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Staphylococcus aureus, a prevalent human pathogen and a leading cause of hospital-acquired infections, is increasingly evolving antibiotic-resistant strains, increasing mortality and morbidity rates. Anti-staphylococcal vaccine research for prevention and treatment has become a priority. Antibodies against specific S. aureus components, toxins, and polysaccharides have demonstrated encouraging results in animal studies regarding protection against colonization or infection. However, human immunization trials have yielded less optimistic outcomes, with no anti-staphylococcal having passed clinical trials up to now. Although multiple formulation attempts triggered strong antibody responses, the vaccines could not effectively prevent S. aureus infections. This article delves into the results of immunotherapeutic strategies against S. aureus in both animal and human studies, discussing the feasibility of adequate immunization approaches against S. aureus in humans. [ABSTRACT FROM AUTHOR]

Diarrhoea represents a significant public health concern worldwide and is responsible for an increase in mortality and morbidity, especially among children but also among adults. Cryptosporidium, one of the most common intestinal protozoan parasites, is the etiological agent of cryptosporidiosis, an acute infection with self-limiting evolution, but that can evolve into severe diarrhoea in children and immunosuppressed hosts. The main species that cause human cryptosporidiosis are C. parvum and C. hominis. Despite the progress made in order to control and monitor cryptosporidiosis at the global level, numerous outbreaks have been reported with the source of infection being food or water. Using Promedmail.org we have performed a review of Cryptosporidium related outbreaks reported in the last 10 years over the world. [ABSTRACT FROM AUTHOR]

Predecessors in the Romanian School of Microbiology established several golden guidelines for the clinical integration of the microbiology laboratory, the clinical rationale behind the infectious disease patients, and the antibiotic administration. However, without a determined mind to continue, strengthen, and nurture the work they have undertaken, professors Ion Cantacuzino, Victor Babes, and Matei Bals' expertise would have vanished [1-3]. Professor Angelescu proved to be the ideal individual right when he was most needed, determined to carry on their legacy, to further advance antibiotic knowledge, and a patient, father-like figure to his younger colleagues. He answered the invitation to become a leading authority at a time when advances in the science of antibiotics had doctors puzzled. The "Angelescu's Guide" was intended to be a lifeline for what would soon become one of the major challenges of the twenty-first century: antibiotic resistance in delicate clinical settings. Actual, achievable strategies for the care of an infectious illness patient are provided below, as are pertinent research recommendations for younger and fresher medical minds. [ABSTRACT FROM AUTHOR]

Despite the global economic development, diarrhoea remains an important health concern worldwide. The epidemiological importance of Shigella spp. infections is very high, being the leading cause of bacterial diarrhoea. Clinically, shigellosis can manifest as watery diarrhoea or dysentery, with bloody stool, accompanied by fever and abdominal pain. Children and the elderly are most susceptible to developing severe forms. In this review, we highlight the rise of antibiotic-resistant Shigella spp. strains and provide an overview of recent shigellosis outbreaks. Shigellosis is an infectious disease that should not be neglected, as evidenced by the many outbreaks reported throughout the world. [ABSTRACT FROM AUTHOR]

Malaria is a serious and, in some unfortunate cases, fatal disease caused by a parasite of the Plasmodium genus. It predominantly occurs in tropical areas where it is transmitted through the bite of an infected Anopheles mosquito. The pathogenesis of malaria is complex and incompletely elucidated. During blood-stage infection, in response to the presence of the parasite, the host's immune system produces proinflammatory cytokines including IL-6, IL-8, IFN-γ, and TNF, cytokines which play a pivotal role in controlling the growth of the parasite and its elimination. Regulatory cytokines such as transforming growth factor- (TGF-) β and IL-10 maintain the balance between the proinflammatory and anti-inflammatory responses. However, in many cases, cytokines have a double role. On the one hand, they contribute to parasitic clearance, and on the other, they are responsible for pathological changes encountered in malaria. Cytokine-modulating strategies may represent a promising modern approach in disease management. In this review, we discuss the host immune response in malaria, analyzing the latest studies on the roles of pro- and anti-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) poses a medical, social, and economic problem. In Romania since 2002, the prevention of HIV transmission and the care for HIV-positive people have been overseen by Governmental Law. HIV infection in Romania has some particularities, such as the high number of HIVinfected patients under treatment and the high percentage of long-term survivors. Romania reported its first case of AIDS to the World Health Organization in 1985, and its first case in the pediatric population in 1989. A year later, a new case definition, based on local possibilities was formulated together with the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC, Atlanta, GA). According to the latest report of the Compartment for Monitoring and Evaluation of HIV/AIDS in Romania, the cumulative number of HIV cases registered between 1985-2021 was 26,171, while the number of people living with HIV at the end of December 2021 was 17,271. [ABSTRACT FROM AUTHOR]

Providential personalities have been writing history since the beginning of times - personalities that could be found within and across Romania's borders [1]. In medicine, such brilliant figures have healed patients through diligence, dedication, and professionalism, but have also passed significant teachings to the next generations. They have rigorously respected an authentic professor's definition, a figure that teaches and prepares specialists for the future. The great medical personalities, Ion Cantacuzino and Victor Babeș, have been mentored by famous professors, have also become famous professors on their own, and they have educated doctors and professors who have carried on their research and medical teaching legacies. Through study, through diligence, and an impressive personal development, their students have also become proficient figures in medicine [1-2]. They have trained personalities in the medical field that could have reached higher peaks, were it not for the political and social climate of their country. Among those, now we shall bring into discussion professor Matei Balș, a remarkable man and teacher, whose contribution focused the necessity of employing strict and correct means of practice, tying together in an organic way the clinical and the laboratory work, a dogma which he has passed on to his students. He has funded the "School of Infectious Diseases" at Colentina Hospital and has formulated teachings that stand the test of time; his working approach is still appropriate and praised today. The current generation as well as future ones not only have the obligation to recognise the exceptional achievements of our ancestors in history, but to also keep them alive and develop upon them, in the interest of the Romanian people, Romania itself, but also for the public health system at an international level [1]. [ABSTRACT FROM AUTHOR]

