RESUMO
BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins. METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication. RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4). CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.).
Assuntos
Antivirais , Hepatite B Crônica , Oligonucleotídeos Antissenso , RNA Viral , Humanos , Antivirais/efeitos adversos , Antivirais/uso terapêutico , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/efeitos adversos , Oligonucleotídeos Antissenso/uso terapêutico , Resultado do Tratamento , RNA Viral/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Injeções SubcutâneasRESUMO
COVID-19 is currently a major health problem, leading to respiratory, cardiovascular and neurological complications, with additional morbidity and mortality. Spinal infections are rare, representing around 1% of all bone infections and comprising less than 2 per 10,000 of all hospitalizations in tertiary care centers. Spondylodiscitis is a complex disease, with challenging diagnosis and management. We report the case of a 45-year-old man, non-smoker hospitalized for severe COVID-19 disease with respiratory failure. Post-COVID-19, in the 8th week after discharge, he was diagnosed by magnetic resonance imaging with spondylodiscitis, but etiology was not confirmed by microbiological investigations. Antibiotics were used, considering the identification of MRSA from cultures of pleural fluid and nasal swab, but surgical intervention was not provided. Clinic, biologic and imagistic were improved, but rehabilitation and long term follow up are necessary. We concluded that spondylodiscitis with spinal abscess is a rare but severe complication post-COVID-19 disease, due to dysbalanced immune response related to the respiratory viral infection, endothelial lesions, hypercoagulation and bacterial superinfection.
Assuntos
COVID-19 , Discite , Doenças do Sistema Nervoso , Masculino , Humanos , Pessoa de Meia-Idade , Discite/diagnóstico , Discite/microbiologia , COVID-19/complicações , Abscesso/complicações , AntibacterianosRESUMO
The COVID-19 pandemic is a new challenge for the diagnosis and treatment of infective endocarditis (IE). Fever and other unspecific symptoms of coronaviral infection could be misleading or masking its manifestations. We present the case of a young patient admitted for persistent fever, profuse sweating, headache, articular pain, myalgias, and weight loss. She reported regression taste and smell disorders compared to a month earlier when diagnosed with moderate COVID-19 pneumonia. While the RT-PCR SARS-COV-2 test was positive, she was admitted to a COVID-19 ward. Investigations of febrile syndrome revealed two positive blood cultures with Streptococcus gordonii and the presence of vegetations on the aortic valve, supporting a certain diagnosis of IE. After six weeks of antibiotic treatment, the patient had clinical and biologic favorable outcomes. Streptococcus gordonii is a common commensal related to the dental biofilm, although there were no caries in our patient. The influence of COVID-19 infection on the human microbiome by modifying the virulence of some commensal germs may be a risk factor for IE pathogenesis on native valves and requires the vigilance of clinicians for suspicion of this disease.
Assuntos
COVID-19 , Endocardite , Endocardite/diagnóstico , Endocardite/tratamento farmacológico , Feminino , Humanos , Pandemias , SARS-CoV-2 , Streptococcus gordoniiRESUMO
Introduction: The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments, and vulnerable biological status. Methods: We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022. Results: The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias, and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases. Conclusion: The co-infection of COVID-19 had a mild impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.
RESUMO
The risk factors of hospitalized COVID-19 and obstructive sleep apnea (OSA) overlap. The aim of this study is to evaluate the prevalence and associated factors of post-COVID-19 OSA in hospitalized adult patients from southeastern Romania. A follow-up study was conducted on patients hospitalized for COVID-19 at the Pneumology Hospital in Galati, Romania, between 2021 and 2022. OSA was evaluated using the Epworth and STOP-BANG questionnaires and nocturnal polygraphy monitoring. Out of 331 patients, 257 were evaluated for sleep apnea in the 12th week. The prevalence of severe OSA was 57.97%. Significant associations were found with male gender, an age over 60, obesity, and cardiovascular co-morbidities. Non-invasive ventilatory therapy (NIV) and a hygienic-dietary regimen were recommended based on severity following a control visit after a month. Developing strategies for diagnosing and monitoring sleep disorders, including home sleep apnea tests and patient education, are the next directions for post-COVID-19 management.
