Infections In Immunocompromised Patients Research Articles

A Retrospective Study of Imaging of Invasive Rhino-Orbital-Cerebral Mucormycosis in the COVID-19 Pandemic in a Tertiary Care Center.

Aim The study aims to analyze the imaging findings of invasive rhino-orbital-cerebral mucormycosis (ROCM) in patients who had COVID-19. Materials and methods This retrospective descriptive study was done on confirmed (culture and histopathology) patients who had a COVID-19 infection. The data was collected from the record section from May 2021 to June 2021. Imaging data were analyzed, and findings were tabulated according to statistical methods. Results Radiological evaluation, including CT and MRI, was done in 48 cases. The ethmoid sinus was the most common sinus involved in 60.41% of cases, followed by the maxillary sinus (52.09%). Unilateral pansinusitis was observed in 21 cases (43.75%). Among periantral extensions, retroantral fat involvement was the most common finding, seen in 24 cases (50%). Lamina papyracea and the walls of the maxillary sinus were involved in eight cases (16.67%). A total of 38 cases (79.17%) exhibited involvement of the extraconal compartment, while 32 cases (66.67%) showed involvement of the intraconal compartment. In intracranial involvement, infarct was noted in 13 cases (27%), and cavernous sinus involvement in nine cases (18.75%). Conclusions ROCM is a life-threatening fungal infection in immunocompromised patients, especially diabetics. Imaging of ROCM plays a pivotal role in early diagnosis, the extent of disease, surgical planning, prognosis, and the response to treatment. Radiologists must know the imaging features and patterns of extension of ROCM.

ST88 ceftazidime-resistant Stenotrophomonas maltophilia is present in the saliva and gingival crevicular fluid of patients with periodontitis and AIDS from São Paulo State, Brazil.

Stenotrophomonas maltophilia (S. maltophilia) is an intrinsically drug-resistant and biofilm-forming bacteria causing infections in immunocompromised humans. This study reports the isolation of five S. maltophilia strains from saliva and gingival crevicular fluid (GCF) of AIDS patients with periodontitis in São Paulo, Brazil, showing resistance to ceftazidime, strong biofilm formation capacity and a close genetic relationship. The presence of S. maltophilia strains in saliva and CGF of patients with AIDS and periodontitis is a concern for the presence and persistence of intrinsically resistant bacteria in the oral environment, enhancing the risk for the development of severe infections in immunocompromised patients.

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review.

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.

PET imaging of Aspergillus infection using Zirconium-89 labeled anti-β-glucan antibody fragments

PurposeInvasive fungal diseases, such as pulmonary aspergillosis, are common life-threatening infections in immunocompromised patients and effective treatment is often hampered by delays in timely and specific diagnosis. Fungal-specific molecular imaging ligands can provide non-invasive readouts of deep-seated fungal pathologies. In this study, the utility of antibodies and antibody fragments (Fab) targeting β-glucans in the fungal cell wall to detect Aspergillus infections was evaluated both in vitro and in preclinical mouse models.MethodsThe binding characteristics of two commercially available β-glucan antibody clones and their respective antigen-binding Fabs were tested using biolayer interferometry (BLI) assays and immunofluorescence staining. In vivo binding of the Zirconium-89 labeled antibodies/Fabs to fungal pathogens was then evaluated using PET/CT imaging in mouse models of fungal infection, bacterial infection and sterile inflammation.ResultsOne of the evaluated antibodies (HA-βG-Ab) and its Fab (HA-βG-Fab) bound to β-glucans with high affinity (KD = 0.056 & 21.5 nM respectively). Binding to the fungal cell wall was validated by immunofluorescence staining and in vitro binding assays. ImmunoPET imaging with intact antibodies however showed slow clearance and high background signal as well as nonspecific accumulation in sites of infection/inflammation. Conversely, specific binding of [89Zr]Zr-DFO-HA-βG-Fab to sites of fungal infection was observed when compared to the isotype control Fab and was significantly higher in fungal infection than in bacterial infection or sterile inflammation.Conclusions[89Zr]Zr-DFO-HA-βG-Fab can be used to detect fungal infections in vivo. Targeting distinct components of the fungal cell wall is a viable approach to developing fungal-specific PET tracers.

Evaluation of Antimicrobial Resistancein Clinical Isolates of Enterococcus spp. Obtained from Hospital Patients in Latvia.