Providential personalities are an essential, unifying, element across cultures, omnipresent in the world's history [1]. Professor Victor Babeș, a distinguished figure in pathology, microbiology and virology, attended high school in Budapest and pursued his higher medical education in Budapest and Wien. He lectures at the pathology department of the University of Budapest at only 18 years of age. In 1885, he co-authored the first Bacteriology Treaty in Paris alongside Cornil. In 1887, he went on to establish the pathology and bacteriology departments at the Faculty of Medicine, in Bucharest. He contributed to the medical world literature with over 1000 papers, written in different languages. Professor Victor Babeș studied bacteria, viruses, parasites and influenced preventive medicine. Overall, he discovered more than 50 new microbes. An entire book may be devoted just to his pathological discoveries (cancer, leprosy, tuberculosis, diphtheria, actinomycosis, anthrax, syphilis, plague, rabies, etc.). In 1912 he published (in Paris) a vast treaty on rabies; he dedicated 90 of his best works to rabies. Victor Babeș National Institute of Research and Development in Pathology and Biomedical Sciences has been founded on the 28th of April 1887 by Professor Victor Babeș. Initially constituted as a "Bacteriology and Pathology Institute", it was able to comply with one of the most demanding medical needs of the time and it has contributed to finding realistic solutions regarding medical organization. In terms of importance and activity, the institute represented a prefiguration of the future Ministry of Health [2]. Professor Babeș's life should be remembered for his works that marked the opening of new horizons and for a personality whose genius echoes to this day. [ABSTRACT FROM AUTHOR]

Acute diarrheal disease remains a major public health issue. Salmonella spp. infection is one of the leading causes of acute diarrheal disease despite the preventive measures implemented. The clinical picture of salmonellosis varies from a common gastroenteritis to enteric fevers which are life-threatening diseases requiring a prompt and correct antibiotic treatment. In this review we present recent salmonellosis outbreaks and point out that Salmonella infections continue to be an important health issue. Numerous outbreaks of Salmonella spp. have been reported worldwide in recent years, indicating that prevention and control programs need to be improved as well as the infectious diseases surveillance, all over the world. [ABSTRACT FROM AUTHOR]

Providential personalities are an essential, unifying, element across cultures, omnipresent in the world's history. They are one of a kind, born every century or even more than a hundred years apart, and their emergence is conditioned by specific factors and even circumstances. Among Romania's historical personalities, Professor Cantacuzino's name and achievements could not be contained within the country's borders. His genius has left its mark not only on the Romanian public health system, or even the nearby Balkan area, but has echoed way further than Europe at that time. The conscious effort he made to offer more than he had previously received stemmed from his exceptional personal development work. A multifaceted persona like few have been, he has managed to acquire great insights into many subjects and, more importantly, he had the character and strength to establish a Healthcare Legacy and an Institute that will soon celebrate 100 years of existence. The current generation and the ones to come should learn their history and praise the achievements of their ancestors, while also preserving and further cultivating them, for the good of Romanian citizens, Romania and the global health system. [ABSTRACT FROM AUTHOR]

Difficult-to-treat infections produced by Pseudomonas aeruginosa have a long evolution with a great impact not only in regard to the patient's health, but also to his well-being, the public health and economy. Considering that not only the antimicrobial resistance, but other characteristics of these strains may be involved in the longue and difficult evolution of this infections; we evaluated the ability to produce biofilm on inert substrate through a microdilution method. We evaluated 25 strains of P. aeruginosa isolated from infections with a longue evolution. Most of the strains produced an important biofilm, especially at 48 hours, presenting an interesting architecture, suggesting the ability to persist. These findings highlight the impact of biofilm production in P. aeruginosa, and underline the importance of finding alternative therapies and a personalised approach. [ABSTRACT FROM AUTHOR]

Natural medicines and in specially herbs spices and extracts for treatment of various diseases were the first medicines used from immemorial times. In treatment of fungal infection the traditional medicine provide a lot of possible extracts from plants with proved effects to cure superficial infections. This work reviews shortly the main remedies from alternative medicine used in different traditional and modern medicine from all over the world and new researches on the efficiency of the old methods of treatment against Candida infections. One of the targets of this paper is to describe the most interesting and active plant extracts in order to be use as alternatives to chemical antifungal products, in treatments against Candida species infections. [ABSTRACT FROM AUTHOR]

The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput 'OMIC' modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host–microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections. [ABSTRACT FROM AUTHOR]

Obiective. Acest studiu și-a propus să efectueze o revizuire sistematică a literaturii existente pentru a evalua efectele COVID-19 la femeile însărcinate și la nou-născuții acestora, estimând, în același timp, posibilitatea transmiterii verticale. Materiale şi metode. Am efectuat o cercetare sistematică a literaturii folosind Pubmed și Google Scholar, acoperind perioada decembrie 2019-noiembrie 2020. Revizuirea a fost efectuată în conformitate cu ghidurile PRISMA. Rezultate. Am inclus 16 studii - recenzii sistematice și metaanalize publicate între mai 2020 și noiembrie 2020 - care s-au concentrat pe rezultatele perinatale ale femeilor însărcinate cu COVID-19 și 7 prezentări de cazuri ale nou-născuților cu transmitere verticală a COVID-19. În general, rata cazurilor de COVID-19 la nou-născuții din mame COVID-19 pozitive a fost de 3% cu CI 95% [1,86, 4,24]). Rata nașterii premature a fost de 16,4%, cu CI 95% [10,5, 22,3], iar rata mortalității și a deceselor fetale a fost de 1,4% (11 studii, 0 până la 4,8%). Dintre cei 7 nou-născuți cu transmitere verticală dovedită, majoritatea s-au născut prematuri, cu greutate bună la naștere și scor APGAR, iar manifestările clinice au fost heterogene; 4 au dezvoltat simptome severe. Evoluțiile atât pentru mamă, cât și pentru nou-născuţi au fost bune în 85% dintre cazuri. Concluzii. În ceea ce privește rata prematurității și rata mortalității la femeile cu COVID-19, rezultatul este similar cu populația generală. Transmiterea verticală este posibilă și pare să aibă loc în aproximativ 3% dintre cazuri. Prognosticul matern și perinatal este favorabil, iar prezentarea clinică a transmiterii în uter a SARS-CoV-2 la nou-născuți este heterogenă. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to perform a systematic review of existing literature to assess the outcomes of pregnancy in women with COVID-19 infection and their newborns while estimating the possibility of vertical transmission. Materials and methods. We conducted a systematic literature research using Pubmed and Google Scholar covering the period from December 2019 to 20th of November 2020. The review was conducted in accordance with PRISMA guidelines. Outcomes. We included 16 studies - systematic reviews and meta-analyses published between May 2020 and November 2020 - which focused on perinatal outcomes of pregnant women with COVID-19 and 7 case reports of neonates with congenital transmission of COVID-19. Overall, the rate of COVID-19 cases in neonates of COVID-19 positive mothers was 3% with 95% CI [1.86, 4.24]). The preterm birth rate was 16.4% with 95% CI [10.5, 22.3] and the rate of stillbirths and foetal deaths was 1.4% (11 studies, 0 to 4.8%). From the 7 newborns with proved vertical transmission, majority were born preterm, with good birth weight and APGAR score and heterogenous symptoms; 4 developed severe symptoms. Overall progress and evolution for both mother and newborn was good. Conclusions. COVID-19 impact on pregnancy outcome is similar to general population in regard to preterm rate and stillbirth rate. Vertical transmission is possible and it seems to occur in about 3% of cases. Overall maternal and perinatal outcome is favourable and clinical presentation of in utero transmission of SARSCoV-2 in newborns is heterogenous. [ABSTRACT FROM AUTHOR]

