Prophylaxis Of Fungal Infections Research Articles

Population Pharmacokinetic Modeling of Posaconazole in Japanese Patients Receiving Fungal Prophylaxis.

Posaconazole is a vital drug to treat and prevent invasive fungal infections. Several factors, such as sex, body weight, total serum proteins, dietary intake, and severe mucositis, affect posaconazole pharmacokinetics (PKs). However, the relevance of other factors that affect the PKs of posaconazole in hematopoietic stem cell transplantation (HSCT) is unknown. This study explored factors influencing the PKs of posaconazole in HSCT recipients and nontransplant patients with hematological diseases. The authors conducted a single-institution, retrospective study. Forty-two Japanese inpatients receiving oral posaconazole tablets as prophylaxis for fungal infections were enrolled in this study. A one-compartment model with first-order absorption was used as the structural pharmacokinetic model. A population PK (PopPK) analysis was performed using a nonlinear mixed-effects modeling program, using a first-order conditional estimation method with interactions. Perl-speaks-NONMEM and R were used to evaluate the goodness of fit and visualize the output. In 29% of the enrolled patients, the serum concentration of posaconazole was <0.5 mcg/mL, considered the effective range. PopPK analysis revealed that the patient had undergone HSCT within 1 year, diarrhea occurred more than 5 times a day, and aspartate aminotransferase were covariates that influenced apparent clearance (CL/F). The CL/F of posaconazole was 1.43-fold higher after HSCT and 1.26-fold higher during diarrhea. PopPK analysis revealed that HSCT, diarrhea, and aspartate aminotransferase were factors associated with the CL/F of posaconazole. The trough concentration of posaconazole may be below the therapeutic range in a few patients with diarrhea and/or after HSCT. As invasive fungal infections in patients with hematologic diseases can be life-threatening, therapeutic drug monitoring of posaconazole is strongly recommended, and patients should be carefully monitored.

Infectious Complications and Mortality in Post-Transplant Lymphoproliferative Disorder Following Solid Organ Transplantation: Experiences of 10 Years in a Single Center

Introduction: An estimated 2 to 20% of patients with solid organ transplants (SOT) are later diagnosed with post-transplant lymphoproliferative disorder (PTLD). These patients receive immunosuppression therapy for SOT, however, there is a paucity of research examining the infection complications and morbidity in those diagnosed with PTLD. Our single center study examined infections following a PTLD diagnosis and the potential risk of morbidity. Methods: We reviewed the Cleveland Clinic electronic medical record (EMR) of SOT patients who were diagnosed with PTLD between 2010 and 2020. 98 patients met the inclusion criteria. These were further stratified by transplant type: 26 liver, 24 renal, 22 lung, 19 heart, and 2 combined heart and lung transplant patients. All data were analyzed using R software. Results: The mean onset of biopsy confirmed PTLD following transplant was 7.13 ± 7.28 years,. Abdominal pain was the most common presenting symptom prompting further work up, seen in 29% of patients. Patients were also diagnosed based on other chief complaints, including fatigue (n = 20), weight loss (n = 16), and fever (n = 14). Additionally, a smaller subset of patients were diagnosed incidentally on imaging. The most frequent primary site of PTLD was the lymphoid tissue / enlarged lymph nodes (34% of patients) and followed by gastrointestinal tract (29%). Elevated lactate dehydrogenase was present in 42% of patients, diagnostic criteria for acute kidney injury in 23%, and hyperuricemia was noted in 16%. Diffuse large B-lymphoma was the most common subtype diagnosed in 72 of 98 patients followed by EBV related. After diagnosis, 60% of PTLD patients presented to the hospital due to infections, with a mean of 49.9 ± 55.3 days following PTLD diagnosis. Of those patients, bacterial infections were the most common (49.3%), followed by viral infections (34.5%), fungal infections (14.9%), and parasitic infections (1.15%). The bacterial infections were predominantly encapsulated organisms including Pseudomonas aeruginosa (33%), Escherichia coli (19%), and Streptococcus pneumoniae (14%). Rituximab was used in 40% of patients following diagnosis while rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) was used in 41% of patients. There was no significant difference in infection risk in the first 100-days, following initiation of rituximab infections were seen in 33%, while the infection risk with R-CHOP was 35% (p = 0.31). Moreover, the most common cause of death was infection seen in 39% of patients, while PTLD itself with progressive disease was the second most common cause of death in 27%. The 6-month mortality following PTLD was 16% with 56% of those deaths being attributed to infection. The one-year mortality rate following PTLD was 25% with 48% of those being attributed to infection. Conclusions: In patients with PTLD diagnosis, the most common cause of death was infection (39%), followed by complications related to PTLD such as progressive disease with multi-organ failure. High serious infection risk may be due to aberrant monoclonal B-cell proliferation which paradoxically leads to decreased cellular immunity. The increased risk of B-cell PTLD in patients with SOT is likely due to the chronic immunosuppression, where patients gain acquired somatic driver mutations leading to a malignant state yet with an increased infection risk. Additionally, there was no difference in infection at 100 days between rituximab chemotherapy compared to R-CHOP. This necessitates the question of initiating viral, bacterial and fungal infection prophylaxis, similar to that following splenectomy or post BMT, should be implemented in patients diagnosed with PTLD. Further larger prospective studies are needed to further analyze the potential need and benefit of prophylactic vaccinations at the time of diagnosis in the PTLD patient population.

