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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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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: 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]

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]

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]

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]

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]

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]

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]

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]

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: 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]

Background Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. Methods We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir–ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. Results Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], −0.50% points [95% confidence interval {CI}: −.69 to −.35]) and death (0.11% vs 0.30%; RD, −0.20 [95% CI: −.24 to −.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD −2.85 [95% CI: −3.94 to −1.76]), immunocompromised persons (RD −1.91 [95% CI: −3.09 to −.74]), and persons aged ≥75 years (RD −1.16 [95% CI: −1.73 to −.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. Conclusions Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a common and potentially dangerous skin cancer, especially for people with weakened immune systems, like those who have had organ transplants or certain blood cancers. These individuals are up to 100 times more likely to develop cSCC compared with the general population. This review discusses the current treatments for cSCC in these high-risk patients, emphasizing the importance of prevention and the variety of treatment options available. Using high-SPF sunscreen and certain medications can help reduce the chances of developing cSCC. Adjusting the medications that suppress the immune system can also lower the risk. Surgery remains the main treatment, with radiation therapy recommended for more serious cases. Other treatments such as chemotherapy and newer targeted therapies have been used, with mixed results. Immunotherapy, which helps the body's own immune system fight the cancer, shows promise but needs more research to ensure it is safe for these vulnerable patients. This study highlights the need for future research to explore personalized treatment plans and combination therapies to improve outcomes for people with weakened immune systems. Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group. [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]

Hepatitis E virus (HEV) is an important emerging pathogen producing significant morbidity in immunosuppressed patients. HEV has been detrimental to solid organ transplant (SOT) patients, cancer patients, and HIV-positive patients, where chronic HEV infections occur. Blood-borne transfusions and multiple cases of chronic HEV infection in transplant patients have been reported in the past few decades, necessitating research on HEV pathogenesis using immunosuppressed animal models. Numerous animal species with unique naturally occurring HEV strains have been found, several of which have the potential to spread to humans and to serve as pathogenesis models. Host immunosuppression leads to viral persistence and chronic HEV infection allows for genetic adaptation to the human host creating new strains with worse disease outcomes. Procedures necessary for SOT often entail blood transfusions placing immunosuppressive patients into a "high risk group" for HEV infection. This scenario requires an appropriate immunosuppressive animal model to understand disease patterns in these patients. Hence, this article reviews the recent advances in the immunosuppressed animal models for chronic HEV infection with emphasis on pathogenesis, immune correlates, and the liver pathology associated with the chronic HEV infections. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time. Methods: SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time. Case presentation: Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th. Conclusion: Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an important opportunistic bacterium, which its resistant form can induce some complications in immunocompromised patients. The bacterium uses several mechanisms to overcome immune responses and makes a resistant form. Toll like receptors (TLRs) are the most well-known innate immune receptors that play key roles in the induction and stimulation of immune responses against bacteria. Accordingly, it has been hypothesised that Pseudomonas aeruginosa may cause significant interactions with the receptors to be resistance to immune responses and make persistence infection. Thus, the main aim of this review article is to discuss the roles played by toll like receptors in the induction of appropriate immune responses and also induction of the bacterium complications. [ABSTRACT FROM AUTHOR]

Patients before and after lung transplantation often have osteoporosis with existing and recent symptomatic insufficiency fractures, which reduce the quality of life and increase general morbidity and mortality. Due to the reduced bone quality with a significantly increased fracture risk, even low-energy trauma results in the risk of acquiring multiple and complex fractures. The rarefied bone substance can be very challenging for subsequent osteosynthetic treatment. Antiosteoporotic medication is always necessary, and osteoanabolic therapy should be discussed in such cases. In the following, we report about the successful osteosynthetic treatment of an immunosuppressed patient with multiple fractures after a fall from low height. To support fracture healing with antiosteoporotic drug therapy, the patient was switched from antiresorptive to osteoanabolic medication, which resulted in complete fracture consolidation over the course of 6 months. There were also no new insufficiency fractures during this period; however, no improvement in bone density was achieved. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in Individuals with various causes of immunosuppression, including malignancy and treatments form malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to deter- mine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) is associated with its presentation in the pediatric population as roseola infantum. Rarely, it is the causative agent of encephalitis, with most cases reported among the immunocompromised population due to reactivation. This review article analyzes the published records of cases labeled HHV-6 encephalitis in immunocompetent adults, aiming to understand the diagnostic methods behind each case and explore the complexities of such a diagnosis. We note significant variability in the methods used to come to a diagnosis of HHV-6 encephalitis, as well as inconsistent approaches to treatment of this condition. Given the rarity of HHV-6 encephalitis in immunocompetent adults, there are no clearly structured diagnostic guidelines for this condition in this patient population. We highlight several diagnostic methods that provide more convincing evidence of true HHV-6 encephalitis and may provide a basis for further development of guidelines for the diagnosis and treatment of this condition. [ABSTRACT FROM AUTHOR]

