Synergism inhibition and eradication activity of silver nitrate/potassium tellurite combination against Pseudomonas aeruginosa biofilm.

OBJECTIVES: Antibiotic resistance, biofilm and persistent infection of Pseudomonas aeruginosa is a perilous challenge in the healthcare system. Hence, a vast number of novel antipseudomonas approaches are currently being pursued. Our group focuses on exploring the efficacy of metal(loid)-based antimicrobials (MBAs) towards novel infection control solutions. METHODS: Initially, nine MBAs were tested for biofilm prevention and eradication efficacy. Synergistic potentials were then screened systematically in a total of 1920 combinatorial MBA concentrations, in laboratory media [CAMHB and LB] and infection-related simulated wound fluid (SWF). The antibiofilm efficacy of the silver nitrate (AgNO3; 'Ag') with potassium tellurite (K2TeO3; 'Te') combination was examined against clinical antibiotic-resistant isolates and compared with the most used antibiotics. The in vitro resistance acquisition test, for exploring the chance of getting future resistance, and meta-analysis, for estimating Ag/Te human cell cytotoxicity, were carried out. RESULTS: The Ag/Te combination was identified as the most effective agent against P. aeruginosa biofilm. The application of the Ag/Te combination was quite effective against all clinical isolates. Comparison of clinical isolates with indicator strains showed clinical isolates are gaining resistance against the antibiotics (especially gentamicin) and Ag, while they are susceptible to Te and particularly the Ag/Te combination. The chance of getting future resistance against Ag/Te as a mixture was remarkably lower than the individual application of each metal. Te has significantly lower human cell cytotoxicity in comparison with Ag. CONCLUSIONS: Te could be an appropriate alternative against P. aeruginosa biofilms (existing or prevention thereof), especially in combination with Ag.

Comparison of influenza type A and B with COVID-19: A global systematic review and meta-analysis on clinical, laboratory and radiographic findings.

We compared clinical symptoms, laboratory findings, radiographic signs and outcomes of COVID-19 and influenza to identify unique features. Depending on the heterogeneity test, we used either random or fixed-effect models to analyse the appropriateness of the pooled results. Overall, 540 articles included in this study; 75,164 cases of COVID-19 (157 studies), 113,818 influenza type A (251 studies) and 9266 influenza type B patients (47 studies) were included. Runny nose, dyspnoea, sore throat and rhinorrhoea were less frequent symptoms in COVID-19 cases (14%, 15%, 11.5% and 9.5%, respectively) in comparison to influenza type A (70%, 45.5%, 49% and 44.5%, respectively) and type B (74%, 33%, 38% and 49%, respectively). Most of the patients with COVID-19 had abnormal chest radiology (84%, p < 0.001) in comparison to influenza type A (57%, p < 0.001) and B (33%, p < 0.001). The incubation period in COVID-19 (6.4 days estimated) was longer than influenza type A (3.4 days). Likewise, the duration of hospitalization in COVID-19 patients (14 days) was longer than influenza type A (6.5 days) and influenza type B (6.7 days). Case fatality rate of hospitalized patients in COVID-19 (6.5%, p < 0.001), influenza type A (6%, p < 0.001) and influenza type B was 3%(p < 0.001). The results showed that COVID-19 and influenza had many differences in clinical manifestations and radiographic findings. Due to the lack of effective medication or vaccine for COVID-19, timely detection of this viral infection and distinguishing from influenza are very important.

Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis.

In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.

Comparison of confirmed COVID-19 with SARS and MERS cases - Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta-analysis.

INTRODUCTION: Within this large-scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID-19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID-19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID-19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid-19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X-ray. The mortality rate in COVID-19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID-19 confirmed cases is lower than in SARS- and MERS-infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.

Global prevalence of colistin resistance in clinical isolates of Acinetobacter baumannii: A systematic review and meta-analysis.