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.

Prophylaxis of Fungal Infections in Transplant Patients:What has Changed in Recent Years?

Objective: The present work aimed to review the invasive fungal infections (IFIs) and antifungal prophylaxis used in the last 20 years in transplant patients to identify the changes that occurred in this period and discuss the most current conducts. Methods: This is a systematic review in which the PubMed database was used, in which scientific articles from the last 20 years were selected, covering clinical trials, randomized controlled trials, systematic reviews of the literature and meta-analyses. Results: According to the present study, posaconazole and voriconazole are the antifungal drugs of choice for IFI prophylaxis in hematopoietic stem cell transplantation (HSCT). However, as posaconazole is not available in the public health system in Brazil, the most viable option remains voriconazole. Regarding IFI prophylaxis in solid organ transplantation (SOT), it was observed that there are variations depending on the transplanted target organ, and there is no evidence of its need in kidney transplantation. Although azoles are also the most used and bring clear benefits in liver and lung transplantation, some current studies have placed echinocandins on the same level, encouraging their use to prevent IFI in these patients. Conclusion: In the last five years, there has been a great shortage of clinical trials comparing different antifungal prophylaxis. New studies are needed to establish the most appropriate protocols for each condition and profile of the transplanted patient.

Efficacy of anti-fungal agents for invasive fungal infection prophylaxis in liver transplant recipients: A network meta-analysis.

At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials, in which 10 anti-fungal approaches were identified. Overall, anti-fungal prophylaxis reduced the rate of IFI (RR 0.30, 95% CI 0.18-0.52) and proven IFI (RR 0.27, 95% CI 0.14-0.53) when compared to placebo. In the network meta-analysis, an equivalent reduction in the rate of IFI was observed in fluconazole (OR 4.70, 95% CI 1.22-18.10), itraconazole (OR 5.82, 95% CI 1.10-30.71) and Liposomal amphotericin B (LAmB, OR 5.74, 95% CI 1.29-25.58) groups when compared with placebo. Anidulafungin might be the most effective agents in IFI prevention; however, this superiority did not meet statistically significance. Our study indicated that fluconazole, echinocandins and LAmB are equivalent in efficacy. Of which, fluconazole is recommended for the prevention of IFI in LTRs due to its efficacy, economics and compliance.

