Emerging Strategies against Non-Typhoidal Salmonella: From Pathogenesis to Treatment.

Even with the intensive efforts by public health programs to control and prevent it, non-typhoidal Salmonella (NTS) infection remains an important public health challenge. It is responsible for approximately 150 million illnesses and 60,000 deaths worldwide annually. NTS infection poses significant risks with high rates of morbidity and mortality, leading to potential short- and long-term complications. There is growing concern among health authorities about the increasing incidence of antimicrobial resistance, with multidrug resistance totaling 22.6% in Europe, highlighting an urgent need for new therapeutic approaches. Our review aims to provide a comprehensive overview of NTS infection. We outline the molecular mechanisms involved in the pathogenesis of NTS infection, as well as the events leading to invasive NTS infection and the subsequent complications associated with it. Given the widespread implications of antimicrobial resistance, our review also presents the global landscape of resistance, including multidrug resistance, and delve into the underlying mechanisms driving this resistance. The rising rates of antibiotic resistance frequently lead to treatment failures, emphasizing the importance of investigating alternative therapeutic options. Therefore, in this review we also explore potential alternative therapies that could offer promising approaches to treating NTS infections.

SARS-CoV-2 Seroprevalence in Children under 5 Years Old-A Regional Seroepidemiological Study.

Background and Objectives: The aim of this research was to assess the spread of SARS-CoV-2 infection; the study was motivated by parental hesitancy regarding child vaccination, and the potential passive immunity of infants acquired through breastfeeding from mothers vaccinated against COVID-19 or infected with SARS-CoV-2. Materials and Methods: We quantified the anti-SARS-CoV-2 immunoglobulin G (IgG) titer in the serum of 743 children under 5 years old, hospitalized between 1 August 2022, and 15 September 2023. Results: Among the participants, 52.76% had an anti-SARS-CoV-2 IgG titer that exceeded the reactivity threshold of the kit used, with an average of 1558.01 U/mL across the entire group. By age-specific categories, SARS-CoV-2 antibody prevalence was 43.04% for 0-12 months, 42.22% for 12-24 months, 61.67% for 24-36 months, 65.17% for 36-48 months, and 68.55% for 48-59 months. Gender analysis revealed 55.32% male participants, with a 52.07% seropositivity rate. Notably, IgG titer correlated positively with the child's age. Gender, admission diagnosis, and emergency department presentation were not variation factors of the IgG titer. Conclusions: The majority of children in the study group demonstrated IgG against SARS-CoV-2, and this rate increased with the child's age. Also, the IgG titer increased with the child's age.

Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant.

The Role of the Gut Microbiota in Anorexia Nervosa in Children and Adults-Systematic Review.

Among the factors incriminated in the appearance of eating disorders, intestinal microbiota has recently been implicated. Now there is evidence that the composition of gut microbiota is different in anorexia nervosa. We gathered many surveys on the changes in the profile of gut microbiota in patients with anorexia nervosa. This review comprehensively examines the contemporary experimental evidence concerning the bidirectional communication between gut microbiota and the brain. Drawing from recent breakthroughs in this area of research, we propose that the gut microbiota significantly contributes to the intricate interplay between the body and the brain, thereby contributing to overall healthy homeostasis while concurrently impacting disease risk, including anxiety and mood disorders. Particular attention is devoted to elucidating the structure and functional relevance of the gut microbiota in the context of Anorexia Nervosa.

Multidrug-Resistant Bacteria in Immunocompromised Patients.

The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to maintain microbial stability by preventing overpopulation with pathogenic bacteria. In immunocompromised patients, microbiota imbalance caused by antibiotic therapy and decreased host immunity favors intestinal overpopulation with pathogenic species, leading to increased bacterial translocation and susceptibility to systemic infections. Infections with multidrug-resistant (MDR) bacteria pose major challenges to the establishment of appropriate treatment and lead to increased mortality. Asymptomatic colonization with MDR bacteria usually precedes infection and tends to persist for long periods of time, and in immunocompromised patients, colonization with MDR bacteria is a risk factor for systemic infections. This review aims to assess the relation between colonization and infection with MDR bacteria in immunocompromised patients such as ICU patients, HIV-positive patients and cancer patients and to identify the prevalence and patterns of MDR bacterial colonization and infection in this category of patients.

Diagnosis, Management, and Prognosis of Cystic Fibrosis-Related Liver Disease in Children.

Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease.

The Immune, Inflammatory and Hematological Response in COVID-19 Patients, According to the Severity of the Disease.