INTRODUCTION: Acinetobacter baumannii antimicrobial resistance is a public health concern in developing and developed countries, especially in the hospital setting. Understanding the antibiotic resistance profile can help to provide better guidelines for the prescription of appropriate antibiotics, reduction of antibiotic resistance, and introducing new and effective treatment options. METHOD: Using the PRISMA guidelines, databases of PubMed, Embase, and Cochrane Library were searched systematically from January 1, 2000, to January 1, 2018. All statistical analyses were carried out via Comprehensive Meta-Analysis Software Version 2.0 (Biostat, Englewood, NJ). Depending on the heterogeneity test, either random or fix effect models were used for determining the pooled prevalence of drug resistance. RESULT: A total of 150 studies were included from 41 countries of six different WHO regional offices worldwide. The highest and the lowest rate of resistance were observed for cefotaxime (99%, 95% CI: 95-99.9) in Africa and colistin (1.1%, 95% CI: 0.3-4.5) in Western Pacific, respectively. Lebanon (17.5%, 95% CI: 16-19) and China (12%, 95% CI: 3.5-32.5) had the highest and Germany (0.2%, 95% CI: 0-2.5) had the lowest rate of resistance for colistin. CONCLUSION: Our analysis showed that prevalence and rate of increased colistin resistance in South-East Asia and Eastern Mediterranean countries are higher than other regions of the world. Therefore, the establishment of appropriate antibiotic usage guidelines should be essential in these countries.

Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis.

INTRODUCTION: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. METHOD: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. RESULT: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5% (95% CI 54.5-79, p < 0.001) of patients had a history of recent travel endemic area or contact with them. The most common symptoms among COVID-19 infected patients were fever 87% (95% CI 73-93, p < 0.001), and cough 68% (95% CI 55.5-74, p < 0.001)), respectively. The laboratory analysis showed that thrombocytosis was present in 61% (95% CI 41-78, p < 0.001) CRP was elevated in 79% (95% CI 65-91, p < 0.001), and lymphopenia in 57.5% (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 81% (95% CI 62.5-87, p < 0.001), consolidation in 73.5% (95% CI 50.5-91, p < 0.001), and ground-glass opacity 73.5% (95% CI 40-90, p < 0.001) of patients. Case fatality rate (CFR) in <15 years old was 0.6%, in >50 years old was 39.5%, and in all range group was 6%. CONCLUSIONS: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region.

In cardiac ischemic disorder, pyroglutamate helix B surface peptide (pHBSP) which derived from erythropoietin causes to increase cell stability. To improve the serum stability of pHBSP, two lipophilic amino acids Arg6, Ala7 were replaced with Fmoc-(Dabcyle)-Lys-OH and Fmoc-Phe-OH during the peptide synthesis. This peptide was subsequently conjugated to PEGylated dendrimer-G2 and labeled with 99mTcO4- to detect cardiac ischemic region. Radiochemical purity (RCP) of 99mTc-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP was evaluated by ITLC method. In addition, the radiopeptide was investigated for stability in human serum and binding affinity to hypoxic cells in myocardium H9c2 cell lines. Biodistribution and SPECT/CT scintigraphy were assessed in cardiac ischemic rats. Radiochemical yield indicated that the anionic dendrimer has a very high potential to complex formation with 99mTcO-4 (RCP > 94%) which was stable in human serum with RCP 89% up to 6 h. The binding of 99mTc- nanoconjugate to hypoxic cells was significantly more than normoxic cells (3-fold higher compared to normoxic cells at 1 h). In biodistribution studies, erythropoietin receptor-Beta common receptor (EPO-BcR)-positive uptake in the cardiac ischemic region was 3.62 ± 0.44% ID/g 30 min post injection. SPECT imaging showed a prominent uptake of 99mTc-nanoconjugate in EPO-BcR expressing ischemic heart.

Global estimate of gastric cancer in Helicobacter pylori-infected population: A systematic review and meta-analysis.