Efficacy and safety of voriconazole as invasive fungal infection prophylaxis in patients with acute myeloid leukemia

Invasive fungal infections (IFIs) are commonly observed in patients, who are at high risk of severe infections during the neutropenic phase. The aim of this retrospective single-center study was to evaluate the efficacy and safety of voriconazole as a fungal prophylaxis after induction chemotherapy for acute myeloid leukemia (AML) in adult patients. Six proven/probable IFIs were diagnosed in 213 patients with AML (median age 61 years, range 18–85), who received a total of 377 induction chemotherapies. This yielded an incidence rate of 1.6% based on all induction cycles administered. Voriconazole prophylaxis was administered as intended in 317 out of 377 (84%) induction cycles until the end of neutropenia with a median duration of 20 days (range: 2–101 days). In conclusion, voriconazole demonstrates efficacy and safety as a first-line IFI prophylaxis comparable to published data on posaconazole, which is the standard fungal prophylaxis recommendation for AML patients in international guidelines today.

Suboptimal plasma concentrations with posaconazole suspension as prophylaxis in critically ill COVID-19 patients at risk of Covid-associated pulmonary aspergillosis.

What is known and objectiveThe safety and efficacy of different antifungal agents in the prophylaxis of invasive fungal infection in patients with haematological disorders are known. We comment on the poor bioavailability of posaconazole suspension to suggest that it is not useful in critically ill COVID patients.CommentThe increased mortality and high incidence of COVID‐associated pulmonary aspergillosis (CAPA) might justify administration of off‐label posaconazole for preventing CAPA, being the only drug officially registered for prophylaxis of fungal infections. We decided to initiate off‐label posaconazole prophylaxis in COVID‐19 patients, who were mechanically ventilated and exposed to high‐dose steroids for progressive pulmonary disease or ARDS. We found that posaconazole suspension was inadequate. Very low trough levels were observed after administration, and the dose adjustments necessary for the therapeutic drug monitoring (TDM) of the drug in our critically ill ICU patients were not useful.What is new and conclusionPosaconazole suspension should not be used to prevent CAPA in COVID‐19 patients on high‐dose steroid therapy.

Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies

Background and aimTriazole, polyene, and echinocandin antifungal agents are extensively used to treat invasive fungal infections (IFIs); however, the optimal prophylaxis option is not clear. This study aimed to determine the optimal agent against IFIs for patients with hematological malignancies.MethodsRandomized controlled trials (RCTs) comparing the effectiveness of triazole, polyene, and echinocandin antifungal agents with each other or placebo for IFIs in patients with hematological malignancies were searched. This Bayesian network meta-analysis was performed for all agents.ResultsThe network meta-analyses showed that all triazoles, amphotericin B, and caspofungin, but not micafungin, reduced IFIs. Posaconazole was superior to fluconazole [odds ratio (OR), 0.30; 95% credible interval (CrI), 0.12–0.60], itraconazole (OR, 0.40; 95% CrI, 0.15–0.85), and amphotericin B (OR, 4.97; 95% CrI, 1.73–11.35). It also reduced all-cause mortality compared with fluconazole (OR, 0.35; 95% CrI, 0.08–0.96) and itraconazole (OR, 0.33; 95% CrI, 0.07–0.94), and reduced the risk of adverse events compared with fluconazole (OR, 0.02; 95% CrI, 0.00–0.03), itraconazole (OR, 0.01; 95% CrI, 0.00–0.02), posaconazole (OR, 0.02; 95% CrI, 0.00–0.03), voriconazole (OR, 0.005; 95% CrI, 0.00 to 0.01), amphotericin B (OR, 0.004; 95% CrI, 0.00–0.01), and caspofungin (OR, 0.05; 95% CrI, 0.00–0.42) despite no significant difference in the need for empirical treatment and the proportion of successful treatment.ConclusionsPosaconazole might be an optimal prophylaxis agent because it reduced IFIs, all-cause mortality, and adverse events, despite no difference in the need for empirical treatment and the proportion of successful treatment.

440 - Comparing Outcomes of Different Anti-Fungal Therapies As Invasive Fungal Infection Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

440 - Comparing Outcomes of Different Anti-Fungal Therapies As Invasive Fungal Infection Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Successful challenge of voriconazole in a patient with posaconazole‐associated minor drug eruption: A case report

Triazole antifungal-associated skin rash is rare. Data on cross-reaction triazole antifungals remain inconclusive and poorly defined. We report successful voriconazole challenge in a patient allergic to posaconazole. A 38-year-old female diagnosed with acute myeloid leukaemia and receiving chemotherapy treatment in our institution developed a maculopapular rash after receiving oral posaconazole for invasive fungal infection prophylaxis. Other potential causes that may have attributed to this response, such as other drugs that the patient was taking and infections, were excluded. Voriconazole, another triazole antifungal, was successfully substituted for posaconazole. This is the first case report of a patient, with a history of posaconazole allergy, successfully challenged with voriconazole.