RESUMO
Kaposi's sarcoma is an AIDS-defining illness and remains the most frequent tumor arising in HIV-infected patients with multifactorial etiology. We present a case of a 30-year-old Caucasian male with an 18-year history of HIV infection. The patient was presented with a one-week history of fever, non-productive cough, and skin lesions. There was an associated weakness and weight loss in a duration of 6 months. Clinical examination showed fever, generalized lymphadenopathy, lower limb edema, ascites, and violaceous cutaneous eruption comprising patches, plaques, and nodules. He also had a red nodule on the left conjunctiva, as well as on his oral mucosa. His CD4+ count was below 10/mm3 and ARN-HIV viral load was above 100,000 c/mL, in relation to the antiretroviral failure after five drug regimens. The role of co-infections in oncogenesis and the course of Kaposi's sarcoma were considered in recent studies. Delayed diagnosis of Kaposi's sarcoma in the present case resulted in a negative impact for this patient during the COVID-19 pandemic.
RESUMO
BACKGROUND: Infective endocarditis (IE) management is challenging, usually requiring multidisciplinary collaboration from cardiologists, infectious disease specialists, interventional cardiologists, and cardiovascular surgeons, as more than half of the cases will require surgical procedures. Therefore, it is essential for all healthcare providers involved in managing IE to understand the disease's characteristics, potential complications, and treatment options. While systemic embolization is one of the most frequent complications of IE, the coronary localization of emboli causing acute myocardial infarction (AMI) is less common, with an incidence ranging from 1% to 10% of cases, but it has a much higher rate of morbidity and mortality. There are no guidelines for this type of AMI management in IE. METHODS: This narrative review summarizes the current knowledge regarding septic coronary embolization in patients with IE. Additionally, this paper highlights the diagnosis and management challenges in such cases, particularly due to the lack of protocols or consensus in the field. RESULTS: Data extracted from case reports indicate that septic coronary embolization often occurs within the first two weeks of the disease. The aortic valve is most commonly involved with vegetation, and the occluded vessel is frequently the left anterior descending artery. Broad-spectrum antibiotic therapy followed by targeted antibiotic therapy for infection control is essential, and surgical treatment offers promising results through surgical embolectomy, concomitant with valve replacement or aspiration thrombectomy, with or without subsequent stent insertion. Thrombolytics are to be avoided due to the increased risk of bleeding. CONCLUSIONS: All these aspects should constitute future lines of research, allowing the integration of all current knowledge from multidisciplinary team studies on larger patient cohorts and, subsequently, creating a consensus for assessing the risk and guiding the management of this potentially fatal complication.
RESUMO
Purpose: To screen the neurocognitive impairment persistent post-COVID-19. Patients and Methods: We assessed the neuropsychiatric disorders associated with COVID-19 in a prospective study, by "Mini-Mental State Examination" (MMSE) and Montreal Cognitive Assessment (MoCA) questionnaires, applied in the discharge to COVID-19 hospitalized patients for moderate and severe forms of disease. They were followed-up in 6 and 12 months. Results: The tests were performed in the baseline and were reevaluated after 6 and 12 months. Baseline cognitive dysfunction was found in 12.4% of patients, according to the MMSE test and in 19.7% by the MoCA scores. Overall cognitive dysfunction in COVID-19 was returned to normal after 6 months, although some tasks are more severe and persistently impaired, such as attention, concentration, short memory, and execution skills. The male gender and the degree of hypoxia, related to the severity of COVID-19 infection, were related to cognitive dysfunction in the study group. Conclusion: Cognitive domain impairments related to COVID-19 could persist over 6 months post-acute infectious episode requiring systematic screening for early diagnosis of progressive brain pathologies and rehabilitation.
RESUMO
Vulvovaginitis with Candida spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to present challenges and the decision must balance the risk of fetal toxicity with the benefits to the fetus and mother. Starting from the idea that clotrimazole is the most recommended antifungal in candidal vaginitis in pregnancy, we tested the sensitivity of different species of Candida spp. to other azoles, polyenes, and antimetabolites. This retrospective study (January to June 2019) assessed 663 pregnant women hospitalized for various pregnancy-related symptoms in which samples of phage secretion were taken. The laboratory results confirmed 21% of cases, indicating 140 positive mycologic samples. In this study, vaginal candidiasis was mostly related to the first trimester of pregnancy (53.57%,) and less related in the last trimester (17.14%). Candida albicans was the most frequent isolated strain in this study, accounting for 118 cases, followed by 16 strains of Candida glabrata and 6 cases of Candida krusei. The highest sensitivity for C. albicans was found in azoles, mostly in miconazole (93.2%), while C. krusei was completely resistant to polyene with low sensitivity in antimetabolites and even in some azoles, such as fluconazole. In our study, higher resistance rates to flucytosine were found, with C. glabrata and C. krusei exhibiting greater resistance than C. albicans.
