scholarly journals Mucormycosis: Literature review and retrospective report of 15 cases from Portugal

2021 ◽  
Author(s):  
Beatriz Prista-Leao ◽  
Isabel Abreu ◽  
Ana Claudia Carvalho ◽  
Antonio Sarmento ◽  
Lurdes Santos
Keyword(s):  
Infectious Diseases ◽  
Central Nervous System Involvement ◽  
Invasive Fungal Disease ◽  
Outcome Data ◽  
Therapeutic Drug ◽  
Anatomical Location ◽  
Therapeutic Approaches ◽  
Gastrointestinal Infections ◽  
Duration Of Symptoms ◽  
Electronic Hospital

Background and Purpose: Prevalence of mucormycosis is growing with the increase of the population at risk. Current recommendations for its management are mostly based on retrospective studies. 3 study aimed to present the cumulative experience of an Infectious Diseases Department from a Portuguese hospital in the management of mucormycosis and discuss the potential gaps in the diagnostic and therapeutic approaches of this infection. Materials and Methods: For the purposes of the study, the electronic hospital database was searched for adult patients with mucormycosis from 1996 to 2019 based on the definition provided by the Consensus Definitions of Invasive Fungal Disease. Demographic, clinical, treatment, and outcome data were collected and compared to what had been described in the related literature. Results: In total, 15 cases of mucormycosis were found, including 11 cases with sinus involvement (10 with central nervous system involvement), two pulmonary, and two gastrointestinal infections. Diabetes mellitus (n=7) and corticosteroid therapy (n=7) were frequent risk factors. Median duration of symptoms before the suspicion of diagnosis was 26 days (3-158). The diagnosis was confirmed in 12 patients mostly by histopathology (n=9); the culture was positive only once. Systemic antifungals and surgical debridement were the backbones of treatment; however, side effects, the need for therapeutic drug monitoring, and the anatomical location of lesions added complexity to management. Overall, seven patients died, two of them before the consideration of clinical suspicion. Conclusion: More medications are becoming available for the treatment of mucormycosis. Nevertheless, we believe that its prognosis will only significantly change through the increase of awareness and reduction of the time to diagnosis. An effective multidisciplinary approach among surgeons, infectious diseases specialists, radiologists, microbiologists, and anatomopathologists is critical to the achievement of this goal.

The impact of an electronic hospital system on therapeutic drug monitoring

2021 ◽  
Author(s):  
Paul Firman ◽  
Karen Whitfield ◽  
Ken‐Soon Tan ◽  
Alexandra Clavarino ◽  
Karen Hay
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Hospital System ◽  
The Impact ◽  
Electronic Hospital

Special Issue on "Immunomodulatory and therapeutic approaches against infectious diseases"

2011 ◽  
Vol 1 (5) ◽  
pp. 1-2
Author(s):  
Lavkush Dwivedi
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Human Health ◽  
Immune Stimulation ◽  
Defense System ◽  
Special Issue ◽  
Therapeutic Approaches ◽  
Major Constraint ◽  
The World ◽  
Insight Into

Infectious diseases and consequent immune imbalancesare major constraint in human health managementthroughout the world. However, in recentdecades enormous efforts have been made to elucidatethe immunomodulatory approaches againstinfectious diseases. Immunomodulation is a therapeuticapproach in which we try to intervene inauto regulating processes of the defense system toadjust the immune response at a desired level.The present special issue on cutting edge issues inImmunomodulation like Immune stimulation, Immunesuppression, Immune potentiating and immunereinforcement summarizes our current understandingof this complex mosaic. The accompanyingselection of recent articles from across theworld provides further insight into this topic. 

Isavuconazole: Case Report and Pharmacokinetic Considerations

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 253-256 ◽  
Author(s):  
Francesco Marchesi ◽  
Corrado Girmenia ◽  
Bianca Maria Goffredo ◽  
Emanuela Salvatorelli ◽  
Atelda Romano ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Real Life ◽  
Concomitant Administration ◽  
Invasive Fungal Disease ◽  
High Plasma ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Hepatic Toxicity ◽  
Maintenance Chemotherapy

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a “probable” IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

Functions and potential of lipocalin-2 as fecal biomarker for acute gastrointestinal infections (review of literature)

