Clinical experience with SUBA-itraconazole at a tertiary paediatric hospital

2020 ◽  
Vol 76 (1) ◽  
pp. 249-252
Author(s):  
Joanne Abbotsford ◽  
David A Foley ◽  
Zoy Goff ◽  
Asha C Bowen ◽  
Christopher C Blyth ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Dose Adjustment ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Paediatric Hospital ◽  
Oral Formulations ◽  
Cutaneous Fungal Infection

Abstract Background Itraconazole remains a first-line antifungal agent for certain fungal infections in children, including allergic bronchopulmonary aspergillosis (ABPA) and sporotrichosis, but poor attainment of therapeutic drug levels is frequently observed with available oral formulations. A formulation of ‘SUper BioAvailability itraconazole’ (SUBA-itraconazole; Lozanoc®) has been developed, with adult studies demonstrating rapid and reliable attainment of therapeutic levels, yet paediatric data are lacking. Objectives To assess the safety, efficacy and attainment of therapeutic drug levels of the SUBA-itraconazole formulation in children. Methods A single-centre retrospective cohort study was conducted, including all patients prescribed SUBA-itraconazole from May 2018 to February 2020. The recommended initial treatment dose was 5 mg/kg twice daily (to a maximum of 400 mg/day) rounded to the nearest capsule size and 2.5 mg/kg/day for prophylaxis. Results Nineteen patients received SUBA-itraconazole and the median age was 12 years. The median dose was 8.5 mg/kg/day and the median duration was 6 weeks. Indications included ABPA (16 patients), sporotrichosis (1), cutaneous fungal infection (1) and prophylaxis (1). Of patients with serum levels measured, almost 60% (10/17) achieved a therapeutic level, 3 with one dose adjustment and 7 following the initial dose. Adherence to dose-adjustment recommendations amongst the seven patients not achieving therapeutic levels was poor. Of patients with ABPA, 13/16 (81%) demonstrated a therapeutic response in IgE level. SUBA-itraconazole was well tolerated with no cessations related to adverse effects. Conclusions SUBA-itraconazole is well tolerated in children, with rapid attainment of therapeutic levels in the majority of patients, and may represent a superior formulation for children in whom itraconazole is indicated for treatment or prevention of fungal infection.

Utility of Voriconazole Monitoring and Factors Affecting Its Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation. Single Center Experience From India.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3035-3035
Author(s):  
Gautam Goyal ◽  
Vikram Gota ◽  
Pravin Patil ◽  
Dileep Kumar Achuta ◽  
Libin Mathew ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Fungal Infections ◽  
Conditioning Regimen ◽  
Therapeutic Drug ◽  
Loading Dose ◽  
Large Variability ◽  
Hematopoietic Stem ◽  
Factors Affecting ◽  
Autologous Transplant ◽  
Trough Levels

