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(1) Background: Cutaneous anthrax is a disease caused by a Gram-positive bacillus, spore-forming Bacillus anthracis (BA). Cutaneous anthrax accounts for 95% of all anthrax cases, with mortality between 10-40% in untreated forms. The most feared complication, which can be life-threatening and is rarely encountered and described in the literature, is compartment syndrome. (2) Methods: We report a series of six cases of cutaneous anthrax from the same endemic area. In two of the cases, the disease was complicated by compartment syndrome. The systematic review was conducted according to systematic review guidelines, and the PubMed, Google Scholar, and Web of Science databases were searched for publications from 1 January 2008 to 31 December 2023. The keywords used were: "cutaneous anthrax" and "compartment syndrome by cutaneous anthrax". (3) Results: For compartment syndrome, emergency surgical intervention for decompression was required, along with another three surgeries, with hospitalization between 21 and 23 days. In the systematic review, among the 37 articles, 29 did not contain cases focusing on compartment syndrome of the thoracic limb in cutaneous anthrax. The results were included in a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram. (4) Conclusions: Early recognition of the characteristic cutaneous lesions and compartment syndrome with early initiation of antibiotics and urgent surgical treatment is the lifesaving solution.

Objectives: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management., Methods: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%)., Results: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward., Conclusions: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Polymicrobial meningitis is a rare entity in the adult population, especially in the antibiotic era. However, disorders such as chronic suppurative otitis media (CSOM) or even poor oral hygiene are considered risk factors for the development of such cerebral infection. We report a case of polymicrobial meningitis associated with oto-mastoiditis in a 64-year-old female patient known to have CSOM. The patient presented atypical symptoms for community-acquired meningitis, showing subacute evolution of headache, without fever or neck stiffness. The aerobe microorganisms Streptococcus anginosus and Corynebacterium spp., sensitive to beta-lactamines, and the anaerobe Prevotella spp., resistant to penicillin and metronidazole, were isolated from CSF specimens, while Proteus mirabilis and Enterococcus faecalis were identified from the ear drainage. The diversity of pathogens identified in our case led us to the hypothesis of two different sources of meningitis: otogenic and/or odontogenic. Favorable evolution was obtained after a multi-disciplinary approach, combining surgery and broad-spectrum antibiotics. In addition, we performed a literature review that highlights the low incidence of polymicrobial mixed aerobe-anaerobe meningitis.

Background and Objectives. The intensive care unit (ICU), especially in an infectious disease hospital, is both an area with a high consumption of antibiotics (atb) and a "reservoir" of multidrug-resistant bacteria. We proposed the analysis of antibiotic therapy practices in such a department that treated, in conditions of a pandemic wave, patients with COVID-19 and its complications. Materials and Methods. This was a retrospective transversal study of 184 COVID-19 patients treated in the ICU of a regional infectious disease hospital of Iaşi, Romania, in a 3-month interval of 2020 and 2021. Results. All the included patients (Caucasians, 53% males, with a median age of 68 years, and a Charlton comorbidity index of 3) received at least one antibiotic during their stay in the ICU (43% also had antibiotics prior to hospital admission and 68% in the Infectious Diseases ward). Only 22.3% of the ICU patients had only one antibiotic. A total of 77.7% of them started with an association of two antibiotics, and 19.6% of them received more than three antibiotics. The most-used ones were linezolid (77.2%), imipenem (75.5%), and ceftriaxone (33.7%). The median atb duration was 9 days. No change in the number or type of atb prescription was seen in 2021 (compared to 2020). Only 9.8% of the patients had a microbiological confirmation of bacterial infection. A total of 38.3% of the tested patients had elevated procalcitonin levels at ICU admission. The overall fatality rate was 68.5%, with no significant differences between the two analyzed periods or the number of administered antibiotics. More than half (51.1%) of the patients developed oral candidiasis during their stay in the ICU, but only 5.4% had C. difficile colitis. Conclusion. Antibiotics were widely used in our ICU patients in the presence of a reduced microbiological confirmation of a bacterial co-infection, and were justified by other clinical or biological criteria.

Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug-drug or drug-nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug-nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.

