Cause Of Infections Research Articles

Ascorbic Acid Enhances the Inhibitory Effect of Theasaponins against Candida albicans

Candida albicans (C. albicans) is a main cause of hospital-acquired fungal infections. Combination therapy is promising as a novel anti-C. albicans strategy because of its better efficacy. Theasaponins are pentacyclic triterpenes in the Camellia genus with multiple biological activities. Our previous studies prove that theasaponins display inhibitory activity against C. albicans. Ascorbic acid (VC) is a vitamin found in many plants that shows potential in combination therapy. However, whether VC enhances the activity of theasaponins remains unclear. In this study, the checkerboard micro-dilution method was used to assess the effect of VC (0–80 mmol/L) on the anti-C. albicans effect of theasaponins (0–1000 μg/mL). Then, the effects of theasaponins (31.25 μg/mL), VC (80 mmol/L), and theasaponins (31.25 μg/mL) + VC (80 mmol/L) on C. albicans planktonic cells and different stages of biofilm formation were assessed. Transcriptomic analysis was conducted to investigate the molecular mechanisms. According to the results, VC enhanced the anti-planktonic and anti-biofilm effect of theasaponins against C. albicans. The minimum inhibitory concentration of theasaponins was significantly decreased and the fungicidal efficiency was increased with the addition of VC. VC remarkably aggravated the suppression of theasaponins with regard to various virulence factors of C. albicans, including adhesion, early biofilm formation, mature biofilm, cell surface hydrophobicity, and phospholipase activity. Compared with the theasaponins or VC groups, the level of intracellular reactive oxygen species was higher, while the levels of mitochondrial membrane potential and adenosine triphosphate were lower in the combination group, suggesting more severe oxidative stress, mitochondrial injury, and energy deficiency. Transcriptomic analysis revealed that the combination predominantly suppressed the pathways of glycolysis, glycerophospholipid metabolism, glutathione metabolism, and cysteine and methionine metabolism. This implied that energy deficiency and redox imbalance were associated with the anti-C. albicans activity of the combination. These results prove that VC enhances the inhibitory effect of theasaponins against C. albicans and that the combination has the potential to be used as a topical antifungal therapy or disinfectant.

Genetic characteristics of human parainfluenza viruses 1-4 associated with acute lower respiratory tract infection in Chinese children, during 2015-2021.

Human parainfluenza viruses (HPIVs) are a significant cause of acute lower respiratory tract infections (ALRTIs) among young children and elderly individuals worldwide. The four types of HPIVs (HPIV1-4) can cause recurrent infections and pose a significant economic burden on health care systems globally. However, owing to the limited availability of complete genome sequences, the genetic evolution of these viruses and the development of vaccines and antiviral treatments are hampered. To address this issue, this study utilized next-generation sequencing to obtain 156 complete genome sequences of HPIV1-4, which were isolated from hospitalized children with ALRTIs in six regions of China between 2015 and 2021. This study revealed multiple clades, lineages, or sublineages of HPIVs circulating in mainland China, with a novel clade D of HPIV1 identified as geographically restricted to China. Moreover, this study identified the endemic dominant genotype of HPIV3, lineage C3, which has widely spread and continuously circulated in China. Bioinformatic analysis of the genome sequences revealed that the proteins of HPIV3 possessed the most variable sites, with the P protein showing more diversity than the other proteins among all types of HPIVs. The HN proteins of HPIV1-3 are all under negative/purifying selection, and two amino acid substitutions in the HN proteins correspond to known mAb neutralizing sites in the two HPIV3 strains. These findings provide crucial insights into the genetic diversity and evolutionary dynamics of HPIVs circulating among children in China and may facilitate research on the molecular diagnosis, vaccine development, and surveillance of HPIVs.IMPORTANCEPhylogenetic analysis revealed the prevalence of multiple clades, lineages, or sublineages of human parainfluenza viruses (HPIVs) circulating in mainland China. Notably, a unique evolutionary branch of HPIV1 containing only Chinese strains was identified and designated clade D. Furthermore, in 2023, HPIV3 strains from Pakistan and Russia formed a new lineage within clade C, named C6. The first HPIV4b sequence obtained in this study from China belongs to lineage C2. Evolutionary rate assessments revealed that both the HN and whole-genome sequences of HPIV3 presented the lowest evolutionary rates compared with those of the other HPIV types, with rates of 6.98E-04 substitutions/site/year (95% HPD: 5.87E-04 to 8.25E-03) and 5.85E-04 substitutions/site/year (95% HPD: 5.12E-04 to 6.62E-04), respectively. Recombination analysis revealed a potential recombination event in the F gene of an HPIV1 strain in this study. Additionally, all the newly obtained HPIV1-3 strains exhibited negative selection pressure, and two mutations were identified in the HN protein of two HPIV3 strains at monoclonal antibody-binding sites.