Abstract Abstract 3035 Background: Voriconazole (vori) is used for prophylaxis against fungal infections in BMT. Under and over-dosing of vori may influence the efficacy and safety of therapy, respectively. There is large variability in vori exposure following standard dose administration. Utility of Therapeutic Drug Monitoring (TDM) of vori in patients with invasive mycoses has been demonstrated and recommended that trough concentrations should be maintained between 1–5.5 μg/mL. Based on these observations we started TDM of vori in BMT patients at our centre to target trough plasma concentration of 1–6 μg/mL. Few reports are available on the TDM of vori in BMT. We report our experience. Methods: All patients (autologous-65, allogeneic-64) who received vori prophylaxis during peritransplant period between September 2008 and January 2012 were included. Vori prophylaxis was started atleast 3 days prior to start of conditioning regimen in all patients before April 2011. Since April 2011, patients undergoing autologous transplant received vori 1 day after completion of chemotherapy. All patients above 12 years received oral loading dose of 6 mg/kg (upto maximum of 400 mg) 12 hourly on first day followed by 4mg/kg as maintenance. Intravenous dosing was used if patients had severe mucositis or developed febrile neutropenia. Patients less than 12 years received 7mg/kg 12 hourly continuously. Vori levels were measured on 5th-7th day after start of loading dose. Subsequent levels were done 2– 4 weekly till discontinuation of drug. If first level was < 1 or > 6 μg/ml, each dose was increased or decreased by 50% respectively and levels repeated after a week. Vori was continued for at least 100 days for all patients undergoing allogeneic transplant and longer if patients were on steroids due to graft vs host disease. Autologous transplant patients received it for 28 days. Incidence of breakthrough fungal infection was recorded as definite (blood culture positivity or histological evidence), probable (CT scan evidence with positive fungal PCR or galactomannan positivity) or possible (CT evidence only). Demographic and laboratory factors affecting the levels evaluated were age, sex, height, weight, body surface area (BSA), liver and renal function parameters. Concomitant drugs being used were recorded for any effect on vori levels. Vori levels in plasma were determined by a validated HPLC assay. Paired samples were compared using t-test or Wilcoxin sign rank test. Influence of covariates on vori levels were analyzed by linear regression with backward elimination. Interaction between concomitant drugs and their effects on vori levels was determined by ANCOVA after adjusting for baseline values. Results: One hundred twenty-nine patients were monitored during this period. The median age was 24.6 years. The median number of TDM was 3 (1–32) per patient. High inter and intra-patient variability was observed (coefficient of variation = 73% and 45% respectively). Twenty-eight patients (21.7%) had trough levels < 1 μg/mL after the first monitoring. Twenty-one patients had their dose modified after first monitoring (16 due to very low levels and 5 due to high levels). Thirteen (80%) patients achieved target trough concentration after dose escalation. Dose reduction resulted in sub-optimal levels in 3 of 5 patients. Twenty – four patients who had adequate levels at first TDM had fall in level below 1 μg/mL subsequently during the 2nd or 3rd TDM. This coincided with the introduction of steroids for treatment. Introduction of steroids significantly reduced vori trough levels (presteroid mean- 2.67 μg/ml, post steroid mean- 1.47μg/ml; P=0.014).Similarly use of cyclosporine (CSA) also significantly decreased vori levels (pre CSA mean-2.65μg/ml, post CSA mean-1.91μg/ml; P=0.023). The effect of steroids and CSA on vori levels were independent of each other. None of the demographic or laboratory parameters influenced vori levels. Breakthrough fungal infections were seen in 5 patients (definite-1, probable-3, possible-1). Conclusions: Voriconazole level monitoring should be done in all patients who are on steroids and CSA post transplant. No demographic or laboratory parameter affected voriconazole levels in our study. Incidence of breakthrough fungal infection is low in patients who are monitored with drug levels. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Estimated burden of fungal infections in Kenya

2016 ◽  
Vol 10 (08) ◽  
pp. 777-784 ◽  
Author(s):  
John Abuga Guto ◽  
Christine C Bii ◽  
David W Denning
Keyword(s):  
At Risk ◽  
Fungal Infection ◽  
Tinea Capitis ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Epidemiological Studies ◽  
High Rate ◽  
Asthma Prevalence ◽  
Populations At Risk

Introduction: Kenya is a developing country with a high rate of tuberculosis (TB) and a moderate HIV infection burden. No estimate of the burden of fungal diseases in Kenya is published. Methodology: We used specific populations at risk and fungal infection frequencies from the literature to estimate national incidence or prevalence of serious fungal infections. Used sources were: 2010 WHO TB statistics, Kenya Acquired Immunodeficiency Syndrome (AIDS) Epidemic Update 2012, Kenya Facts and figures 2012, Kenya Demographic and Health Survey 2008-2009. Results: Of Kenya’s population of ~40 million, 43% are under 15 years old and approximately 594,660 Kenyan women get >4 episodes Candida vulvovaginitis annually (2,988/100,000). The HIV/AIDS population at risk of opportunistic infections (OI) is 480,000 and the OI estimates include 306,000 patients with oral thrush (768/100,000), 114,000 with oesophageal candidiasis (286/100,000), 11,900 with cryptococcal meningitis (29/100,000) and 17,000 patients with Pneumocystis pneumonia (42/100,000). Chronic pulmonary aspergillosis following TB has a prevalence of 10,848 cases (32/100,000). The adult asthma prevalence is 3.1% and assuming 2.5% have allergic bronchopulmonary aspergillosis then 17,696 (44/100,000) are affected.  Invasive aspergillosis, candidaemia and Candida peritonitis are probably uncommon. Tinea capitis infects 9.6% of children in Kenya, while fungal keratitis and otomycoses are difficult to estimate. Conclusion: At any one time, about 7% of the Kenyan population suffers from a significant fungal infection, with recurrent vaginitis and tinea capitis accounting for 82% of the infections. These estimates require further epidemiological studies for validation.