Formulation and Characterization of Itraconazole as Nanosuspension Dosage Form for Enhancement of Solubility

Abstract&#x0D;             Itraconazole is a triazole antifungal given orally for the treatment of oropharyngeal and vulvovaginal candidiasis, for systemic infections including aspergillosis, candidiasis,  and for the prophylaxis of fungal infections in immunocompromised patients.&#x0D;            The study aimed to formulate a practical water-insoluble Itraconazole, with insufficient bioavailability as nanosuspension to increase aqueous solubility and improve its dissolution and oral bioavailability.&#x0D;           Itraconazole nanosuspension was produced by a solvent-antisolvent nanoprecipitation method in the presence of different stabilisers (Poloxamer-188, HPMCE5) at different ratios with the drug alone or combination with surfactant(tween 80, SLS).&#x0D;          The results exhibit that the particle sizes of all prepared itraconazole formulations were in the nano size.  The best formula (F6) has a particle size.  ( 42  ) nm and Zeta potential of (- 21.86 ) mV.  In vitro cumulative release from the nanosuspension was (88 %) at (30) min when compared to the pure drug (13%) and lyophilized nanoparticles (98.2%) at (30)min. Effect of different parameters was investigated.&#x0D;           Fourier transforms infrared spectroscopy(FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD), Scanning electron microscope( SEM) was done for the optimized  nanoparticles prepared by lyophilization technique&#x0D;         Thus, Nanosuspension appears to be an encouraging approach to formulate Itraconazole nanosuspension with high solubility and dissolution rate.&#x0D;  &#x0D;  &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;  &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;  &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;  &#x0D;  &#x0D;  &#x0D; Keywords: Itraconazole, Nanoprecipitation method, Nanosuspension&#x0D;          

Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations.

SummaryPosaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.

PS1552 THE INCIDENCE RATES AND RISK FACTORS OF ATYPICAL INFECTIONS IN PATIENTS WITH LYMPHOMA WHO RECEIVED AUTOLOGOUS STEM CELL TRANSPLANTATION

Background:Autologous stem cell transplantation (ASCT) is an intermediate risk group for infections according to National Comprehensive Cancer Network (NCCN) guideline. Based on the risk of infection, experts recommend prophylaxis for fungal infections with fluconazole or micafungin if mucositis is accompanied, and prophylaxis for Pneumocystitis jirovecii (P. jirovecii) infection with trimethoprim‐sulfamethoxazole (TMP‐SMX) for 3 to 6 months after transplantation. For varicella zoster virus (VZV) reactivation, acyclovir or famcyclovir or valacyclovir is recommended as prophylaxis for 6 to 12 months after ASCT. However, there is a lack of evidence to support this guideline.Aims:In this study we performed a nationwide population‐based study to provide information regarding the incidence and risk factors of atypical infections such as fungal, viral or PJP in patients were performed ASCT in the South Korea.Methods:Using the Korean Health Insurance Review and Assessment Service database, the patients with lymphoma who received ASCT from 2003 to 2016 were retrospectively analyzed. Atypical infection is identified by international classification of disease (ICD) codes of each infection or ATC(Anatomical Therapeutic Chemical) codes of medicines for treatment. Oral Candidiasis, Herpes simplex virus (HSV), and Epstein‐Barr virus (EBV) infection were excluded because these are considered to non‐pathogenic in clinical field. The patients undergoing allogenic stem cell transplantation (AlloSCT) were excluded.Results:The total number of patients with lymphoma undergoing ASCT was 2147, median age was 48 years (range 2–70). The cumulative incidence of fungal infection is 10.4%, viral is 20.0% and PJP is 5.5% in lymphoma. In multivariate analysis, TBI (HR 1.702, p = 0.0390), and previous fungal infection (HR 1.701, p = 0.0398) were independent significant risk factors for fungal infection. The multivariate analysis showed that TBI (HR 2.524, p &lt; 0.0001), previous infection history (HR 1.351, p = 0.0046) and prophylaxis (HR 1.633, p = 0.0001) were independent risk factors for viral infection. The multivariate analysis showed that prophylaxis (HR 2.647, p = 0.0002) were independent risk factors for PJP infection.Summary/Conclusion:In this study, patients with lymphoma who underwent ASCT showed relative high risk of viral infection (CIR 20.0%) and previous viral infection, TBI conditioning and non‐prophylaxis were independent risk factors for viral infection. So patients with lymphoma who planed ASCT should be considered prophylaxis for 2years after ASCT. Especially, patient who treated with TBI conditioning and have previous viral infection should receive prophylactic anti‐viral agents.