B-212 Laboratory Performance in Molecular Detection of Mycobacterium tuberculosis Through Analysis of External Quality Assessment Program Results: WHO-Recommended Tests Outperform Others

Abstract Background In 2022, tuberculosis caused 11,200 deaths in Brazil and 1,300,000 globally. With 87,344 new cases, it remains a leading infectious cause of death, second only to COVID-19. Prompt detection is critical, particularly with the growing resistance to rifampicin and isoniazid, highlighting the need for molecular testing. External Quality Assessment Programs (EQAP) are essential to ensure the accuracy, reliability, and harmonization of laboratory results amid the complexities of M. tuberculosis infection. Here, we evaluate the overall performance of participating laboratories (labs) in three EQAP related to tuberculosis: M. tuberculosis molecular detection (MTB), Rifampicin resistance detection (RIF), and Isoniazid resistance detection (INH). All are organized by a Brazilian provider accredited according to the ABNT NBR ISO/IEC 17043:2011 standard. Methods The EQAP samples were suspensions containing human cells, with or without the addition of cultured, inactivated, and lyophilized M. tuberculosis. Labs received two samples quarterly for testing accuracy, sensitivity, and specificity. We computed these metrics along with participant and round numbers. The Mann-Kendall test assessed accuracy trends over time. Furthermore, kit type accuracies for in-vitro diagnostic (IVD) vs. laboratory-developed tests (LDT), World Health Organization recommended (WHO-recommended) vs. other kits (non-WHO), and methods (qPCR vs. PCR) were compared using chi-square tests and odds-ratio calculations. Results In the MTB EQAP (2018-2022), 63 labs participated over 20 rounds, with 22 (range: 6-48) labs per round on median, achieving 96.6% accuracy (853/883), 97.5% sensitivity (556/570), and 94.9% specificity (297/313). The Mann-Kendall test found no significant accuracy trends over time (τ = -0.91, p = 0.36). IVDs outperformed LDTs with 97.8% (751/768) vs. 87.9% (102/116) accuracy (OR=6.0, 95%CI 3.42-20.9, p<0.0001). WHO-recommended kits were more accurate than non-WHO kits, 98.2% (674/686) vs. 90.4% (179/198) (OR=5.96, 95%CI 1.05-12.7, p<0.0001). qPCR exceeded the accuracy of PCR, 97.2% (833/857) versus 74% (20/27) (OR=12.1, 95%CI 4.8-32.9, p<0.0001). For RIF EQAP (2020-2022), 49 laboratories in 9 rounds, with 25 (range: 18-42) laboratories per round on median, showed 97.4% accuracy (297/305), 97.2% sensitivity (176/181), and 97.6% specificity (121/124). In the INH EQAP (2021-2022), 7 laboratories over 7 rounds, with 4 (range: 2-5) laboratories per round on median, reached 95.2% accuracy (20/21), 100% sensitivity (4/4), and 94.1% specificity (16/17). Differences between types of kits and methods for RIF and INH, as well as trends over time, were not significant or could not be calculated due to the limited number of samples. Conclusions The MTB EQAP underscored the high participation and suitability of labs, along with excellent diagnostic performance; IVD kits were 6 times more likely to yield adequate results than LDTs. WHO-recommended kits were 5.9 times more likely to produce adequate results than non-WHO kits. qPCR was 12.6 times more likely to achieve adequate results than PCR. Despite fewer participants in RIF and INH, their performance rates were high; more data are needed for conclusive results on kit and method types. This study affirms the quality of molecular diagnostics for tuberculosis in Brazil, informs on kit and method selection, and underscores the critical role of EQAPs in combating a significant global health issue.