scholarly journals Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Alan Chin ◽  
Steven A. Pergam ◽  
David N. Fredricks ◽  
Andrew N. Hoofnagle ◽  
Kelsey K. Baker ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Medical Condition ◽  
Solid Organ Transplantation ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

ABSTRACT The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

scholarly journals A pharmacoepidemiology study of local fungal infections in skin and venereal diseases outpatient department of a rural tertiary care hospital

2020 ◽  
Vol 9 (4) ◽  
pp. 616
Author(s):  
Preety Bansal ◽  
Seema Baishnab
Keyword(s):  
Fungal Infection ◽  
Fungal Infections ◽  
Tertiary Care ◽  
Antifungal Drugs ◽  
Care Hospital ◽  
Dermatology Department ◽  
Number Of Patients ◽  
Common Skin ◽  
Cutaneous Fungal Infection ◽  
Number Of Males

Background: Fungal infections of the skin were the 4th most common skin disease in 2010 affecting 984 million people. An estimated 20-25% of the world’s population has some form of fungal infection. Dermatophytes are fungi that cause superficial infections of the skin, commonly referred to as tinea infections.Methods: This was a prospective and an observational study conducted from February 2018 to January 2019 in Dermatology Department. Prescriptions included all newly diagnosed patients with cutaneous fungal infection of both sex who attended dermatology OPD. Factors considered were sociodemographic parameters, the disease encountered and number of patients in each group and number of patients who received antifungal therapy (oral and topical) etc.Results: 1000 prescriptions were analysed of patients between 18 to 65 years of age with cutaneous fungal infections. There were a greater number of males (57.4%) than females (42.6%). The average number of antifungal drugs prescribed per prescription was 2.33. Majority of the patients were prescribed itraconazole (82.30%) followed by terbinafine (9.70%) and fluconazole (8.0%).Conclusions: The most common oral antifungal drug used was itraconazole. Ketoconazole and Terbinafine were the most commonly used topical agents respectively.

Important Infections Due To Molds

2018 ◽  
Author(s):  
Timothy Ando
Keyword(s):  
Invasive Aspergillosis ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Antibody Therapy ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Intravenous Route ◽  
Dematiaceous Fungi ◽  
Liver Function Testing

Mold-based fungal infections have become increasingly important over several decades, paradoxically because advances in medical practice have allowed patients with chronic medical conditions to live longer and have lives that are more productive. Allergic bronchopulmonary aspergillosis can affect those individuals with an atopic predisposition. Use of direct antimold antifungal agents can decrease the number of steroid treatment courses and monoclonal antibody therapy used in these patients. Pulmonary invasive aspergillosis remains the most important opportunistic mold infection among immunocompromised patients. Surrogate markers of diagnosis can include β-d-glucan or Aspergillus galactomannan antigen testing, although the specificity of both tests is not robust. There are three general classes of antifungal agents in use, with less nephrotoxic options. With safer therapeutic options, empirical treatment occurs with tremendous frequency among otherwise immunosuppressed individuals. Thus, clinicians will need to maintain a high suspicion for mold infections that can be resistant to a previously used antifungal therapy. Attention to liver function testing during long-term use of these advanced-generation azole antifungal agents, and at times therapeutic drug monitoring with blood levels, will be needed. The echinocandin class of antifungal agents does not have hepatic or renal toxicity in general, but these agents need to be administered via an intravenous route. With routine use of agents that have activity against aspergillosis, fusariosis, mucormycosis, or other mold infections become evident for a minority of at-risk patients. This review contains 5 figures, 3 tables and 90 references Key words: allergic bronchopulmonary aspergillosis, dematiaceous fungi, Exserohilum, fusariosis, invasive aspergillosis, mucormycosis, Scedosporium

Monitoring Plasma Voriconazole Levels May Be Essential To Avoid Subtherapeutic Levels.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 594-594
Author(s):  
S. Trifilio ◽  
G. Pennick ◽  
J. Pi ◽  
J. Zook ◽  
M. Golf ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Fungal Infections ◽  
Pharmacokinetic Profile ◽  
Hematologic Malignancies ◽  
Therapeutic Drug ◽  
Extensive Metabolizers ◽  
Therapeutic Success ◽  
Drug Levels ◽  
Days Of Therapy ◽  
Multiple Drugs

