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Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology. [ABSTRACT FROM AUTHOR]

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 2 of 3) summarizes the current state of laboratory and point-of-care diagnostic testing and highlights the expanding role of nucleic acid amplification in the expedited diagnosis and management of patients with acute pharyngitis. It discusses preanalytical, analytical, and postanalytical variables that impact the performance of culture, rapid antigen, and nucleic acid amplification testing. Finally, it sets the stage for part 3, which discusses the emerging role of biomarkers in the management of individuals with acute pharyngitis. [ABSTRACT FROM AUTHOR]

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This article (part 1 of 3) summarizes the impact of acute pharyngitis on the health care system and reviews the etiologic agents of acute pharyngitis, including both emerging and reemerging pathogens that health care providers should consider when evaluating their patients. Finally, it sets the stage for parts 2 and 3, which discuss the current and evolving state of diagnostic testing for acute pharyngitis. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of this study was to determine the short- and long-term outcomes of the non-operative management of acute left-sided complicated diverticulitis (ALCD) in severely immunocompromised patients (IMS group) and compare them with immunocompetent patients (IC group). The secondary aim was to assess the necessity of an elective surgery following a successful prior non-operative management in the IMS group after a non-operative management of the first episode of ALCD. Methods: Patients presented with their first episode of ALCD between 2012 and 2018 were retrospectively reviewed. Only severely immunosuppressed patients were considered for the analysis, including the following: long-term oral or intravenous steroid intake, current malignancy undergoing chemotherapy, chronic kidney disease on hemodialysis, or solid organ transplant with immunosuppressive medication. For each group, demographic data, severity of the episode, management decisions (conservative or operative), and short- and long-term outcomes were recorded and compared. A sub-analysis of patients with ALCD associating and abscess (modified Hinchey classification Ib/II) was performed. Results: A total of 290 patients were included in the study: 50 among the IMS and 240 among the IC group. The rate of emergent surgery was higher in the IMS group (50.0% vs. 22.5%, p < 0.001) and was associated with increased morbidity (72.4% vs. 50.0%, p = 0.041) and mortality (24.1% vs. 4.3%, p = 0.003). The duration of the hospital stay was significantly longer in the IMS group (15 vs. 8 days, p < 0.001). The final stoma rate was significantly higher in the IMS group (82.1% vs. 22.9, p < 0.001), with a median follow-up of 51.4 months. A total of 141 patients presented ALCD with an abscess; 25 in the IMS and 116 in the IC group. There was a higher rate of surgical intervention among the IMS group as the initial treatment approach (24.0% vs. 5.2%, p = 0.002), even though the conservative treatment had a similar rate of success (81.3% vs. 92.0%, p = 0.178). The recurrence rate following a non-operative approach was similar (IMS: 31.2% vs. 35.4% in the IC group, p = 0.169). Furthermore, 81.2% of non-operatively managed IMS patients (13 out of 16) did not require a surgical intervention at the end of the follow-up, with similar findings in the IC group (78/96, 81.2%, p = 0.148). Conclusion: Medical treatment of immunosuppressed patients during their first ALCD episode associated with an abscess is feasible, with a high success rate and results comparable with the IC group. Moreover, taking into account the readmission rates, the need for emergent surgery of the recurrence, and the perioperative mortality and morbidity in the IMS group, conservative management with no differed scheduled surgery seems to be a safe option in this subgroup of patients. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, an antibiotic‐resistant opportunistic pathogen, poses significant challenges in treating infections, particularly in immunocompromised individuals. This review explores current and future innovative approaches to suppress its growth and virulence. We delve into the bacterium's virulence factors, discussing existing strategies like antibiotics, bacteriophages, probiotics, and small‐molecule inhibitors. Additionally, novel approaches, including RNA interference, CRISPR‐Cas systems, and nanotechnology, show promise in preclinical studies. Despite advancements, challenges persist, prompting the need for a multifaceted approach targeting various aspects of P. aeruginosa pathogenesis for effective infection management. This review provides a comprehensive perspective on the status and future directions of innovative strategies against P. aeruginosa. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether mortality differed between initial invasive mechanical ventilation (IMV) or noninvasive ventilation (NIV) followed by delayed IMV in immunocompromised patients with sepsis. DESIGN: Retrospective analysis using the National Data Center for Medical Service claims data in China from 2017 to 2019. SETTING: A total of 3530 hospitals across China. PATIENTS: A total of 36,187 adult immunocompromised patients with sepsis requiring ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality. Patients were categorized into NIV initiation or IMV initiation groups based on first ventilation. NIV patients were further divided by time to IMV transition: no transition, immediate (= 1 d), early (2-3 d), delayed (4-7 d), or late (= 8 d). Mortality was compared between groups using weighted Cox models. Over the median 9-day follow-up, mortality was similar for initial NIV versus IMV (adjusted hazard ratio [HR] 1.006; 95% CI, 0.959-1.055). However, among NIV patients, a longer time to IMV transition is associated with stepwise increases in mortality, from immediate transition (HR 1.65) to late transition (HR 2.51), compared with initial IMV. This dose-response relationship persisted across subgroups and sensitivity analyses. CONCLUSIONS: Prolonged NIV trial before delayed IMV transition is associated with higher mortality in immunocompromised sepsis patients ultimately intubated. [ABSTRACT FROM AUTHOR]