Background and Objective: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated with antibiotics. This study addresses the rising concern of antimicrobial resistance (AMR) in Enterococci, focusing on the prevalence of vancomycin-resistant enterococcus (VRE) strains. Materials and Methods: The pilot study involved 140 Enterococci isolates collected between 2021 and 2022 from two multidisciplinary hospitals (with and without local therapeutic drug monitoring protocol of vancomycin) in Latvia. Microbiological assays and whole genome sequencing were used. AMR gene prevalence with resistance profiles were determined and the genetic relationship and outbreak evaluation were made by applying core genome multi-locus sequence typing (cgMLST). Results: The acquired genes and mutations were responsible for resistance against 10 antimicrobial classes, including 25.0% of isolates expressing resistance to vancomycin, predominantly of the vanB type. Genetic diversity among E. faecalis and E. faecium isolates was observed and seven potential outbreak clusters were identified, three of them containing sequence types ST6, ST78 and ST80. The prevalence of vancomycin resistance was highest in the hospital without a therapeutic drug-monitoring protocol and in E. faecium. Notably, a case of linezolid resistance due to a mutation was documented. Conclusions: The study illustrates the concerning prevalence of multidrug-resistant Enterococci in Latvian hospitals, showcasing the rather widespread occurrence of vancomycin-resistant strains. This highlights the urgency of implementing efficient infection control mechanisms and the need for continuous VRE surveillance in Latvia to define the scope and pattern of the problem, influencing clinical decision making and planning further preventative measures.

The buoyancy of cryptococcal cells and its implications for transport and persistence of Cryptococcus in aqueous environments.

Cryptococcus is a genus of saprophytic fungi with global distribution. Two species complexes, C. neoformans and C. gattii, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil, trees, and avian guano. More recently, C. gattii has been implicated in infections in marine mammals, suggesting that inhalation of liquid droplets or aerosols from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Water transport has also been suggested to play a role in the spread of C. gattii from tropical to temperate environments. However, the dynamics of fungal survival, persistence, and transport via water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the media in which cells are suspended, with formation of a halocline interface significantly slowing the rate of settling of cryptococcal cells through water, resulting in persistence of C. neoformans within 1 cm of the air-water interface for over 60 min and C. gattii for 4-6 h. Our data also showed that during culture in yeast peptone dextrose media (YPD), polysaccharide accumulating in the supernatant formed a raft that augmented buoyancy and further slowed settling of cryptococcal cells. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.

Phenotypic characterization of cryptic species in the fungal pathogen Histoplasma.

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, Histoplasma, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by Histoplasma through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that Histoplasma is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of Histoplasma to identify phenotypic traits that differentiate between these species: Histoplasma capsulatum sensu stricto, Histoplasma ohiense, Histoplasma mississippiense, Histoplasma suramericanum, and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of Histoplasma and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including Histoplasma, and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus Histoplasma, H. capsulatum sensu stricto (ss), H. ohiense, H. mississippiense, and H. suramericanum, and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of Histoplasma but also for clinicians, as the Histoplasma species could determine the outcome of disease and treatment needed.

Characterization of virus‒host recombinant variants of the hepatitis E virus.

Hepatitis E virus (HEV) is a major cause of viral hepatitis. HEV can lead to chronic infection in immunocompromised patients. Ribavirin treatment is currently used to treat such chronic infections. Recently, seven virus-host recombinant viruses were characterized in immunocompromised patients. These viruses have incorporated a portion of a human gene fragment into their genome. We studied the consequences of these insertions on the replication capacity. We found that these inserted fragments could enhance virus replication for five of the seven recombinant variants. We also showed that the recombinant variants with replicative advantages were less sensitive to ribavirin in vitro. Finally, we found that the mechanisms leading to such a replicative advantage do not seem to rely on the post-translational modifications introduced by the human gene fragment that could have modified the function of the viral protein. The mechanisms involved in improving the replication of such recombinant viruses remain to be explored.

Predictions of Immunodominant Epitope Peptides From the AsaA Type VI Secretion System in Acinetobacter baumannii: A Computational Approach.

Introduction Acinetobacter baumannii, designated as a priority pathogen by the World Health Organization (WHO), is responsible for recalcitrant infections in immunocompromised patients. The type VI secretion system (T6SS) is a class of macromolecular secretion machines, contributing to its virulence. The aim of this study is thus to predict the immune-dominant epitope peptides from theAcinetobacter T6SS-associated protein of A. baumannii(AsaA). Methods AsaA protein retrieval from the bacteria was carried out using computational platforms and the evaluation of antigenicity and allergenicitywas performed. The T-cell epitopes of major histocompatibility complex class II binders were identified followed by molecular docking of the immune-dominant epitopes with human leukocyte antigen alleles using the ClusterPro server (https://cluspro.org/help.php). Additionally, the B-cell epitopes were predicted. Results Immune-informatic analysis showed immune-dominant peptides in the most favored regions with promising interactions with HLAalleles DP, DQ, DR, and toll-like receptor showing high binding capacity. Conclusion In the present investigation, epitope 1 (LILFLIGNY) was found to be a promising candidate for the synthesis of vaccines. However, it requires further experimentation for its immunological memory and response.

