study is, therefore, to present the first National multimodal quality and safety improvement strategy plan for the LTCF in the Republic of Cyprus. The current program focused on the intensification of COVID-19 epidemiological surveillance, the promotion of educational training on best practises in infection control and prevention, and the implementation of additional non-pharmaceutical interventions (NPIs), according to the recommendations of ECDC (European Centre for Disease Prevention and Control) and WHO (World Health Organization). This innovative program fostered the interconnectivity and collaboration among the local authorities, academia and the local leaders of the LTCF. In addition, this program reinforced the importance of volunteerism and active participation of medical students in the National initiatives against the COVID-19 pandemic. The effectiveness of the adopted multimodal advanced care-safety planning program is appraised based on the reported new confirmed COVID-19 cases among LTCF healthcare workers and occupants, after the introducing and implementation of the selected NPIs. This multimodal strategy plan seems to be capable of reducing significantly the number of new cases of COVID-19 infections in LTCF and as a result, to also affect the residents' death number.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.

Etiology and Outcome of Candidemia in Neonates and Children in Europe: An 11-year Multinational Retrospective Study.

BACKGROUND: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia. MATERIAL AND METHODS: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients' demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality. RESULTS: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8-2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed. CONCLUSIONS: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.