Influence of hypoxic conditions on Trichosporon asahii virulence in a Galleria mellonella infection model.

Background: Immunosuppression is encountered in patients with oncologic, transplant, and autoimmune disorders. The purpose of this study is to provide guidance for physicians treating surgical hand and upper extremity (UE) infections in immunosuppressed (IS) patients. Methods: We retrospectively reviewed our database of patients presenting with UE infections over 3 years. IS patients were matched randomly to non-IS patients. Patient background, infection presentation, surgical evaluation, and microbiology variables were recorded. Infection variables included mechanism, location, and type. Outcomes included inpatient length of stay (LOS) and need for repeat drainage. Results: We identified 35 IS and 35 non-IS out of 409 UE infection patients. Patients most commonly had a hematologic malignancy (34%) as their IS class, and the most frequent immunosuppressive medication was glucocorticoids (57%). IS patients were more likely to be older and less likely to have a history of drug abuse or hepatitis C virus infections. IS infections were more likely to have idiopathic mechanisms, more likely to involve deeper anatomy such as joints, bone, tendon sheath, or muscle/fascia, and less likely to present with leukocytosis. IS cultures more commonly exhibited atypical Mycoplasma or fungus. There was no difference between IS and non-IS patients regarding LOS or recurrent drainage. Conclusions: Mechanism and white blood cell count are less reliable markers of infection severity in IS patients. Physicians treating infections in IS patients should maintain a higher suspicion for deeper involved anatomy and atypical microbiology. Nonetheless, with careful inpatient management and closer surveillance, outcomes in IS patients can approach that of non-IS patients.

Cryptococcal infection in non-HIV immunosuppressed patients – Three case reports in a nephrology setting

This retrospective study evaluated the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for detecting infections in immunosuppressed CKD patients. Data from immunosuppressed CKD patients who were suspected of having an infection and admitted to Jinling Hospital from 2018-2022 were retrospectively analyzed. The patients were divided into the conventional microbiological testing (CMT)-confirmed infection group (Group I), clinically diagnosed infection group (Group II), and exclusion of infection group (Group III), and the efficiencies of microbiological detection with mNGS and CMT were compared. In the 303 patients included in this study, 2 (1, 3) types of immunosuppressants were used for a median duration of 7 (2, 50) months. In Group I, 38.79% of the mNGS results were completely consistent with the CMT results, 27.88% were partially consistent, and 33.33% were inconsistent. In Group II, 57.69% of the infecting pathogens were detected by mNGS. Furthermore, 2 patients in Group III had positive NGS results. mNGS outperformed CMT in terms of the time to a positive test and the detection of mixed or rare microbial pathogens (p < 0.05). The sensitivity and accuracy of the detection of infectious pathogens were greater for mNGS than for CMT (p = 0.014). mNGS can improve the sensitivity and accuracy of infectious pathogen detection in immunosuppressed CKD patients. mNGS is a promising emerging technique for detecting pathogens in CKD patients, with potential benefits in speed and sensitivity, and may provide more diagnostic evidence for the detection of mixed, opportunistic, and rare infectious pathogens.

A model for HCMV infection in immunosuppressed patients

The regulation of fungal cell wall biosynthesis is crucial for cell wall integrity maintenance and directly impacts fungal pathogen virulence. Although numerous genes are involved in fungal cell wall polysaccharide biosynthesis through multiple pathways, the underlying regulatory mechanism is still not fully understood. In this study, we identified and functionally characterized a direct downstream target of SomA, the basic-region leucine zipper transcription factor MeaB, playing a certain role in Aspergillus fumigatus cell wall integrity. Loss of meaB reduces hyphal growth, causes severe defects in galactosaminogalactan-mediated biofilm formation, and attenuates virulence in a Galleria mellonella infection model. Furthermore, the meaB null mutant strain exhibited hypersensitivity to cell wall-perturbing agents and significantly alters the cell wall structure. Transcriptional profile analysis revealed that MeaB positively regulates the expression of the galactosaminogalactan biosynthesis and β-1,3-glucanosyltransferase genes uge3, agd3, and sph3 and gel1, gel5, and gel7, respectively, as well as genes involved in amino sugar and nucleotide sugar metabolism. Further study demonstrated that MeaB could respond to cell wall stress and contribute to the proper expression of mitogen-activated protein kinase genes mpkA and mpkC in the presence of different concentrations of congo red. In conclusion, A. fumigatus MeaB plays a critical role in cell wall integrity by governing the expression of genes encoding cell wall-related proteins, thus impacting the virulence of this fungus.IMPORTANCEAspergillus fumigatus is a common opportunistic mold that causes life-threatening infections in immunosuppressed patients. The fungal cell wall is a complex and dynamic organelle essential for the development of pathogenic fungi. Genes involved in cell wall polysaccharide biosynthesis and remodeling are crucial for fungal pathogen virulence. However, the potential regulatory mechanism for cell wall integrity remains to be fully defined in A. fumigatus. In the present study, we identify basic-region leucine zipper transcription factor MeaB as an important regulator of cell wall galactosaminogalactan biosynthesis and β-1,3-glucan remodeling that consequently impacts stress response and virulence of fungal pathogens. Thus, we illuminate a mechanism of transcriptional control fungal cell wall polysaccharide biosynthesis and stress response. As these cell wall components are promising therapeutic targets for fungal infections, understanding the regulatory mechanism of such polysaccharides will provide new therapeutic opportunities.