High-risk clones of Pseudomonas aeruginosa contaminate the drinking water networks of French cities

Pseudomonas aeruginosa is a major opportunistic pathogen responsible for severe infections in immunocompromised patients. The contamination of drinking water networks (DWNs) with this pathogen is underestimated, as it is mostly in the state of persister cells undetected by the recommended monitoring technique. We collected water samples from eight cities distant from each other and searched for P. aeruginosa using a culture-based method that resuscitates persister cells. The genomes of isolates were sequenced. Five DWNs of the eight tested (62.5%) were contaminated with P. aeruginosa, of which four were contaminated with high-risk clones (ST308, ST395). Surprisingly, the ST308 isolates retrieved from the four independent and distant DWNs were clonal. Most P. aeruginosa isolates shared a genomic island conferring tolerance to copper-ions. The population structure of the collection may result from both a common source of contamination by plumbing supplies and the selection of clones sharing genetic elements that presumably aided their propagation in DWNs.

A novel lentiviral vector-based approach to generate CAR T cells targeting Aspergillus fumigatus

Abstract Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as chimeric antigen receptor (CAR) T cells, are direly needed. Here, we propose a novel approach to generate Aspergillus fumigatus (AF)-CAR T cells using the scFv domain of AF-269-5 mAb and a lentiviral vector system. These cells successfully targeted mature hyphal filaments of representative clinical and reference AF isolates and elicited potent release of cytotoxic effectors and type 1 T-cell cytokines. Furthermore, AF-CAR T cells generated from peripheral blood mononuclear cells of four healthy human donors and expanded with cytokine stimulation (IL-2, IL-7+IL-15) regimens significantly suppressed mycelial growth of AF-293 after 18 h of co-culture. Moreover, cyclophosphamide-immunosuppressed NSG mice with invasive pulmonary aspergillosis that received two doses of 5 million AF-CAR T cells on days 0 and 2 after AF infection showed significantly reduced morbidity on day 4 post-infection (p<0.001) and significantly improved 7-day survival (p=0.049) compared to mice receiving non-targeting control T cells. In conclusion, we developed a novel lentiviral strategy to obtain AF-CAR T cells with high targeting efficacy, yielding significant anti-AF activity in vitro and short-term protection in vivo.

UV-C side-emitting optical fiber-based disinfection: a promising approach for infection control in tight channels.

The growth of pathogenic bacteria in moist and wet surfaces and tubing of medically relevant devices results in serious infections in immunocompromised patients. In this study, we investigated and demonstrated the successful implementation of a UV-C side-emitting optical fiber in disinfecting medically relevant pathogenic bacteria (Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus [MRSA]) within tight channels of polytetrafluoroethylene (PTFE). PTFE is a commonly used material both in point-of-use (POU) water treatment technologies and medical devices (dental unit water line [DUWL], endoscope). For a 1-m-long PTFE channel, up to ≥6 log inactivation was achieved using a 1-m-long UV side-emitting optical fiber (SEOF) with continuous 16-h exposure of low UV-C radiation ranging from ~0.23 to ~29.30 μW/cm2. Furthermore, a linear model was used to calculate the inhibition zone constant (k`), which enables us to establish a correlation between UV dosage and the extent of inactivated surface area (cm2) for surface-bound Escherichia coli on a nutrient-rich medium. The k` value for an irradiance ranging from ~150 to ~271.50 μW/cm2 was calculated to be 0.564 ± 0.6 cm·cm2/mJ. This study demonstrated the efficacy of SEOFs for disinfection of medically relevant microorganisms present in medically and domestically relevant tight channels. The impact of the results in this study extends to the optimization of operational efficiency in pre-existing UV surface disinfection setups that currently operate at UV dosages exceeding the optimal levels.IMPORTANCEGermicidal UV radiation has gained global recognition for its effectiveness in water and surface disinfection. Recently, various works have illustrated the benefit of using UV-C side-emitting optical fibers (SEOFs) for the disinfection of tight polytetrafluoroethylene (PTFE) channels. This study now demonstrates its impact for disinfection of medically relevant organisms and introduces critical design calculations needed for its implementation. The flexible geometry and controlled emission of light in these UV-SEOFs make them ideal for light distribution in tight channels. Moreover, the results presented in this manuscript provide a novel framework that can be employed in various applications, addressing microbial contamination and the disinfection of tight channels.