Introduction: Risk reduction of TORCH congenital infections mainly involves prevention of infection prepregnancy and during pregnancy by educating the target population. We developed and tested a support system for women who would like to conceive and for pregnant women. Objectives: We assesed the usability of www.torch.ro website and MAMI smartphone application in a group of adult women of fertile age (18-49 years old). Our second aim was to asses the knowledge gain following their use in a group of pregnant women. Methods: We evaluated the usability, credibility, loyalty and appearance using Standardized User Experience Percentile Rank Questionnaire (SUPR-Q) which was completed online by 171 women of childbearing age. For knowledge evaluation, we developed a test-questionnaire and distributed to 61 pregnant women. Results: The participants had a good experience, as reflected by SUPR-Q of 4.47 out of 5. 74% of users have qualified as promoters, which imply that they are likely to recommend the website/app; the best scoring categories were trust, credibility and loyalty - score of 4.49/5. Majority (59.6%, n = 102) answered that they will definitely apply the measures of prevention of TORCH infections acquired in case of a next/future pregnancy and 28.7% (n = 49) said they will probably do so. There was an increase in the number of correct answers for almost all the questions, with a maximum increment of 21.3% for individual questions. Overall, there was a difference of plus 86 correct answers after exposure which represents 16% increase compared to initial number of correct answers of 535. Conclusion: End-user experience of website and smartphone app MAMI was evaluated as positive by the participants. The tools are trustworthy, credible and women who have used them are very likely to recommend them hence increasing the awareness about TORCH infections prevention. [ABSTRACT FROM AUTHOR]

The purpose of this review is to carry out an overall evaluation of the scientific literature on the selection of the best candidate as an animal translation model. We used the PubMed/MEDLINE, Web of Science Core Collection and medRxiv/BioRxiv (preprint materials) databases for original research published in English to September 2020. Review research was conducted in accordance with the preferred reporting elements for systematic reviews and meta-analysis (PRISMA). The inclusion criteria were: establishing animal models (mouse, ferret, dog, cat, primates, etc.) for SARSCoV-2, prophylaxis, therapy and vaccines. The exclusion criteria were: books, guidelines and protocols, population genetics. This review highlights the distinct advantages and limitations of each animal model, which should be taken into account in the design of studies, the interpretation of pathogenic mechanisms or extrapolation of the results of therapy or vaccines in humans. In order to generate results that are consistent, reproducible and comparable between studies, it is necessary to harmonize the protocols for experimentation on animal models. [ABSTRACT FROM AUTHOR]

In the context of increasing resistance to antimicrobials, therapeutic alternatives must be developed, one of which may be the administration of autologous bacterial vaccine. There are few studies in the literature reporting the immune and clinical response to autologous vaccine administration. In this study we tried to evaluate the clinical effect of the administration of the autologous bacterial vaccine to people with dermatological diseases for which the classical therapy did not bring the desired results. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis is an often-overlooked condition that otherwise negatively impacts both the individual and the community, prompting major public health concerns. Early diagnosis and treatment, as well as collaboration between specialties including surgery and parasitology, are essential for avoiding complications and disease relapse. To better illustrate this, we present the case of an elderly person with a rare localization of the disease at the muscular level. The patient underwent numerous surgical interventions, and received multiple courses of antiparasitic treatment over the course of 40 years as a result of the multivisceral dissemination of the parasite. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. Its pathogenesis is multifactorial and involves the overlap between four main processes: alteration of the keratinization, increased sebum production, colonization with Cutibacterium acnes, and inflammation. The role of oxidative stress (OS) has been intensively studied in inflammatory skin conditions such as psoriasis, vitiligo, or atopic dermatitis. However, the involvement of OS in the pathogenesis of acne is less known. The evidence accumulated over the last decade suggests that in the case of acne patients, there is an imbalance between oxidants and antioxidants. In this review, we analyzed studies that evaluated markers of OS in patients with acne, published in the last ten years, with the aim of providing new insights into the pathogenesis of acne. [ABSTRACT FROM AUTHOR]

Botulism occurs by ingestion of canned food contaminated with Clostridium botulinum. In most cases, the incriminated canned foods are homemade; commercial products only occasionally produce the disease, due to improper handling and storage after purchase. In Romania, the most common sources of food botulism are homemade pork products (ham, bacon, salami, meat and sausages preserved in lard). The disease occurs in small outbreaks. Out of several serotypes of C. botulinum, the predominant serotype in our country is type B. The Laboratory of Anaerobic and Zoonotic Infections in Cantacuzino Institute performs in vivo reference laboratory diagnosis of botulinum food poisoning, using the mouse lethality assay for detection of the toxin in the sample and for toxin typing. Between 2003 and 2017, our laboratory tested 576 biological samples for the diagnosis of botulism: patient blood serum samples (80%), food samples (19.02%) and autopsy fragments from deceased patients (0.8%). Type B botulinum toxin was detected in 50% of the total number of blood serum samples received for testing and a single serum was positive for type E toxin. 5% of the tested food samples were positive for type B toxin. Until 2007, the geographic origin of positive samples that we received for testing showed high incidence of food botulism in the center and west of the country. Starting 2007, we received more samples from several eastern counties, many of them being confirmed as positive. Until mid 2009, we frequently received insufficient amounts of patient serum, and we could not determine the toxin serotype. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis (Nm) is the pathogen carried asymptomatically in the nasopharynx but which under certain conditions can produce meningitis or even multi-organ failure. Experimental induction of meningitis in an animal model is necessary for testing new nanopharmaceutical products. Thus, the aim of the study was to establish the concentration of Nm capable of inducing the disease. We carried out 2 studies where we tested different concentrations of Nm obtained by the nephelometric and spectrophotometric methods. In the first study we included 20 BALB/c mice, and in the second 24. Local and general clinical signs, complete with body temperature values, body weight, hematological, microbiological and histopathological examination were important indicators for the assessment of the establishment of meningitis. The clinical results have pronounced depression in the first 2 days after inoculation, then the general condition will appear. The microbiological and histopathological examination indicated the presence of bacteria at the brain level and specific meningeal lesions only in the case of the second attempt, but the early mortality, requires additional testing of the bacterial concentration that induces meningites in a stable and persistent way so that treatment against the condition can be tested later. [ABSTRACT FROM AUTHOR]

