Opportunistic Infections Research Articles

Epinephrine and norepinephrine regulate the expression of virulence factors in Gallibacterium anatis

Gallibacterium anatis is a member of the Pasteurellaceae family and is an opportunistic pathogen that causes gallibacteriosis in chickens. Stress plays a relevant role in promoting the development of pathogenicity in G. anatis. Epinephrine (E) and norepinephrine (NE) are relevant to stress; however, their effects on G. anatis have not been elucidated. In this work, we evaluated the effects of E and NE on the growth, biofilm formation, expression of adhesins, and proteases of two G. anatis strains, namely, the hemolytic 12656-12 and the nonhemolytic F149T biovars. E (10μM/mL) and NE (30 and 50μM/mL) increased the growth of G. anatis 12656-12 by 20% and 25%, respectively. E did not affect the growth of F149T, whereas 40μM/mL NE decreased bacterial growth by 25%. E and NE at a dose of 30-50μM/mL upregulated five fibrinogen adhesins in the 12565-12 strain, whereas no effect was observed in the F149T strain. NE increased proteolytic activity in both strains, whereas E diminished proteolytic activity in the 12656-12 strain. E and NE reduced biofilm formation (30%) and increased Congo red binding (15%) in both strains. QseBC is the E and NE two-component detection system most common in bacteria. The qseC gene, which is the E and NE receptor in bacteria, was identified in the genomic DNA of the 12565-12 and F149TG. anatis strains via PCR amplification. Our results suggest that QseC can detect host changes in E and NE concentrations and that catecholamines can modulate the expression of several virulence factors in G. anatis.

Deciphering the inhibitory mechanism of antimicrobial peptide pexiganan conjugated with sodium-alginate chitosan-cholesterol nanoparticle against the opportunistic pathogen Acinetobacter baumannii

The emergence of antibiotic resistance is one of the most challenging problems of modern times as the armory of conventional antibiotics is quickly exhausting due to the rapid rise of resistance in pathogenic microorganisms. Acinetobacter baumannii, a potential member of ESKAPE group of bacteria, has a great deal of clinical importance causing severe nosocomial infections which often become life-threatening. According to the World Health Organization (WHO), antimicrobial resistance accounts for 2-3 million deaths every year across the world. Since the pathogen has the remarkable ability to acquire or upregulate various resistant determinants in the form of secreting of β-lactamase, aminoglycoside modifying enzymes, uplifting the function of efflux pumps or altering the target sites of different antibiotics; conventional antibiotic therapy often falls short to eradicate the infection. As a possible solution, the application of alternative therapy is therefore the need of the hour. Here we emphasize potentiating the antimicrobial efficacy of pexiganan, a well-known antimicrobial peptide against Gram-negative bacteria. Conjugation with nanoparticles composed of sodium-alginate and chitosan-cholesterol has increased the antimicrobial effect of the peptide on this opportunist pathogen. The evaluation of the bactericidal analysis and minimum inhibitory concentration indicates this nanocomposite can kill the bacteria at a very low concentration (3 μg/ml). When applied to the bacterial biofilm, the key factor for producing recalcitrant infection; our synthesized complex could effectively reduce the biomass in a dose-dependent manner. Later we enfold the mechanism of killing by measuring oxidative stress, cell membrane perforation by biochemical analysis. Our analysis indicates this unique nanocomposite can bypass the need of antibiotic treatment by its pore-forming ability on bacterial membrane. The nominal in-vivo toxicity and non-specific mode of action make it an interesting candidate for future therapeutics.

Antibiofilm and antivirulence efficacy of Pleurotus platypus methanolic extract against Staphylococcus aureus through ROS generation and cell membrane disruption

Multi-drug resistance is recognized as a significant worldwide public health concern in the current century. Biofilm formation further exacerbates bacterial resistance to antibacterial medications, host immunological responses, and phagocytosis, resulting in long-lasting chronic illnesses. Investigating natural resources is a very potent approach for developing alternative anti-infective medications to effectively control multi-drug resistant bacterial infections. In this study, a unique mushroom species namely Pleurotus platypus had been discovered from the Terai-Duars region of West Bengal, India. The myco-chemical profiling and preliminary chemical analysis of Pleurotus platypus methanolic extract determined the significant presence of metabolites belonging to several major chemical classes such as flavonoid, alkaloid, triterpenoid, polyphenol, benzoic acids, coumarin, flavone etc. Most intriguingly, the extract possessed effective antibacterial, antibiofilm and antivirulence properties against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus, one of the most notable drug-resistant opportunistic and nosocomial pathogens. Mechanistically, the mushroom extract enhanced the production of Reactive Oxygen Species (ROS) inside the targeted bacteria, causing alterations in membrane potential, damage to the cellular membrane and further release of intracellular DNA, destined to cell death. Moreover, the methanolic extract reported the eradication of pre-existing biofilms from the urinary catheter surface, hinting towards its future application in the related field. To summarize, Pleurotus platypus methanolic extract could be an excellent alternative antibacterial and antibiofilm therapeutic candidate for the effective management of Staphylococcus infections with improved outcome.