2021 ◽  
Vol 66 (6) ◽  
pp. 371-373
Author(s):  
Ekaterina Dmitrievna Lyutsova ◽  
M. D. Gospodinova ◽  
Y. D. Bocheva
Keyword(s):  
Infectious Diseases ◽  
Structure Function ◽  
Acute Diarrhea ◽  
Morbidity And Mortality ◽  
Diagnosis And Treatment ◽  
Lipocalin 2 ◽  
Review Of Literature ◽  
Gastrointestinal Infections ◽  
Non Invasive ◽  
Intestinal Infections

Despite the visible progress in reducing morbidity and mortality from intestinal infections and acute diarrhea associated with them, especially in childhood, the problem of their diagnosis and treatment remains relevant. The article discusses the structure, function and application of lipocalin-2 in infectious diseases as a non-invasive biomarker of bacterial inflammation in the intestine.

scholarly journals Nasopharyngeal Microbiota Profiles in Rural Venezuelan Children Are Associated With Respiratory and Gastrointestinal Infections

2020 ◽  
Author(s):  
Lilly M Verhagen ◽  
Ismar A Rivera-Olivero ◽  
Melanie Clerc ◽  
Mei Ling J N Chu ◽  
Jody van Engelsdorp Gastelaars ◽  
...  
Keyword(s):  
Treatment Options ◽  
Therapeutic Approaches ◽  
Gastrointestinal Infections ◽  
Differential Abundance ◽  
Associated Bacteria ◽  
16S Sequencing ◽  
Forest Models ◽  
Random Forest Models ◽  
Tract Infections ◽  
Klebsiella Spp

Abstract Background Recent research suggests that the microbiota affects susceptibility to both respiratory tract infections (RTIs) and gastrointestinal infections (GIIs). In order to optimize global treatment options, it is important to characterize microbiota profiles across different niches and geographic/socioeconomic areas where RTI and GII prevalences are high. Methods We performed 16S sequencing of nasopharyngeal swabs from 209 Venezuelan Amerindian children aged 6 weeks–59 months who were participating in a 13-valent pneumococcal conjugate vaccine (PCV13) study. Using random forest models, differential abundance testing, and regression analysis, we determined whether specific bacteria were associated with RTIs or GIIs and variation in PCV13 response. Results Microbiota compositions differed between children with or without RTIs (P = .018) or GIIs (P = .001). Several species were associated with the absence of infections. Some of these health-associated bacteria are also observed in developed regions, such as Corynebacterium (log2(fold change [FC]) = 3.30 for RTIs and log2(FC) = 1.71 for GIIs), while others are not commonly observed in developed regions, such as Acinetobacter (log2(FC) = 2.82 and log2(FC) = 5.06, respectively). Klebsiella spp. presence was associated with both RTIs (log2(FC) = 5.48) and GIIs (log2(FC) = 7.20). Conclusions The nasopharyngeal microbiota of rural Venezuelan children included several bacteria that thrive in tropical humid climates. Interestingly, nasopharyngeal microbiota composition not only differed in children with an RTI but also in those with a GII, which suggests a reciprocal interplay between the 2 environments. Knowledge of region-specific microbiota patterns enables tailoring of preventive and therapeutic approaches.

scholarly journals Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3256 ◽  
Author(s):  
Alessandro Rizzo ◽  
Simona Tavolari ◽  
Angela Dalia Ricci ◽  
Giorgio Frega ◽  
Andrea Palloni ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Anatomical Location ◽  
Therapeutic Approaches ◽  
Extrahepatic Cholangiocarcinoma ◽  
Future Directions ◽  
Molecular Features ◽  
Heterogenous Group ◽  
Systemic Treatments ◽  
Molecular Landscape ◽  
Hepatobiliary Tumors

Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions.

scholarly journals An Overview on ERAP Roles in Infectious Diseases

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 720 ◽  
Author(s):  
Irma Saulle ◽  
Chiara Vicentini ◽  
Mario Clerici ◽  
Mara Biasin
Keyword(s):  
Infectious Diseases ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Therapeutic Approaches ◽  
Optimal Length ◽  
Mhc I ◽  
Control Factors ◽  
Histocompatibility Complex ◽  
Toxoplasma Gondii Infection ◽  
Deficient Mice

Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8+ T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.

scholarly journals Opioids and Infectious Diseases: A Converging Public Health Crisis