Pharmacokinetics and probability of target attainment for micafungin in normal-weight and morbidly obese adults.

The rising pandemic of obesity means an increasing number of obese patients who require antimicrobial therapy for serious infections. Micafungin is an echinocandin drug frequently used as therapy or prophylaxis for fungal infections, predominantly with Candida species. In order to maximize the efficacy of micafungin in obese patients, the dose that corresponds to optimal exposure for each obese individual needs to be identified. We performed a prospective study in 16 obese and 8 normal-weight healthy subjects with a weight ranging from 61.5-184 kg (ClinicalTrials.gov Identifier: NCT03102658). A population pharmacokinetic model was developed and used to simulate several dosing regimens to evaluate the PTA for relevant MICs to define the optimal dose using the pharmacokinetic/pharmacodynamic target of an AUC/MIC ratio above 5000. Total body weight was found to be most predictive for CL and V. Simulations showed that a 100 mg dose results in a PTA of >90% in patients weighing ≤125 kg infected with a Candida species having an MIC of 0.016 mg/L. The maintenance dose should be increased to 200 mg in patients >125 kg infected with a Candida species with an MIC of 0.016 mg/L. For an MIC of 0.032 mg/L, a 300 mg maintenance dose is recommended above 125 kg weight. Furthermore, we demonstrate that patients can benefit from a loading dose (i.e. twice the maintenance dose). We present easy-to-use dose recommendations for obese patients, based on both weight and target MIC, that result in adequate exposure in patients with body weight up to 190 kg.

Prophylaxie des infections post-allogreffe : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Allogeneic hematopoietic stem cell transplantation is a curative treatment for many hematological diseases. However, this procedure causes the patient to be susceptible to infection. Prophylactic treatments are administered in clinical practice even thought the level of evidence of their effectiveness is not always high. In addition, changes in the transplantation procedures - use of reduced intensity conditioning, development of alternative graft sources - must lead to a rethinking of attitudes towards prophylaxis. Our working group based its recommendations on a review of referential articles and publications on the subject found in the literature. These recommendations concern the prophylaxis of infections caused by HSV1, HSV2, varicella zoster, and hepatitis B, as well as anti-bacterial and digestive decontamination prophylaxis, prevention of pneumocystis, toxoplasmosis, tuberculosis, as well as prophylaxis of fungal infections. Other infectious agents usually involved in infections post-allotransplant have been the subject of another set of recommendations from the French Society of Bone Marrow Transplantation and Cellular Therapy.

Posaconazole for Prophylaxis of Fungal Infection in Pediatric Patients with Acute Myeloid Leukemia undergoing Induction Chemotherapy

Posaconazole for Prophylaxis of Fungal Infection in Pediatric Patients with Acute Myeloid Leukemia undergoing Induction Chemotherapy

Quantifying the medication burden of kidney transplant recipients in the first year post-transplantation.

