Search Results (32)

Background and objectives: Due to resistance and the lack of treatment options, hospital-acquired Acinetobacter baumannii (A. baumannii) infections are associated with high mortality. This study aimed to analyze the characteristics of patients with infections caused by multidrug-resistant (MDR) A. baumannii and patients’ clinical outcomes as well as determine the risk factors for mortality in a tertiary care teaching hospital. Materials and methods: A retrospective cohort study including 196 adult patients with A. baumannii strains isolated from different clinical specimens in the Hospital of the Lithuanian University of Health Sciences in 2016, 2017, 2020, and 2021 was conducted. Data on patients’ characteristics, comorbid diseases, treatment, length of hospital and ICU stay, and outcome were collected. Carbapenemase-producing isolates were detected phenotypically. To determine risk factors for in-hospital mortality, logistic regression analysis was performed. Results: There were 60 (30.6%) women and 136 (69.4%) men with a mean age of 61.7 ± 16.6 years (range, 52–74). More than three-fourths (76.5%, n = 150) of the patients had at least one comorbid disease. The highest number of A. baumannii strains were isolated from patients hospitalized in ICUs (43.4%, n = 85). A. baumannii strains producing three types of β-lactamases were more frequently isolated from women than men (77.8% vs. 22.2%, p = 0.006). Infections caused by A. baumannii strains producing two types of β-lactamases were significantly more often treated with combination therapy than infections caused by strains producing one type of β-lactamase (78.9% vs. 60.0%, p = 0.019). Patients with A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) stayed significantly shorter at the ICU compared to patients with A. baumannii strains with no detected β-lactamases (median of 9, IQR 2–18, vs. median of 26, IQR 7–38, p = 0.022). Death occurred in 58.7% (n = 115) of patients. Logistic regression analysis showed that a duration of the effective antibiotic treatment of ≤6 days, invasive mechanical ventilation, combination therapy, aged >58 years, and the absence of co-infection were independent predictors of in-hospital mortality. Conclusions: MDR A. baumannii infections pose a significant threat to human health not only due to multidrug resistance but also due to high mortality. The mortality rate of patients with MDR A. baumannii infection was high and was associated with age, invasive mechanical ventilation, the duration of effective antibiotic treatment, no co-infection, and combination therapy. Therefore, it is of utmost importance to reduce the prevalence of MDR A. baumannii infections in healthcare facilities by applying preventive measures and to administer timely effective treatment once A. baumannii infection is detected. Full article

This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury. Full article

Background and Objectives: Growing antibiotic resistance among bacteria is a global issue that is becoming harder and more expensive to solve. Traditional treatment options are becoming less effective, causing more fatal outcomes of nosocomial infections. Since the development of new antibiotics has stagnated in the last decade, a novel approach is needed. Materials and Methods: Graphene-based materials are being developed and tested for various applications, and the medical field is no exception. We tested 98 clinical A. baumannii strains for antibiotic resistance, AMP-C production and the effectiveness of a graphene oxide and silver nanoparticle hybrid nanocomposite. The disc diffusion method was used to determine antibiotic susceptibility results. Antibiotic discs containing cefotaxime, cloxacillin and clavulanate were used to detect AMP-C production. The effectiveness of the GO–Ag hybrid nanocomposite was determined by counting colony forming units (CFUs) after a suspension of A. baumannii and the GO–Ag hybrid nanocomposite was plated on MH agar and incubated overnight to grow colonies. Results: In our research, we found that A. baumannii strains are resistant to the majority of commonly used antibiotics. Antibiotic resistance levels and AMP-C production can be factors, indicating the better effectiveness of the graphene oxide and silver nanoparticle hybrid nanocomposite. Conclusions: In this study, a GO–Ag hybrid nanocomposite was shown to have the potential to fight even the most problematic bacteria like A. baumannii. Full article