Background: Romania is one of the European countries reporting very high antimicrobial resistance (AMR) rates and consumption of antimicrobials. We aimed to characterize the AMR profiles and clonality of 304 multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) strains isolated during two consecutive years (2018 and 2019) from hospital settings, hospital collecting sewage tanks and the receiving wastewater treatment plants (WWTPs) located in the main geographical regions of Romania. Methods: The strains were isolated on chromogenic media and identified by MALDI-TOF-MS. Antibiotic susceptibility testing and confirmation of ESBL- and CP- producing phenotypes and genotypes were performed. The genetic characterization also included horizontal gene transfer experiments, whole-genome sequencing (WGS), assembling, annotation and characterization. Results: Both clinical and aquatic isolates exhibited high MDR rates, especially the Ab strains isolated from nosocomial infections and hospital effluents. The phenotypic resistance profiles and MDR rates have largely varied by sampling point and geographic location. The highest MDR rates in the aquatic isolates were recorded in Galați WWTP, followed by Bucharest. The Ab strains harbored mostly blaOXA-23, blaOXA-24, blaSHV, blaTEM and blaGES, while Pa strains blaIMP, blaVIM, blaNDM, blaVEB, blaGES and blaTEM, with high variations depending on the geographical zone and the sampling point. The WGS analysis revealed the presence of antibiotic resistance genes (ARGs) to other antibiotic classes, such as aminoglycosides, tetracyclines, sulphonamides, fosfomycin, phenicols, trimethoprim-sulfamethoxazole as well as class 1 integrons. The molecular analyses highlighted: (i) The presence of epidemic clones such as ST2 for Ab and ST233 and ST357 for Pa; (ii) The relatedness between clinical and hospital wastewater strains and (iii) The possible dissemination of clinical Ab belonging to ST2 (also proved in the conjugation assays for blaOXA-23 or blaOXA-72 genes), ST79 and ST492 and of Pa strains belonging to ST357, ST640 and ST621 in the wastewaters. Conclusion: Our study reveals the presence of CP-producing Ab and Pa in all sampling points and the clonal dissemination of clinical Ab ST2 strains in the wastewaters. The prevalent clones were correlated with the presence of class 1 integrons, suggesting that these isolates could be a significant reservoir of ARGs, being able to persist in the environment. [ABSTRACT FROM AUTHOR]

One of the main concerns of the medical community during the COVID-19 pandemic has been the management of the immunosuppression accompanying the disease, particularly in ICU (Intensive Care Unit) patients. More recently, the focus has shifted towards the management of the persistent immunosuppression post-acute COVID-19 and its complications. The rate of healthcare-associated infections (HAIs) had been declining before the pandemic, but has since started to increase once more. Due to multiple factors - unnecessary antibiotherapy, disorganized medical facilities, inadequate personal protection equipment etc. - there have been increasing reports of coinfections and secondary infections with multidrug-resistant bacteria in COVID-19 patients. We present a case report of a patient with no history of clinically overt immunosuppression before developing critical SARS-CoV-2 pneumonia. The patient had no need for antibiotic treatment during his hospitalization and was discharged in a stable state, being consequently readmitted multiple times for different healthcare-associated multidrug-resistant infections, over time developing other hospital-related complications. The case raises a discussion about the bidirectional relationship between post-COVID immunosuppression and the possible inadvertent excess in antibiotic therapy that has accompanied the pandemic. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection increases the risk of multi-organ systemic complications and venous and arterial thromboembolism. The development of vaccines has proven to be an effective method to combat severe forms of infection. Adverse effects reported after COVID-19 vaccination consisted of local injection site reaction, fatigue, myalgia, or fever as well as sporadic cases of vaccine-induced thrombotic immune thrombocytopenia, especially viral vector vaccines. Objectives: The aim of the study was to evaluate the repeated dose toxicity of a candidate vaccine against SARS- CoV-2, a test in which several parameters were analyzed, including coagulation factors. Materials and methods: The test included 120 rats, of both sexes, divided into six groups (main group, recovery group and control group) at which the human dose, 10X human dose and 1 control adjuvant were tested. The vaccine was administered intranasally, 4 times every two weeks. The final day was after the last administration to the main group and another 30 days from the last administration to the recovery group. On day 0 and the final day, blood was collected for hematological, biochemical, immunological examinations and coagulation tests (Fibrinogen, Prothrombin Time-PT, Activated Partial Thromboplastin Time-aPTT and Thrombin Time-TT). Results: Fibrinogen, in the case of all groups, increased on the final day, except for females from the recovery groups where this parameter decreased by 25%. PT, aPTT and TT, regardless of group or sex, had low values compared to the initial time of the study. On day 0, the values of the coagulation factors were homogeneous, the fibrinogen being between 155- 347mg / dL, PT 25.5-57.8 sec, aPTT 61.9-120 sec and TT values of 53-60 sec. On the final day, the group analysis also showed unit values. Fibrinogen increased between 90-116%, PT decreased by 48-71%, aPTT decreased by 59-80%, and TT had values lower by 10-14% compared to the initial day. Conclusions: Increased fibrinogen associated with decreased PT and aPTT is common in human clinical pathology. Fibrinogen, PT, aPTT and TT are the standard parameters of blood clotting assessed in toxicity tests. The results obtained in the study represent a preliminary phase which, corroborated with the results of the other tests, supports the conclusion that the candidate vaccine does not have toxicological potential, the coagulation factors not being influenced after its repeated administration. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting intertriginous skin areas of young adults. Although HS was historically defined as an infectious disease, the role of microorganisms in its pathogenesis is now controversial. We investigated the lesion microbiota of a recently diagnosed 24-year-old male patient with axillary HS, who shared features of the metabolic syndrome. The microbiological analysis of the patient's lesion was indicative of colonization with bacteria including aerobes - Staphylococcus (S.) aureus, S. lugdunensis, S. epidermidis, anaerobes - Anaerococcus (A.) octavius, and microaerophiles - Cutibacterium (C.) acnes; this last one was also isolated in monoculture from a patient's healthy skin control sample. In vitro antibiotic susceptibility evaluation revealed Methicillin-resistant S. aureus (MRSA) and highly susceptible S. lugdunensis and S. epidermidis. Profiles of A. octavius and C. acnes showed that both strains were susceptible to Vancomycin, Clindamycin, Doxycycline and Linezolid; the anaerobe was Benzylpenicillin-resistant and Tetracycline and the microaerophile was intrinsically Metronidazole-resistant. We conclude that the intralesional microbial diversity in this case shows low variety of species and similarities to healthy skin microbiota, although the presence of S. aureus, particularly MRSA, S. lugdunensis or C. acnes - frequently involved in chronic skin pathologies - may be relevant for the disease severity. MRSA carriage in the patient's lesion represents a significant epidemiological risk for the healthcare environment. Antibiotic treatment in the early stages of HS should be administered with caution. Extended studies of HS microbiota could identify relevant colonization patterns for the outcome of the disease and offer important keys for selecting personalised, efficient therapeutic schemes. [ABSTRACT FROM AUTHOR]