RESUMO
Oral lesions are early indicator of immunosuppression, leading to HIV new diagnoses. The type of oral lesions can reveal opportunistic diseases that are correlated with the severity of immune depletion. Highly active antiretroviral therapy decreases the incidence of opportunistic oral infections, whereas a large variety of lesions are frequently experienced in people with HIV. Overlapping pathogenic mechanisms and multiple contributing etiologies are related to unusual, atypical oral lesions that are challenging in the clinical practice. We present a rare case of eosinophilic granuloma of the tongue in an older male HIV patient with severe immunosuppression due to the failure of antiretroviral treatment. Differential diagnoses considered squamous carcinoma, lymphoma, viral, fungal or bacterial infections and autoimmune disorders, as well as the influence of HIV immune disfunctions or the influence of cannabidiol use. The histopathologic and immunohistochemistry examination clarified the inflammatory reactive benign substrate of the lesion, although future survey of the oral lesions is essential.
RESUMO
Mucormycosis is a rare fungal infection, with high mortality, commonly associated with diabetes, malignancies, immunosuppressive therapy, and other immunodeficiency conditions. The emergence of mucormycosis cases has been advanced by the COVID-19 pandemic. Clinical presentation is variable, from asymptomatic to persistent fever or localized infections. We present a case of a Romanian old man, without diabetes or other immunodepression, with COVID-19 who developed severe rhino-orbital mucormycosis and bacterial superinfections, with Pseudomonas aeruginosa and Klebsiella pneumoniae. The late diagnostic and antifungal treatment was related to extensive lesions, bone and tissue loss, and required complex reconstruction procedures. We review the relationships between mucormycosis, COVID-19, and bacterial associated infections. The suspicion index of mucormycosis should be increased in medical practice. The diagnostic and treatment of COVID-19-Associated-Mucormycosis is currently challenging, calling for multidisciplinary collaboration.
RESUMO
Preventing mother-to-child HIV transmission is a strategy to eliminate new infections to move toward a world free of HIV/AIDS. The aim of this study is to assess the effectiveness of the perinatal infection prevention program in a single center from southeast Romania. Newborns of HIV-positive mothers from 2005 to 2020 were followed-up until the age of two in a retrospective study. The transmission rate from HIV-positive mothers to living children was zero, but neonatal mortality, preterm birth and birth defects were still high. The peculiarity of our study is the high proportion of mothers with a nosocomial pattern of HIV transmission. Intensifying the efforts for accurate implementing the interventions for the prevention of mother-to-child HIV transmission, a long time follow-up for HIV-exposed uninfected children and new research on related HIV pregnancies are necessary to reach the objective of a new generation free of HIV.
RESUMO
Psoriasis can be paradoxically associated with human immunodeficiency virus (HIV) infection, having a prevalence similar to the general population but with a more severe evolution. In the genetically predisposed patients with the CW*0602 haplotype, HIV infection can be a triggering factor and a first sign of infection, and lesions can spontaneously remit with immune reconstruction after antiretroviral therapy. Our patient is a 34 year-old male with recent HIV infection, in spite of being for over 10 years the partner of an HIV-positive patient with whom the patient has two HIV-positive children. The patient was diagnosed with psoriasis 7 years ago and was treated topically. The physical examination at HIV diagnosis was overall favorable, with skin findings compatible with disseminated vulgar psoriasis. Following antiretroviral treatment with Triumeq the patient had a favorable viral response, with complete viral suppression after 12 weeks, but the pre-existent psoriasis lesions worsened. Methotrexate (MTX) treatment followed for 12 weeks, with partial improvement of psoriatic dermatitis. This medication was continued for 1 year, but the lesions reappeared, possibly due to treatment resistance. MTX treatment for psoriasis in the HIV-infected patient was beneficial, but limited to one year, leaving biologics as possible treatment following therapy under strict monitoring for adverse effects, T-lymphocyte CD4+ and viral levels.
RESUMO
Although basal cell carcinoma is a well-known tumor with confirmed clinical and histopathology traits, prognosis factors and treatment options, new facets of this tumor emerge as innovative approach methods develop. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) allow a basal cell carcinoma's in vivo analysis of its depth of invasion, tumor margins prior to surgical approach and the tumor's response to a non-invasive treatment, evaluating simultaneously the tumor's vasculature. By RCM and OCT analysis, basal cell carcinoma has registered a groundbreaking discovery regarding a small (but with predictive factor potential) trait - the cleft, developing in between the tumor islands/nodules/chords and the surrounding tumor stroma; it was considered to date as a consequence of the tissue's histopathology processing. RCM and OCT revealed that the "clefting artifact", as it is frequently found in the medical literature, is not actually an artifact of laboratory processing, but a tumor trait found in vivo, with apparent mucin deposits. This review aims at merging the methods of evaluating basal cell carcinoma, both non-invasive (dermoscopy, RCM, OCT) and invasive ones (histopathology - with newly proposed classification), with special emphasis on the cleft issue - its assessment with the aforementioned techniques, with potential implications in the patient's prognosis.