There is information regarding the rates of gastric cancer (GC) in different populations and the important role of Helicobacter pylori in GC development; however, no comprehensive study has yet been performed to investigate the prevalence of GC in H. pylori-infected patients. PubMed, Embase, and Cochrane Library through January 1, 2000 were searched without language restrictions. Quality of included studies was assessed with a critical appraisal checklist recommended by the Joanna Briggs Institute. All of the analyses were conducted using Comprehensive Meta-Analysis Software Version 2.0 and Stata 14.0. Forty-four studies from 17 countries were included. The pooled frequency of GC was 17.4% (95% confidence interval: 16.4-18.5) in H. pylori-infected population. The frequency of GC among H. pylori-infected population varied markedly across countries. The highest rate of GC was observed in H. pylori-infected individuals from Asian countries. The frequency of GC was relatively high in H. pylori-infected population in the world. However, the eradication of H. pylori might be a promising strategy for GC prevention, especially in high-risk populations such as Asian countries.

The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a prolonged and disabling functional gastrointestinal disorder with the incidence rate of 18% in the world. IBS could seriously affect lifetime of patients and cause high economic burden on the community. The pathophysiology of the IBS is hardly understood, whereas several possible mechanisms, such as visceral hypersensitivity, irregular gut motility, abnormal brain-gut relations, and the role of infectious agents, are implicated in initiation and development of this syndrome. Different studies demonstrated an alteration in B-lymphocytes, mast cells (MC), T-lymphocytes, and cytokine concentrations in intestinal mucosa or systemic circulation that are likely to contribute to the formation of the IBS. Therefore, IBS could be developed in those with genetic predisposition. Infections' role in initiation and exacerbation of IBS has been investigated by quite several clinical studies; moreover, the possible role of some pathogens in development and exacerbation of this disease has been described. It appears that the main obligatory pathogens correspond with the IBS disease, Clostridium difficile, Escherichia coli, Mycobacterium avium subspecies paratuberculosis, Campylobacter concisus, Campylobacter jejuni, Chlamydia trachomatis, Helicobacter pylori, Pseudomonas aeruginosa, Salmonella spp, Shigella spp, and viruses, particularly noroviruses. A number of pathogenic parasites (Blastocystis, Dientamoeba fragilis, and Giardia lamblia) may also be involved in the progression and exacerbation of the disease. Based on the current knowledge, the current study concludes that the most common bacterial, viral, and parasitic pathogens may be involved in the development and progression of IBS.

A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Nucleic Acid Amplification Tests for Tuberculous Meningitis.

The diagnosis of tuberculous meningitis (TBM) is difficult and poses a significant challenge to physicians worldwide. Recently, nucleic acid amplification (NAA) tests have shown promise for the diagnosis of TBM, although their performance has been variable. We undertook a systematic review and meta-analysis to evaluate the diagnostic accuracy of NAA tests with cerebrospinal fluid (CSF) samples against that of culture as the reference standard or a combined reference standard (CRS) for TBM. We searched the Embase, PubMed, Web of Science, and Cochrane Library databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. All statistical analyses were performed with STATA (version 14 IC; Stata Corporation, College Station, TX, USA), Meta-DiSc (version 1.4 for Windows; Cochrane Colloquium, Barcelona, Spain), and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) software. Sixty-three studies comprising 1,381 cases of confirmed TBM and 5,712 non-TBM controls were included in the final analysis. These 63 studies were divided into two groups comprising 71 data sets (43 in-house tests and 28 commercial tests) that used culture as the reference standard and 24 data sets (21 in-house tests and 3 commercial tests) that used a CRS. Studies which used a culture reference standard had better pooled summary estimates than studies which used CRS. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the NAA tests against culture were 82% (95% confidence interval [CI], 75 to 87%), 99% (95% CI, 98 to 99%), 58.6 (95% CI, 35.3 to 97.3), and 0.19 (95% CI, 0.14 to 0.25), respectively. The pooled sensitivity, specificity, PLR, and NLR of NAA tests against CRS were 68% (95% CI, 41 to 87%), 98% (95% CI, 95 to 99%), 36.5 (95% CI, 15.6 to 85.3), and 0.32 (95% CI, 0.15 to 0.70), respectively. The analysis has demonstrated that the diagnostic accuracy of NAA tests is currently insufficient for them to replace culture as a lone diagnostic test. NAA tests may be used in combination with culture due to the advantage of time to result and in scenarios where culture tests are not feasible. Further work to improve NAA tests would benefit from the availability of standardized reference standards and improvements to the methodology.

Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease.

Recent studies have been considered to symbiotic interactions of the human gastrointestinal microbiota and human lifestyle-related disorders. The human gastrointestinal microbiota continuously stimulates the immune system against opportunistic and pathogen bacteria from infancy. Changes in gastrointestinal microbiota have been associated with numbers of human diseases such as allergic diseases, autoimmune encephalitis, atherosclerosis, colorectal cancer, obesity, diabetes etc. In this review article, we evaluate studies on the roles of human gastrointestinal microbiota and interference pathogenicity in allergic diseases, obesity, and diabetes. Several studies indicated association between allergic diseases and changes in bacterial balance such as increased of Clostridium spp., some species of Bifidobacterium spp., or decreased of Bacteroidetes phylum and some species of Bifiobacterium spp. and production of specific short-chain fatty acids due to food type, delivery modes of infant, infant evolvement environment and time of getting bacteria at an early-life age. In addition, obesity and diabetes are associated with food type, production of short chain fatty acids undergo fermentation of the intestinal microbiota, metabolic endotoxemia, endocannabinoid system and properties of the immune system. Well-characterized underlying mechanisms may provide novel strategies for using prebiotic and probiotic to prevent and treatment of allergic diseases, obesity, diabetes, and other lifestyle-related disorders.

Latent tuberculosis infection in transplant candidates: a systematic review and meta-analysis on TST and IGRA.

INTRODUCTION: The diagnostic accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for latent tuberculosis infection (LTBI) in transplant candidates is uncertain. METHODS: Pubmed, Embase and Cochrane library were searched to identify relevant studies. Quality of included studies was assessed with RevMan5 software (via GUADAS2 checklist). Accuracy measures of IGRAs and TST assays (sensitivity, specificity and others) were pooled with random effects model. Data were analyzed by STATA and Meta-DiSc. RESULTS: Twenty-eight studies were selected for full review, and 16 were included in the final analysis. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for TST were 46% [95% confidence interval (CI) 38-54%], 86% (95% CI 75-93%), 46.3% (95% CI 40-52), 88.7% (95% CI 87-89), 3.3 (95% CI 1.6-6.4), 0.63 (95% CI 0.52-0.77) and 5 (95% CI 2-12), respectively. For QFT-G, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 58% (95% CI 41-73%), 89% (95% CI 77-95%), 72.7% (95% CI 68-76), 80.6% (95% CI 78-82), 5.3 (95% CI 2.0-14.0), 0.47 (95% CI 0.30-0.75) and 11 (95% CI 3-46), respectively. Likewise, for T-SPOT.TB, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 55% (95% CI 40-70%), 92% (95% CI 87-95%), 60.4% (95% CI 47-72), 90.2% (95% CI 86-92), 6.7 (95% CI 4.0-11.1), 0.52 (95% CI 0.31-0.85) and 16 (95% CI 7-37), respectively. CONCLUSIONS: IGRAs were more sensitive and specific than the TST with regard to the diagnosis of LTBI in the transplant candidates. They have added value and can be complementary to TST.

Relationship of human herpes virus 6 and multiple sclerosis: A systematic review and meta-analysis.