Objectives: Detection of carbapenemase-producing Enterobacterales (CPEs) is sometimes difficult with AmpC-hyperproducing Enterobacterales (AHEs), as they may falsely be classified as CPEs. Here, we present a rapid Carbapenem Inactivation Method (rCIM) optimized for AmpC producers (rCIM-A) that allows rapid and easy discrimination between AHEs and CPEs.Methods: Enterobacterales (n = 249), including natural AmpC producers, AHEs, CPEs and non-carbapenemase-producing carbapenem-resistant control strains were evaluated, using Carba NP, rCIM and rCIM-A. The rCIM-A differs from the rCIM by the addition of cloxacillin (400 μg/mL) to the initial antibiotic incubation step.Results: The rCIM-A yielded a sensitivity and specificity of 84.26% (95% CI: 76.00%-90.55%) and 99.29% (95% CI: 96.11%-99.98%), respectively, while those of the rCIM were 86.11% (95% CI: 78.13%-92.01%) and 80.85% (95% CI: 73.38%-86.99%), respectively; those of Carba NP were lower at 84.04% (95% CI: 75.05%-90.78%) and 91.37% (95% CI: 85.41%-95.46%), respectively, due to indeterminate results. The rCIM-A was capable of discriminating between AHEs and true CPEs, but still failed to identify OXA-23-producing Proteus mirabilis isolates and remained only partially reliable for identifying IMI-like producers and a few MBL (2 NDM-1, 1 LMB-1, 1 TMB-1 and 1 IMP-13) producers. One chromosomally encoded AmpC variant, MIR-10, gave repeatedly positive results using all three tests and was thus considered a false positive.Conclusions: Specificity for AHEs greatly improved with the rCIM-A without altering the test performance for the other resistance mechanisms. It may replace the rCIM as a cheap, easy, rapid and accurate CPE detection test. [ABSTRACT FROM AUTHOR]

Recent research has highlighted the role of oxidative stress in the pathogenesis of HPV-related lesions, especially in neoplastic diseases. Oxidative stress and chronic inflammation are the most important cofactors that HPV requires to persist and induce a malignant process. Data on the role of oxidative stress in benign lesions associated with HPV infection, such as genital and non-genital warts, is scarce and further research is needed. We have determined markers of oxidative stress in the serum of 26 patients with palmoplantar warts and 28 healthy subjects. We have investigated representative markers for the four main molecular targets of oxidative stress, nucleic acids - 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipids - 4-hydroxynonenal (4-HNE), carbohydrates - pentosidine, and proteins - thiol-disulfide homeostasis parameters (TDHP): total thiol (TT), native thiol (NT), and disulfides (DS). The serum levels of oxidative stress markers, 4-HNE, 8-OHdG, and pentosidine, were statistically significantly higher in patients with warts in comparison to the control group (p < 0.01). Regarding TDHP, we have found that TT levels were statistically significantly higher in the patient group compared to the control one (p < 0.05). Even though NT and DS levels were reported to be higher in the patient group compared to the control one, no statistical significance was established (p > 0.05). Our results show enhanced oxidative stress damage in patients with palmoplantar warts and provide valuable data in understanding the molecular mechanisms involved in the pathogenesis of HPV infection. To the best of our knowledge, this is the first study to evaluate both 4-HNE and pentosidine in patients with palmoplantar warts. [ABSTRACT FROM AUTHOR]

Chronic infections represent an important burden on the healthcare system and have a significant impact on the patients' quality of life. While Staphylococcus spp. are commensal bacteria, they can become pathogenic, leading to various types of infections. In this study we aimed to characterize the virulence profiles of staphylococcal strains involved in difficult-to-treat skin and soft tissue infections, from both phenotypic and genotypic points of view. Phenotypic ability of the strains to secrete soluble virulence factors was assessed by a culturing dependent assay and their capacity to develop biofilms on inert substrate was screened by an adapted crystal violet microtiter method. We also tested the presence of several virulence genes by PCR. Most of the studied strains were isolated from purulent secretions of acne lesions and frequently secreted two or three soluble virulence factors. Most frequently secreted soluble virulence factors were caseinase (89%), lipase (71%) and lecithinase (67%). Almost half of the strains produced a well-represented biofilm. The molecular characterization showed the presence of the genes cna, hlg, clfA, and clfB. Staphylococcal strains that produce difficult-to-treat skin and soft tissue infections seem to be characterized by an enhanced ability to produce different soluble virulence factors and to develop biofilms in vitro. Further studies need to be developed in other Staphylococcus spp. infections in order to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Background: The present study aims the characterization of antibiotic resistance phenotypes and encoding genes in bacterial strains isolated from some Romanian aquatic fishery lowland salted lakes. Material/Methods: This study was conducted on 44 bacterial strains, mainly belonging to species used as microbiological indicators of fecal pollution isolated from four natural fishery lakes. All strains were tested for their antibiotic susceptibility by disk diffusion method. Simplex and multiplex PCR were performed to identify the β-lactams antibiotic resistance genes (blaNMD, blaOXA−48, blaVIM, blaIMP, blaCTX−M, blaTEM), sulfonamides (Sul1, Sul2), tetracyclines (TetA, TetB, TetC, TetD, TetM), aminoglycosides (aac3Ia), vancomycin (VanA, VanB, VanC), macrolides (ermA, ermB, ermC) as well as the plasmid-mediated quinolone resistance (PMQR) markers (QnrA, QnrB, QnrS), and class 1 integrons (Int1, drfA1-aadA1). Results: The Enterococcus spp. isolates exhibited phenotypic resistance to vancomycin (35 %) and macrolides (erythromycin) (75 %); from the vancomycin – resistant strains, 5 % harboured VanA (E. faecalis), while the erythromycin resistant isolates were positive for the ermA gene (E. faecalis − 10 %, E. faecium − 5 %). The Gram- negative rods (GNR) exhibited a high level of resistance to β-lactams: cefuroxime (63 %), cefazolin (42 %), ceftriaxone (8 %), ceftazidime and aztreonam (4 % each). The genetic determinants for beta-lactam resistance were represented by blaCTX−M−like (33 %), blaNDM−like and blaIMP−like (8.33 %) genes. The resistance to non-β-lactam antibiotics was ascertained to the following genes: quinolones (QnrS − 4.16 %); sulfonamides (Sul1–75 %, Sul2–4.16 %); aminoglycosides (aac3Ia − 4.16 %); tetracyclines (tetA – 25 %, tetC − 15 %). The integrase gene was found in more than 50 % of the studied strains (58.33 %). Conclusions: The cultivable aquatic microbiota from fishery lakes is dominated by enterococci and Enterobacterales strains. The GNR strains exhibited high levels of β-lactam resistance mediated by extended spectrum beta-lactamases and metallo-β-lactamases. The Enterococcus sp. isolates were highly resistant to macrolides and vancomycin. The high level and diversity of resistance markers, correlated with a high frequency of integrons is suggesting that this environment could act as an important reservoir of antibiotic resistance genes with a great probability to be horizontally transmitted to other associated species from the aquatic sediments microbiota, raising the potential zoonotic risk for fish consumers. [ABSTRACT FROM AUTHOR]