Effects of a SigH mutation on tigecycline resistance and the SigH-RshA interaction in Mycobacteroides abscessus

Abstract Mycobacteroides abscessus is an opportunistic pathogen ubiquitous in the environment owing to its ability to remain viable on nutrient-poor surfaces. It is a frequent cause of infections in the cosmetic industry, with patients being infected through cutaneous invasive procedures such as tattooing, piercings and cosmetic surgeries. In immunocompromised hosts, infections can be severe and difficult to treat as M. abscessus has many intrinsic and acquired resistances to different classes of antibiotics. Tigecycline, a tetracycline derivative introduced two decades ago, is a broad-spectrum antibiotic with activity on bacteria that are resistant to many existing antibiotics. Unfortunately, tigecycline-resistant strains of M. abscessus have been reported in recent years. This study aimed to investigate the resistance mechanism of CL7, a tigecycline-resistant, spontaneous mutant derived from M. abscessus ATCC 19977. CL7 notably had a 7 amino-acid truncation in the SigH protein, a sigma factor (transcriptional activator) responsible for mycobacterial responses to environmental stress. RNA sequencing showed that sigH and other genes were up-regulated in CL7 (as compared to ATCC 19977). The gene set enrichment analysis demonstrated that the SigH regulon was significantly over-represented among these genes up-regulated in CL7. A bacterial-2-hybrid assay was performed to investigate the effect of the mutation on the SigH interaction with RshA, the anti-sigma factor that inhibits SigH intracellularly. The results, supported by RNA sequencing, showed that the interaction between RshA and the mutant SigH was impeded. This reduced interaction could lead to a decreased inhibition of SigH by RshA, causing the up-regulation of the sigH gene. Coupled with the RNA polymerase, SigH would then up-regulate genes under its regulation, leading to tigecycline resistance. In general, this study enhances our understanding of tigecycline resistance mechanisms in M. abscessus, and contributes to the development of novel antibacterial therapies and diagnostic tools for managing M. abscessus infections.

Rapidly growing knowledge of Mycobacterium smegmatis: A case series and review of antimicrobial susceptibility patterns

Mycobacterium smegmatis is a rapidly growing nontuberculous mycobacterium that is rarely isolated from clinical specimens and is frequently considered to be a contaminant. We conducted a retrospective review of mycobacterial cultures positive for M. smegmatis from 1998 to 2023 at our institution to evaluate the clinical significance of recovering this mycobacterium. Antimicrobial susceptibility patterns were also determined. Twenty-two M. smegmatis isolates were identified from 17 patients, 12 of whom met criteria for clinical chart review. M. smegmatis was deemed a cause of infection in 5/5 isolates from skin or soft tissue, 3/3 from bone, 1/1 from blood, and 0/3 from respiratory specimens. All cases thought to be significant were treated with at least 2 active agents for periods varying from 2 weeks up to 8 months. 18 isolates had antimicrobial susceptibility testing performed and all were susceptible to doxycycline, imipenem, linezolid, moxifloxacin, trimethoprim/sulfamethoxazole, and tobramycin while all isolates were resistant to clarithromycin. When recovered in culture, the presence of M. smegmatis should be correlated with clinical presentation as it may represent a true infection.

Revision and Infection Rate in 728 Shunt-Treated Adult Hydrocephalus Patients—a Single-Center Retrospective Study

Hydrocephalus is a common diagnosis worldwide that is treated with shunts and is associated with potential life-threatening risks of shunt dysfunction and infection. We investigated differences in rates of shunt revisions and infections including various factors in patients with different causes of hydrocephalus. We also studied causes of infections and efficacy of perioperative antibiotic regimens. Our objective was to identify patients at risk of higher revision and infection rates after shunt treatment. We conducted a retrospective single-center cohort study including 728 adult patients who underwent shunt surgery between 2013 and 2019 at our center. Overall revision rate was 20.1%, and infection rate was 4.8%. Infection was detected in 24% of all revisions. The main location for a positive culture was cerebrospinal fluid (67.5%), frequently caused by Cutibacterium acnes (60%). Younger age and prior shunts were the only predictors confirmed in multivariate Cox regression as significantly increasing the risk of revision surgery. Multivariate Cox regression analysis of infection risk factors showed that obstructive hydrocephalus, prior shunt, and cloxacillin significantly increased risk of shunt infection. We found revision and infection rates in accordance with other studies. We showed a significantly increased risk in younger patients. Previous shunts also increased the risk of revisions and infections. We showed a small but significant effect of perioperative prophylaxis with broader-spectrum antibiotics compared with cloxacillin. Our study identified a group of younger patients with congenital hydrocephalus and prior implants with an increased risk of shunt infection in whom additional preventive measures should be employed.

