Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia.

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18-30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5-10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

Emerging Fungal Pathogen Rhodotorula Species Isolated From a Patient With a Lung Malignancy.

Rhodotorula is a genus of ubiquitous pigmented yeast found in the environment and as a commensal of human and animal microbiota. Previously considered nonpathogenic, Rhodotorula has emerged as an important cause of nosocomial and opportunistic infections in susceptible patients. While Rhodotorula spp. are common commensals in healthy individuals, the yeast may overgrow in patients with compromised immune systems causing disease. Herein, we provide a detailed presentation of a rare case involving a 79-year-old Caucasian female with a lung malignancy who developed massive cavitations in her lungs. The patient's lung tissue was cultured and grew an unidentified species of the genus Rhodotorula. The patient's health declined rapidly, and she expired due to hypoxemia. Clinicians must recognize patient groups potentially at risk for infection with Rhodotorula spp. Early identification and initiation of appropriate interventions are crucial in reducing mortality associated with this opportunistic fungal infection.

"Click" amphotericin B in prodrug nanoformulations for enhanced systemic fungemia treatment.

Severe nephrotoxicity and infusion-related side effects pose significant obstacles to the clinical application of Amphotericin B (AmB) in life-threatening systemic fungal infections. In pursuit of a cost-effective and safe formulation, we have introduced multiple phenylboronic acid (PBA) moieties onto a linear dendritic telodendrimer (TD) scaffold, enabling effective AmB conjugation via boronate chemistry through a rapid, high yield, catalysis-free and dialysis-free "Click" drug loading process. Optimized AmB-TD prodrugs self-assemble into monodispersed micelles characterized by small particle sizes and neutral surface charges. AmB prodrugs sustain drug release in circulation, which is accelerated in response to the acidic pH and Reactive Oxygen Species (ROS) in the infection and inflammation. Prodrugs mitigate the AmB aggregation status, reduce cytotoxicity and hemolytic activity compared to Fungizone®, and demonstrate superior antifungal activity to AmBisome®. AmB-PEG5kBA4 has a comparable maximum tolerated dose (MTD) to AmBisome®, while over 20-fold increase than Fungizone®. A single dose of AmB-PEG5kBA4 demonstrates superior efficacy to Fungizone® and AmBisome® in treating systemic fungal infections in both immunocompetent and immunocompromised mice.

An Observational Study of Fungal Infections in COVID-19: Highlighting the Role of Mucormycosis in Tertiary Healthcare Settings.

Background Fungal infections, especially mucormycosis, have remarkably surged during the coronavirus disease 2019 (COVID-19) era, especially during the second wave peak of the pandemic raising the concern of the clinicians for the admitted patients. Steroid therapy, diabetes, and other immunocompromised states are more commonly associated with COVID-19-associated mucormycosis (CAM). Aim and objective The aim of this study is to ascertain the prevalence of fungal infections amidst the second wave of the COVID-19 pandemic and discern the associated risk factors. Materials and methods During the second peak of COVID-19, samples were received in the microbiology laboratory from all clinically suspected mucormycosis patients. These samples underwent processing for potassium hydroxide (KOH) wet mount, fungal culture on Sabouraud's dextrose agar (SDA) medium, and COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) testing. All relevant clinical and associated risk factors were tabulated and analyzed. Results Among the 107 suspected cases of mucormycosis, 39 (36.4%) were confirmed positive for COVID-19 via RT-PCR, while 68 (63.6%) tested negative. Males exhibited a predominant infection rate, with the rhinocerebral system being the most commonly affected site. Significantly higher mortality rates were observed in COVID-19-associated mucormycosis (CAM) patients (33.4%) compared to those without COVID-19 (5.9%), with a notable p-value of 0.0005. CAM patients also demonstrated a higher frequency of ICU admissions (77%) compared to non-COVID-19-associated mucormycosis patients (21.4%), a statistically significant finding (p-value of 0.007). Additionally, immunocompromised states, diabetes, and the administration of oxygen therapy were identified as significant risk factors in CAM (p < 0.05). Notably, mucormycosis accounted for the majority of fungal isolates (48.27%) among COVID-19 patients. Conclusion Mucormycosis infection is more commonly seen in COVID-19-infected patients as compared to non-COVID-19 patients, especially with comorbidities such as diabetes mellitus, steroid usage, and other immunocompromised states.

Increased susceptibility to Mycobacterium avium complex infection in miniature Schnauzer dogs caused by a codon deletion in CARD9.

Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility to MAC infections in a canine breed. Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait. A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9. Whole genome sequencing of 2 MAC-infected dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide ß-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1. While CARD9-deficient knockout mice are susceptible to experimental challenges by fungi and mycobacteria, Miniature Schnauzer dogs with systemic MAC susceptibility represent the first spontaneous animal model of CARD9 deficiency, which will help to further elucidate host defense mechanisms against mycobacteria and fungi and assess potential therapies for animals and humans.

Disseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review.

BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. CASE PRESENTATION: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.

Exploring Sociodemographic Factors in Allergic Fungal Rhinosinusitis in a Northern California Patient Population.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis (CRS) that has previously been associated with younger age and Black patients. However, the role of demographic and socioeconomic factors in AFRS severity remains to be fully elucidated. OBJECTIVE: The objective of this study was to determine whether demographic and socioeconomic factors are associated with incidence of AFRS, as well as with disease severity in Northern California. METHODS: A retrospective cohort study was conducted of adult patients with AFRS and CRS from 2010 to 2019. AFRS was determined by the Bent and Kuhn criteria, and severity was assessed by radiographic evidence of cranioorbital invasion and other clinical parameters. Chi-square and t-test were used to assess demographic and socioeconomic differences between AFRS and CRS cohorts, and multivariable logistic regression was used to assess risk factors for severe AFRS. RESULTS: Black patients represented 26.2% (55/210 patients) of the AFRS group and 4.9% (842/17,300 patients) of the CRS group, with pairwise comparison of race/ethnicity categories showing that the AFRS group had significantly higher proportions of Black race/ethnicity compared with other race/ethnicities (p < 0.01). AFRS and CRS groups differed significantly by age, with mean ages of 48.7 and 51.0 years, respectively (p = 0.04). There were no significant differences in gender, Medicaid status, comorbidities, and socioeconomic status measures. Multivariate logistic regression showed that Black patients had higher odds of having severe AFRS (adjusted odds ratio = 2.29; 95% confidence interval: 1.18-4.45). CONCLUSION: AFRS has a unique predilection for Black patients, and severe disease is also more likely in this population.

Endemic Fungal Infective Endocarditis Caused by Coccidioides, Blastomyces and Histoplasma Species in the United States.

We describe a recent case of Coccidioides bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of endemic fungal infective endocarditis in the United States caused by Coccidioides, Blastomyces, and Histoplasma. Symptoms preceded infective endocarditis diagnosis by several months. Patients with Coccidioides and Blastomyces infective endocarditis were younger with fewer comorbid conditions. Valvular involvement was relatively uncommon in Blastomyces infective endocarditis (27%). Fungemia was noted in patients with infective endocarditis due to Histoplasma (30%) and Coccidioides (18%). Mortality rates for infective endocarditis were high (Histoplasma, 46%; Coccidioides, 58%; Blastomyces, 80%); infective endocarditis was commonly diagnosed post-mortem (Coccidioides, 58%; Blastomyces, 89%). Most surviving patients with infective endocarditis (Histoplasma, 79%; Coccidioides, 80%) underwent valve surgery along with prolonged antifungal therapy. The two surviving patients with Blastomyces infective endocarditis received antifungal therapy without surgery.

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells.

Monocyte-derived dendritic cells (MDDCs) are key players in the defense against fungal infection because of their outstanding capacity for non-opsonic phagocytosis and phenotypic plasticity. Accordingly, MDDCs rewire metabolism to meet the energetic demands for microbial killing and biomass synthesis required to restore homeostasis. It has been commonplace considering the metabolic reprogramming a mimicry of the Warburg effect observed in tumor cells. However, this may be an oversimplification since the offshoots of glycolysis and the tricarboxylic acid (TCA) cycle are connected in central carbon metabolism. Zymosan, the external wall of Saccharomyces cerevisiae, contains ß-glucan and α-mannan chains that engage the C-type lectin receptors dectin-1/2 and Toll-like receptors. This makes it an optimal fungal surrogate for experimental research. Using real-time bioenergetic assays and [U-13C]glucose labeling, central hubs connected to cytokine expression were identified. The pentose phosphate pathway (PPP) exhibited a more relevant capacity to yield ribose-5-phosphate than reducing equivalents of NADPH, as judged from the high levels of isotopologues showing 13C-labeling in the ribose moiety and the limited contribution of the oxidative arm of the PPP to the production of ROS by NADPH oxidases (NOX). The finding of 13C-label in the purine ring and in glutathione unveiled the contribution of serine-derived glycine to purine ring and glutathione synthesis. Serine synthesis also supported the TCA cycle. Zymosan exhausted NAD+ and ATP, consistent with intracellular consumption and/or extracellular export. Poly-ADP-ribosylated proteins detected in the nuclear fractions of MDDCs did not show major changes upon zymosan stimulation, which suggests its dependence on constitutive Fe(II)/2-oxoglutarate-dependent demethylation of 5-methylcytosine by TET translocases and/or demethylation of histone H3 lysine 27 by JMJD demethylases rather than on NOX activities. These results disclose a unique pattern of central carbon metabolism following fungal challenge, characterized by the leverage of glycolysis offshoots and an extensive recycling of NAD+ and poly(ADP-ribose).