INTRODUCTION: The aim of this study was to evaluate the immune and inflammatory responses in COVID-19 patients by dosing specific IgM and IgG total antibodies and interleukin 6, correlating them with the hematological and biochemical blood parameters and comparing them by the form of the disease. MATERIALS AND METHODS: One hundred twenty-five patients with polymerase chain reaction-confirmed COVID-19, hospitalized between 15.03.2020 and 1.07.2020 in the Clinical Hospital of Infectious Diseases "Sf. Parascheva" Iasi, were tested by chemiluminescence for the presence of anti-SARS-CoV-2 IgM and IgG and IL-6 in the serum. The results were correlated with the results of the CBC count and serum biochemical parameters detected on the admission day. The patients presented different forms of the disease (asymptomatic, mild, moderate, severe, and critical) according to World Health Organization (WHO) criteria for the clinical management of COVID-19. RESULTS: The amplitude of the immune response was directly correlated with the form of the disease. In the asymptomatic/mild form patients, the IL-6 and CRP concentrations were significantly higher and eosinophil count was significantly lower compared with the reference interval. In the moderate form, the concentrations of IL-6, CRP, and IgG were significantly higher, compared with the reference interval, while eosinophil count and eGFR were significantly lower. In severe/critical COVID-19 patients, IL-6, CRP, NLR, PLR, glucose, AST, urea, creatinine, and eGFR were significantly higher compared with the reference interval, while eosinophil count was significantly lower. IL-6 boosted in all forms of COVID-19, with a major increase in severe and critical patients. IL-6, neutrophil count, % neutrophils, NLR, PLR, CRP, AST, and urea increased with the severity of the SARS-CoV-2 infection, and the lymphocyte count, % lymphocytes, eosinophil count, % eosinophils, and hemoglobin decreased with the increased severity of COVID-19. CONCLUSIONS: The amplitude and the moment of appearance of the immune response depended on the form of the disease. IgM generally occurred in the first 14 days of illness, and IgG appeared beginning with the second week of disease. IgG titer increased rapidly until the fourth week of disease and decreased slowly after 4 weeks. The amplitudes of all the tested inflammatory and serological markers depended on the COVID-19 form, increasing somewhat in the moderate forms and even more in the critical ones. The lymphocyte and eosinophil count are able to predict the risk of severe COVID-19.

The Role of the Gut Microbiome in Psychiatric Disorders.

The role of the gut microbiome in mental health has been of great interest in the past years, with several breakthroughs happening in the last decade. Its implications in several psychiatric disorders, namely anxiety, depression, autism and schizophrenia, are highlighted. In this review were included relevant studies on rodents, as well as human studies. There seems to be a connection between the gut microbiome and these pathologies, the link being emphasized both in rodents and humans. The results obtained in murine models align with the results acquired from patients; however, fewer studies regarding anxiety were conducted on humans. The process of sequencing and analyzing the microbiome has been conducted in humans for several other pathologies mentioned above. Additionally, the possible beneficial role of probiotics and postbiotics administered as an aid to the psychiatric medication was analyzed.

Anti-RBD IgA and IgG Response and Transmission in Breast Milk of Anti-SARS-CoV-2 Vaccinated Mothers.

The appearance of the severe acute respiratory syndrome virus-2 (SARS-CoV-2) has had a significant impact on the balance of public health and social life. The data available so far show that newborns and young children do not develop severe forms of COVID-19, but a small proportion of them will still need hospitalization. Even though young children represent an important vector of the infection, vaccination at such a young age was not yet considered. Thus, the question of whether potentially protective antibodies against SARS-CoV-2 could be provided to them via breast milk or across the placenta, as "passive immunity", still stands. MATERIALS AND METHODS: Between January-July 2021, we have conducted a prospective study that aimed to measure the immunoglobulin (Ig) A and IgG anti-SARS-CoV-2 titers in the breast milk of 28 vaccinated lactating mothers, sampled at 30 and 60 days after the second dose of the anti-SARS-CoV-2 Pfizer or Moderna mRNA vaccines. Anti-RBD reactive IgA and IgG antibodies were detected and quantified by a sandwich enzyme-linked immunosorbent assay. RESULTS: Anti-RBD IgA and IgG were present in all breast milk samples, both in the first and in the second specimens, without a significant difference between those two. The anti-RBD IgA titers were approximately five-times higher than the anti-RBD IgG ones. The anti-RBD IgA and IgG titers were correlated with the infants' age, but they were not correlated with the vaccine type or mother's age. The anti-RBD IgA excreted in milk were inversely correlated with the parity number. CONCLUSIONS: Anti-SARS-CoV-2 IgA and IgG can be found in the milk secretion of mothers vaccinated with mRNA vaccines and, presumably, these antibodies should offer protection to the newborn, considering that the antibodies' titers did not decrease after 60 days. The antibody response is directly proportional to the breastfed child's age, but the amount of anti-RBD IgA decreases with the baby's rank. The antibody response did not depend on the vaccine type, or on the mother's age.

Cytokines and Chemokines in Breastmilk of SARS-CoV-2 Infected or COVID-19 Vaccinated Mothers.