2019 ◽  
Vol 220 (3) ◽  
pp. 346-349 ◽  
Author(s):  
Tara A Schwetz ◽  
Thomas Calder ◽  
Elana Rosenthal ◽  
Sarah Kattakuzhy ◽  
Anthony S Fauci
Keyword(s):  
Public Health ◽  
Infectious Diseases ◽  
Opioid Use Disorder ◽  
Soft Tissue Infections ◽  
Opioid Use ◽  
Therapeutic Approaches ◽  
Predisposing Factor ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Immunodeficiency Virus

Abstract A converging public health crisis is emerging because the opioid epidemic is fueling a surge in infectious diseases, such as human immunodeficiency virus infection with or without AIDS, the viral hepatitides, infective endocarditis, and skin and soft-tissue infections. An integrated strategy is needed to tailor preventive and therapeutic approaches toward infectious diseases in people who misuse and/or are addicted to opioids and to concurrently address the underlying predisposing factor for the infections—opioid use disorder. This commentary highlights the unique and complementary roles that the infectious diseases and substance use disorder communities can play in addressing this crisis of dual public health concerns.

A Prospective Study of Voriconazole Therapeutic Drug Monitoring (TDM) in Patients with Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1018-1018
Author(s):  
Jack Seki ◽  
Joseph Brandwein ◽  
Richard Ward ◽  
Narinder Paul ◽  
Heather Russell ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Clinical Outcomes ◽  
Invasive Fungal Disease ◽  
Response To Therapy ◽  
Therapeutic Drug ◽  
Consolidation Chemotherapy ◽  
Oral Medications ◽  
A Prospective Study ◽  
Kinetics Of ◽  
Slow Metabolizers

Abstract Abstract 1018 Poster Board I-40 Background: Voriconazole (VOR) is an expanded spectrum azole that is often used to treat suspected or proven invasive aspergillosis (IA). VOR plasma drug levels are not routinely monitored and their correlation with clinical response and toxicity is unclear. We sought to clarify the kinetics of levels in patients started on VOR and their relationship with CYP2C19 genotype and clinical outcomes. Methods: We prospectively enrolled inpatients undergoing induction or consolidation chemotherapy for AML who were able to take oral medications and started on VOR for suspected invasive aspergillosis (IA). All patients received an initial intravenous loading dose of 6mg/kg bid for two doses, then 200mg bid. VOR dose could be increased at the physician's discretion. Trough VOR levels (μg/mL) were monitored at days 0,2,4,6 and performed using HPLC. Patients also underwent genotyping for CYP2C19. Clinical and radiologic responses were graded independently by two physicians. Hepatotoxicity was correlated to peak VOR levels. Results: We enrolled 33 patients of which 60.6% were male and 39.4% female. Mean age was 60.2±15.4 yrs. The distribution of peak VOR levels was as follows: <2 μg/mL (n=6); 2-6 μg/mL (n=22); >6 μg/mL (n=5). Mild hepatotoxicity (liver enzymes greater than 2x baseline) was seen in 6/22 (27.2%) of patients with levels between 2-6 μg/mL and 1/5 (20%) of patients with levels >6 μg/mL. No hepatotoxicity was noted in those with peak VOR <2 μg/mL. No significant correlation was seen in mg/kg dose of VOR and levels. Of the 33 patients, 19 (57.6%) met the EORTC/MSG criteria for possible, probable, or proven invasive fungal disease. Of these 9 (47.4%) patients had a response to therapy. Mean peak VOR levels in responders vs. nonresponders was 3.78 vs. 3.12 (p=0.63). Response to therapy was 2/2 (100%) if levels were <2 μg/mL, 6/14 (42.9%) if levels were 2-6 μg/mL, and 1/3 (33%) if levels were >6 μg/mL. Breakthrough infections occurred in 5/33 (15.2%) patients given VOR, all of whom had peak levels between 2-6 μg/mL. Genotyping was performed on 11/33 (33.3%) patients and included slow metabolizers (n=5; median peak VOR 3.0), rapid metabolizers (n=5; median peak VOR 3.0) and undetermined (n=1). Genotype did not correlate with clinical outcomes. Conclusions: The majority of patients attained voriconazole levels > 2 μg/mL by day 6 of treatment. Voriconazole levels do not appear to predict response to therapy or breakthrough infection although mild hepatotoxicity can occur if levels are >2 μg/mL. Disclosures: Seki: Astellas: Honoraria; Pfizer: Honoraria; Merck: Consultancy, Honoraria, Research Funding. Kumar:Merck: Honoraria; Pfizer: Honoraria.

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