Background In immunocompromised individuals, trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis has adverse events, and the optimal dosage is unclear. The objective of this study was to assess efficacy and safety of intermittent versus daily TMP/SMX for PCP prophylaxis. Methods This systematic review included randomized controlled trials (RCTs) indexed in the Cochrane Central Register of Controlled Trials, PubMed, Ichushi, or Embase databases, published from database inception to September 2023. The inclusion criteria were adults taking intermittent or daily TMP/SMX for PCP prophylaxis. Risk of bias was assessed using the Cochrane risk-of-bias tool. The primary outcomes were PCP incidence, PCP-related mortality, and adverse events requiring temporary or permanent TMP/SMX discontinuation. Results Four RCTs (N = 2808 patients) were included. PCP incidence did not differ significantly between the intermittent and daily regimen groups (risk ratio [RR], 1.17 [95% confidence interval {CI},.89–1.53]; certainty: very low). There was no PCP-related mortality in the 3 RCTs reporting its outcome. Compared with the daily regimen group, the intermittent regimen group experienced significantly fewer adverse events requiring temporary or permanent TMP/SMX discontinuation (RR, 0.51 [95% CI,.42–.61]; certainty: low) Conclusions This systematic review and meta-analysis suggests that intermittent TMP/SMX regimens for PCP prophylaxis may be more tolerable than daily regimens and may have similar efficacy. Further RCTs are needed to apply this to current practice. Clinical Trials Registration. PROSPERO (CRD42022359102). [ABSTRACT FROM AUTHOR]

Background Polymicrobial pericarditis is an extremely rare and lethal form of pericarditis. Prompt initiation of appropriate antimicrobial treatment and pericardial drainage are crucial. Case summary A 57-year-old immunocompromised male patient presented to the emergency department due to dyspnoea, chest pain, and fever lasting for 7 days. Following clinical, laboratory, and imaging work-up, he was found to have pericardial effusion with signs of tamponade. After pericardiocentesis through subxiphoid and apical approaches, 800 mL of gross purulent fluid was obtained. Blood and pericardial fluid cultures confirmed the diagnosis of polymicrobial purulent pericarditis (Staphylococcus aureus and Bacteroides vulgatus). Further work-up revealed minor peritoneal effusion, and paracentesis fluid culture revealed the presence of S. aureus and, additionally, Candida albicans. After treatment initiation with intravenous antibiotics, pericardial, drainage and supportive measures, the patient's condition initially improved despite the development of constrictive pericarditis. However, he suddenly deteriorated after 37 days of hospitalization and passed away after 51 days of hospitalization. Discussion To the best of our knowledge, this is the first report of purulent pericarditis and purulent peritoneal effusion in the settings of S. aureus bacteraemia with an absent primary infection focus. Clinicians should be aware of treatment options for purulent pericarditis and consider intrapericardial fibrinolysis, especially in patients not suited for more invasive pericarditis treatment. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19. Case Presentation: We report a case of an immunocompromised patient who was treated for mantle cell lymphoma and was suffering from B-cell depletion. The patient developed persistent COVID-19, which was confirmed by real-time polymerase chain reaction (RT-PCR) tests in only sputum and bronchoalveolar fluid which remained positive for at least 112 days. The patient was successfully treated with SARS-CoV-2 convalescent plasma. Conclusion: It could be of interest to investigate the RT-PCR results of SARS-CoV-2 in sputum/bronchoalveolar lavage samples from immunocompromised patients with unexplained pneumonia. [ABSTRACT FROM AUTHOR]

Objective : Myroides species are mostly low-grade opportunistic pathogens and infect immunocompromised patients. Reports of Myroides spp. increased from clinical samples due to unique developments in molecular microbiology. However, clinical importance of this microorganism in intensive care units' patients is debated. We aimed to determine whether Myroides spp. strains isolated from urinary catheter cultures of patients in intensive care units are led to an infection or colonization by examining the risk factors of the patients between January 2018 and December 2022. Materials and Methods : In a university hospital, the patients who Myroides spp.isolated from urine cultures in intensive care units between January 2018 and December 2022 were included in the study. The method and reasons of taking urine samples, the presence of a urinary catheter, blood cultures samples in terms of urinary sepsis, the antimicrobial susceptibility of the isolates, and hospital stay were evaluated retrospectively. Also, control culture samples were taken after 24 and 72 hours by changing the urinary catheters of these patients. Results:  Thirty-six patients were enrolled to the study. Urine cultures were taken for investigate the source of infection in 23 patients, and nine for control urinary culture and in three patients for macroscopic urine blurred and in one patient to detect colonization before urinary surgery. There was not any blood culture positivity found. All Myroides spp. isolated patients had urinary catheter. Average length of hospital stay was determined as 41.3 days (7-355). A total 34 of the 36 isolated Myroides spp. were pan-drug resistant. Antibacterial treatment was not initiated in any of the patients. Urinary catheters change after first isolation of Myroides spp. was recommended in all patients. After the patients' urinary catheters were changed, Myroides spp. were not grown in the control culture samples taken 24 and 72 hours after. Conclusion : As a result of our study, Myroides spp. were isolated especially in patients with long hospital stays and urinary catheters. It was determined that the patients were controlled without treatment, only with urinary catheter replacement. We believe that this agent should be evaluated as having a very high rate of urinary colonization, and the urinary catheter should be changed first, urinary symptoms should be followed up, and unnecessary antimicrobial use should be avoided. [ABSTRACT FROM AUTHOR]