Infection with human herpes viruses has been suggested to contribute to multiple sclerosis (MS), while interaction between human herpes 6 (HHV6) and MS remain unclear yet. Here, we conducted a meta-analysis on the relationship of HHV6 infection and MS. All related studies were collected from major databases. The analyses were performed by STATA 14 and Comprehensive Meta-Analysis V2.0 softwares. Pooled odds ratios (ORs) and 95%CIs were calculated from the raw data of the including studies by the random effects models when I2 > 50% and fix model when I2 < 50%. Thirty nine studies were included in the meta-analysis that 34 studies used molecular assays and 7 studies used serological assays for diagnosis of HHV6 infected cases. The relationship of HHV6 and MS was significant in healthy control group by yielding a summary OR of (2.23 [1.5-3.3], p = 0.06). A significant HHV6 association with MS were in the studies with >6 score that used serum/blood sample with OR of (6.7 [95%CI 4.8-8.6], p < 0.00001) and in serological studies, IgM positive titer in other neurological diseases (OND) control group was significant with OR of (8.3 [95%CI 3-24.07], p < 0.00001). This study has been showed that there were significant relationship between MS and HHV6 infection.

Risk of gastric cancer in association with Helicobacter pylori different virulence factors: A systematic review and meta-analysis.

INTRODUCTION: It has been proposed that specific analysis of Helicobacter pylori virulence factors can be suitable for predicting of post H. pylori infection disorders like gastric cancer (GC). The present study was designed to evaluate the association between different virulence factors of H. pylori and GC. METHODS: Studies investigated the association between virulence factors of H. pylori and GC were collected from the several databases. All analysis was performed by Comprehensive Meta-Analysis V2.2 software (Biostat, Englewood, NJ, USA). RESULTS: Based on a comprehensive literature search, 25 eligible studies were included for meta-analyses. Infection with cagA- and vacA s1m1-positive H. pylori strains were significantly associated with increased risk of GC (OR of [2.82 (95% CI 1.96-4.06), P < 0.001]) and ([1.75 (95% CI 1.04-2.96), P 0.034)], respectively. CONCLUSIONS: Infection by H. pylori strains with positive vacA s1m1 and the cagA genes can significantly increase the risk of GC. The association between the vacA s1m1 and the cagA and GC, suggests that screening of these genes may be helpful for identifying populations at higher risk for GC.

The comparison of MAMA PCR and SSCP PCR to study chromosomal resistance against Ciprofloxacin and Nalidixic acid in Escherichia coli and Klebsiella pneumoniae.

The mutation in gyrA and parC genes alters amino acids. Also, it causes resistance against Fluoroquinolones in E. coli and K. pneumoniae. The purpose of this study was to diagnose the significant mutation of gyrA (ser83-asp87) and parC (ser80-glu84) genes through using MAMA PCR and SSCP PCR methods. In so doing, the isolated samples were collected. Then, utilizing agar disc diffusion method, the researchers performed antibiotic sensitivity test. Moreover, Fluoroquinolones resistance was confirmed by E-test method (MIC experiment). Furthermore, the obtained data from MAMA PCR method were sequenced accidentally. According to the findings, among 103 isolated samples, 65 samples (63/2%) were belonged to E. coli and 38 samples (36/8%) to K. pneumoniae. In all E. coli that resisted to Ciprofloxacin, at least one mutation were observed. Also, at least one mutation was observed in all K. pneumoniae samples that resisted to Ciprofloxacin. However, four mutation points were detected for each of seven samples and, interestingly, there was no mutation in five sensitive samples to Ciprofloxacin. In addition, the results revealed that the mutation in gyrA and parC genes was closely related to Quinolones resistance. Based on the findings, preparing an infection control program in Iran is highly required.

Human immunodeficiency virus in patients with tuberculous meningitis: systematic review and meta-analysis.

INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals are at increased risk for all forms of extrapulmonary tuberculosis (TB), including tuberculous meningitis (TBM). This study aimed to investigate the frequency of HIV in patients with TBM. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched for articles including relevant data. Stata version 14.0 (StataCorp, College Station, Texas, USA) was used to analyse the data. RESULTS: Twenty studies were identified. The pooled frequency of HIV among adult patients with TBM was 38.0% (95% CI: 21.0-57.0; I2 = 97%). In children (under the age of 15 years), 6.0% (95% CI: 1.0-13.0; I2 = 0.0%) had HIV infection. In patients with bacterial meningitis other than TBM, 36.0% (95% CI: 19.0-53.0; I2 = 100%) were HIV-infected. CONCLUSIONS: A relatively high frequency of HIV in patients with TBM was indicated by our study. Establishment of diagnostic criteria and effective treatment strategies for TBM/HIV co-infection are recommended for better management of patients with TBM+HIV.

Oral pathogenesis of Aggregatibacter actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a Gram-negative, facultative anaerobic bacillus that causes periodontal diseases such as localized aggressive periodontitis (LAP) and. consequently. bone resorption. The potential virulence factors of this organism are powerful leukotoxin, lipopolysaccharide (LPS), cell surface-associated materials, enzymes, and less well-defined virulence factors that will modulate the activity of the host defenses. This organism can induce bone resorption by various virulence factors in periodontal disease. In this review article, we reviewed the pathogenic roles of A. actinomycetemcomitans in periodontal disease and the mechanism which can induce bone resorption. Findings from several studies indicate that the interaction between virulence factors and the host immune system's response often progress bone resorption in periodontal disease. In this organism, GroEL, DnaK, HtpG, LTX, CDT, LPS, and cell surface-associated materials produce cytokines when exposed to the immune system. The produced cytokines are the main cause of tissue destruction and bone resorption in A. actinomycetemcomitans inflammation in periodontal disease.

Novel pentafluorosulfanyl-containing triclocarban analogs selectively kill Gram-positive bacteria.

Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization. IMPORTANCE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.

Insights into the Synergistic Antibacterial Activity of Silver Nitrate with Potassium Tellurite against Pseudomonas aeruginosa.

The constant, ever-increasing antibiotic resistance crisis leads to the announcement of "urgent, novel antibiotics needed" by the World Health Organization. Our previous works showed a promising synergistic antibacterial activity of silver nitrate with potassium tellurite out of thousands of other metal/metalloid-based antibacterial combinations. The silver-tellurite combined treatment not only is more effective than common antibiotics but also prevents bacterial recovery, decreases the risk of future resistance chance, and decreases the effective concentrations. We demonstrate that the silver-tellurite combination is effective against clinical isolates. Further, this study was conducted to address knowledge gaps in the available data on the antibacterial mechanism of both silver and tellurite, as well as to give insight into how the mixture provides synergism as a combination. Here, we defined the differentially expressed gene profile of Pseudomonas aeruginosa under silver, tellurite, and silver-tellurite combination stress using an RNA sequencing approach to examine the global transcriptional changes in the challenged cultures grown in simulated wound fluid. The study was complemented with metabolomics and biochemistry assays. Both metal ions mainly affected four cellular processes, including sulfur homeostasis, reactive oxygen species response, energy pathways, and the bacterial cell membrane (for silver). Using a Caenorhabditis elegans animal model we showed silver-tellurite has reduced toxicity over individual metal/metalloid salts and provides increased antioxidant properties to the host. This work demonstrates that the addition of tellurite would improve the efficacy of silver in biomedical applications. IMPORTANCE Metals and/or metalloids could represent antimicrobial alternatives for industrial and clinical applications (e.g., surface coatings, livestock, and topical infection control) because of their great properties, such as good stability and long half-life. Silver is the most common antimicrobial metal, but resistance prevalence is high, and it can be toxic to the host above a certain concentration. We found that a silver-tellurite composition has antibacterial synergistic effect and that the combination is beneficial to the host. So, the efficacy and application of silver could increase by adding tellurite in the recommended concentration(s). We used different methods to evaluate the mechanism for how this combination can be so incredibly synergistic, leading to efficacy against antibiotic- and silver-resistant isolates. Our two main findings are that (i) both silver and tellurite mostly target the same pathways and (ii) the coapplication of silver with tellurite tends not to target new pathways but targets the same pathways with an amplified change.