Kodamaea ohmeri: A rare yeast causing invasive infections in immunocompromised patients.

Kodamaea ohmeri is a rare, recognized pathogen that has previously been isolated from environmental sources. The patients commonly affected by this yeast include immunocompromised as well as immunocompetent patients having several associated risk factors. We report three cases in which K. ohmeri was isolated from blood using Bact T/ALERT. Identification was carried out by MALDI-TOF MS (Vitek-MS, BioMérieux, Marcy-l'Etoile, France) in addition to color characteristics on chromogenic media. The patients had diminished immune response on account of a multitude of comorbidities. K. ohmeri can be misidentified as Candida tropicalis, Candida albicans, or Candida hemolounii by conventional methods; correct and timely identification can be achieved by MALDI-TOF MS. Antifungal susceptibility breakpoints for K. ohmeri are currently not defined. An Echinocandin was added to the treatment regimen of all three of the cases. Identification of K. ohmeri using conventional methods is difficult and unusual yeasts should be carefully observed, especially upon prolonged incubation.

Replacement of sulfonamide by sulfoximine within a helicase-primase inhibitor with restricted flexibility

Helicase-primase is an interesting target for the therapy of herpes simplex virus (HSV) infections. Since amenamevir is already approved for varicella-zoster virus (VZV) and HSV in Japan and pritelivir has received breakthrough therapy status for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in me-too approaches. Here, we describe the attempt to improve nervous tissue penetration in Phaeno Therapeutics drug candidate HN0037 to target the latent reservoir of HSV by installing less polar moieties, mainly a difluorophenyl instead of a pyridyl group, and replacing the primary sulfonamide with a methyl sulfoximine moiety. However, all obtained stereoisomers exhibited a weaker inhibitory activity on HSV-1 and HSV-2.

Complete sequence of carbapenem-resistant Ralstonia mannitolilytica clinical isolate co-producing novel class D β-lactamase OXA-1176 and OXA-1177 in Japan.

In 2020, the Ralstonia mannitolilytica strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e., imipenem, meropenem, and doripenem). Whole-genome sequencing revealed that the complete genome consists of two replicons, a 3.5-Mb chromosome and a 1.5-Mb large non-chromosomal replicon which has not been reported in R. mannitolilytica, and referred to as the "megaplasmid" in this study based on Cluster of Orthologous Group of proteins functional analysis. The strain JARB-RN-0044 harbored two novel OXA-60 and OXA-22 family class D β-lactamase genes blaOXA-1176 and blaOXA-1177 on the megaplasmid. Cloning experiments indicated that Escherichia coli recombinant clone expressing blaOXA-1176 gene showed increased minimum inhibitory concentrations (MICs) of imipenem, meropenem, and doripenem, indicating that blaOXA-1176 gene encodes carbapenemase. In contrast, E. coli recombinant clone expressing blaOXA-1177 gene showed increased MICs of piperacillin and cefazolin, but not of carbapenem. Interestingly, the 44.6 kb putative prophage region containing genes encoding phage integrase, terminase, head and tail protein was identified in the downstream region of blaOXA-1176 gene, and comparative analysis with some previously reported R. mannitolilytica isolates revealed that the prophage region was unique to strain JARB-RN-0044. The existence of a highly carbapenem-resistant R. mannitolilytica isolate may raise human health concerns in Japan, where the population is rapidly aging.IMPORTANCERalstonia mannitolilytica is an aerobic non-fermenting Gram-negative rod commonly found in aquatic environments and soil. The bacteria can occasionally cause severe hospital-acquired bloodstream infections in immunocompromised patients and it has been recently recognized as an emerging opportunistic human pathogen. Furthermore, some R. mannitolilytica isolates are resistant to various antimicrobial agents, including β-lactams and aminoglycosides, making antimicrobial therapy challenging and clinically problematic. However, clinical awareness of this pathogen is limited. To our knowledge, in Japan, there has been only one report of a carbapenem-resistant R. mannitolilytica clinical isolate from urine by Suzuki et al. in 2015. In this study, whole-genome sequencing analysis revealed the presence and genetic context of novel blaOXA-1176 and blaOXA-1177 genes on the 1.5 Mb megaplasmid from highly carbapenem-resistant R. mannitolilytica isolate and characterized the overall distribution of functional genes in the chromosome and megaplasmid. Our findings highlight the importance of further attention to R. mannitolilytica isolate in clinical settings.

Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication

Virus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy.

Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients.

Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients.

Molecular monitoring of viral infections in immunocompromised patients in a large university hospital in Italy: reflections after thirteen years of real-life activity

PurposeThis study aimed to investigate the prevalence and viral reactivations of clinical interest in the immunocompromised patient with particular focus on hematologic and solid organ transplant recipients.MethodsMolecular screening data of CMV, EBV, JCV and BKV from 2011 to 2023 were analyzed. This extensive time span allowed the access to more than 100,000 samples from over 20,000 patients treated at Policlinico Umberto I. It was possible to temporally investigate patient attendance patterns, average age distribution, seasonality of infections, and positivity rates of the analyzed viruses.ResultsBetween 2019 and 2022 a significant reduction in organ transplants performed and in the positive molecular detection of EBV, JCV and BKV was observed. Additionally, there has been a noteworthy decrease in CMV reactivations, with a reduction of up to 50% starting in 2019. A remarkable reduction of 39% in the rate of CMV viral reactivation has been also achieved in SOT between 2016 and 2023.ConclusionThe years following 2019 were profoundly impacted by the COVID-19 pandemic era. This period resulted in a substantial reduction in healthcare services and hospital visits. Furthermore, the introduction of the drug Letermovir in Italy in 2019 demonstrated remarkable efficacy, evidenced by a reduction in CMV reactivations. Additionally, the adoption of a novel clinical approach centered on personalized therapy facilitated improved management of immunocompromised patients.

Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients

BackgroundDeficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6 or JC virus. MethodsHerein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity. Results and ConclusionsOur results demonstrate that posoleucel is enriched for central and effector memory CD4+ and CD8+ T cells with specificity for posoleucel target viruses and expressing a broad repertoire of T cell receptors. Antigen-driven upregulation of cell-surface molecules and production of cytokine and effector molecules indicative of proliferation, co-stimulation, and cytolytic potential demonstrate the specificity of posoleucel and its potential to mount a broad, polyfunctional, and effective Th1-polarized antiviral response upon viral exposure. We also show the low risk for off-target and nonspecific effects as evidenced by the enrichment of posoleucel in memory T cells, low frequency of naive T cells, and lack of demonstrated alloreactivity in vitro. The efficacy of posoleucel is being explored in four placebo-controlled clinical trials in transplant recipients to treat and prevent viral infections (NCT05179057, NCT05305040, NCT04390113, NCT04605484).

Genotypic Detection of Carbapenems Resistance Genes in Acinetobacter baumannii Isolated from Urinary Tract Infection Patients

Acinetobacter baumannii is a Gram-negative bacterium characterized by its short, round, rod-shaped morphology. It is an opportunistic pathogen that poses a significant threat, particularly to immunocompromised patients, often those with hospital stays lasting less than 90 days. Between June 2022 and July 2023, 214 urine samples were collected from individuals suspected of having urinary tract infections (UTIs). These samples were subjected to antibiotic resistance testing, focusing on detecting specific genes related to carbapenem resistance, namely blaNDM, blaKPC, and blaVIM.The study's results revealed a notable trend in antibiotic resistance among the bacterial isolates. Ceftazidime, cefotaxime, and ceftriaxone, commonly used antibiotics for UTIs, showed a high resistance rate among the tested isolates. This resistance highlights the challenges healthcare professionals face when treating UTIs caused by Acinetobacter baumannii. On the other hand, the isolates displayed a comparatively lower resistance rate to imipenem and meropenem, two necessary carbapenem antibiotics. This lower resistance to carbapenems is encouraging as these drugs are often considered the last line of defense against multidrug-resistant bacterial infections. The presence of carbapenem resistance genes, such as blaNDM, blaKPC, and blaVIM, in the Acinetobacter baumannii isolates is of particular concern. These genes confer resistance to carbapenem antibiotics, crucial for treating severe infections caused by multidrug-resistant bacteria. In conclusion, the study aims to study the growth of antibiotic resistance in Acinetobacter baumannii, especially in urinary tract infections in immunocompromised patients with more extended hospital stays. It also highlights the need for Surveys and periodic examinations to detect the spread of bacteria and their resistance. Keywords: Carbapenems, UTI, genes, blaNDM, blaKPC, and blaVIM.