INTRODUCTION: The COVID-19 disease and anti-SARS-CoV-2 vaccination were accompanied by alterations in several inflammatory markers. The aim of our research was to check to what extent such cytokines are transferred to infants via the breastmilk of SARS-CoV-2-infected or vaccinated mothers. Thus, we wanted to check if breastfeeding is safe during SARS-CoV-2 infection or after COVID-19 mRNA-vaccination. MATERIAL AND METHOD: The Luminex Multiplexing Assay was used for quantifying 10 cytokine in the human breastmilk of SARS-CoV-2-infected or COVID-19-vaccinated mothers, compared with anti-SARS-CoV-2 IgG naïve mothers. Two milk samples were collected at 30 and 60 days either after the booster dose or afterthe onset of symptoms. A single milk sample was collected from the mothers within the control group. RESULTS: The cytokine concentrations were mostly found within the reference intervals for all mothers. The status of the vaccinated/infected mother, the age of the breastfed child, the parity of the mother and the maternal age were variation factors of the above-mentioned cytokine concentrations. The type of birth and the presence of IgG in the milk had no influence on these cytokine concentrations in milk. Furthermore, no statistically significant differences were recorded between the cytokine concentrations of the two milk samples. CONCLUSION: Our study provides data that support the safety of breastfeeding in the case of mild COVID-19 infection or after Pfizer or Moderna vaccinations.

What Doesn't Kill Them Makes Them Stronger: The Impact of the Resistance Patterns of Urinary Enterobacterales Isolates in Patients from a Tertiary Hospital in Eastern Europe.

(1) Background: The evolution of bacterial resistance to antibiotics is one of the factors that make infectious pathology an extremely dynamic field, also inducing a significant burden on public health systems; therefore, continuous updates on the bacterial resistance to antibiotics and their particular regional patterns is crucial for the adequate approach of various infectious diseases. (2) Methods: We retrospectively analyzed 354 patients with Enterobacterales urinary tract infections (UTIs), determined their antibiotic resistance pattern, thus aiming to correlate them with the outcome and other specific markers of poor prognosis. (3) Results: The most frequent causative agent was Escherichia coli, representing 64.6% of all UTIs. We identified 154 patients resistant to multiple antibiotic classes, of which 126 were multidrug-resistant (MDR), 17 were extensive drug-resistant (XDR) and 11 were pandrug-resistant (PDR). Moreover, 25 isolates were resistant to carbapenems (CRE), 25 were difficult-to-treat (DTR), and 84 were extended-spectrum cephalosporin-resistant (ESC), with only 95 isolates susceptible to all tested antibiotics. Mortality ranged from 1% for UTIs caused by isolates susceptible to all tested antibiotics, to 24% for the ones caused by DTR or CRE isolates. Other significant risk factors associated with mortality were: prolonged hospital stay (p = 0.0001), Charlson comorbidity index ≥ 3 (p = 0.02), urinary catheterization (p = 0.001), associated respiratory pathologies (p = 0.004), obesity (p = 0.047), a history of previous hospitalizations (p = 0.007), inappropriate empiric antibiotic regimen (p = 0.001), or hyper inflammatory status (p = 0.006). Basically, we observed that a multiple regression model comprising urinary catheterization, inappropriate empiric anti-biotherapy, obesity, and respiratory comorbidities exhibits the best correlation with mortality rate in patients with UTI (R = 0.347, R2 = 0.12). (4) Conclusions: By focusing on the novel resistance patterns, our study provides complementary evidence concerning the resistance profiles found in an Eastern European region, as well as their prognostic implications in patients with UTI.

Optimization of triplex real time PCR for detecting Staphylococcus aureus mecA, pvl and nuc genes.

Multiplex polymerase chain reaction (PCR) allows simultaneous detection of two or more genes, using the same reaction conditions, and so it is possible the rapid detection of methicillin resistant Staphylococcus aureus strains (MRSA) in clinical specimens. This study aimed to implement, for the first time in our laboratory, a triplex real time PCR (RT-PCR) technique for detection of genes encoding resistance to oxacillin and synthesis of Panton Valentine leukocidin (pvl), a pathogenicity factor characteristic for community acquired strains (CA-MRSA). The application of this method will permit the epidemiological surveillance of circulating strains and early application of prevention measures.

Antibiotic resistance of non-fermenting Gram-negative bacilli isolated at a large Infectious Diseases Hospital in North-Eastern Romania, during an 11-year period.