Purpose: Therapeutic drug monitoring (TDM) of voriconazole (VCZ) should be mandatory for all pediatric patients with invasive fungal infections (IFIs). The narrow therapeutic index, inter-individual variability in VCZ pharmacokinetics, and genetic polymorphisms cause achieving therapeutic concentration during therapy to be challenging in this population. Methods: The study included 44 children suffering from IFIs treated with VCZ. Trough concentrations (Ctrough) of VCZ ware determined by the HPLC-FLD method. Identification of the CYP2C19*2 and CYP2C19*17 genetic polymorphisms was performed by PCR–RFLP. The correlation between polymorphisms and VCZ Ctrough was analyzed. Moreover, the effect of factors such as dose, age, sex, route of administration, and drug interactions was investigated. Results: VCZ was administered orally and intravenously at a median maintenance dosage of 14.7 mg/kg/day for a median of 10 days. The VCZ Ctrough was highly variable and ranged from 0.1 to 6.8 mg/L. Only 45% of children reached the therapeutic range. There was no significant association between Ctrough and dosage, age, sex, route of administration, and concomitant medications. The frequencies of variant phenotype normal (NM), intermediate (IM), rapid (RM) and ultrarapid metabolizers (UM) were 41%, 18%, 28%, and 13%, respectively. Ctrough of VCZ were significantly higher in NM and IM groups compared with RM, and UM groups. Conclusion: The Ctrough of VCZ is characterized by inter-individual variability and a low rate of patients reaching the therapeutic range. The significant association exists in children between VCZ Ctrough and CYPC19 phenotype. The combination of repeated TDM and genotyping is necessary to ensure effective treatment. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms. Methods: A retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed. Results: A total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients. Conclusion: Critically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients. [ABSTRACT FROM AUTHOR]

Establishing suitable in vitro culture conditions for microorganisms is crucial for dissecting their biology and empowering potential applications. However, a significant number of bacterial and fungal species, including Pneumocystis jirovecii, remain unculturable, hampering research efforts. P. jirovecii is a deadly pathogen of humans that causes life-threatening pneumonia in immunocompromised individuals and transplant patients. Despite the major impact of Pneumocystis on human health, limited progress has been made in dissecting the pathobiology of this fungus. This is largely due to the fact that its experimental dissection has been constrained by the inability to culture the organism in vitro. We present a comprehensive in silico genome-scale metabolic model of Pneumocystis growth and metabolism, to identify metabolic requirements and imbalances that hinder growth in vitro. We utilise recently published genome data and available information in the literature as well as bioinformatics and software tools to develop and validate the model. In addition, we employ relaxed Flux Balance Analysis and Reinforcement Learning approaches to make predictions regarding metabolic fluxes and to identify critical components of the Pneumocystis growth medium. Our findings offer insights into the biology of Pneumocystis and provide a novel strategy to overcome the longstanding challenge of culturing this pathogen in vitro. Author summary: Pneumocystis jirovecii is a human pathogen that causes life-threatening pneumonia in hundreds of thousands of immunocompromised individuals each year. Neither this fungus nor its close relative, the mouse pathogen Pneumocystis murina, can be cultured in vitro, and this is significantly hindering scientific progress. Therefore, we developed a comprehensive genome-scale metabolic model for P. murina using bioinformatics, software tools, and recently published genome data, and we used this metabolic model to predict critical components required for growth of the fungus. Our findings suggest that a subset of amino acids and specific lipids are essential for Pneumocystis survival. Additionally, we employed non-classical Flux Balance Analysis and Reinforcement Learning approaches to optimise ingredients for a Pneumocystis growth medium. This novel methodology has provided new insights into Pneumocystis metabolism and offers a potential approach to overcoming the challenge of culturing this pathogen in vitro, which would accelerate progress towards the development of improved diagnostics and therapies. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) pose a significant threat to immunocompromised individuals, leading to considerable morbidity and mortality. Prompt and accurate diagnosis is essential for effective treatment. Here we develop a rapid molecular diagnostic method that involves three steps: fungal enrichment using affinity-magnetic separation (AMS), genomic DNA extraction with silicon hydroxyl magnetic beads, and detection through a one-pot system. This method, optimized to detect 30 CFU/mL of C. albicans in blood and bronchoalveolar lavage (BAL) samples within 2.5 h, is approximately 100 times more sensitive than microscopy-based staining. Initial validation using clinical samples showed 93.93% sensitivity, 100% specificity, and high predictive values, while simulated tests demonstrated 95% sensitivity and 100% specificity. This cost-effective, highly sensitive technique offers potential for use in resource-limited clinical settings and can be easily adapted to differentiate between fungal species and detect drug resistance. IFIs pose a significant threat to immunocompromised individuals, and there is an urgent need for rapid and sensitive diagnostic assays. Here, the authors present a rapid molecular diagnostic method based on magnetic fungal enrichment and CRISPR-based detection. [ABSTRACT FROM AUTHOR]

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host's innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during T. gondii infection. In this study, the ROP5 from the PRU strain of T. gondii was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates T. gondii infection and provides new clues for strategies to prevent and control toxoplasmosis. [ABSTRACT FROM AUTHOR]

Early detection of severe acute respiratory syndrome coronavirus 2 infection by diagnostic tests can prompt actions to reduce transmission and improve treatment efficacy, especially for vulnerable groups such as immunocompromised individuals. Recent evidence suggests that sampling the throat in addition to the nose improves clinical sensitivity during early infection for both antigen and molecular coronavirus disease 2019 tests. We urge test manufacturers to validate tests for use with throat swab, in combination with nasal swabs. [ABSTRACT FROM AUTHOR]