RESUMO
Kaposi's sarcoma (KS) was peculiarly described in the first notified cases of the acquired immunodeficiency syndrome as an opportunistic condition. However, the medical progress and the development of active antiretroviral therapy allowed the control of the HIV/AIDS epidemic, although the features of KS have changed throughout the past decades. The purpose of our study is to assess the epidemiological and clinical features of AIDS related KS in Romanian patients. A retrospective follow-up study was achieved in a single infectious diseases' clinic from Galati-Romania, between 2001 and 2021. Referring to 290 new HIV diagnosed cases from our clinic retained in care, the prevalence of KS was 3.4%. The main characteristics of patients with KS are a median age of 33, a predominance of males, prevalent severe systemic forms of diseases, frequent association of past or concomitant tuberculosis, and context of immune reconstruction syndrome. The mortality rate was 70%. KS has occurred in patients with delayed HIV diagnoses and inadequate adherence to therapy. Early recognition of both infections, the close monitoring of latent or symptomatic tuberculosis, improving the antiretroviral adherence and raising the access to oncologic procedures in Romanian HIV patients could improve their prognosis related to KS.
RESUMO
PURPOSE: This study aimed at identifying the main antimicrobial resistance of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli) pathogens in a Romanian infectious diseases hospital. This antimicrobial resistance is a global threat, having high rates of multidrug resistance and limited treatment options. PATIENTS AND METHODS: This retrospective study (2016-2020) assessed the antimicrobial resistance of ESKAPE pathogens isolated from the patient's biological samples. The microbiological diagnosis was performed by classical culture methods. The antimicrobial susceptibility analysis used the Kirby-Bauer disk-diffusion method and the method of minimum inhibiting concentration with the automated Vitek, according to the CLSI (Clinical and Laboratory Standards Institute) standards. RESULTS: Included in this study were 4293 bacterial isolates: 67% Gram-negative bacilli, 31% Gram-positive cocci and 2% other morphotinctorial bacteria. ESKAPE pathogens were found in 97% of the bacterial isolates strains; E. coli (38.26%) and Staphylococcus aureus (26%) were the most prevalent. Most bacterial strains were isolated from urine cultures (45.6%), skin and soft tissue secretions/collections (35.9%) and also blood cultures (4.2%). Increased antimicrobial resistance was observed for methicillin-resistant Staphylococcus aureus (MRSA)s, extended spectrum beta-lactamase producing (ESBL) Enterobacterales, carbapenem-resistant (CR) Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. No vancomycin resistance was found for Enterococcus faecium. The highest prevalence rates of multidrug resistance were found in methicillin-resistant Staphylococcus aureus (86.6%), Acinetobacter baumannii (36.8%), Pseudomonas aeruginosa (29.1%) and Klebsiella pneumoniae (24.4%). CONCLUSION: ESKAPE pathogens are frequently isolated in the infectious diseases hospital, with main antimicrobial resistance: ESBL, MRSA and CR. The local antimicrobial resistance pattern is essential in updating the local protocols and for appropriately prescribing antibiotics. Streamlining microbiological diagnosis and aligning with the European standards for antimicrobial susceptibility testing are necessary steps in harmonizing the regional network for good antimicrobial resistance control practices.
RESUMO
The first cases of COVID-19 were reported in Wuhan Province, in China, in December 2019, spreading rapidly around the world. The World Health Organization (WHO) declared this pandemic at the beginning of March 2020 and, at the same time, the first patient in GalaÈi County was confirmed. Both the global and the regional epidemiological evolutions have taken place with variations in incidence, which have been graphically recorded in several "waves". We conducted a retrospective study on cases of COVID-19 infection, hospitalized between March and June 2020 in an infectious diseases clinic from Galati, in the south-east of Romania. The present paper describes the "first-wave" regional epidemiological and clinical-biological features and the evolution of the COVID-19 pandemic. A poor outcome was related to late presentation to hospital, old age, and over six comorbid conditions including Alzheimer's disease. The high death rate among people from long-term care institutions is the consequence of the cumulative risk factors associated with immune senescence and inflammation, while COVID-19 is more likely a contributing factor to lower life expectancy.