Background and Objectives : Human immunodeficiency virus infection and the acquired immunodeficiency syndrome (HIV/AIDS) pandemic are unquestionably the most serious public crisis of our time. Identifying, preventing, and treating HIV-associated comorbidities remains a challenge that must be addressed even in the era of antiretroviral therapy. Materials and Methods : In this study, we aimed to characterize the aspects of newly diagnosed patients with HIV/AIDS, during 2021-2022 in Northeastern Romania. We reviewed the frequency and associated comorbidities of these patients in correspondence with national and global results. Results : Our study found that of all newly diagnosed HIV cases (167 cases-74 cases in 2021 and 98 cases in 2022), 49.70% were diagnosed with HIV infection and 50.30% had AIDS. Based on sex correlated with the CD4+ T-lymphocyte level, the most affected were males, with a lower CD4+ T-lymphocyte level overall. The average HIV viral load was 944,689.55 copies/mL. Half of males had an abnormal ALT or AST (39.53% and 49.61%); as for the females, less than a quarter had an increased value of ALT or AST, respectively (18% and 26%). The most frequent co-infections were as follows: oral candidiasis (34.73% of patients), hepatitis B (17.37% of patients), and SARS-CoV-2 infection (8.38%), followed by hepatitis C (6.39%), tuberculosis (TB), syphilis, toxoplasmosis, Cryptococcus , Cytomegalovirus infections. Males were more affected than females, with a higher percentage of co-infections. The prescribed antiretroviral treatment focused on a single-pill regimen (79.04%) to ensure adherence, effectiveness, and safety. Therefore, 20.96% had been prescribed a regimen according to their comorbidities. Conclusions : Our study found a concerning rise in the incidence of HIV in 2022 compared to that in 2021 in Northeastern Romania, because of the rise in post-SARS-CoV-2 pandemic addressability. Advanced immunodeficiency and the burden of opportunistic infections characterize newly diagnosed HIV patients. The physicians should keep in mind that these patients may have more than one clinical condition at presentation.

Background and Objectives . Being an enterically transmitted pathogen with a growing prevalence in developed countries, hepatitis E virus (HEV) infection remains an underdiagnosed disease in Eastern Europe. As far as Romania is concerned, only a few studies address this issue. Our goal was to estimate the prevalence of serum anti-HEV IgA/IgM/IgG antibodies in a group of patients admitted to the Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi. Materials and Methods. The cross-sectional study consisted of enrollment of 98 patients admitted to the clinic for COVID-19 over a period of three months in 2020. Results . The median age in our study was 73 years, with an equal gender ratio and with a predominance of people from the urban environment (75%). The overall HEV antibody seroprevalence was 12.2%. The main risk factors associated with HEV infection were consumption of water from unsafe sources (58.3% HEV-positive patients vs. 26.7% HEV-negative patients, p = 0.026) and improperly cooked meat (58.3% HEV-positive patients vs. 23.2% HEV-negative patients, p = 0.01). Zoonotic transmission was an important criterion in our study, with patients reporting contact with pigs, poultry, rats, or other farms animals, but no significant differences were found between HEV antibody positive and negative groups. Conclusions . The seroprevalence rate of HEV antibodies was similar to other previous reports from our area but higher than in most European countries. The fact that HEV antibodies were detected in patients without identifiable risk factors for hepatitis E is evidence of subclinical infection as a silent threat.

Controlling the spread of coronavirus disease 2019 (COVID-19) includes institute isolation, quarantine measures and appropriate clinical management, which all require effective screening, diagnostic and prognostic tools. The present study aimed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin (Ig)A detection and determine the potential association with the clinical course of COVID-19 and the levels of inflammation. In the present study, the presence of IgA and IgG SARS-CoV-2 antibodies in 75 consecutive patients with confirmed COVID-19 infection was investigated. No significant differences were found between the IgA positive and negative groups, regarding the presence of symptoms, haematological and inflammatory variables, or the presence of pneumonia. In the majority of cases, antibody detection was comparable, for example, 79.7% of patients in the IgA positive group exhibited both types of antibodies, while 80.9% of patients in the IgA negative group were also IgG negative. A total of four patients in the IgA negative group presented with anti-SARS-CoV-2 IgG antibodies. Early detection of IgA was more frequent in patients who later developed severe forms of the disease. In addition, the IgG SARS-CoV-2 antibody response was higher in patients with the severe form of the disease., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Vâţă et al.)