Background Kidney transplantation is an effective treatment, but it is not a cure. Since the risk of graft rejection and the presence of comorbid conditions remain for a lifetime, medications are necessary. Objective To examine the prescription medication burden of adult kidney transplant recipients from 3- to 12-months post-transplantation. Setting All five adult kidney transplant units in Victoria, Australia. Method As part of a larger intervention study, we conducted a retrospective review of prescription refill records and medical records containing the history of medication changes of 64 participants who completed the study. The complexity of the medication management was studied, and we looked at the burden of maintaining the medications supply. Outcome measures Pill burden, administration frequency, dose changes frequency, immunosuppressive medication changes, the estimated out-of-pocket costs of medications and frequency of pharmacy visits. Results At 3months, the average daily pill burden was 22 (SD = 9) whilst at 12months, it was 23 (SD = 10). Some participants required long-term prophylaxis of fungal infections up to 4 times a day whilst those with diabetes had to manage up to 4 insulin doses a day. The average out-of-pocket cost per person and the frequency of pharmacy visits at 6, 9 and 12months post-transplantation remained relatively unchanged. Conclusion The medication regimen prescribed for kidney transplant recipients is complex and for most patients, it did not simplify over time post transplantation. Strategies are needed to support patients in managing the complexity of their medication regimen following kidney transplantation.

Timing Determination of Invasive Fungal Infection Prophylaxis According to Immune Function in HSCT Patients.

Patients who receive a hematopoietic stem cell transplantation (HSCT) exhibit an immune defect after recovering from neutropenia. The current guidelines do not recommend fungal prophylaxis in these patients, except for grades III to IV GVHD in HSCT. Thus, the timing for the initiation and cessation of IFI prophylaxis in immune-compromised patients remains a challenging endeavor. We retrospectively analyzed patients who received auto or allo-HSCT and monitored their immune function after recovering from neutropenia by measuring the levels of IgG, IgA, IgM, as well as the number of T, B, NK cells. We found that the level of IgG and NK cell count exhibited a significant difference with the incidence of IFI by logistic regression (p = 0.000 vs. 0.000, respectively) and conditional logistic regression (p = 0.009 vs. p = 0.002). The initiation of IFI prophylaxis was determined to be IgG < 7 mg/mL and NK cell count < 6.5 × 104/mL by an receiver operating characteristic curve separately. Tests in parallel increased the test sensitivity and specificity. Thus, the optimal timing for initiating prophylaxis in patients after HSCT could be IgG < 7 mg/mL or NK cell count < 6.5 × 104/mL. Future large-scale prospective clinical trials are required to verify these findings. Patients who are immuno-compromised after auto or allo-HSCT may benefit from a lower fungi infection incidence with immune surveillance and proper fungal prophylaxis.

Retrospective analysis of goal drug level attainment of posaconazole for invasive fungal infection prophylaxis in patients with acute myeloid leukemia pre- and post-switch to tablet formulation.

Posaconazole is approved for invasive fungal infection prophylaxis in patients with hematologic malignancies. Posaconazole suspension is plagued by poor oral absorption and dietary requirements that are difficult for patients to meet. The delayed-release tablet formulation of posaconazole may be taken without regards to meals and has significantly better oral absorption than posaconazole suspension. We sought to determine if a switch to posaconazole tablets improved steady-state drug level attainment for invasive fungal infection prophylaxis in patients with acute myeloid leukemia. All adult inpatients with acute myeloid leukemia undergoing chemotherapy, who received posaconazole for invasive fungal infection prophylaxis between 2012 and 2015, were included. The primary outcome was proportion of patients with first posaconazole level greater than 700 ng/mL. Secondary outcomes included proportion of patients with first posaconazole level greater than 1000 ng/mL, invasive fungal infection within 100 days, and adverse drug events. Forty patients received posaconazole tablets and 34 patients received suspension. Posaconazole levels were significantly higher at first measurement in patients receiving tablet than suspension (1296 ng/mL vs. 788 ng/mL, p < 0.01). Thirty-seven patients receiving tablets had a serum drug level greater than 700 ng/mL on first measurement versus 18 receiving suspension (p < 0.01). Patients receiving tablets were also more likely to have a serum drug level over 1000 ng/mL on first measurement (26 vs. 11, p < 0.01). Rates of invasive fungal infection and adverse events were not statistically different. Patients receiving posaconazole tablets attained significantly higher serum drug levels than those receiving suspension.

Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis

To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.