In Romania, cervical cancer is the second most frequent neoplasm among women of 15 to 44 years of age, mainly due to a lack of prevention efforts. The purpose of this study is to assess the current knowledge and attitude towards HPV infection and immunization among medical students. Such information is vital in order to properly assess the current shortcomings of our medical system in the struggle of lowering cancer incidence. A cross-sectional questionnaire-based study was carried out in 2016 and in 2018 on a total of 1,133 participants (median age of 21.9 years, 572 students in 2016 and 562 in 2018). No statistical differences between males and females regarding knowledge of HPV vaccine were found (chi-square 0.046, df = 1, p = 0.83). Moreover, between the 2016 and the 2018 groups, no noticeable changes in HPV awareness and information were observed (2016: chi-square: 0.003, df = 1, p = 0.955; and 2018: chi-square: 0.061, df = 1, p = 0.805). Even though the participants have noted reliable media and medical staff as their main sources of information, our study revealed poor general knowledge, no improvement in perception, and a lack of prophylactic action. [ABSTRACT FROM AUTHOR]

In the context of SARS-CoV-2 infection, the identification of a vaccine has become vital for stopping the pandemic. The consortium formed by the OncoGen Center and the Cantacuzino Institute (CI) evaluates a candidate vaccine whose vaccine component is represented by a combination of peptides specifically recognized by the 2 components of the adaptative immune system. Each new vaccine must undergo mandatory tests, even if they are currently accelerated or overlapping, with the consent of the European Medicines Agency (EMA). One of the tests relates to repeated dose toxicity. The aim was to setup a protocol for repeated dose toxicity testing in rats, the results of which would allow the transition to the clinical phase I dossier. The protocol was designed based on EMA guidelines for vaccine safety testing and rat-human translation. The proposed human dose, route of administration and repeat administration were taken into account. Clinical signs, immunological and biochemical parameters will be analysed. Histological examination will be performed on 34 organs. The protocol was approved by the ethics committee of the CI and authorized by the competent authority. In order to evaluate the repeated dose toxicity of a vaccine candidate against COVID-19, we propose a robust, replicable, effective and translational study protocol. [ABSTRACT FROM AUTHOR]

Introduction: It is estimated that one in five pregnant women is affected by depression and the consequences of undiagnosed and unaddressed depression are detrimental for the future mother, her baby and ultimately the entire family unit [1]. Hepatitis B virus (HVB) infection is one of the TORCH infections (toxoplasmosis, other -HVB, etc., rubella, cytomegalovirus, herpes viruses), known as major contributors to prenatal infantile mortality and morbidity [2]. Case report: We report the case of a pregnant woman with multiple risk factors for depression, who was diagnosed during pregnancy with chronic HBV infection. Her personal background cumulated with her psychosocial situation led to severe depression late in the pregnancy which was recognised and addressed by the medical team involved in her care. Depression in pregnancy is reported to be associated with a risk for premature birth, intrauterine growth restriction and non-optimal neuromotor development; hence a new diagnosis of an infection associated with possible foetal complications was likely the last factor added to already a fragile psychic. The newborn had intrauterine growth restriction and received appropriate prophylactic measures to prevent HBV infection. The authors would like to emphasize that the role of the medical team involved in the care of pregnant women should not limit to delivering a healthy baby but the team should look into mother's psychological health as early recognition of depression impact the course of both medical and emotional health of the entire family. Furthermore, the authors are taking the opportunity to raise awareness among medical professionals in regard to the possible outcomes of a new diagnosis of infection in pregnancy on the psychological status of the pregnant woman. [ABSTRACT FROM AUTHOR]

Lately, the microbiome has received increasing attention, being a research theme frequently addressed in multiple studies. Through the new techniques and establishment of novel protocols, especially in the field of molecular biology, together with the results from in vitro, in vivo preclinical and clinical studies carried out on an impressive number of patients with various pathologies, scientists have established ample associations between the microbiome composition and certain cancers or the treatment response. In some types of cancer, the role of microorganisms has been incriminated, which by their presence can activate certain signaling pathways or produce some metabolites that ultimately affect the cellular functioning. For some microorganisms such as Fusobacterium nucleatum or toxigenic Bacteroides fragilis in colorectal cancer, the possible mechanisms of action have been already described. Despite this fact, numerous studies are still needed in order to determine whether bacterial presence triggers the neoplastic process or the gut microbial abundance in affected patients is the result of other changes taking place. The identification of specific microorganisms in people from high-risk groups, those with early stage or advanced/metastatic cancer or the ones with inadequate response to treatment, could represent the beginning of a novel approach in the field of cancer prevention, diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Mother-to-child transmission of viral blood bome diseases (BBD) may be prevented with efficient measures of prophylaxis. Some of the most frequent viruses involved in mother-to-child transmission are HBV, HIV and HCV. Our main objectives were to assess the mother-to-child transmission of BBD - HBV, HCV and HIV, to evaluate the risk factors associated with these viruses transmission in a hospital from Romania, especially in childbearing women diagnosed at the moment of birth, along with defining the importance of midwives. We conducted a retrospective, descriptive study, from January 2017 to December 2018 at a District Hospital for Obstetric Gynecology in Romania. A total of 7,020 childbearing women were monitored. Only 73 childbearing women presented BBD (61 HBV infections, 7 HCV infections and 5 HIV infections). Mother-to-child transmission rate of BBD was 12.32% (N=9 newborns) and the most frequent BBD transmitted to newborns was HIV infection. There were no cases of HBV mother-to-child transmission. The most important risk factors for transmission of abovementioned viral infections were found to be episiotomy, cervical rupture and early membrane rupture. There is a need for joint effort of all healthcare providers including the midwives in order to improve the control of BBD transmission from pregnant women to their newborns. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is a group of associated chronic systemic inflammatory immune-mediated rheumatic diseases affecting axial and peripheral joints and entheses. The aim of the present study was to identify what parameters are useful to determine in order to better understand the correlation between the disease activity/severity and the microbiological results/immune status against intestinal and/or urogenital pathogens. Microorganisms known to trigger SpA, including Klebsiella spp., Yersinia spp., Salmonella spp., Campylobacter spp. and Chlamydia spp., were analyzed in various specimens (stool, urine, synovial fluid and serum) collected from 27 randomly selected SpA patients and 26 healthy controls using a combined direct and indirect approach relying on conventional culture technique and nucleic acid-based assays together with serological testing by ELISA. Although Escherichia coli derived from phylogroup A prevailed in the gut microflora of the patients and controls, differences were observed regarding the representatives of the other phylogroups with a higher prevalence of E.coli members of phylogenetic group B1 in the stool specimens of patients. Antibodies against the targeted species were detected in SpA patients and controls, and the serological profiles of the former were more diverse and complex. In conclusion, the detection of anti-bacterial antibodies combined with other specific laboratory investigations should be more extensively used to monitor SpA patients in association with their symptoms and in order to determine and administer more effective therapeutics. [ABSTRACT FROM AUTHOR]