Antibacterial and anti-biofilm efficacy of selenium nanoparticles against Pseudomonas aeruginosa: Characterization and in vitro analysis

Pseudomonas aeruginosa (P. aeruginosa), a Gram-negative opportunistic pathogen, poses significant treatment challenges due to its antibiotic resistance and biofilm formation. This study investigates the anti-bacterial and anti-biofilm activities of chemically synthesized selenium nanoparticles (SeNPs) against P. aeruginosa. SeNPs were synthesized using ascorbic acid as a reducing agent and characterized. Biofilm formation was quantified using a modified microtiter plate method, and the anti-biofilm efficacy of SeNPs was evaluated using confocal microscopy and SEM. The P.aeruginosa isolates exhibited high resistance to piperacillin-tazobactam (60%) and ceftazidime (59%). SeNPs demonstrated a round shape with a diameter of 15-18 nm. UV-Vis spectra showed a peak at 275 nm, and XRD analysis revealed crystalline peaks corresponding to selenium. The FTIR spectra confirmed the presence of various functional groups. SeNPs significantly reduced biofilm formation in a dose-dependent manner, with MIC50 and MIC90 values of 60 μg/mL and 80 μg/mL, respectively. Confocal microscopy and SEM analysis showed a notable decrease in biofilm thickness and bacterial adherence post-SeNPs treatment. These findings suggest that SeNPs could be a promising alternative or adjunctive treatment option for combating antibiotic-resistant P. aeruginosa infections. Further research is warranted to explore the clinical applications of SeNPs in treating biofilm-associated infections.

Microbiome and network analysis reveal potential mechanisms underlying Carassius auratus diseases: The interactions between critical environmental and microbial factors

Despite the rapid development of research on aquatic environment microbiota, limited attention has been paid to exploring the complex interactions between microbial communities and aquatic environments. Particularly, the mechanisms underlying fish diseases based on such dynamic interactions remain unknown. This study aimed to address the gap by conducting microbiome and co-occurrence network analyses on the typical freshwater aquaculture systems. High-throughput 16S rRNA gene sequencing results revealed significant differences in the microbiota between the disease and healthy groups. Notably, disease mortality varied consistently with the gradient of relative abundance of Proteobacteria (intestine, R2 = 0.46, p < 0.05) and Cyanobacteria (gill, R2 = 0.67, p < 0.01), indicating their potential use as diagnostic criteria. Furthermore, the elevated hepatosomatic index, NO3-N, COD and TC (sediment) were directly correlated with diseases (r > 0.54, p < 0.01). Mean concentrations of NO3-N, COD and TC were elevated by 78.87%, 25.63% and 44.2%, respectively, in ponds where diseases occurred. Quantitative analysis (qPCR) revealed that Aeromonas sobria infected hosts through a potential pathway of “sediment (4.4 × 105 copy number/g)-water (1.1 × 103 copy number/mL)-intestine (1.2 × 106 copy number/g)”. Similarly, the potential route for Aeromonas veronii was sediment (4.9 × 106 copy number/g) to gill (5.1 × 105 copy number/g). Additionally, the complexity of microbial networks in the intestine, water, and sediment was significantly lower in the disease group, although no similar phenomenon was observed in the gill microbial network. In summary, these findings reveal that elevated concentrations of crucial environmental factors disrupt the linkages within microbiota, fostering the growth of opportunistic bacteria capable of colonizing fish gut or gills. This offers new insights into potential mechanisms by which environmental factors cause disease in fish.