Abstract There are limited data on the effects of drug levels on therapeutic success in fungal infections. Low itraconazole trough levels have been associated with breakthrough fungal infections (Glasmacher et al. Mycoses1999;42:443–51). Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections (Smith et al. Antimicrob Agents Chemother2006;50:1570–2). Success rate in patients with mean voriconazole plasma levels &lt;0.5 μg/mL was 46% compared to 56% with mean plasma levels &gt;0.5 μg/mL (www.fda.gov/ohrms/dockets/ac/01/briefing/3792b2_02_FDA-voriconazole.htm). The period after HSCT is characterized by the use of multiple drugs that can affect the liver cytochrome P450 system. The CYP450 isoenzyme 2C19 plays a significant role in voriconazole metabolism, and exhibits significant genetic polymorphism. Homozygous extensive metabolizers have a significantly lower exposure to voriconazole than heterozygous extensive metabolizers and poor metabolizers. Steady-state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1–5 levels per patient; median 2). Most patients had undergone allogeneic HSCT. Drug levels were monitored using HPLC (Pennick et al. Antimicrob Agents Chemother2003;47:2348–50). The daily voriconazole dose (divided into 2) was 200 mg (n=4), 400 mg (n=151), 500 mg (n=20), 600 mg (n=18), and 800 mg (n=8); corresponding to 2.0–16.3 mg/kg (median 5.4). The voriconazole levels were &lt;0.2–12.5 μg/mL (median 1.2). In keeping with the non-linear pharmacokinetic profile of the drug, a strong correlation was not seen between the dose and levels (figure). Figure Figure The table below shows the relationship between levels and dose. While the amount of drug administered in mg/kg was significantly higher when the levels were &gt;5.0 μg/mL, there was no consistent relationship between dose and level below that threshold. Voriconazole level n Dose (mg) Dose (mg/kg) P (Dose in mg/kg; compared to the &gt;5.0 level group) &lt;0.2 (undetectable) 30 (15%) 400 (200–800) 5.6 (3.5–11.5) 0.008 0.2–0.5 25 (12%) 400 (400–800) 6.2 (3.8–10.2) 0.18 &gt;0.5 to 2.0 70 (35%) 400 (400–800) 5.2 (3.7–13.3) 0.062 &gt;2.0 to 5.0 53 (26%) 400 (400–800) 4.9 (2.0–9.8) 0.0008 &gt;5.0 23 (11%) 400 (400–800) 6.9 (3.4–16.3) These data show that in adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on the data on the FDA files, 27% of these levels would be associated with a lower likelihood of response. Based on the data of Smith et al, 65% of these levels would be associated with a higher likelihood of failure. We suggest that future voriconazole studies should incorporate prospective therapeutic drug monitoring, and that pending further clarification, consideration should be given to checking levels in patients receiving the drug for confirmed, life-threatening fungal infections.

scholarly journals Relationship Between Acanthosis Nigricans and Fungal Infection: Clinical and Histopathological findings

2021 ◽  
pp. 1-7
Author(s):  
Joon Woo Jung ◽  
Eun Hye Hong ◽  
Eun Joo Park ◽  
Kwang Joong Kim ◽  
Kwang Ho Kim
Keyword(s):  
Fungal Infection ◽  
Medical Records ◽  
Acanthosis Nigricans ◽  
Fungal Infections ◽  
Fungal Spores ◽  
Skin Condition ◽  
Skin Changes ◽  
Clinical Difference ◽  
Cutaneous Fungal Infection ◽  
The Relationship