ABSTRACTInfections with Scedosporium spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be correlated with their multidrug resistance. The development of alternative treatment strategies has become crucial. Here, we investigate the in vitro and in vivo activity of luliconazole (LLCZ) against Scedosporium apiospermum (including its teleomorph Pseudallescheria boydii) and Lomentospora prolificans. The LLCZ MICs were determined for a total of 37 isolates (31 L. prolificans isolates, 6 Scedosporium apiospermum/P. boydii strains) according to EUCAST. Furthermore, the LLCZ antifungal activity was tested in vitro, using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] growth kinetics assay and biofilm assays (crystal violet and XTT assay). In addition, a Galleria mellonella infection model was used for in vivo treatment assays. The MIC90 of LLCZ was determined to be 0.25 mg/L for all tested pathogens. Growth was inhibited within 6 to 48 h of the start of incubation. LLCZ inhibited biofilm formation in both preadhesion stages and late-stage adhesion. In vivo, a single dose of LLCZ increased the survival rate of the larvae by 40% and 20% for L. prolificans and Scedosporium spp., respectively. This is the first study demonstrating LLCZ activity against Lomentospora prolificans in vitro and in vivo and the first study showing the antibiofilm effect of LLCZ in Scedosporium spp.IMPORTANCELomentospora prolificans and S. apiospermum/P. boydii are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. Lomentospora prolificans is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. Our study shows the effect of luliconazole (LLCZ) against L. prolificans and Scedosporium spp. in vitro, as well as in an in vivo infection model. These data reveal the previously unknown inhibitory effect of LLCZ against L. prolificans and its antibiofilm effect in Scedosporium spp. It represents an extension of the literature regarding azole-resistant fungi and could potentially lead to the development of future treatment strategies against these opportunistic fungal pathogens.

Human cytomegalovirus (CMV) and varicella zoster virus (VZV) are two herpes viruses associated with severe infections in immunosuppressed or immunodeficient patients. For example, bone marrow transplant recipients are especially susceptible to CMV infections and juvenile leukemia patients are vulnerable to VZV infections (Gershon, 1980; Meyers et al, 1986). Three approaches are used to control these infections: antiviral drugs, active immunization with attenuated viruses, and passive immunization with hyperimmune immunoglobulin preparations. Two nucleoside analogs, 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG) and acyclovir (ACV), have recently been studied for treatment of CMV infections. Although DHPG (Koretz, et al, 1986) and, in some cases, ACV (Balfour, et al, 1982), have some efficacy in treating CMV-infected patients, their use is limited by toxic effects and neither is effective against CMV pneumonia (Wade, et al, 1982; Myers, 1985). Antiviral drug therapy against severe VZV infections, however, is more promising. Both ACV and vidarabine, for example, are effective in reducing the severity of VZV infections in immunosuppressed patients (Vilde, et al, 1986).

The Risk of HBV Breakthrough Infection in Immunosuppressive Patients with High Ratio of HBcAb-Positive Blood Components Transfusion

Radiosensitization of hypoxic tumor cells in vitro by nitric oxide

Microbial Translocation and Infectious Diseases: What Is the Link?

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is associated with high mortality in immunosuppressed patients. Few studies have correlated serum viral load with histopathological findings in this setting. Gastrointestinal biopsies from 28 immunosuppressed patients showing CMV cytopathic effect were studied by immunohistochemistry (IHC) and in situ hybridization (ISH). Quantitative evaluation of CMV-infected cells was correlated with clinicopathologic data, including plasma PCR. 85.7% (24/28) of our patients had detectable viremia. Viral load did not correlate with concentration of CMV-infected cells in tissue, type of infected cell (endothelial, epithelial, smooth muscle, or stromal), microscopic mucosal ulceration, CMV inclusions in multiple sites within the GI tract, endoscopic findings, or presence of systemic symptoms. All PCR-negative cases (4/28) occurred in late onset CMV infection or disease. Most cases of biopsy-proven GI CMV infection and disease are associated with positive viremia by plasma PCR. We found no correlation between viral load and any of the clinicopathologic parameters analyzed in our study. Some cases of late-onset CMV infection and disease may have no detectable CMV viremia by PCR. Key words: Cytomegalovirus (CMV), immunohistochemistry, in situ hybridization, gastrointestinal.

Chapter 9 - Respiratory infections in immunosuppressed patients

Induction of mutations in V79-4 mammalian cells under hypoxic and aerobic conditions by the cytotoxic 2-nitroimidazole-aziridines, RSU-1069 and RSU-1131: The influence of cellular glutathione

Background: Saprochaete clavata infection is an emerging issue in immunosuppressed patients, causing fulminant fungaemia. The purpose of this systematic review of cases is to retrieve all cases of S. clavata infection and describe oral lesions as the first manifestation of S. clavata infection. Methods: We report the first case of intraoral S. clavata infection in Acute Myeloid Leukemia (AML) affected subject, presenting as multiple grayish rapidly growing ulcerated swellings, and provide a review of all published cases of infection caused by S. clavata, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, conducted by searching SCOPUS, Medline, and CENTRAL databases. Only articles in English were considered. Individual patient data were analyzed to identify risk factors for S. clavata infection. Results: Seventeen of 68 retrieved articles were included in the review reporting data on 96 patients (mean age 51.8 years, 57 males and 38 females). Most cases were disseminated (86) with a 60.2% mortality rate. Ninety-five were hematological patients, with AML being the most common (57 cases). Conclusions: S. clavata infection in immunosuppressed patients has a poor prognosis: middle-age patients, male gender and Acute Myeloid Leukemia should be considered risk factors. In immunosuppressed patients, the clinical presentation can be particularly unusual, imposing difficult differential diagnosis, as in the reported case.

Tuberculosis in immunosuppressed patients