Background and objective: Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen that not only possesses intrinsic resistance to many classes of antibiotics, but is also capable of rapidly developing antimicrobial resistance during treatment. The aim of this study was to determine the characteristics of resistance of A. baumannii strains to β-lactams and other tested antibiotics, to evaluate the associations between the phenotypes of resistance to β-lactams and other tested antibiotics, and to evaluate the changes in antibiotic resistance of A. baumannii strains over 5 years by comparing the periods of 2016–2017 and 2020–2021. Materials and methods: A total of 233 A. baumannii strains were isolated from different clinical specimens of patients treated at the Hospital of Lithuanian University of Health Sciences in 2016–2017 (n = 130) and 2021–2022 (n = 103). All clinical cultures positive for A. baumannii were analyzed. The type of β-lactamase was detected by phenotypic methods using ESBL plus AmpC screen disk tests and the combination meropenem disk test. Results: In both periods, all A. baumannii strains were resistant to ciprofloxacin; resistance to carbapenems, piperacillin/tazobactam, gentamicin, and tobramycin was noted in more than 80% of strains. A comparison of two periods showed that the percentages of A. baumannii strains producing two or three types of β-lactamases were significantly greater in 2021–2022 than in 2016–2017 (94.2% and 5.8% vs. 17.7% and 2.3%, respectively, p < 0.001). Isolates producing two or three types of β-lactamases were more often resistant to tigecycline, tetracycline, and doxycycline than strains producing one type of β-lactamase (p < 0.001). Conclusions: The frequency of isolation of A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) or three types of β-lactamases (AmpC, KPC, and ESBL) and the resistance rates to ampicillin/sulbactam, tigecycline, tetracycline, and doxycycline were significantly greater in 2020–2021 as compared with 2016–2017. The production of two or three types of β-lactamases by A. baumannii strains was associated with higher resistance rates to tetracyclines. Full article

Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFN$\mathsf{\alpha }$, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFN$\mathsf{\alpha }$–remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFN$\mathsf{\alpha }$ combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFN$\mathsf{\alpha }$ can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections. Full article

Background and objectives: The aim of our study was to analyze the concentrations of inflammatory markers in the nasal tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls of different age groups, as well as to find associations between age, inflammation development, and NPs. Materials and methods: Patients were divided into two groups—patients with CRSwNPs and control subjects who had nasal surgery for another reason beside CRS. Our analysis was performed across three different age groups (18–30 years, 31–50 years, and 51 years and more). Tissue biopsies from the sinus cavity for all study participants were taken and frozen at −80 °C, until use. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-21, and IL-22, were quantified using a magnetic bead-based multiplex assay. Results: In the group aged 18–30 years, the levels of inflammatory markers IL-1, IL-2, IL-5, and IL-22 were significantly higher in patients with CRSwNPs than the control subjects. Among patients aged 31–50 years, significantly higher concentrations of IL-2, IL-4, IL-5, and IL-22 were recorded in patients with CRSwNPs, as compared to the control subjects. In the oldest group (aged 51 years and more), patients with CRSwNPs had significantly higher concentrations of IL-2, IL-4, and IL-22, as compared to the control group. In the CRSwNP group, only the concentration of IL-21 was significantly higher among patients aged 31–50 years, as compared with those aged 51 years and older (p = 0.013). Conclusions: IL-2 and IL-22 levels were significantly higher in patients with CRSwNP than the control, across all age groups. Only the concentration of IL-21 was higher among patients with CRSwNP in the middle age group, as compared to the oldest group. IL-2, IL-4, and IL-22 levels correlated with the severity of CRSwNPs. Elevated concentrations of IL-2, IL-4, and IL-22 were determined in patients’ groups with higher sinonasal outcome test (SNOT-22) scores, pointing to more severe clinical symptoms. Full article