Liposomal amphotericin for secondary prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. METHOD: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed. RESULT: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively. CONCLUSION: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.

High prevalence of dermatophytosis of the feet in acral melanoma of the foot.

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis.

Surgical procedures for the treatment of fungal periprosthetic infection following hip arthroplasty: a systematic scoping review.

Background: There has been limited literature synthesizing the therapeutic effects of surgical procedures for fungal periprosthetic joint infection (PJI) following hip arthroplasty. The authors' current study aims to comprehensively review and analyze those relevant literature, and carefully make recommendations for future clinical practices. Methods: Our current study was carried out in accordance with the PRISMA 2020 statement. Studies regarding the surgical management of fungal PJI following hip arthroplasty were collected via a thorough search of PubMed, Embase and Google scholar databases. The search was lastly performed in March 2023. Non-English language, reviews, articles with duplicated data, and articles without clear information about the type of fungal pathogens and treatment options were excluded. The authors evaluated their systematic review compliance by using AMSTAR 2 criteria and fell in moderate quality. Clinical outcomes of different surgical procedures were evaluated, and a binary logistic regression model was used to identify the risks associated with treatment failure. Data analyses were performed using the SPSS version 19.0. Results: A total of 33 articles encompassing 80 patients with fungal PJI following hip arthroplasty were identified. Candida albicans was the most frequently isolated fungus (56.3%, 45/80). The overall treatment success was achieved in 71.1% (54/76) of the reported cases. Univariate analysis showed that the differences of success rate were not significant between publication periods, genders, ages, specimen collection methods, and fungal pathogens. Treatment success rate was 47.4% (9/19) in fungal PJI cases with bacterial co-infection, significantly lower than those without [vs. 79.0% (45/57), P=0.017]. The pooled success rate for surgical debridement, spacer implantation, resection arthroplasty, one-stage revision, and two-stage revision was 50.0% (4/8), 42.9% (3/7), 55.0% (11/20), 86.7% (13/15), and 88.5% (23/26), respectively, with significant differences between them (P=0.009). A binary logistic regression model showed that bacterial co-infection and surgical option were the two significant risk factors associated with treatment failure for fungal PJI following hip arthroplasty. Discussion: Regarding the surgical treatment of fungal PJI following hip arthroplasty, patients with bacterial co-infection, and those treated with surgical procedures such as debridement, spacer implantation, and resection arthroplasty should be aware of the higher risks of failure. Nonetheless, future multiple-centre cohort studies are required to establish the optimal treatment.

Survival from Rhino-Orbital-Cerebral Mucormycosis in SARS-CoV-2-Positive Diabetic Patients: Two Case Reports.

Introduction: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare angioinvasive fungal infection known to be associated with high morbidity and over 50% mortality. ROCM is becoming more common due to an increase in predisposing immunocompromising comorbidities as well as COVID-19. Case Presentations: We report 2 cases - a 75-year-old woman with diabetes and a 39-year-old man with recurrent diabetic ketoacidosis. Both presented initially with acute sinonasal symptoms, were positive for SARS-CoV-2, and diagnosed with acute ROCM. Both underwent mutilating surgical therapy as well as high-dose amphotericin B treatment. With continued oral antifungal treatment, patient 1 showed stable symptoms despite radiographically increasing disease and died of urosepsis 5 months after first surgery. With posaconazole treatment, patient 2 recovered from the disease and showed no clinical sign of disease progression after 1 year. Conclusion: Despite the rarity of the disease, ROCM should be considered if the findings of clinical and radiological examination fit, so that a delay in treatment initiation can be avoided. As our both cases show, survival from ROCM is possible - albeit at a high cost.

Pathological caudal skeleton of an ichthyodectiform fish from the Upper Cretaceous Niobrara Formation of western Kansas, USA.