Background Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear. Methods This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii , and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result. Results A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease. Conclusions Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week. [ABSTRACT FROM AUTHOR]

The immunocompromised population was disproportionately affected by the severe acute respiratory syndrome coronavirus 2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. Although the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here, we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises. [ABSTRACT FROM AUTHOR]

Background The immunological determinants of delayed viral clearance and intrahost viral evolution that drive the development of new pathogenic virus strains in immunocompromised individuals are unknown. Therefore, we longitudinally studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune responses in relation to viral clearance and evolution in immunocompromised individuals. Methods Among Omicron-infected immunocompromised individuals, we determined SARS-CoV-2–specific T- and B-cell responses, anti-spike immunoglobulin G (IgG) and IgG3 titers, neutralization titers, and monoclonal antibody (mAb) resistance–associated mutations. The 28-day post-enrollment nasopharyngeal specimen defined early (reverse-transcription polymerase chain reaction [RT-PCR] negative ≤28 days) or late (RT-PCR positive >28 days) viral clearance. Results Of 30 patients included (median age, 61.9 [interquartile range, 47.4–72.3] years; 50% females), 20 (66.7%) received mAb therapy. Thirteen (43.3%) demonstrated early and 17 (56.7%) late viral clearance. Patients with early viral clearance and patients without resistance-associated mutations had significantly higher baseline interferon-γ release, and patients with early viral clearance had a higher frequency of SARS-CoV-2–specific B cells at baseline. In non-mAb-treated patients, day 7 IgG and neutralization titers were significantly higher in those with early versus late viral clearance. Conclusions An early robust adaptive immune response is vital for efficient viral clearance and associated with less emergence of mAb resistance–associated mutations in Omicron-infected immunocompromised patients. This emphasizes the importance of early SARS-CoV-2–specific T- and B-cell responses and thereby provides a rationale for development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical surveillance and the lack of predictable seasonal dynamics limit the public health response. Wastewater-based epidemiology (WBE) has recently been used globally as a key metric in determining prevalence of severe acute respiratory syndrome coronavirus 2 in the community, but its application to other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, applying reverse-transcription quantitative polymerase chain reaction and partial G-gene sequencing to track RSV levels and variants in the community. We report increasing detection of RSV in wastewater concomitant with increasing numbers of positive clinical cases. Analysis of wastewater-derived RSV sequences permitted identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance and aid the management of RSV by informing the timely deployment of pharmaceutical and nonpharmaceutical interventions. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The aim of this review was to summarise the current knowledge on host‐related factors that contribute to the development and severity of staphylococcal scalded skin syndrome (SSSS) in children.A comprehensive assessment and analysis of the existing literature on SSSS clinical features, pathogenesis and susceptibility factors.SSSS is a blistering skin disease caused by circulating exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus), almost exclusively affecting infants, young children and immunocompromised individuals. ETs possess serine protease activity and target desmoglein‐1 (Dsg‐1) in the superficial epidermis. While the role of S. aureus ETs and site of action are well‐described, other host factors such as impaired immune responses to ETs, poor renal clearance and genetic factors are crucial for the onset of and/or the severity of SSSS in children.The fate of desmosomal fractions after cleavage by ETs, as well as the role of dermal inflammatory cell infiltrates remain to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Strongyloidiasis a neglected tropical disease is known to cause severe disease among immunosuppressed and has not been studied extensively in Sri Lanka. Parasitological diagnostic approaches based on faecal microscopy and culture often fail to detect low-intensity infections. This study investigates the presence of strongyloidiasis among selected immunocompromised individuals using parasitological, molecular and serological techniques. Methods: Adult patients with immunocompromising conditions admitted to three tertiary care hospitals in Sri Lanka were recruited. A faecal sample and 2 ml of venous blood were collected. The faecal samples were subjected to direct faecal smear and cultures (agar plate, charcoal and Harada-Mori) and polymerase chain reaction (PCR) using species specific primers designed for Strongyloides stercoralis. The presence of Strongyloides IgG antibodies was tested in the collected serum samples using DRG Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) kits. The PCR products of the positive samples were sequenced using Sanger sequencing method. Results: A total of 260 patients were recruited to this study, out of which 160 provided faecal samples and 122 provided blood samples. Out of the 160 faecal samples, none were positive for strongyloidiasis by direct smear, charcoal and Harada-Mori cultures. Only one sample (0.6%) was positive by agar plate culture. Out of the 123 samples subjected to PCR, 14 (11.4%), including the culture positive patient, were positive for S. stercoralis. Sequencing results of the PCR products indicated 100% similarity to S. stercoralis. Out of the 122 serum samples subjected to ELISA, 20 (16.4%), including the culture positive patient, were positive for Strongyloides IgG antibodies. However, sociodemographic, exposure factors, clinical features were not significantly associated with the presence of strongyloidiasis infection. Conclusions: Strongyloidiasis is present among the immunocompromised population in Sri Lanka, even in the absence of a significant relationship with associated factors. It is advisable to screen such patients with highly sensitive tests such as PCR for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains. Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells. Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms Case description: We present a case report of a 56-year-old patient with HAEC1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%. Conclusion: lanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy. [ABSTRACT FROM AUTHOR]