Optic Neuritis and its Prevalence in Immunocompromised Patients: A Review Article

Optic neuritis is an inflammation that affects the optic nerve, causing vision loss, eye pain, and changes in color perception. The condition can be associated with autoimmune diseases such as multiple sclerosis (MS) or infections, especially in immunocompromised individuals such as HIV/AIDS patients or those undergoing chemotherapy. In these individuals, optic neuritis usually results from opportunistic infections like toxoplasmosis and syphilis, complicating diagnosis and treatment. In immunocompetent patients, optic neuritis may indicate autoimmune diseases like MS or neuromyelitis optica (NMO), with better prognoses when treated early with corticosteroids. However, in immunocompromised individuals, the prognosis tends to be worse due to underlying infections and a limited response to immunosuppressive treatment. The management of optic neuritis involves anti-inflammatory therapies and, in cases of infections, specific antimicrobials. Continuous clinical and visual follow-up is also crucial. Studies suggest that clinical outcomes vary depending on the etiology and the patient's immune status, highlighting the need for personalized therapeutic strategies. Early diagnosis is critical to improving vision and quality of life for patients.

3D Printable Alginate-Chitosan Hydrogel Loaded With Ketoconazole Exhibits Anticryptococcal Activity.

Natural polymers have recently been investigated for various applications, such as 3D printing and healthcare, including treating infections. Among microbial infections, fungal diseases remain overlooked, with limited therapeutic options and high recurrence. Cutaneous cryptococcosis is an opportunistic fungal infection triggered by mechanical inoculation or hematogenous dissemination of the yeast that causes cryptococcal pneumonia and meningitis. Every year, Cryptococcus neoformans endanger the lives of immunosuppressed hosts, resulting in 180,000 deaths per year. Nonetheless, healthy individuals can also be affected by this fungal infection. Cryptococcosis has a restricted and expensive therapeutic regimen with no topical approach to skin manifestations. This study sought to create a 3D printable biodegradable polymeric hydrogel carrying ketoconazole, a low-cost antifungal drug with reported anticryptococcal activity. The developed hydrogel exhibited good 3D printability and rheological properties, including a pseudoplastic behavior. The FTIR spectra of cross-linked hydrogels revealed interactions between alginate and Ca+2, referred to as the egg-box model, indicated by the decrease in peaks at 1600 and 1410 cm-1. Furthermore, the hydrogel loaded with ketoconazole showed remarkable antifungal activity against C. neoformans strains indicated by inhibition zones, which cross-linking did not seem to affect its antifungal performance. The developed material remained structurally stable for up to 12 days (288 h) in swelling studies, and preliminary cytotoxicity performed with V79 cells indicates potential for invivo studies and topical application.

Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens.

The opportunistic pathogen Pseudomonas aeruginosa develops increasing resistance toward even the most potent antibiotics. Like other bacteria, the pathogen produces a number of virulence factors including metallophores, which constitute an important group. Pseudomonads produce the iron-chelating metallophore (siderophore) pyochelin, which, in addition to its iron-scavenging ability, is an effector for the transcriptional regulator PchR in its FeIII-bound form (ferripyochelin). In the present study, docking studies predicted a major ferripyochelin binding site in PchR, which prompted the exploration of nor-pyochelin analogues to produce tight binding to PchR, and thereby upregulation of the pyochelin metabolism. In addition, we investigated the effects of using the analogues to bind the antimicrobial cations GaIII and InIII. Selected analogues of nor-pyochelin were synthesized, and their GaIII- and InIII-based complexes were assessed for antimicrobial activity. The results indicate that the GaIII complexes inhibit the pathogens under iron-limited conditions, while the InIII-based systems are more effective in iron-rich media. Several of the GaIII complexes were shown to be highly effective against a multidrug-resistant P. aeruginosa clinical isolate, with minimum inhibitory concentrations (MICs) of ≤1 μg/mL. Similarly, two of the InIII-based systems were particularly effective against the isolate, with an MIC of 8 μg/mL. These results show high promise in comparison with other, traditionally potent antibiotics, as the compounds generally indicated low cytotoxicity toward mammalian cells. Preliminary mechanistic investigations using pseudomonal transposon mutants suggested that the inhibitory effects of the InIII-based systems could be due to acute iron deficiency as a result of InIII-bound bacterioferritin.

Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections.

Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes against Pseudomonas aeruginosa PAO1, both planktonic and in biofilms. After the in vitro tests, toxicity and efficacy were assessed in a P. aeruginosa PAO1 infection model using Galleria mellonella larvae. Histones were also evaluated in combination with ciprofloxacin (Cpx) and gentamicin (Gm). Our results demonstrate antimicrobial activity of all three histones against P. aeruginosa PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption. In vitro studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in G. mellonella larvae, and both increased larvae survival when infected with P. aeruginosa PAO1. Although in vitro synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted in vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as P. aeruginosa.IMPORTANCEThe constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstrated in vivo efficacy without associated toxicity in an acute infection model of Pseudomonas aeruginosa PAO1 in Galleria mellonella larvae. The bactericidal effect of these proteins also resulted in biomass reduction of P. aeruginosa PAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.

Complete genome of the opportunistic pathogen Nocardia vulneris strain LPB4002 and its biosynthetic potential.

The complete genome sequence of the opportunistic pathogen Nocardia vulneris is reported. The strain N. vulneris LPB4002 was isolated from a clinical sample of a patient with actinomycetoma. The reported genome comprises a single 9,489-Kb closed chromosome, with 8,584 protein-coding genes and 68% GC content.

Isolation of Shewanella algae from blue crabs (Callinectes sapidus) in Northwestern Adriatic Sea

Abstract Blue crab (Callinectes sapidus) is one of the last reported invasive species that have colonized the Italian coasts, in particular the lagoons of the northern Adriatic Sea. Their massive presence is compromising shellfish farming, causing a serious economic crisis among the valley populations. To limit the economic damage, blue crabs have been introduced as human food in the Italian markets. This study aimed to evaluate the microbiological contamination of blue crab as potential risk to human health. From July 2023 to April 2024, 72 blue crabs were collected in coastal lagoons and 5-6 nm from the coast of the Emilia Romagna Region. Microbiological analysis revealed Shewanella algae as one of the most commonly identified microorganisms (18/72, 25%). Shewanella was isolated on Chromagar Vibrio™ and TCBS after an enrichment step in Alkaline Saline Peptone Water. Colony morphology, Gram stain, and biochemical tests (oxidase, catalase) sustained Shewanella identification, later confirmed by MALDI-TOF MS (MALDI Biotyper® Sirius, Bruker Daltonics). S. algae is a Gram-negative, rod-shaped, aerobic microorganism widely distributed in seawater, freshwater, and soil. In humans, it is considered an opportunistic pathogen, especially in people with impaired immune systems. Shewanellosis has been strongly associated with seawater exposure and typically arises in hot months. Clinical manifestations include skin and soft tissue infections, otitis media, keratitis, biliary tract infections, vertebral discitis, and bloodstream infections. Notably, in the last years, S. algae infections have increased globally, even in healthy young people. The present study suggests blue crabs as a potential source of S. algae throughout the year. The increasing identification of S. algae in marine waters worldwide, as well as in marine-derived foods like blue crabs, underscores the growing importance of S. algae as an emerging pathogen and its impact on public health. Key messages • Shewanella algae is an opportunistic pathogen, increasingly isolated in marine water and seafood. • Blue crab is an invasive species that has recently conolonised the Italian coasts.

Proteomic approach to identify host cell attachment proteins provides protective Pseudomonas aeruginosa vaccine antigen FtsZ

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes severe nosocomial infections in susceptible individuals due to the emergence of multidrug-resistant strains. There are no approved vaccines against P. aeruginosa infections nor candidates in active clinical development, highlighting the need for novel candidates and strategies. Using a cell-blot proteomic approach, we reproducibly identified 49 proteins involved in interactions with human lung epithelial cells across four P. aeruginosa strains. Among these were cell division protein FtsZ and outer membrane protein OpmH. Escherichia coli BL21 cells overexpressing recombinant FtsZ or rOpmH showed a 66- and 15-fold increased ability to attach to 16HBE14o− cells, further supporting their involvement in host cell attachment. Both antigens led to proliferation of NK and CD8+ cytotoxic T cells, significant increases in the production of IFN-γ, IL-17A, TNF and IL-4 in immunised mice and elicited strong antigen-specific serological IgG1 and IgG2c responses. Immunisation with FtsZ significantly reduced bacterial burden in the lungs by 1.9-log CFU and dissemination to spleen by 1.8-log CFU. The protective antigen candidate, FtsZ, would not have been identified by traditional approaches relying on either virulence mechanisms or sequence-based predictions, opening new avenues in the development of an anti-P. aeruginosa vaccine.