Background: Oral rehydration is the main treatment of acute diarrhea in children. This study was undertaken to evaluate the efficacy and safety of xyloglucan and gelose (agar-agar) plus oral rehydration solution (ORS) compared with placebo and ORS for reduction of acute diarrhea symptoms in children., Methods: In a randomized, double-blind, placebo-controlled trial, children with acute gastroenteritis received xyloglucan/gelose plus ORS (n = 50) or placebo plus ORS (n = 50) for 5 days. Demographic, clinical, anthropometric and laboratory parameters were recorded and analyzed., Results: Xyloglucan/gelose plus ORS reduced the total number of type 7 and 6 stools on the Bristol Stool Form scale ( p = 0.040 and p = 0.015, respectively, compared to placebo plus ORS), and had a rapid onset of action, evident 6 hours post-treatment. Xyloglucan/gelose plus ORS also improved associated clinical symptoms (apathy, vomiting, flatulence, and blood in stool). compared with placebo plus ORS. Except for a generalized rash of unknown causality in a patient receiving placebo plus ORS, all other adverse events (dehydration, n = 7, cough, n = 1, exacerbation of vomiting, n = 1) were deemed unrelated to study medication., Conclusions: Xyloglucan/gelose plus ORS was effective and safe in treating acute diarrhea in children.

Background: Streptococcus agalactiae (Group B Streptococcus) is recognized as the etiologic agent of newborn and infant meningitis, aged up to 90 days, starting from the colonization of the maternal genital or gastrointestinal tract, but it is rarely responsible for meningitis in old infants., Case Presentation: We present the case of a 9 month-old infant diagnosed with S. agalactiae meningoencephalitis associated with chronic gastroesophageal reflux disease treated with a proton pump inhibitor (PPI)., Conclusion: The use of a PPI is a risk factor for ultra-late onset of Group B Streptococcus meningitis. The use of PPI in infants should be closely monitored in the light of changes in the gut microbiota, in the oropharyngeal and of the respiratory tract colonization, potentially with pathogenic flora.

Fatal Familial Insomnia (FFI) is a genetic prion disease caused by a point mutation in the prion protein gene (PRNP) characterized by prominent thalamic atrophy, diffuse astrogliosis and moderate deposition of PrP Sc in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrP Sc detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrP Sc concentration of about 1 × 10 -14  g/ml. In contrast, PrP Sc was not detected in OM samples from healthy controls and patients affected by other neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and frontotemporal dementia. These results indicate that the detection limit of these assays is in the order of a single PrP Sc oligomer/molecule with a specificity of 100%.

The outcome of chronic HBV infection is variable; approximately one half of individuals transition to an inactive carrier state, 30% progress to cirrhosis, and the remainder to chronic hepatitis. Ten different HBV genotypes and many subtypes have been identified with distinct geographical distributions. Over the years, a lot of studies presented the efficiency of different genotyping methods; for this reason we aimed to present a cost efficient genotyping diagnosis algorithm of CHB infected patients, especially useful to identify those at risk of disease progression and determine optimal anti-viral therapy as useful instrument for physicians.