Introduction: With the growing population of immunocompromised individuals, opportunistic fungal pathogens pose a global health threat. Candida species, particularly C. albicans and non-albicans Candida species such as C. glabrata, are the most prevalent pathogenic fungi. Azoles, especially fluconazole, are widely used therapeutic options. Objective: This study investigates how C. glabrata adapts to fluconazole, with a focus on understanding the factors regulating fluconazole tolerance and its relationship to resistance. Methods: This study compared the factors regulating fluconazole tolerance between C. albicans and C. glabrata. We analyzed the impact of temperature on fluconazole tolerance, and requirement of calcineurin and Hsp90 for maintenance of fluconazole tolerance. We isolated colonies from edge, inside and outside of inhibition zone in disk diffusion assays. And we exposed C. glabrata strain to high concentrations of fluconazole and investigated the mutants for development of fluconazole resistance and tolerance. Results: We found temperature modulated tolerance in the opposite way in C. albicans strain YJB-T1891 and C. glabrata strain CG4. Calcineurin and Hsp90 were required for maintenance of fluconazole tolerance in both species. Colonies from inside and outside of inhibition zones did not exhibited mutated phenotype, but colonies isolated from edge of inhibition zone exhibited diverse phenotype changes. Moreover, we discovered that high concentrations (16-128 mg/mL) of fluconazole induce the simultaneous but parallel development of tolerance and resistance in C. glabrata, unlike the sole development of tolerance in C. albicans. Conclusion: This study highlights thatwhile tolerance to fluconazole is a common response in Candida species, the specific molecular mechanisms and evolutionary pathways that lead to this response vary between species. Our findings emphasize the importance of understanding the regulation of fluconazole tolerance in different Candida species to develop effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Identification of the opportunistic fungus Pneumocystis jirovecii in respiratory specimens presents challenges, particularly in differentiating between colonization and active infection. The present study assessed a probe-based real time PCR (qPCR) diagnostic effectiveness in patients with diverse underlying conditions, particularly those with COVID-19 and pulmonary insufficiency. Methods: To set up the qPCR, clinical samples from 281 patients with respiratory ailments were tested. Subsequently, a descriptive study was conducted on 112 patients with pulmonary insufficiency with and without COVID-19 suspected of P. jirovecii infection. All specimens were subjected to DNA extraction followed by nested PCR and qPCR targeting the mitochondrial large subunit (mtLSU)- rRNA gene. Results: Based on nested PCR and qPCR, P. jirovecii was identified in 40 out of 281 patients, with slight variations in positive samples observed across dilutions. Three patients who tested positive in nested PCR yielded negative results in probe-based qPCR. Conversely, three patients who tested positive in probebased qPCR yielded negative results in nested PCR. Considering nested PCR as the golden standard, probe-based qPCR demonstrated good diagnostic performance, with 92.5% sensitivity and 98.7% specificity. Based on cycle threshold (Ct) values, the positive cases were categorized: =32 as infection, >35 as colonization, and a grey zone between these values (32 < X = 35). The analysis of 112 PCP-suspected patients revealed a prevalence ranging from 6.25% (nested PCR) to 7% (probe-based qPCR). Conclusions: This study suggested Ct values to differentiate Pneumocystis pneumonia/colonization in immunocompromised patients. To further augment the diagnostic sensitivity, it is recommended to integrate qPCR results with clinical parameters and biomarkers to offer a more precise understanding of Pneumocystis-related conditions. [ABSTRACT FROM AUTHOR]

Introduction: Capnocytophaga canimorsus is a Gram-negative bacterium found in the oral flora of dogs and cats, transmitted to humans through bites, licks, or scratches. Infections can lead to severe manifestations, including meningitis, particularly in immunocompromised individuals. Case Presentation: A 46-year-old immunocompetent man presented with somnolence, headache, and fever after being licked by his dog. Neurological examination revealed signs of meningeal irritation, and cerebrospinal fluid analysis showed an elevated white cell count and protein levels consistent with bacterial meningitis. Treatment followed Dutch guidelines with amoxicillin, ceftriaxone, and dexamethasone, resulting in rapid clinical improvement. Microbiological confirmation of C. canimorsus followed later. The patient was treated with antibiotics for the duration of 1 week and remained symptom-free after being discharged. Conclusion: C. canimorsus meningitis, although rare, poses diagnostic challenges due to its variable presentation and slow growth in culture. Empirical therapy guided by susceptibility testing contributes to favorable outcomes. This case underscores the importance of considering a C. canimorsus infection in patients with animal exposure and of taking diagnostic findings, precedent, and clinical response into account when determining the treatment duration. [ABSTRACT FROM AUTHOR]

Purpose: Invasive Pulmonary Fungal Infections (IPFIs) represent a diagnostic and therapeutic challenge. The exact role of surgery is not well defined. This study analyzes our experience with surgical treatment of IPFI in immunocompromised pediatric patients and, secondarily, compares IPFI caused by Aspergillus spp. with other fungal infections. Methods: This is a retrospective review (2000–2019) of patients with IPFI surgically treated at our pediatric institution. Statistical analysis was used to compare data between Aspergillus spp. and non-Aspergillus IPFI. Results: Twenty-five patients (64% female) underwent 29 lung resections. Median age at surgery was 7.19 years (1.63–19.14). The most frequent underlying condition (64%) was acute leukemia. Surgical indications included persistence or worsening of symptoms and pathological image findings (52%) or asymptomatic suspicious lesions in patients scheduled for intensive cytotoxic treatments or hematopoietic stem cell transplantation (48%). All patients underwent atypical lung resections, except one lobectomy. Aspergillus spp. was the most frequently isolated pathogen (68%). Follow-up was 4.07 years (0.07–18.07). Surgery-related mortality was 0%, but 4 patients died in the 100 days following surgery (2 due to disseminated fungal infection); the remaining 21 did not show signs of IPFI recurrence. Non-specific consolidations on CT scan were more frequent in non-Aspergillus IPFI (p < 0.05). Conclusion: Surgical treatment of IPFI should be considered as a part of the treatment in selected pediatric immunocompromised patients, and it may have both diagnostic and therapeutic advantages over non-surgical management. When there is clinical suspicion of IPFI but CT scan shows unspecific alterations, the possibility of a non-Aspergillus IPFI should be considered. [ABSTRACT FROM AUTHOR]