Mortality in Stray Kittens under Eight Weeks Old: Focusing on Congenital Malformations.

Neonatal and pediatric mortality in kittens could be associated with bacterial infections, complications from inadequate management, congenital malformations, neonatal isoerythrolysis, parasitic diseases, and viral diseases. The complexity of causes, coupled with kittens' physiological and immunological immaturity, complicates the diagnosis and treatment of disease, highlighting the necessity for preventive measures. This study aimed to identify the leading causes of death and the occurrence of congenital malformations in stray kittens. Necropsies were performed on 68 kittens, all aged under two months. Results indicated that respiratory lesions were the leading cause of death in the youngest group, while gastrointestinal problems were more prevalent in older groups. Infectious causes were predominant across all age groups. Congenital malformations were observed in 40% of the animals, with megaesophagus, cardiovascular anomalies, bone defects, and kidney defects being the most prevalent. The findings underscore the critical importance of hygiene in preventing infections and related complications. Promoting sterilization and sanitary control in stray cats is essential to reduce overpopulation and improve living conditions.

The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection

Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infections in the United States, known for triggering severe disease by hyperactivation of the host response. In this study, we determine the impact of the sympathetic nervous system (SNS) on CDI disease severity. Mouse models of CDI are administered inhibitors of SNS activity prior to CDI. Chemical sympathectomy or pharmacological inhibition of norepinephrine synthesis greatly reduces mortality and disease severity in the CDI model. Pharmacological blockade or genetic ablation of the alpha 2 adrenergic receptor ameliorates intestinal inflammation, disease severity, and mortality rate. These results underscore the role of the SNS and the alpha 2 adrenergic receptor in CDI pathogenesis and suggest that targeting neural systems could be a promising approach to therapy in severe disease.

In vitro and in vivo assessment of the competence of a novel lytic phage vB_EcoS_UTEC10 targeting multidrug resistant Escherichia coli with a robust biofilm eradication activity

Escherichia coli (E. coli) is a leading cause of human infections worldwide and is considered a major cause of nosocomial infections, sepsis, meningitis and diarrhea. Lately, there has been an alarming increase in the incidence of antimicrobial resistance among clinical E. coli isolates. In the current study, a novel bacteriophage (phage) vB_EcoS_UTEC10 was isolated and characterized. The isolated phage showed high stability over wide temperature and pH ranges beside its promising bacteriolytic activity against multidrug resistant (MDR) E. coli isolates. In addition, vB_EcoS_UTEC10 showed a marked antibiofilm capability against mature E. coli biofilms. Genomic investigation revealed that vB_EcoS_UTEC10 has a double stranded DNA genome that consists of 44,772 bp comprising a total of 73 open reading frames (ORFs), out of which 35 ORFs were annotated as structural or functional proteins, and none were related to antimicrobial resistance or lysogeny. In vivo investigations revealed a promising bacteriolytic activity of vB_EcoS_UTEC10 against MDR E. coli which was further supported by a significant reduction in bacterial load in specimens collected from the phage-treated mice. Histopathology examination demonstrated minimal signs of inflammation and necrosis in the tissues of phage-treated mice compared to the degenerative tissue damage observed in untreated mice. In summary, the present findings suggest that vB_EcoS_UTEC10 has a remarkable ability to eradicate MDR E. coli infections and biofilms. These findings could be further invested for the development of targeted phage therapies that offer a viable alternative to traditional antibiotics against resistant E. coli.