Unlabelled: Given its epidemic potential and development of severe forms of disease, viral meningitis (VM) is a serious public health problem., Aim: to characterize the main clinical, epidemiologic features, the etiology and treatment of VM cases admitted to the Iasi Infectious Diseases Hospital, in 2012., Material and Methods: We retrospectively analyzed the medical records of the patients admitted for viral meningitis at the Iasi "St. Parascheva" Infectious Diseases Hospital in the interval January 1- December 31, 2012 (98 cases). The etiologic diagnosis was made by determining the IgM/IgG antibodies against Coxsackie virus and/or West Nile virus in blood/CSF., Results: There was a fourfold increase in the number of cases as compared to the average for the years 2009-2011. Most cases (73.5%) were children aged 1 to 14 years. 61.8% of patients were males, 51.7% from urban areas. The most common symptom was headache (85.7%), followed by fever (77.6%), and vomiting (66.3%). Neck stiffness was absent in 28.6% cases. In43.5% of the 39 patients serologically investigated a Coxsackie virus infection was confirmed and 1/20 was positive for West Nile virus; three varicella-zoster virus infections and one mumps infection were diagnosed clinically. 68.3% of the patients received first-line antibiotic treatment., Conclusions: The illness mainly affected children, fever and neck stiffness being sometimes absent. The etiology was known in 22.4% of cases; enter viruses being the most frequent causative agent. Most patients received antibiotic therapy. The course was favorable in all cases.

NADPH oxidase Nox5 subtype expression is significantly increased in vascular smooth muscle cells (SMCs) underlying fibro-lipid atherosclerotic lesions. The mechanisms that up-regulate Nox5 are not understood. Consequently, we characterized the promoter of the human Nox5 gene and investigated the role of various proinflammatory transcription factors in the regulation of Nox5 in human aortic SMCs. The Nox5 promoter was cloned in the pGL3 basic reporter vector. Functional analysis was done employing 5' deletion mutants to identify the sequences necessary to effect high levels of expression in SMCs. Transcriptional initiation site was detected by rapid amplification of the 5'-cDNA ends. In silico analysis indicated the existence of typical NF-kB, AP-1, and STAT1/STAT3 sites. Transient overexpression of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 increased significantly the Nox5 promoter activity. Chromatin immunoprecipitation demonstrated the physical interaction of c-Jun/AP-1 and STAT1/STAT3 proteins with the Nox5 promoter. Lucigenin-enhanced chemiluminescence, real-time PCR, and Western blot assays showed that pharmacological inhibition and the silencing of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 reduced significantly the interferon γ-induced Ca(2+)-dependent Nox activity and Nox5 expression. Up-regulated Nox5 correlated with increases in intracellular Ca(2+), an essential condition for Nox5 activity. NF-kB, AP-1, and STAT1/STAT3 are important regulators of Nox5 in SMCs by either direct or indirect mechanisms. Overexpressed Nox5 may generate free radicals in excess, further contributing to SMCs dysfunction in atherosclerosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pulmonary toxoplasmosis occurs mainly in immunosuppressed patients and its diagnosis mainly relies upon biological confirmation of the parasite. We present the case of a 47 years patient in medullar aplasia after induction chemotherapy for acute lymphoblastic leukemia that developed pulmonary infiltrates of parasitic origin. The diagnosis of pulmonary toxoplasmosis was established after identification of the parasite in brochioloalveolar lavage fluid (BAL) and peripheral blood. Serological tests are of limited utility in immunosuppressed patients. We used classical methods for the diagnosis of parasitosis but they are being replaced by molecular methods. Polymerase Chain Reaction (PCR) allows a highly specific and sensitive diagnosis on any sample but it cannot be performed in any center.

Unlabelled: Acute gastroentritis is one of the most common diseases in humans, and continues to be a significant cause of morbidity worldwide., Aims: To determine the bacterial pathogens associated with gastroenteritis in patients admitted to the Iasi Infectious Diseases Hospital in the last ten years., Material and Methods: A total of 40481 stool samples were examined using conventional methods., Results: Bacteria were found in 7.36% of cases, and parasites in 9.64%; 83% of the cases were viral, micotic, or disbiotic. The bacterial etiology was dominated by Salmonella spp. (58.34%), Shigella spp. (27.08%), Yersinia enterocolitica 03 (8.53%), Campylobacter spp. (1.31%), other bacterial pathogens (EPEC, Aeromonas hydrophilla/caviae/sobria, Plesiomonas shigelloides, Bacillus cereus, Staphylococcus aureus, etc) being detected in 3.74% of the cases. Of the Salmonella species, group B (51.99%) followed by group D (45.23%) were most common. Shigella sonnei and Shigella flexneri were found in almost the same proportion (49.45% and 49.70%, respectively); Shigella boydii was isolated in only 0.85% of cases. The trend of gastroenteritis caused by bacterial pathogens is decreasing: from 355 cases in 2001 to 105 cases in 2010; three peaks have been recorded in 2002, 2005 (when Salmonella typhi was isolated in a patient), and 2008 (469, 409, and 252 cases, respectively). Bacterial gastroenteritis affected both sexes almost equally (122 males and 118 females). The most affected age groups were: 0 - 4 years, 15 - 24 years, 5 - 14 years and 25 - 39 years., Conclusions: Laboratory investigations are essential in determining the etiology of gastroenteritis. Its unpredictable incidence justifies the human and material efforts aimed at controlling the spread of potentially epidemic acute gastroenteritis.