Background: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. Methods: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. Results: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). Conclusion: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis. [ABSTRACT FROM AUTHOR]

Background: The potential efficacy of early combination therapy, based on an antiviral plus a monoclonal antibody, for COVID-19 in severely immunocompromised patients is matter of debate. Objectives: Our aim was to describe the impact on clinical outcomes of COVID-19 treatments in severely immunocompromised individuals, evaluating differences between a combination and a monotherapy. Methods: We included severely immunocompromised outpatients with mild-to-moderate COVID-19 who received an early treatment (either monotherapy with nirmatrelvir/ritonavir or remdesivir or the combination of an antiviral plus sotrovimab). We then assessed differences between the two treatment strategies on three main outcomes (30-day mortality, access to emergency department, hospitalization), separately and as a composite by using a propensity score weighted (PSW) approach. Results: Eighty one severely immunocompromised patients were included, 39 receiving early combination therapy and 42 receiving monotherapy. No significant difference was observed in the 30-day mortality rate and hospitalization rate between subjects in the two groups, while access to the emergency department following treatment administration was significantly higher in people who received a combination therapy. After applying the PSW, it was observed that combination therapy impacted favourably on the composite outcome, in a statistically significant fashion. In addition, PSW approach for mortality showed that age was the only significant factor influencing the death as stand-alone outcome. Conclusions: Early combination therapy showed a favourable impact on a composite outcome (including mortality, hospitalizations and access to emergency department) in severely immunocompromised hosts who were all vaccinated. However, further studies are needed to support our results. [ABSTRACT FROM AUTHOR]

Pulmonary cryptococcosis is an uncommon invasive fungal infection of the lungs seen in immunocompromised individuals but increasingly reported among the immunocompetent. We report a rare case of pulmonary cryptococcosis in an immunocompetent host highlighting its unique clinical and radiological presentation. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed HIV‐negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV‐negative immunocompromised patients. Methods: In this retrospective cohort study at the University Health Network, we included all HIV‐negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28‐day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non‐SOT patients. Results: Of 160 non‐HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21–87] years). PCP presentation in SOT recipients (n = 14) was more severe than non‐SOT patients (n = 104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p =.037), shortness of breath (100% vs. 75/104 [74.3%], p =.037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p =.040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p =.044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p =.176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p <.0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p =.0007) in SOT patients was different from non‐SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non‐SOT patients (aOR [CI95%]: 12.25 [3.08–48.62], p <.001). Conclusion: PCP presentation and outcomes in SOT recipients are more severe than in non‐SOT patients. Further studies are required to explore the biological reasons for this difference. [ABSTRACT FROM AUTHOR]

Patients who undergo organ transplantation are advised to use contraception for health optimization, yet limited data exists on safe contraceptive options for this population. This study investigates the infection risk of intrauterine devices (IUDs) in patients who have received a solid organ transplant by evaluating the incidence of pelvic inflammatory disease (PID). We performed a retrospective chart review of subjects with a solid organ transplant who used an IUD between the years of January 2007 to February 2021. We included subjects ages 22–55 years at the time of IUD placement. We abstracted demographic information, transplant type, IUD type, immunosuppressive medications, screening for sexually transmitted infections, and diagnosis of PID. We identified 29 subjects that met the inclusion criteria. Six subjects had a copper IUD (21%) and 23 had a levonorgestrel IUD (79%). The most common organ transplanted was a kidney (n = 10) and liver (n = 10) while five subjects had multiple organs transplanted. Twenty‐five (86.2%) subjects took immunosuppressive medications at the time of IUD insertion. Twenty‐four (82.8%) patients had their IUD placed after transplantation. The average time of IUD use was 2.5 years.. In our study of IUD use in patients with solid organ transplantation, no patients developed PID. IUDs are a safe contraceptive option for immunosuppressed transplant patients. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long‐term SARS‐CoV‐2 infection with the pre‐VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi‐species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS‐CoV‐2 among immunocpromised patients. [ABSTRACT FROM AUTHOR]

Histoplasma capsulatum (H. capsulatum) is considered to be one of the most extensively spread dysmorphic fungi worldwide. Histoplasmosis primarily impacts patients with weakened immune systems and can result in a diverse range of clinical manifestations. In immunocompetent patients, the disease may manifest as a self-limiting or asymptomatic infection; however, in immunocompromised individuals, it can occur as a debilitating, disseminated disease. Diagnosing histoplasmosis may be challenging. A medical professional that specializes in treating endemic fungal illnesses is better able to assist with an accurate and timely diagnosis since they have a deeper grasp of these illnesses. Consequently, the process of diagnosing histoplasmosis might be difficult for less experienced physicians. The case presented is an example of the myriad faces that histoplasmosis can take on, mimicking other common infectious or malignant conditions, leading to extensive work-up and invasive procedures in establishing the diagnosis of this otherwise benign condition. We hereby report the case of disseminated histoplasmosis in a young immunocompetent female patient. [ABSTRACT FROM AUTHOR]