Background and objective: Serologic testing is a useful additional method for the diagnosis of COVID-19. It is also used for population-based seroepidemiological studies. The objective of the study was to determine SARS-CoV-2 seroprevalence in healthcare workers of Kaunas hospitals and to compare two methods for specific SARS-CoV-2 antibody testing. Materials and Methods: A total of 432 healthcare workers in Kaunas hospitals were enrolled in this study. Each participant filled a questionnaire including questions about their demographics, contact with suspected or confirmed COVID-19, acute respiratory symptoms, and whether they contacted their general practitioner, could not come to work, or had to be hospitalized. Capillary blood was used to test for SARS-CoV-2 specific immunoglobulin G (IgG) and immunoglobulin M (IgM) a lateral flow immunoassay. Serum samples were used to test for specific IgG and IgA class immunoglobulins using semiquantitative enzyme-linked immunosorbent assay (ELISA) method. Results: 24.77% of study participants had direct contact with a suspected or confirmed case of COVID-19. A total of 64.81% of studied individuals had at least one symptom representing acute respiratory infection, compatible with COVID-19. Lateral flow immunoassay detected SARS-CoV-2 specific IgG class immunoglobulins in 1.16% of the tested group. Fever, cough, dyspnea, nausea, diarrhea, headache, conjunctivitis, muscle pain, and loss of smell and taste predominated in the anti-SARS-CoV-2 IgG-positive group. Using ELISA, specific IgG were detected in 1.32% of the tested samples. Diarrhea, loss of appetite, and loss of smell and taste sensations were the most predominant symptoms in anti-SARS-CoV-2 IgG-positive group. The positive percent agreement of the two testing methods was 50%, and negative percent agreement was 99.66%. Conclusions: 1.16% of tested healthcare workers of Kaunas hospitals were anti-SARS-CoV-2 IgG-positive. The negative percent agreement of the lateral flow immunoassay and ELISA exceeded 99%. Full article

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Full article

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 h was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39–49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI. Full article

Objective: The aim of this study was to determine what factors are associated with sputum culture conversion after 1 month of tuberculosis (TB) treatment.
Materials and methods: A total of 52 patients with new drug susceptible pulmonary TB were included in the study. Patients completed St. George respiratory questionnaire (SGRQ), they were asked about smoking, alcohol use, living conditions and education. Body mass index (BMI) measurements, laboratory tests (C reactive protein [CRP], vitamin D, albumin) were performed, and chest X-ray was done. After 1 month of treatment sputum culture was repeated.
Results: Culture conversion after 1 month of treatment was found in 38.5% cases. None of investigated social factors appeared to have an effect on conversion, but worse overall health status (as reported in SGRQ) and longer duration of tobacco smoking were detected in the ‘‘no conversion’’ group. Concentrations of albumin, CRP, X-ray score and the time it took Mycobacterium tuberculosis culture to grow also differed. Patients who scored 30 or more on SGRQ were more than 7 times as likely to have no conversion. However, the most important factor predicting sputum culture conversion was sputum smear grade at the beginning of treatment: patients with grade of 2+ or more had more than 20-fold higher relative risk for no conversion. Using receiver operating characteristic curve analysis, we also developed a risk score for no conversion.
Conclusions: The most important factors in predicting sputum culture conversion after 1 month of treatment were grades of acid-fast bacilli in sputum smears at time of diagnosis and scores of SGRQ. Full article

Background and objective: Lithuania belongs to the group of countries with a high-incidence of tuberculosis (TB). Some scientific studies show that the interferon-gamma release assay is more accurate and correlates more highly with TB exposure as compared to the tuberculin skin test (TST). This study aimed at comparing the efficacy between the T SPOT TB and TST for diagnosing TB among Lithuanian adults.
Materials and methods: Individuals with diagnosed TB, healthcare workers with known risk for TB and individuals without any known risk for TB underwent clinical examinations, interviews about their history of TB exposure and chest radiography. Then the TST and the T SPOT TB were performed on patients.
Results: A positive T SPOT TB was more common in the group with diagnosed TB compared to healthcare workers and the low risk for TB groups (97.5%, 36.4%, and 0%, respectively, P < 0.01). Positive TST results did not differ between the groups with diagnosed TB and the healthcare workers (92.5% vs. 95.5%, P > 0.05). Agreement between TST and T SPOT TB was poor (kappa 0.14, P > 0.05). T SPOT TB had higher specificity and sensitivity compared to TST (area under the ROC 0.9 ± 0.04, P < 0.01, vs. 0.5 ± 0.06, P > 0.05).
Conclusions: The T SPOT TB showed greater accuracy in diagnosing TB than TST did. Positive T SPOT TB result but not the TST was more common in patients with diagnosed TB. Full article