Prevalence and outcome of candidemia among paediatric cancer patients: A single centre experience from India

BackgroundCandida species are one of the leading causes of invasive fungal infections in pediatric patients with cancer, resulting in increased treatment related morbidity and mortality. There is limited data with respect to demography and outcomes of candidemia among children with cancer, especially from lower-middle income countries. MethodsIn this retrospective observational study conducted over a 4-year Period (January-2017 to December-2021), children less than 15 years with cancer, treated at a tertiary oncology centre in India and diagnosed with candidemia were included. Data with respect to risk factors, species types, treatment, complications and mortality was gathered. ResultsOne-hundred and ten children with candidemia were included. The most common underlying malignancy was acute leukemia seen in 72 (66%) patients. Seventy-five (68%) patients had neutropenia (<0.5 × 10^9/L) at the time of diagnosis of candidemia. In addition, 35 (32%) and 34 (30%) patients had prolonged exposure to steroids and antibiotics respectively. Non-albicans Candida species was isolated in majority (90%) of the cases. Fifty-seven patients required some form of modification of therapy for underlying malignancy. The 30-day mortality of the entire cohort was 36% and was 73% for patients admitted to the intensive care unit. On multivariate analysis, only prolonged use of antibiotics [odds ratio: 2.7(1.1-6.7); p =0.027] was found to be significantly associated with worse 30-day mortality. ConclusionThe present study highlights the burden of candidemia among children with cancer. Despite prompt therapy, our cohort experienced increased mortality, primarily associated with prolonged antibiotic usage. These findings reinforce the critical importance of strict adherence to infection control guidelines and prudent antibiotic stewardship practices to improve patient outcomes.

The deadly dance of alveolar macrophages and influenza virus.

Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the "macrophage disappearance reaction", which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution.

Construction of core genome multi-locus sequence typing schemes for population structure analyses of Nocardia species

Nocardia, a member of the Actinobacteria phylum, populates diverse habitats globally, with certain species being the cause of various clinical infections in humans. There is paucity of data regarding the population structure of this genus and of established genomic-based phylogenetic methods. We examined the whole genome sequences of 193 isolates spanning five major pathogenic Nocardia species sourced from public databases, encompassing diverse geographic regions. Using the chewBBACA pipeline, a species-specific core genome multilocus sequence typing (cgMLST) schema was created for N. cyriacigeorgica, N. farcinica, N. brasiliensis, N. wallacei, and N. abscessus. Additional genomic features that were examined included virulence factor (VF) profile, total length and open-reading frame count, the core genome length and core gene count, and GC content. Our findings indicated that: (i) N. brasiliensis diverges significantly from the other four species, underscoring its distinct evolutionary trajectory; (ii) the population structures of all species were polyclonal, with phylogenetic clustering occurring in the minority of isolates; (iii) clonal complexes were largely restricted to specific geographical locations, rather than demonstrating a global distribution, and (iv) initial evidence suggests no direct common-source transmission amongst the studied strains. Our study establishes a comprehensive genome-based phylogenetic methodology for population structure of Nocardia species.

Clinical experience with ceftazidime/avibactam for the treatment of extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae in neonates and children.

Klebsiella pneumoniae is a significant cause of healthcare-associated infections, resulting in high morbidity and mortality rates due to limited treatment options. In this study, we aimed to evaluate the treatment outcomes and the safety of Ceftazidime-avibactam in infections caused by extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae in pediatric patients. This study included pediatric patients who received ceftazidime-avibactam treatment due to extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae infections, monitored in the pediatric intensive care, neonatal intensive care, and pediatric wards of Cukurova University Faculty of Medicine between 2022 and 2023. Patients' microbiological responses, clinical responses, medication side effects, and 30-day survival rates were evaluated. Eleven pediatric patients were included in the study, of whom nine were male (81.8%). The median age at the initiation of ceftazidime-avibactam treatment was 15months (range: 14days-183months). Sepsis was diagnosed in 9 patients (81.8%). Two premature infants (27 and 35weeks) were admitted to the neonatal ICU. Regarding the Klebsiella pneumoniae strains, 10 (91%) were extensively drug-resistant (XDR), and 1 (9%) was pandrug-resistant (PDR). Eight strains (72.7%) were carbapenem-resistant, and 9 (81.8%) were colistin-resistant. Microbiological response was noted in 8 patients (72.7%), clinical response was evident in 6 patients (54.5%). The 30-day survival rate was 54.5%, with six patients surviving. In our study, ceftazidime-avibactam has been identified as a significant treatment option for resistant Klebsiella pneumoniae infection in critically ill children and premature infants with sepsis and organ failure, and it has been found to be well tolerated.