INTRODUCTION: Increased antibiotic resistance of non-fermenting Gram-negative bacilli (NFGNB) associated with increased morbidity and mortality makes the infections they produce a major public health problem. This study aims to assess the evolution of antibiotic susceptibility and the level of NFGNB antibiotic resistance. METHODS: We carried out a retrospective study on 994 NFGNB strains which had been isolated in the Clinical Laboratory of the "Sf. Parascheva" Clinical Hospital of Infectious Diseases, Iasi, during a period of 11 years (2008-2018). RESULTS: Of the 994 NFGNB analyzed, 322 were Acinetobacter spp. and 672 Pseudomonas aeruginosa. Also, 882 NFGNB were isolated from non-sterile sites, in which there was a higher burden of P. aeruginosa strains (n=617). Acinetobacter spp. presented over 70% resistance to the majority of antibiotics. Three pandrug-resistant P. aeruginosa strains were identified. The rate of colistin resistance was 2.91% for P. aeruginosa and 3.33% for Acinetobacter spp. A comparative analysis of the antibiotic susceptibility of strains isolated from non-sterile sites versus sterile sites revealed statistically significant differences only for Acinetobacter spp. The percentage of resistant strains was significantly higher in tracheobronchial aspirate compared to sputum. CONCLUSIONS: The results show that Acinetobacter spp. is substantially more resistant to antibiotics compared to P. aeruginosa and that the use of medical devices can favor the occurrence of infections with multidrug-resistant strains.

Insights into multidrug-resistant K. pneumoniae urinary tract infections: From susceptibility to mortality.

The incidence of urinary tract infections (UTIs) caused by Klebsiella pneumoniae has exhibited an increasing trend and has become a high burden for many public health systems, especially in hospital settings. Multidrug resistance associated with the production of extended-spectrum ß-lactamases (ESBL) among K. pneumoniae isolates is endemic in Southeastern Europe. We retrospectively analyzed 75 cases admitted to 'St. Parascheva' Clinical Hospital of Infectious Diseases in Iasi, Romania, during the first 6 months of 2019 (January 1 to June 30), who had a confirmed diagnosis of K. pneumoniae UTI at discharge. From a total of 75 patients, 34 (45.3%) presented ESBL+ K. pneumoniae. The mean age was 66 years (70.1 for the ESBL+ patients vs. 62.6 for the ESBL- patients, P=0.0365). There was a symmetrical sex distribution (37 men vs. 38 women). Of these, 22 men had ESBL+ K. pneumoniae UTIs, compared to only 15 with an ESBL- strain, P=0.0087. Another risk factor for ESBL+ K. pneumoniae UTIs was the presence of hospitalization in the past 6 months; 20 (58.82%) patients with ESBL+ infections were previously hospitalized, compared to only 5 (12.19%) patients with ESBL- strains, P<0.0001. The urinary catheter carriers presented an increased prevalence of ESBL+ infections (15/34 vs. 5/41, P=0.0012). Regarding mortality, ESBL+ infections caused 6 fatalities, compared to only 1 death in the ESBL- group, P=0.0166. ESBL+ K. pneumoniae strains represent an important cause of healthcare-related UTIs, with a significantly higher mortality rate compared to ESBL- strains. Early identification and adequate management of the risk factors incriminated in ESBL+ UTIs should be a priority for physicians in order to limit the dissemination of the ESBL-producing strains and thus to improve the outcome of these patients.

Tuberculous Meningitis in Children and Adults: A 10-Year Retrospective Comparative Analysis.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal form of Mycobacterium tuberculosis infection, which has a high rate of neurological complications and sequelae. OBJECTIVES: Our study offers a real-world infectious disease clinic perspective, being thus representative for the clinical environment of developing countries. METHODS: We performed a retrospective analysis of the 127 adult and 77 pediatric cases diagnosed with TBM in the Infectious Disease Hospital of the School of Medicine of Iasi, Romania between 2004-2013. RESULTS: Definite diagnosis of TBM was established in 31% of children but in only 20% of adults (p = 0.043). A contact with an individual with pulmonary tuberculosis was documented in 30% of children vs. 13% of adults (p = 0.0007). Coma occurred in 19% of patients (similar in children and adults); other consciousness abnormalities were seen in 27% of children and in 72% of adults (p = 0.000001). Cranial nerve palsies occurred prior to therapy in 9% of cases (12% vs 7% of children and adults, respectively, p>0.05), and developed 2-7 days after treatment initiation in 10% (12 vs 9%). CSF cultures were positive for M. tuberculosis in 24% of patients (31% vs. 20%, p>0.05). Overall mortality was 7.35%, similar for children and adults. Yet, permanent neurological sequelae, which were seen in 23% of patients occurred significantly more frequent in children vs. adults (36% vs. 14%, respectively, p = 0.0121). In conclusion, our retrospective analysis on a significant number of cases of TBM identified striking differences between children and adults: while children were in an earlier stage at the admission, they associated a higher frequency of neurological sequelae and miliary pattern, and they were more likely to have normal CSF protein levels and positive cultures of CSF.