Background: Acanthosis nigricans (AN) is a skin condition that presents clinically with hyperpigmented, hyperkeratotic, and velvety skin changes, especially in the intertriginous areas. The intertriginous areas are also susceptible to superficial cutaneous fungal infections. The potential relationship between AN and cutaneous fungal infection has not been investigated. Objective: The aim of this study was to determine the relationship, if any, between AN and fungal infection, both clinically and pathologically. Methods: A retrospective review was performed using electronic medical records and histology of biopsy slides obtained from 29 patients who were diagnosed with AN by two dermatopathologists. Comparison was made between the clinical and pathological findings of AN with fungal infection (ANFI+) and AN without fungal infection (ANFI-). Results: Among the 29 patients with AN, fungal spores were detected on the biopsy slides of 18 patients (62.1%) and appeared in the epidermal furrow more often than in the epidermal ridge. No significant clinical difference was found between the ANFI+ and ANFI- groups; however, in the ANFI+ group, lesions were more prevalent in the neck area (p = 0.048). In addition, the ANFI+ biopsy slides revealed more papillomatosis than ANFI- biopsy slides (p = 0.006). Conclusion: Fungal infection tends to appear in combination with AN when more severe papillomatosis is also present.

scholarly journals The burden of serious fungal infections in Azerbaijan

2021 ◽  
Vol 8 ◽  
pp. 204993612110439
Author(s):  
Ravil M. Huseynov ◽  
Samir S. Javadov ◽  
Ali Osmanov ◽  
Shahin Khasiyev ◽  
Samira R. Valiyeva ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Epidemiological Data ◽  
Chronic Obstructive ◽  
Reference Laboratory ◽  
Adult Women ◽  
Cd4 Cell Count ◽  
Using Data ◽  
Oesophageal Candidiasis

Background: Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km2 and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels. Methods: Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling. Results: The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count <200 µl–1 we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15–55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC). Discussion: In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved via establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays.

scholarly journals Real-Life Assessment of the Safety and Effectiveness of the New Tablet and Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal Infections via Analysis of 343 Courses

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Frank P. Tverdek ◽  
Sang Taek Heo ◽  
Samuel L. Aitken ◽  
Bruno Granwehr ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Hematological Malignancy ◽  
Fungal Infections ◽  
Real Life ◽  
Serum Levels ◽  
Invasive Fungal Infections ◽  
Life Assessment ◽  
Cancer Center ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Grade 3

ABSTRACT Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. Delayed-release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis for patients with hematological malignancy. A retrospective cohort of all consecutive adult inpatients with hematological malignancy who received ≥3 days of tablet or intravenous posaconazole therapy for primary IFI prophylaxis at the M. D. Anderson Cancer Center between 1 December 2013 and 31 December 2015 was established. Clinical information was collected and correlated with low posaconazole serum levels (<700 ng/ml). Rates of IFIs and safety events were assessed. A total of 1,321 courses of posaconazole were administered at the M. D. Anderson Cancer Center during the study period, of which 343 courses were assessed for prophylactic safety and effectiveness. Seventy-nine patients (23%) had posaconazole serum level measurements available for interpretation. Acute myeloid leukemia was the primary malignancy (62%), with 20% of all patients having previously received a stem cell transplant. The median posaconazole level was 1,380 ng/ml (interquartile range, 864 to 1,860 ng/ml). Low posaconazole levels (<700 ng/ml) were observed for 14 patients (18%). Proven or probable breakthrough IFIs occurred in 8 patients (2%); posaconazole therapeutic drug monitoring (TDM) was performed for 6 of those patients, all with levels above 700 ng/ml. Overall, 19% of patients experienced grade 3 or 4 liver injury, manifesting primarily as hyperbilirubinemia and being correlated with serum levels of >1,830 ng/ml. Although hepatotoxicity in a small percentage of patients is of concern, posaconazole tablets appeared to be generally safe and effective. As all breakthrough IFIs for which TDM was performed occurred in patients with levels of >700 ng/ml, and a posaconazole level of >1,830 ng/ml was correlated with grade 3 or 4 liver toxicity, further studies are needed to assess the role of TDM.

scholarly journals The Prediction and Prognosis of Fungal Infection in Lung Transplant Recipients—A Retrospective Cohort Study in South Korea

2021 ◽  
Vol 7 (8) ◽  
pp. 639
Author(s):  
Yae-Jee Baek ◽  
Yun-Suk Cho ◽  
Moo-Hyun Kim ◽  
Jong-Hoon Hyun ◽  
Yu-Jin Sohn ◽  
...  
Keyword(s):  
Cohort Study ◽  
South Korea ◽  
Fungal Infection ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Transplant Recipients ◽  
Tertiary Center ◽  
Lung Transplant Recipients

(1) Background: Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods: The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results: Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions: Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.

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