Fabrication, characterization, and in vitro studies of Selenium-substituted hydroxyapatite coatings

Abstract The increasing demand for hydroxyapatite (HA) coatings with enhanced functionality have led to novel materials with compositions that are more closely resembling those of natural bone apatites. In the present study, selenium-substituted (Se–HA) powders with various Se quantities were prepared by chemical precipitation. By applying suspension plasma spray (SPS), the surface of Ti substrates was coated with corresponding Se-HA coatings. The microstructural and physicochemical properties of the powders and the coatings were studied. Analysis by x-ray diffraction indicates that SeO3 2− replaced the PO4 3− groups, affecting the crystal structure and crystallinity of HA. As the extent of Se substitution increases, the lattice volume expands and the crystallinity decreases. The synthesized Se-HA powders were confirmed to be calcium-deficient apatite through energy-dispersive x-ray spectroscopy. However, the high temperature of SPS accelerated volatilization of P, increasing the Ca/(P + Se) ratio of the coatings, whereas the chemical valence state of Se remained unchanged. The Se–HA coating exhibited a high bonding strength of &gt;33 MPa, fully meeting the requirement of 15 MPa as coating implant materials. Dissolution behavior tests indicate that the Se–HA coatings had high solubility in comparison to the HA coating. As the substitution degree of Se increased, the dissolution rate also increased, which greatly enhanced the capacity to generate a bone-like apatite layer. In vitro cell experiments indicate that the Se–HA coatings exhibited excellent biocompatibility, and facilitated adhesion and proliferation of osteoblast MC3T3-E1, even in the presence of fluorine. Furthermore, antibacterial properties of Se–HA coatings were also indicated by inhibition of Staphylococcus aureus, which is the main cause of most infections after orthopedic surgeries. Thus, the Se–HA coatings have potential as implant coating materials for orthopedic applications.

Mycoplasma hominis as Cause of Extragenital Infection in Patients with Hypogammaglobulinemia: Report of 2 Cases and Literature Review.

Mycoplasma hominis can be a part of human urogenital tract microbiome, and it is a frequent cause of urogenital infections. In rare cases, it can also cause extragenital infections, especially in immunocompromised patients. In this case series, we report two cases and provide a literature review of extragenital infections caused by M. hominis in patients with hypogammaglobulinemia. Patient 1 was a 61-year-old woman with diffuse large B-cell lymphoma who, after rituximab-containing chemotherapy and CAR-T therapy, developed M. hominis spondylodiscitis. Patient 2 was a 50-year-old woman with congenital hypogammaglobulinemia who developed disseminated M. hominis infection involving pleura, muscles, and right ankle. Antibiotic therapy with levofloxacin and doxycycline for 10weeks in patient 1 and with levofloxacin alone for 6weeks in patient 2 led to infection resolution. The literature review identified 14 additional cases reporting M. hominis extragenital infection in patients with hypogammaglobulinemia. M. hominis should also be suspected as an etiological agent of extragenital infection in patients with B-cell immunodeficiency with a clinical picture of persistent, standard-culture negative infection, particularly with arthritis or abscess formation. Even if M. hominis can grow on standard bacterial medium, in suspected cases molecular methods should be promptly used for correct diagnostic work-up and successful therapy.

Vancomycin Resistant Enterococci and Trend of Antimicrobial Susceptibility in Urine Cultures

Background: Enterococci are emerging nosocomial pathogen showing resistance to broad spectrum antibiotics. As reported by the center for disease control and prevention, enterococci (13.9%) are the second leading cause of urinary tract infection, after Escherichia coli. After the first report of vancomycin-resistant enterococci in England (1988), India reported its first vancomycin resistant enterococci isolate from New Delhi (1999). The prevalence of vancomycin resistant enterococci ranges from 1-9%, in India. To evaluate the prevalence of vancomycin resistant enterococci among urinary isolates and to check their antimicrobial resistance pattern. Methods: A retrospective observational study conducted at a tertiary care hospital. Data were analysed from November, 2017 to October, 2018. A total of 12,129 urine samples were received and subjected to culture on HiCrome UTI agar (Hi-Media laboratories, Mumbai) and incubated at 37 °C for a period of 18-24 hours. Antimicrobial susceptibility was performed using Kirby–Bauer disc diffusion method. Identification was done on the basis of colony colour and species identification was done by using biochemical test as per standard laboratory protocol. In one case automated siemens microscan walkaway identification system was used for confirmation. Results: Enterococci were isolated in 4.06% from urine cultures out of which 7.52% were vancomycin resistant. Most of the vancomycin resistant enterococci isolate (86.49%) were multi drug resistant. Conclusion: In vancomycin resistant enterococci related urinary tract infection, nitrofurantoin can be used as an appropriate first choice in uncomplicated cases and linezolid should be reserved for serious and complicated urinary tract infections.