Background and aim: Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients.
Materials and methods: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immu- nofixation to test for the presence of intrathecal specific OCB.
Results: HLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present.
Conclusions: OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS. Full article

Despite the recent advances in the diagnosis of tuberculosis, treatment of the disease, for the most part, remains the same as it was half a century ago. In recent years only two new antituberculosis drugs have been approved by the European Medicines Agency and Food and Drug Administration. Though the prevalence of this disease is slowly decreasing all over Europe, new challenges appear. One of them is multidrug-resistant tuberculosis (MDR-TB). This problem is especially prominent in Lithuania, which is one of the 27 high MDR-TB burden countries in the world and falls behind neighboring countries in terms of the prevalence of the disease. The objective of this paper was to review the situation of tuberculosis and MDR-TB in Lithuania, and current available methods of treatment, control and diagnosis of this disease. Full article

Background and objective: Since the influence of etiological factors on the course and outcomes of acute pancreatitis (AP) is not fully understood yet, the aim of the study was to compare the outcomes of alcoholic and biliary severe acute pancreatitis (SAP).
Materials and methods: We investigated 81 patients with alcoholic and biliary SAP. Demographic data, etiologic factors, severity scores, intra-abdominal pressure, imaging studies, interventions, and treatment outcomes were prospectively entered into specially maintained database and subsequently analyzed.
Results: No statistically significant difference was observed in the prevalence of SAP in biliary and alcoholic AP groups (P = 0.429). Although, in the biliary SAP group patients were predominantly elderly women (P = 0.003), the total in-hospital stay was longer in alcoholic SAP patients (P = 0.021). The abdominal compartment syndrome developed more frequently (P = 0.041) and necrosectomy was more frequently performed in alcoholic SAP group (not statistically significant). Although not statistically significant, a lower mortality rate among biliary SAP patients (25.0% vs. 13.5%) was observed.
Conclusions: We defined a trend toward decreased incidence of infected necrosis in larger volume (≥30%) pancreatic necrosis, absence of abdominal compartment syndrome, lower rate of necrosectomies, shorter in-hospital stay, and an insignificantly reduced mortality rate in biliary SAP patients, indicating more favorable course of biliary SAP. Full article

Increasing resistance of Escherichia coli (E. coli) to antibiotics, especially to the third-generation cephalosporins, has prompted studies on widespread resistance genes such as bla_CTX-M and differentiation of E. coli to phylogenetic groups. The aim of this study was to determine the associations between the CTX-M type and the phylogenetic group, the site of infection, and coresistance in Lithuanian E. coli isolates producing β-lactamases.
Material and Methods. A total of 90 E. coli ESBL strains were recovered from the lower respiratory tract, the urinary tract, sterile body sites, wounds, and other body sites between 2008 and 2012. The E. coli isolates resistant to at least 2 antibiotics with different modes of action along with resistance to cefotaxime were considered as multiresistant. The bla_CTX-M, bla_TEM, bla_OXA-1, and blaSHV genes, the phylogenetic groups, and the resistance profiles were analyzed.
Results. Of the 90 isolates, 84 (93.3%) were classified as multiresistant and 6 (6.6%) as resistant. The bla_CTX-M-15 gene was the most prevalent gene followed by the bla_CTX-M-14 and bla_CTX-M-92 genes. The logistic regression analysis revealed the associations between CTX-M-15 and resistance to ceftriaxone, between CTX-M-14 and resistance to cefoxitin, aztreonam, ampicillin/sulbactam, ticarcillin/clavulanic acid, and tobramycin, and between CTX-M-92 and resistance to cefepime, piperacillin/tazobactam, gentamicin, and tobramycin.
Conclusions. The results of this study showed a significant association between CTX-M-15, CTX-M-14, and CTX-M-92 β-lactamases and resistance to some antibiotics as well as CTX‑M-14 β-lactamase and phylogenetic group A in the Lithuanian population. The associations between the CTX-M type and the site of infection were not determined. Full article