RESUMO
Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival.
RESUMO
Cytokines involved in pathogenesis of psoriasis such as interleukins (IL-1ß, IL-6, IL-17, IL-22, IL-23), interferon-α, tumor necrosis factor-α and interferon-γ can also become therapeutic targets. Research currently uses murine models of imiquimod-induced psoriatic-type dermatitis in order to analyze potentially helpful phytotherapeutics for psoriasis treatment: Curcuma longa, Aloe vera, Nigella sativa, Rubia cordifolia, Smilax china, Thespesia populnea, Wrightia tinctoria, Scutellaria baicalensis, Cassia tora, Pongamia pinnata and various Chinese herbal formulas. Psoriasis is a chronic inflammatory disease with complex pathogenic mechanisms that yield abnormal immune responses with clinical and morphological echoes (erythematous, scaly plaques with a histopathological basis made up of alterations i.e. keratinocyte aberrant proliferation, parakeratosis or chronic inflammation). The current therapeutic approach has only been able to manage the disease, without ensuring a certified treatment, thus giving rise to the need for better medications. This novel therapeutic approach has shown promising results in preclinical studies, giving hope for future phytochemical animal-based studies.
RESUMO
We report on the genomic characterization of 47 multi-drug resistant, carbapenem resistant and ESBL-producing K. pneumoniae isolates from the influent (I) and effluent (E) of three wastewater treatment plants (WWTPs) and from Romanian hospital units which are discharging the wastewater in the sampled WWTPs. The K. pneumoniae whole genome sequences were analyzed for antibiotic resistance genes (ARGs), virulence genes and sequence types (STs) in order to compare their distribution in C, I and E samples. Both clinical and environmental samples harbored prevalent and widely distributed ESBL genes, i.e. blaSHV, blaOXA, blaTEM and blaCTX M. The most prevalent carbapenemase genes were blaNDM-1, blaOXA-48 and blaKPC-2. They were found in all types of isolates, while blaOXA-162, a rare blaOXA-48 variant, was found exclusively in water samples. A higher diversity of carbapenemases genes was seen in wastewater isolates. The aminoglycoside modifying enzymes (AME) genes found in all types of samples were aac(6'), ant(2'')Ia, aph(3'), aaD, aac(3) and aph(6). Quinolone resistance gene qnrS1 and the multi-drug resistance oqxA/B pump gene were found in all samples, while qnrD and qnrB were associated to aquatic isolates. The antiseptics resistance gene qacEdelta1 was found in all samples, while qacE was detected exclusively in the clinical ones. Trimethroprim-sulfamethoxazole (dfrA, sul1 and sul2), tetracyclines (tetA and tetD) and fosfomycin (fosA6, known to be located on a transpozon) resistance genes were found in all samples, while for choramphenicol and macrolides some ARGs were detected in all samples (catA1 and catB3 / mphA), while other (catA2, cmIA5 and aac(6')Ib / mphE and msrE) only in wastewater samples. The rifampin resistance genes arr2 and 3 (both carried by class I integrons) were detected only in water samples. The highly prevalent ARGs preferentially associating with aquatic versus clinical samples could ascribe potential markers for the aquatic (blaSHV-145, qacEdelta1, sul1, aadA1, aadA2) and clinical (blaOXA-1, blaSHV-106,blaTEM-150, aac(3)Iia, dfrA14, oqxA10; oqxB17,catB3, tetD) reservoirs of AR. Moreover, some ARGs (oqxA10; blaSHV-145; blaSHV-100, aac(6')Il, aph(3')VI, armA, arr2, cmlA5, blaCMY-4, mphE, msrE, oqxB13, blaOXA-10) showing decreased prevalence in influent versus effluent wastewater samples could be used as markers for the efficiency of the WWTPs in eliminating AR bacteria and ARGs. The highest number of virulence genes (75) was recorded for the I samples, while for E and C samples it was reduced to half. The most prevalent belong to three functional groups: adherence (fim genes), iron acquisition (ent, fep, fyu, irp and ybt genes) and the secretion system (omp genes). However, none of the genes associated with hypervirulent K. pneumoniae have been found. A total of 14 STs were identified. The most prevalent clones were ST101, ST219 in clinical samples and ST258, ST395 in aquatic isolates. These STs were also the most frequently associated with integrons. ST45 and ST485 were exclusively associated with I samples, ST11, ST35, ST364 with E and ST1564 with C samples. The less frequent ST17 and ST307 aquatic isolates harbored blaOXA-162, which was co-expressed in our strains with blaCTX-M-15 and blaOXA-1.