A case of VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome presenting as progressive multisystem involvement with parenchymal infiltrates following infection with Epstein Barr virus

AbstractVEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory, and somatic) syndrome is a rare multisystem disease affecting predominantly males over 50 and manifesting as widespread progressive inflammatory sequelae and haematological dysfunction. We describe a patient who presented with systemic symptoms of fevers, night sweats and weight loss, and developed progressive inflammatory sequelae including cutaneous lesions, haematological dysfunction, lymphadenopathy, migratory inflammatory arthropathies, with new pulmonary infiltrates, following infection with Epstein Barr Virus. Laboratory investigations, bronchoscopy, bone marrow biopsy and imaging were consistent with an inflammatory aetiology. The constellation of organ system involvement, laboratory, biopsy, and imaging results were suspicious for VEXAS syndrome, and this diagnosis was confirmed by identification of a somatic mutation in the UBA1 gene following extensive exclusion of infectious and autoimmune causes. Interestingly the onset of the VEXAS syndrome coincided with serological confirmation of Epstein Barr Virus raising the importance of further exploration into the underlying aetiology of VEXAS syndrome.

Tropical eosinophilia: Case series on varying presentations

ABSTRACT Eosinophilia can be due to both infectious and non-infectious causes, many of which may be clinically indistinguishable. Filariasis, a tropical and subtropical infection, is caused by Wuchereria bancrofti, Brugia timori (B. timori), and Brugia malayi. Filariasis is conventionally diagnosed by demonstration of microfilaria in the peripheral blood smear. The disease may be missed if one is not aware of the possibility. We report two cases in two individuals with eosinophilia due to filaria resulting in tropical pulmonary eosinophilia and deep vein thrombosis (DVT). They had complete symptomatic improvement after a 3-week course of diethylcarbamazine (DEC) +/- ivermectin.

Laryngotracheal stenosis: a single-center retrospective analysis of endoscopic treatment strategies and recurrence.

Laryngotracheal stenosis is a process of fibrosis that results in airway obstruction; it may be congenital or acquired. Acquired cases are due to iatrogenic, traumatic, infectious and autoimmune causes. Patients present with a spectrum of breathing difficulties that might be fatal. This article presents a unique retrospective cross-sectional study of patients with laryngotracheal stenosis who had endoscopic dilatation, and some had open surgical procedures to describe the evolution after the therapy, to compare the outcomes of the dilatation in comparison to surgical interventions and associated complications in other studies, to provide knowledge to help in dealing with these patients, and to enable educated, independent patient decision-making. In this observational and descriptive study, we aimed to highlight the clinical features, management, and treatment outcomes among twenty-nine patients with laryngotracheal stenosis who were managed by open and endoscopic surgical intervention over a period of 5 years. Data were collected retrospectively from the patients' medical records from February 2016 until July 2022 at a hospital in Jerusalem, which is a tertiary healthcare facility and the only referral center for similar cases from the West Bank, East Jerusalem, and Gaza, with a population of around 8 million. Tables and graphs are used to highlight the statistical study's findings. Data were analyzed using Microsoft Excel software. Twenty-nine patients were involved in the study, with an average age of 32.2 years; 51.7% of them were males. The patients had one or more chronic conditions, such as hypertension and coronary artery disease. The majority of patients (65.5%) had stenosis as a result of orotracheal intubation, and the most common site was the subglottic (68.9%). According to the Cotton-Myer classification, 44.8% of the patients were classified in grade III, 34.4% were included in grade I, 13.7% in grade II, and 6.8% in grade IV. Six patients (20.68%) received surgery for stenosis, and 23 patients had an endo-laryngeal dilatation. Restenosis happened in (58.6%). Mortality rates are almost negligible. Subglottic stenosis is still a challenging condition to manage. The authors describe a single-center experience approach dealing with these conditions. Long-term follow-up for these cases is mandatory as the recurrence rate is still high.

Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.