A series of 12 contiguous caudal vertebrae of an ichthyodectiform fish from the Smoky Hill Chalk Member of the Niobrara Formation is described. The vertebral centra exhibit extensive overgrowth of pathological bone and there is additional pathological bone within the centra and intervertebral spaces, which together resulted in the coossification of most centra. The extent of the pathology is greatest on preural vertebrae 1-3 and decreases anteriorly, which suggests that the pathology began posteriorly and progressed anteriorly. In addition to the pathological overgrowth on bones, the specimen preserves features interpreted as calcified and/or ossified soft tissues associated with the neural and haemal canals. The pathologies are unlike previously described examples of bony pathologies in fish, and it is suggested that they resulted from combined bacterial and fungal infections. As the pathologies developed, they would have adversely impacted the fish's swimming and feeding abilities, and presumably eventually led to the fish's death.

Atypical Pleural Effusion in an Immunocompetent Patient With Valley Fever: A Case Study and Review of the Literature.

Valley fever is a fungal infection, commonly of the lungs, caused by Coccidioides immitis or Coccidioides posadasii. This disease is endemic to the southwestern United States, Central America, and South America. Infected individuals are typically asymptomatic but may develop community-acquired pneumonia. On rare occasions, coccidioidomycosis can present with severe complications in addition to the pulmonary manifestation. In this study, a 58-year-old immunocompetent male presented to the Emergency Department with a cough, night sweats, and pleuritic chest pain. Despite the administration of broad-spectrum antimicrobials, he developed a large right pleural effusion that did not resolve following thoracentesis. Serology was positive for Coccidioides, and the patient was referred to a thoracic surgeon due to persistent effusion. It is rare for patients with coccidiomycosis to develop a large pleural effusion requiring surgical intervention, especially in immunocompetent individuals. This case highlights the importance of monitoring patients with unresolved acute pneumonia in endemic areas and considering Coccidioides as a possible etiology.

Cutaneous Mucormycosis in Buffalos in the Brazilian Amazon Biome.

This is the first description of cutaneous mucormycosis in buffalo in the Brazilian Amazon biome. All buffalo showed apathy, inappetence, weight loss, reluctance to move, and prolonged sternal decubitus. Of the four affected animals, two died 15 and 30 days after the appearance of clinical signs. In the initial phase, the skin lesions were rounded areas with dry central regions, sensitive to palpation, with protruding edges and diameters ranging from 8 cm to 15 cm. These areas of necrosis were isolated or coalescing and present mainly on the limbs and sides. In an advanced stage of the disease, there was detachment of the skin from the necrotic areas with extensive wound formation, which sometimes exposed the subcutaneous tissue. The histopathology of the skin showed a multifocal inflammatory infiltrate composed of intact and degenerated eosinophils surrounded by epithelioid macrophages. At the center of these areas was a focally extensive area of epidermal ulceration characterized by intact and degenerated neutrophils, the necrosis of epithelial cells, and the accumulation of fibrin and erythrocytes. The mycological culture was positive for Rhizopus sp. The diagnosis of cutaneous dermatitis caused by Rhizopus sp. was based on clinical signs, macroscopic and histopathological findings, and the identification of the fungus by mycological and molecular techniques.

Development and validation of machine learning-based models for predicting healthcare-associated bacterial/fungal infections among COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work. OBJECTIVE: We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection. METHODS: In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability. RESULTS: A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769. CONCLUSIONS: Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies.

INTRODUCTION: The incidence of invasive fungal diseases (IFDs) has risen in hematologic malignancy patients due to neutropenia. While posaconazole is recommended as the first-line antifungal prophylaxis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and voriconazole is an alternative, there is currently no direct comparison data available to assess their relative effectiveness. METHOD: We retrospectively reviewed eligible patient charts from January 2017 to February 2019 to identify breakthrough IFD rates, drug adverse event frequency, and drug acquisition cost in AML/MDS patients. RESULTS: Forty-eight patients received 130 chemo cycles, with 50 (38%) cycles prescribed posaconazole and 80 (62%) prescribed voriconazole as primary IFD prophylaxis. The incidence rates of IFD in the posaconazole group were 8% (4 out of 50), of which two were probable and two were possible infections, while 6.26% (5 out of 80) of patients in the voriconazole group developed IFD, with four possible infections and one probable infection (p = 0.73). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events, with six patients compared to two patients in the posaconazole group (p = 0.15). The drug acquisition cost of posaconazole is 5.62 times more expensive than voriconazole. CONCLUSION: The use of voriconazole instead of posaconazole for 130 chemo cycles would save $166,584.6. Posaconazole and voriconazole have comparable efficacy and safety in preventing IFD in AML and MDS patients receiving chemotherapy. However, posaconazole is more costly than voriconazole.

Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.

Background: Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. Methods: In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Results: Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. Conclusions: A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.