Occupational Hazards: The Impact of Streptococcus suis Infections in Portuguese Pig Farming

Abstract Background In Portugal, the commensal and opportunistic bacteria Streptococcus suis is prevalent among pigs. Recognizing its public health significance, this systematic review investigates the relationship between occupational exposure in pig farming and the incidence of S. suis infections among workers. The importance of this study is to identify high-risk occupational activities and formulate effective public health interventions. Methods This review analyzed 20 scientific studies from 1986 to 2023 on human infections with S. suis in Portugal. The primary sources included articles in Portuguese from databases like MedLine, Scopus, and Pubmed. Studies were selected based on their focus on occupational exposure and the details provided on epidemiological context, clinical presentations, and outcomes. Results The review found that 85% of infection cases occurred in occupational settings, particularly among butchers (53%) and pig breeders or handlers (29%). Clinical manifestations predominantly included acute bacterial meningitis, with significant occurrences of neurosensory hearing loss as a sequelae. The average age of affected individuals was 44, predominantly male. Conclusions The study confirms a significant correlation between occupational exposure in pig farming and S. suis infections in humans. The findings underscore the need for stringent occupational health measures and integrated approaches encompassing human, animal, and environmental health under the One Health initiative. Innovations in public health interventions recommended include enhanced surveillance, improved workplace hygiene, and targeted health education for at-risk populations. Key messages • Occupational exposure in pig farming is a significant risk factor for S. suis infections in humans. • Integrative One Health approaches are essential for preventing S. suis infections in occupational settings.

Urogenital colonization and pathogenicity of E. Coli in the vaginal microbiota during pregnancy

This study explores the role of the vaginal microbiota (VM) in the pathophysiology of asymptomatic bacteriuria (ASB) in a cohort of 1,553 pregnant women. Worldwide, E. coli remains the most common etiological agent of bacteriuria during pregnancy and also a major causative agent of newborn infections. A healthy VM is typically characterized by low diversity and is dominated by lactic acid-producing species, notably those from the Lactobacillus genus. Our results point to decreases in Lactobacillus spp associated with an increase of gut-microbiota-associated species from the Enterobacterales order. Escherichia coli exhibited the most pronounced increase in abundance within the VM during bacteriuria and was notably associated with ASB. Molecular typing and antimicrobial resistance characterization of 72 metagenome assembled E. coli genomes (MAGs) from these pregnant women revealed a genomic signature of extraintestinal pathogenic E. coli (“ExPEC”) strains, which are involved in various extraintestinal infections such as urinary tract infections, newborn infections and bacteremia. Microbial diversity within the vaginal samples from which an E. coli MAG was obtained showed a substantial variation, primarily marked by a decrease in abundance of Lactobacillus species. Overall, our study shows how disruption in key bacterial group within the VM can disrupt its stability, potentially leading to the colonization by opportunistic pathogens.

Pathogen-specific social immunity is associated with erosion of individual immune function in an ant

Contagious diseases are a major threat to societies in which individuals live in close contact. Social insects have evolved collective defense behaviors, such as social care or isolation of infected workers, that prevent outbreaks of pathogens. It has thus been suggested that individual immunity is reduced in species with such ‘social immunity’. However, this hypothesis has not been tested functionally. Here, we characterize the immune response of the ant Lasius niger using a combination of genomic analysis, experimental infections, gene expression quantification, behavioural observations and pathogen quantifications. We uncover a striking specialization of immune responses towards different pathogens. Systemic individual immunity is effective against opportunistic bacterial infections, which are not covered by social immunity, but is not elicited upon fungal infections, which are effectively controlled by social immunity. This specialization suggests that immune layers have evolved complementary functions predicted to ensure the most cost-effective response against a wide range of pathogens.

Inhibition of Pseudomonas aeruginosa Carbonic Anhydrases, Exploring Ciprofloxacin Functionalization Toward New Antibacterial Agents: An In-Depth Multidisciplinary Study.