Objectives: The symptoms of herpes simplex viruses type 1 (HSV‐1) infections might be severe and persistent in immunocompromised patients in whom they reactivate at a high frequency. The development of Acyclovir (ACV) resistant strains due to long‐term treatment with antiviral agents in those patients is not uncommon. The aim of the present study was to assess the virucidal effect of commercially available mouthwashes against ACV‐resistant HSV‐1 strains. Materials and Methods: Two acyclovir‐resistant HSV‐1 strains were exposed for 30 s to essential oil‐based (Listerine Fresh Burst® and Listerine Zero®), chlorhexidine gluconate 0.2% (Hexidyl®) and povidone‐iodine 7.5% (Betadine Gargle®) mouthwashes. Loss of virus infectivity was determined by means of plaque reduction assays in a cell culture system. Results: All 4 of the tested solutions significantly reduced virus infectivity, with the essential oil‐based and povidone‐iodine mouthwashes being slightly more efficacious, compared to chlorhexidine. Conclusion: The findings of this analysis revealed that the tested oral rinses demonstrated in‐vitro antiviral activity against ACV‐resistant HSV. Comparative clinical trials are required to establish the clinical effectiveness of daily use of oral rinses in reducing the appearance of oral HSV lesions in immunocompromised patients. [ABSTRACT FROM AUTHOR]

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. Policy statements from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, policy statements from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent. The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. All policy statements from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged #24 months. METHODS: Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. RESULTS: Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occurred through day 151. CONCLUSIONS: Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown. [ABSTRACT FROM AUTHOR]

We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient’s blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients. [ABSTRACT FROM AUTHOR]

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 10 weeks in patient 1 and with levofloxacin alone for 6 weeks 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. [ABSTRACT FROM AUTHOR]

Purpose: Malignant otitis externa (MOE) is a rare form of invasive osteomyelitis of the external ear canal. It is typically caused by Pseudomonas aeruginosa in immunocompromised patients. The diagnosis is clinical, and the initial treatment involves systemic antibiotics or antifungal therapy. Surgery is usually only considered when medical treatment has failed. Although hyperbaric oxygen therapy (HBOT) is recommended for refractory osteomyelitis, there are no specific guidelines for MOE. Methods: This is a retrospective study that evaluates clinical data, treatment, and results obtained in patients diagnosed with MOE treated with HBOT at the Pedro Hispano Hospital between 2007 and 2022. Results: During the study period, fifteen patients diagnosed with MOE were admitted for treatment with HBOT. All patients received antibiotic and/or antifungal therapy, and three required surgical intervention before starting HBOT. The pathology was successfully managed on all patients. Conclusions: HBOT may be an effective adjuvant treatment option in patients with MOE but it lacks robust scientific evidence. However, its therapeutic value should not be underestimated due to the good results and few adverse effects reported in recent retrospective studies and case reports. [ABSTRACT FROM AUTHOR]

A 76-year-old male diagnosed with sarcoidosis presented with atraumatic left anterior knee pain. Initial imaging of the left lower extremity revealed an eccentrically-based lytic lesion in the mid-distal femur with cortical erosion and an additional lytic lesion in the proximal tibia. Magnetic resonance imaging (MRI) demonstrated an aggressive lesion in the proximal tibia with surrounding marrow edema, cortical breach, and erosion into the distal patellar tendon. Given concern for metastatic bone lesions, a18-fluorodeoxyglucose positron emission tomography/computed tomography scan (FDG PET/CT) was performed which demonstrated concordant hypermetabolic lytic lesions at the left mid-distal femur and the left proximal tibia, as well as hypermetabolic diffuse lymphadenopathy. The patient was presumed to have metastatic lung cancer based on the presence of lung nodules. Due to concern for impending pathologic fracture, the patient underwent open biopsy with a plan for prophylactic fixation of both lesions. Intra-operatively, however, both lesions were found to contain pus, from which cultures ultimately grew Cryptococcus neoformans. This is a case of disseminated skeletal cryptococcosis masquerading as metastatic cancer in a patient without classic risk factors for disseminated cryptococcosis (defined as extrapulmonary evidence of infection). Classically, disseminated cryptococcosis is thought to occur in severely immunocompromised patients, such as those with human immunodeficiency virus (HIV) or organ transplant recipients. This case highlights the need to maintain a high index of suspicion in patients with underlying immunocompromising conditions, including less common conditions such as sarcoid, who present with bony lesions. This case report then discusses the diagnostic evaluation and treatment of disseminated skeletal cryptococcosis. [ABSTRACT FROM AUTHOR]