Lichen planus (LP) is an immune-mediated inflammatory disease that particularly affects the skin and mucous membranes. Its etiology remains elusive, however some trigger factors, including viral or bacterial antigens, drugs and metals, have been postulated. There is a higher prevalence of hepatitis C virus (HCV) infection among patients with LP, with some geographical variations. HCV is an enveloped RNA virus that belongs to the Flaviviridae family and in most instances causes chronic liver infections. It has been hypothesized that HCV may contribute to LP development, but the link between the two disorders is not fully understood. It is still debatable whether HCV leads to the occurrence of LP lesions directly by replication inside the infected cells or indirectly by activating immunological pathways. Molecular studies have revealed HCV RNA in specimens collected from patients with LP. The autoimmune theory was also suggested given that several studies have revealed viral replication and immune response activation associated with autoantibody synthesis. The aim of this review is to summarize the main potential mechanisms involved in the association between LP and HCV infection. Understanding the link between the two disorders may shed some light on the pathogenesis of LP, which is a challenging issue. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common tumour of the oral cavity, associated with significant morbidity and mortality. It is a multifactorial condition, both genetic and environmental factors being involved in its development and progression. Its pathogenesis is not fully elucidated, but a pivotal role has been attributed to inflammation, strong evidence supporting the association between chronic inflammation and carcinogenesis. Moreover, an increasing number of studies have investigated the role of different mediators of inflammation in the early detection of OSCC. In this review, we have summarized the main markers of inflammation that could be useful in diagnosis and shed some light in OSCC pathogenesis. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The host's immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis is a neglected zoonotic infection that is distributed worldwide and prioritised by WHO for control efforts. The burden of human cystic echinococcosis is poorly understood in most endemic regions, including eastern Europe. We aimed to estimate the prevalence of abdominal cystic echinococcosis in rural areas of Bulgaria, Romania, and Turkey.Methods: We did a cross-sectional ultrasound-based survey that recruited volunteers from 50 villages in rural areas of Bulgaria, Romania, and Turkey. These villages were in provinces with annual hospital incidence of cystic echinococcosis within the mid-range for the respective countries. All people who attended a session were allowed to participate if they agreed to be screened. Abdominal ultrasound screening sessions were hosted in public community structures such as community halls, primary health-care centres, schools, and mosques. Lesions were classified using an adapted WHO classification. We reported the prevalence of abdominal cystic echinococcosis adjusted by sex and age through direct standardisation, using the country's rural population as a reference.Findings: From July 1, 2014, to Aug 3, 2015, 24 693 individuals presented to screening sessions and 24 687 underwent ultrasound screening. We excluded a further six indivduals due to missing data, leaving 24 681 people in our analysis. Abdominal cystic echinococcosis was detected in 31 of 8602 people screened in Bulgaria, 35 of 7461 screened in Romania, and 53 of 8618 screened in Turkey. The age and sex adjusted prevalence of abdominal cystic echinococcosis was 0·41% (95% CI 0·29-0·58) in Bulgaria, 0·41% (0·26-0·65) in Romania, and 0·59% (0·19-1·85) in Turkey. Active cysts were found in people of all ages, including children, and in all investigated provinces.Interpretation: Our results provide population-based estimates of the prevalence of abdominal cystic echinococcosis. These findings should be useful to support the planning of cost-effective interventions, supporting the WHO roadmap for cystic echinococcosis control.Funding: European Union Seventh Framework Programme. [ABSTRACT FROM AUTHOR]

Over the last decade, chronic wounds such as venous or arterial ulcers, diabetic foot ulcers, pressure sores, and nonhealing surgical wounds were brought into the spotlight of the medical community, due to their increasing prevalence and to their significant economic burden. Vascular impairment represents the main cause of chronic ulceration, while the infection is the most frequent complication. Chronic infections persist and progress despite an adequate antimicrobial regimen and are typically caused by mono- or polymicrobial biofilms. The persistent bacterial colonization of the wound, as well as the longterm use of antibiotics predispose to the development of nosocomial infections with resistant strains, with the risk of life-threatening septic complications, especially in immunocompromised individuals. In this article, we perform a thorough literature review, in order to answer the main controversies regarding the involvement of planktonic and/or biofilm bacteria in the healing process of chronic wounds. Furthermore, we aim to analyse the utility of antimicrobial treatment in non-healing wounds, and to establish its main end-points, for the optimal benefit of the patients. [ABSTRACT FROM AUTHOR]

Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches. [ABSTRACT FROM AUTHOR]

Objectives: Fast and accurate diagnostic tests to identify carbapenemase-producing Enterobacteriaceae (CPE) are mandatory for proper antimicrobial therapy and implementing infection control measures. Here, we have developed a rapid Carbapenem Inactivation Method (rCIM) for CPE detection. Methods: The rCIM consists of the incubation of a potential carbapenemase producer with meropenem discs and use of the resulting supernatant to challenge a susceptible indicator strain. Growth of the indicator strain is monitored using a nephelometer. The performances of the rCIM were compared with theCIM and Carba NPtests using a collection of 113 well-characterized carbapenem-resistant enterobacterial isolates, including 85 carbapenemase producers and 28 non-carbapenemase producers. In addition, rCIM was compared with the Carba NP test and PCR sequencing in a prospective analysis of 101 carbapenem-resistant enterobacterial isolates addressed to the French National Reference Center for Antimicrobial Resistance in July 2017. Results and discussion: The rCIM correctly identified 84/85 carbapenemase producers and 28/28 non-carbapenemase producers, yielding a sensitivity of 99% and a specificity of 100%, slightly higher than the CIM and Carba NP test. In the prospective validation study, the rCIM showed a sensitivity and specificity of 97% and 95%, respectively. Two cephalosporinase-hyperproducing Enterobacter cloacae gave false-positive results, whereas an IMI-17-producing Enterobacter asburiae gave a false-negative result. The result was, however, positive when the isolate was grown on selective antibiotic-containing media. Conclusions: The rCIM is a rapid (less than 3 h), cheap and accurate test for the detection of CPEs, which can be implemented in low-resource settings, making it a useful tool for microbiology laboratories. [ABSTRACT FROM AUTHOR]