Ciprofloxacin (CPX) is one of the most employed antibiotics in clinics to date. However, the rise of drug-resistant bacteria is dramatically impairing its efficacy, especially against life-threatening pathogens, such as Pseudomonas aeruginosa. This Gram-negative bacterium is an opportunistic pathogen, often infecting immuno-compromised patients with severe or fatal outcomes. The evidence of the possibility of exploiting Carbonic Anhydrase (CA, EC: 4.2.1.1) enzymes as pharmacological targets along with their role in P. aeruginosa virulence inspired the derivatization of CPX with peculiar CA-inhibiting chemotypes. Thus, a large library of CPX derivatives was synthesized and tested on a panel of bacterial CAs and human isoenzymes I and II. Selected derivatives were evaluated for antibacterial activity, revealing bactericidal and antibiofilm properties for some compounds. Importantly, promising preliminary absorption, distribution, metabolism, and excretion (ADME) properties in vitro were found and no cytotoxicity was detected for some representative compounds when tested in Galleria mellonella larvae.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review.

Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.

Updated insights into adverse events associated with mepolizumab: a disproportionality analysis from the FDA adverse event reporting system database

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is used to treat severe eosinophilic asthma and other eosinophilia-related conditions. Given its growing use, there is a pressing need for the latest data to improve the understanding and management of its adverse events (AEs). This study aimed to investigate the safety of mepolizumab by analyzing the pharmacovigilance database of the US Food and Drug Administration.MethodsThe AE signals associated with mepolizumab from 2015 to 2024 were analyzed and the correlations using reporting ratios (RORs) quantified. Subgroup analyses were conducted to understand AEs in individuals ≤ 18 years of age. We also used time-to-onset (TTO) analysis to examine AE occurrence patterns.ResultsIn total, 82,478 AE reports linked to mepolizumab therapy were included. Our analysis, involving 24,156 patients, revealed a predominance of female patients, with the highest incidence of AEs occurring in those aged 18–65 years. Disproportionality analyses revealed significant signals across various system organ classifications (SOCs), most prominently respiratory, thoracic, and mediastinal disorders (ROR = 5.12, 95% confidence intervals [CI] 5.03–5.21), infections and infestations (ROR = 1.86, 95% CI 1.81–1.90), and immune system disorders (ROR = 1.14, 95% CI 1.08–1.21). The highest ROR was found for asthma crisis (ROR = 104.90, 95% CI 95.31–115.44) at the preferred term (PT) level, and the other notables were coronavirus infection (ROR = 7.33, 95% CI 6.05–8.88) and coronavirus disease 2019 (COVID-19) (ROR = 1.34, 95% CI 1.23–1.47). A subgroup analysis of patients ≤ 18 years old identified four significant SOC signals, with the highest ROR in respiratory, thoracic, and mediastinal disorders (ROR = 5.28, 95% CI 4.17–6.68). PT analysis revealed significant AEs, such as wheezing, bronchospasm, and chest discomfort. TTO analysis revealed that 18.5% of AEs occurred within the first 30 days of treatment. The Weibull shape parameter indicated an “early failure-type” pattern for mepolizumab-associated AEs, underscoring the need for vigilant monitoring during the initial stages of therapy.ConclusionOur study highlights the importance of post-market surveillance for monitoring the safety of mepolizumab, which revealed significant AE signals, particularly for respiratory diseases, infections, and immune system complications. The association with opportunistic infections, including COVID-19, highlights the need for vigilant surveillance and further research.

Evaluation of Multi-antibiotic Resistance Index (MAR) and Molecular Characterization of Pseudomonas aeruginosa Isolated in Pathological Products from Chad

Pseudomonas aeruginosa is a bacterium present in several ecological niches causing opportunistic infections in humans. In developing countries like Chad, this bacteria is responsible for various human pathologies. High-priority pathogens, such as Salmonella and Shigella, represent a particularly heavy burden in low- and middle-income countries, as do Pseudomonas aeruginosa and Staphylococcus aureus, which pose serious problems in health centers. The objective of this study was to evaluate the multi-antibiotic resistance index and to carry out a molecular characterization of Pseudomonas aeruginosa isolated in pathological products from Chad using by rep-PCR (GTG)5. Antibiotic resistance phenotypes were obtained by interpreting the results of our previous study on antimicrobial resistance of Pseudomonas aeruginosa isolated from human infections in N'Djamena, Chad. In this study, two phenotypes were obtained that is XDR and MDR. Thus, 24/36 of strains came from urine and 29/36 strains were MDR. The multi-antibiotic resistance (MAR) indexes varied from 0.33 to 0.86. The rep-PCR allowed good discrimination of Pseudomonas aeruginosa strains in this study. These isolates were grouped based on characteristic bands appearing in their genetic fingerprint profiles. In this study, Pseudomonas aeruginosa strains isolated from urinary tract infections and pus were classified as XDR and MDR type strains.