Background: During the ongoing outbreak of clade II monkeypox virus (MPXV), many U.S. patients were prescribed tecovirimat, an antiviral drug that was made available under an expanded access Investigational New Drug (EA-IND) program. We evaluated EA-IND data to summarize characteristics of treated patients, outcomes, and serious adverse events (SAEs). Methods: We evaluated data from patients prescribed tecovirimat from May 29, 2022, through July 10, 2023. Baseline patient characteristics, clinical courses, and outcomes were evaluated via intake forms, outcome forms, and patient diaries. Data were summarized in aggregate by human immunodeficiency virus (HIV) status and by comorbidities of special interest. Reported SAEs were also compiled. Results: Tecovirimat was prescribed for over 7100 patients in the United States, most often for lesions in sensitive anatomical areas, such as certain anogenital lesions (83.5%; 5135 out of 6148 patients), and pain (52.5%; 3227 out of 6148 patients). The demographic and clinical characteristics mirrored those of patients worldwide. Among the 7181 patients with returned intake forms, 1626 also had returned outcome forms (22.6%). Many patients with severe immunocompromise (e.g., HIV with CD4 counts <200 cells/μl) received multiple courses of tecovirimat (43.1%; 22 out of 51 patients), including intravenously, and often experienced poor outcomes (35.3%; 18 out of 51 patients). Overall, 223 SAEs and 40 deaths were reported. Most SAEs were among patients who were severely immunocompromised, one of whom experienced hallucinations after tecovirimat was administered at twice the standard dose. Conclusions: Tecovirimat was used extensively. The returned EA-IND data suggest that life-threatening or protracted infections occurred in persons who were severely immunocompromised. SAEs were not commonly reported. The EA-IND data are not definitive; controlled clinical trial data are essential to elucidating if and how tecovirimat should be used. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. Methods: A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Results: Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Conclusions: Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies. [ABSTRACT FROM AUTHOR]

Objectives: Vaccination is the best preventive measure for SARS-CoV-2 infection; however, efficacy is lower in cancer patients. During the pandemic period, Mexico was characterized by the use of seven different COVID-19 vaccine platforms, and oncologic patients were not prioritized for vaccination. We report the outcomes of COVID-19 in cancer patients after the beginning of the national vaccine campaign in Mexico. Methods: All patients with cancer and COVID-19 diagnosed at Instituto Nacional de Cancerología from 14 February 2021 to 28 February 2022 were included. Primary outcomes were the proportion of individuals who required hospital admission and/or invasive mechanical ventilation, according to the vaccination status; 30-day mortality; the period of infection; and other cancer-related variables. Results: A total of 691 patients were included; 524 (76%) had solid tumors (STs), and 167 (24%) had hematologic malignancies (HMs). Patients infected in the first two periods, had lower rates of vaccination and higher rates of mortality and hospitalization compared to those infected in the Omicron period. In the multivariate analysis, vaccination status was independently associated with hospitalization in patients with STs (aOR 0.38, 95%CI 0.19–0.75, p = 0.005), but it was not associated with invasive mechanical ventilation and 30-day mortality. In those with HMs, vaccination status was not associated with any outcome; in this group, only recent chemotherapy and time of infection were associated with invasive ventilation. Conclusions: Vaccination significantly reduced hospital admissions in patients with STs. Infections occurring during the Omicron period were associated with improved outcomes in both ST and HM patients. Despite having a lesser impact in immunosuppressed patients, vaccination is an essential strategy, and access to vaccination campaigns in patients with cancer needs to be prioritized. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis has a high incidence and a poor prognosis. Early recognition is important to facilitate timely initiation of adequate care. Sepsis screening tools, such as the (quick) Sequential Organ Failure Assessment ((q)SOFA) and National Early Warning Score (NEWS), could help recognize sepsis. These tools have been validated in a general immunocompetent population, while their performance in immunocompromised patients, who are particularly at risk of sepsis development, remains unknown. Methods: This study is a post hoc analysis of a prospective observational study performed at the emergency department. Inclusion criteria were age ≥ 18 years with a suspected infection, while ≥ two qSOFA and/or SOFA criteria were used to classify patients as having suspected sepsis. The primary outcome was in-hospital mortality. Results: 1516 patients, of which 40.5% used one or more immunosuppressives, were included. NEWS had a higher prognostic accuracy as compared to qSOFA for predicting poor outcome among immunocompromised sepsis patients. Of all tested immunosuppressives, high-dose glucocorticoid therapy was associated with a threefold increased risk of both in-hospital and 28-day mortality. Conclusion: In contrast to NEWS, qSOFA underestimates the risk of adverse outcome in patients using high-dose glucocorticoids. As a clinical consequence, to adequately assess the severity of illness among immunocompromised patients, health care professionals should best use the NEWS. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia causes challenging infections in immunocompromised patients, exhibiting increasing resistance to multiple antimicrobials and possessing various virulence genes, including emerging resistance to trimethoprim‐sulfamethoxazole. A total of 80 clinical isolates of S. maltophilia were collected from multiple hospitals in Tehran, Iran. This study conducted an analysis of antibiotic susceptibility by disc diffusion method and E‐test assay, resistance and virulence gene frequencies were examined by PCR‐sequencing, and multilocus sequencing typing (MLST) was performed for strain typing. Across the tested isolates, we observed notably high resistance rates for imipenem 80 (100%), meropenem 78(97.5%), and ceftazidime 72 (90%), while trimethoprim‐sulfamethoxazole (SXT) showed a lower resistance rate of 2 (2.5%). Minocycline and levofloxacin demonstrated the highest susceptibility rates, with 70 (87.5%) and 80 (100%), respectively. The prevalence of antibiotic resistance genes blaL1, and blaL2 was 71 (88.75%) and 76 (95%), respectively. Additionally, the PCR analysis revealed that the frequency of virulence genes (fliC, virB, papD, pilU, hlyIII, stmPr1, and stmPr2) was 78 (97.5%), 77 (96.25%), 58 (72.5%), 77 (96.2%), 76 (95%), 31 (38.75%), and 80 (100%), respectively. Resistance to SXT isolate belong to the sequence type (ST15) and exhibits allelic profiles of (10, 29, 21, 21, 32, 32, and 10). The data obtained from our investigation have indicated that SXT remains an efficacious antibiotic and also highlighted the importance of effective management, identification of resistant isolates, and typing methods to address the global prevalence of antibiotic resistance in S. maltophilia. [ABSTRACT FROM AUTHOR]