Introduction. Resistance to carbapenems represents a public health across the world. Screening for carbapenem resistance can be done starting from the antibiogram, but confirmatory methods are usually performed in reference centers. Methods for rapid identification of carbapenemase activity are required to empower laboratories to detect carbapenemases and raise signals for infectious disease physicians, antibiotic stewardship teams and hospital hygiene specialists. Materials and methods. Eppendorf tubes containing Klebsiella pneumoniae strains with carbapenemase activity (KPC-1, NDM-1, OXA-48) and others with no carbapenemase activity (K. pneumoniae ATCC 700603 and E. coli ATCC 25922), as well as positive and negative controls were incubated at 37 °C with varying concentrations of Meropenem. After incubation, samples were spun down until a pellet formed and the supernatant was used to challenge an exponentially growing E. coli culture. This second culture was followed with nephelometric measurements every half hour. Experiments were carried out in three technical replicates. The statistical analysis was done with R (version 3.3.3) and graphs generated in RStudio (version 1.0.136) with ggplot2 (version 2.1.0). Mann Whitney U Test with the assumption of independent samples was used to analyse the results. Results. The doses of Meropenem were chosen after dose ranging experiments and multiple incubation times (from 30 minutes to two hours) were tested in order to evaluate the robustness of the method. In the cases where the antibiotic was first incubated with strains that had carbapenemase activity, the growth of Escherichia coli ATCC 25 922 was non-hindered, matching that of controls. In the absence of carbapenemase activity and in the case of negative controls, the growth indicator strain was inhibited. Statistically significant differences were identified for 0.3, as well as a 0.5 McFarland index as early as 1.5 hours total work time. Conclusions. The discovery of carbapenem resistance has direct clinical, as well as epidemiological implications. Among the mechanisms implicated in resistance to carbapenems, the presence of a carbapenemase is one of the most worrying from an epidemiological standpoint. This new tool we describe herein can be performed in all clinical microbiology laboratories, with no extra expense (as opposed to CarbaNP and BlueCarba tests). [ABSTRACT FROM AUTHOR]

The increasing burden of invasive biofilm-related staphylococcal infections has led to a dire need for new agents to prevent biofilm formation. Bacteriophages may hypothetically alter a biofilm through several mechanisms, including induction of depolymerizing enzymes and lysis of persistent bacteria. We have assessed the influence of commercially available bacteriophage cocktails on Staphylococcus spp. clinical strains viability and biofilm formation. We analyzed 83 staphylococcal strains from patients consecutively admitted to a Romanian infection reference center from October 2014 through May 2015; the strains were characterized by phenotypic and genetic tools for their resistance and virulence features and for their phyliation. Experiments were performed in triplicate. Methicillin-susceptible strains were significantly more susceptible to all tested phages: 1.7-fold higher susceptibility for PYO, 1.4-fold for INTESTI, 2.9-fold for PHAGYO, 2.7-fold for PHAGESTI and 3.9-fold for STAPHYLOCOCCAL; t030 strains were significantly more susceptible to PYO and INTESTI compared with t127 strains. We identified a significant decrease in biofilm formation in the presence of both low and high PYO and INTESTI concentrations (P < 0.001). In conclusion, Staphylococcus strains from Romania displayed fairly good susceptibility to commercially available bacteriophages. We have also ascertained there is phage-driven in vitro inhibition of biofilm formation, the results potentially impacting prevention of prosthetic infections. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) represents a growing public health problem worldwide. Infections with such bacteria lead to longer hospitalization times, higher healthcare costs and greater morbidity and mortality. Thus, there is a greater need for rapid detection methods in order to limit their spread. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are a series of epidemiologically-important microorganisms of great concern due to their high levels of resistance. This review aimed to update the background information on the ESKAPE pathogens as well as to provide a summary of the numerous phenotypic and molecular methods used to detect their AMR mechanisms. While they are usually linked to hospital acquired infections, AMR is also spreading in the veterinary and the environmental sectors. Yet, the epidemiological loop closes with patients which, when infected with such pathogens, often lack therapeutic options. Thus, it was aimed to give the article a One Health perspective. [ABSTRACT FROM AUTHOR]

Chronic venous leg ulcers (CVLU) account for the final outcome of a far wider disease spectrum referred to as chronic venous disease. Physiological wound healing involves a three-stage process, with the coagulation/ inflammatory, granulation and epithelialization phases occurring successively. In the case of chronic wounds, such as CVLUs, the tissue damage and repair are misbalanced, resulting in the ulcer's lodging in a particular wound stage - the inflammation or granulation stage -, consequently impairing progression towards wound healing. Failure to rebuild the skin integrity may be due to a large number of factors, either endogenous - host factors determining or maintaining breaches in the protective barrier of the skin -, or exogenous, such as microbial biofilm infections. The future research should focus upon the study of wound microenvironment. The detection of specific biomarkers of chronic wound healing, as well as the discovery of therapeutic agents that target molecules involved in the pathogenic cascade would change the course of the disease. [ABSTRACT FROM AUTHOR]

Although controlled by vaccination long ago, diphtheria may become a re-emergent disease as a result of at least two factors: the circulation of toxigenic strains in endemic areas (countries of former CSI, some of them neighbouring countries of Romania) and the lack of interest of the local health institutions for surveillance of this very low incidence disease. The aim of this study was to evaluate the carriage of potentially toxigenic Corynebacterium strains in healthy people in Romania. In this study, 1120 biological samples were analysed consisting of swabs, nasal exudates and conjunctival secretions collected from 730 healthy individuals from eight different geographic regions of the country, in order to establish carriage of potentially toxigenic strains belonging to the Corynebacterium genus. 129 strains of the Corynebacterium species were isolated and identified by phenotypic and molecular methods: Corynebacterium pseudodiphtheriticum (n = 76), C. propinquum (n = 34), C. striatum (n = 9), C. macginleyi (n = 2), C. glucuronolyticum/seminale (n = 2), C. group F1(n = 6). These species are saprophytic species for the upper respiratory tract, some of them being an opportunistic pathogen especially in immunocompromised hosts. The present data require the attention of clinicians, epidemiologists and microbiologists since diphtheria is an infectious disease that could re-emerge. [ABSTRACT FROM AUTHOR]