Material and Methods: We performed QuantiFERON-TB Gold in Tube (QFT-G) in blood and CSF at 40 children diagnosed with TB meningitis and at 39 children with non TB meningitis, admitted between October 2006 and December 2009., Results: The CSF analyses were suggestive for TB at 27 patients and only 14 had positive culture. The sensitivity of QFT-G in CSF was 72.72% and 69.44% in blood; specificity 96.96% in CSF and 89.18% in blood; the positive predictive value was 96% in CSF and 86.2% in blood; negative predictive value was 78.04% in CSF and 75% in blood. The sensitivity of TST was 61.76% and specificity 82.05%. The sensitivity of the culture from CSF was only 35%. The sensitivity and specificity of QFT-G was higher than TST and culture and better in CSF than in blood., Conclusions: The determination of alpha-interferon in serum and CSF is useful diagnostic marker of tuberculosis who could improve the management of TB meningitis.

Unlabelled: The aim of the study was to investigate the particularities of the clinical manifestation and evolution of tuberculous meningitis at children., Material and Method: The study was made between January 2000 and December 2008 in Clinic of Infectious Diseases IaSi and Emergency County Hospital ,,Sf. Ioan cel Nou" Suceava on a group of 169 children with tuberculous meningitis., Results: The majority (78.1%) of patients had poor socio-economic conditions and 22.4$ had a family TB contact. The onset of the symptoms was atypical in infants and small children with fever associated with digestive, neurological or pulmonary manifestations. The admission in hospital was delayed in 56.8% of patients and 39.05% had a severe general status with coma. The positive diagnosis was based on cytological and biochemical features of CSF, results of QuantilFERON. TB Gold, pulmonary images, family TB contact and evolution under anti-tuberculous therapy. We observed a high rate of complications represented by hydrocephaly (28.9%). 18 patients died (4 infants), the cause of dead being meningeal coma or complications., Conclusion: The diagnosis of tuberculous meningitis at children remains a problem because of the atypical clinical manifestation, the delay of initiating the therapy causing high mortality and frequent complications.

This paper reviews literature data on the hepatitis C virus. Hepatitis C virus is a positive-sense, single-stranded RNA virus. It is a genetically variable virus and it is estimated that the dominant viral sequence changes every few weeks. At least 6 genotypes are now recognized. All of this genotypes appear to have a similar effect on the liver but, the duration and response to therapy is strongly influenced by them. A complete understanding of this virus will greatly facilitate new antiviral agents.

Hyperplastic growth and expression of gamma-glutamyl transpeptidase were induced in adult rat hepatocytes using a model of chemical hepatocarcinogenesis. The hyperplastic response was maximal at 10 weeks after initiation of the model, at which time some 20-25% of the cross-sectional area of liver sections showed hepatocyte expression of gamma-glutamyl transpeptidase. The altered growth patterns appeared to be independent of carcinoma development since at 12 months after initiation only one of 10 animals showed evidence of hepatocellular carcinoma. A 43,000 dalton protein of isoelectric point 6.9 was solubilized by DNASE I from nuclei derived from livers at 10 weeks after initiation of the regime. This protein was scarcely detectable in the nuclei of control livers or in control and treated livers at other times after initiation of the regime. These observations suggest that alterations to a prominent nonhistone protein associated with the transcriptionally active fraction of chromatin occurred during hyperplastic growth of hepatocytes induced by chemical carcinogens.