Background: Accurate identification of the etiology of lower respiratory tract infections (LRTI) is crucial, particularly for immunocompromised patients with more complex etiologies. The advent of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, assessments of the clinical diagnostic value of targeted NGS (tNGS) in immunocompromised patients with LRTI are limited. Methods: To evaluate the diagnostic value of tNGS in immunocompromised patients with LRTI, a total of 88 patients, of whom 54 were immunocompromised, were enrolled. These patients underwent tNGS testing of bronchoalveolar lavage fluid (BALF). Results from both metagenomic next-generation sequencing (mNGS) and conventional microbiological tests (CMT) were also available for all participants. The performance of tNGS was assessed by comparing its findings against mNGS, CMT, and the clinical composite diagnosis. Results: In the cohort of 88 patients, tNGS showed comparable diagnostic value to mNGS and was significantly superior to CMT. Compared to CMT and composite reference standard, tNGS showed sensitivity of 94.55% and 90.48%, respectively. In immunocompromised patients, despite a more diverse pathogen variety, tNGS maintained similar sensitivity to mNGS and outperformed CMT. tNGS positively influenced etiologic diagnosis and antibiotic decision-making in 72.72% of cases, leading to a change in antibiotic regimen in 17.05% of cases. We also compared the detection of microbial nucleic acids by tNGS with mNGS and found that tNGS could identify 87.99% of the microbial nucleic acids identified by mNGS. Conclusion: In summary, our study demonstrated that tNGS offers promising clinical diagnostic accuracy in immunocompromised patients, as evidenced by its favorable comparison with CMT, the composite reference standard, and mNGS. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to report a case of acute myeloid leukemia (AML) complicated by Aeromonas veronii infection-induced bacteremia and to review relevant literature on the etiology, prevention, treatment, and prognosis of bacteremia in immunocompromised populations, aiming to reduce mortality in individuals with hematologic and other end-stage diseases and improve patient outcomes. Methods and results: We reported the case of a 23-year-old male patient with relapsed AML characterized by AML1:ETO and ASXL positivity, classified as a high-risk group. The patient presented with fever, abdominal pain, diarrhea, nausea, and vomiting after consuming partially cooked fish. The patient was admitted with high leucocytes, C-reactive protein, procalcitonin, and interleukin-6 levels. Peripheral blood high-throughput sequencing (Next-Generation Sequencing NGS) confirmed infection with Aeromonas veronii, while an abdominal CT scan indicated a liver abscess with gas formation. Culture of the drainage fluid from the ultrasound-guided liver abscess puncture demonstrated growth of Aeromonas veronii. Based on the sensitivity results, the patient was treated with intravenous ciprofloxacin and cefoperazone-sulbactam. After treatment with antibiotics, blood transfusion, liver protection, and azacitidine 100 mg ih, combined with dry white sand(interferon alpha-1B, interleukin-2, and thalidomide), the critical condition of the patient improved, and he was discharged. This study was approved by the Ethics Committee of Medical Research in the Second Affiliated Hospital of Henan University of Science and Technology. Informed consent was obtained from this patient and we have obscured the patient's identifying information. All methods were carried out in accordance with relevant guidelines and regulations. Conclusion: When patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) is an infectious disease caused by the gram-positive, anaerobic bacterium C. difficile. The vulnerable populations for CDI include the elderly, immunocompromised individuals, and hospitalized patients, especially those undergoing antimicrobial therapy, which is a significant risk factor for this infection. Due to its complications and increased resistance to treatment, CDI often leads to longer hospital stays. This study aimed to determine the average length of hospital stay (LOS) of Polish patients with CDI and to identify factors affecting the LOS of infected patients. Methods: The study analyzed medical records of adult patients treated with CDI in one of the biggest clinical hospitals in Poland between 2016–2018. Information encompassed the patient's age, LOS results of selected laboratory tests, number of antibiotics used, nutritional status based on Nutritional Risk Screening (NRS 2002), year of hospitalization, presence of diarrhea on admission, systemic infections, additional conditions, and undergone therapies. The systematic collection of these variables forms the foundation for a comprehensive analysis of factors influencing the length of stay. Results: In the study period, 319 patients with CDI were hospitalized, with a median LOS of 24 days (min–max = 2–344 days). The average LOS was 4.74 days in 2016 (median = 28 days), 4.27 days in 2017 (median = 24 days), and 4.25 days in 2018 (median = 23 days). There was a weak negative correlation (Rho = -0.235, p < 0.001) between albumin level and LOS and a weak positive correlation between NRS and LOS (Rho = 0.219, p < 0.001). Patients admitted with diarrhea, a history of stroke or pneumonia, those taking certain antibiotics (penicillins, cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, colistin), and those using proton pump inhibitors, exhibited longer hospitalizations (all p < 0.001) or unfortunately died (p = 0.008). None of the individual predictors such as albumin level, Nutritional Risk Screen, pneumonia, stroke, and age showed a statistically significant relationship with the LOS (p > 0.05). However, the multivariate regression model explained a substantial portion of the variance in hospitalization length, with an R-squared value of 0.844. Conclusions: Hospitalization of a patient with CDI is long. Low albumin levels and increased risk of malnutrition were observed in longer hospitalized patients. Longer hospitalized patients had pneumonia, stroke, or surgery, and were admitted for a reason other than CDI. [ABSTRACT FROM AUTHOR]

Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization. [ABSTRACT FROM AUTHOR]