Infections caused by free-living amoebae pose a significant public health threat owing to growing populations of immunocompromised hosts combined with diagnostic delays, treatment difficulties, and high case fatality rates. Nasopharyngeal infections caused by Acanthamoeba are rare and the optimal treatment is not well established. We report a case of Acanthamoeba rhinosinusitis in a patient with chronic lymphocytic leukemia who presented with headaches and chronic rhinosinusitis refractory to multiple courses of antibiotics. A diagnosis of Acanthamoeba rhinosinusitis was established through broad-range polymerase chain reaction testing on sinus tissue. The patient had a favorable response to treatment, which included surgical debridement, cessation of immunosuppressants, and a three-drug regimen consisting of miltefosine, fluconazole, and sulfadiazine.

While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.

UNASSIGNED: Fluconazole is commonly used to treat and prevent fungal infections caused by Candida and Cryptococcus species. Although there have been reports of fatal arrhythmias induced by fluconazole, such as torsades de pointes, there have been minimal reports of mild, non-fatal arrhythmias associated with it, which may have been overlooked in clinical practice. We encountered a case of frequent premature ventricular contractions induced by fluconazole during the treatment of HIV-related pulmonary cryptococcosis. Herein, we report a case of frequent premature ventricular contractions (PVCs) induced by fluconazole, along with a literature review.
UNASSIGNED: A 47-year-old man diagnosed with human immunodeficiency virus-related pulmonary cryptococcosis experienced an irregular heartbeat during antifungal therapy with fluconazole at 400 mg once daily. A 12-lead electrocardiogram was conducted, which displayed frequent unifocal PVCs originating in the right ventricular outflow tract without QT prolongation. After reducing the dose of fluconazole to 200 mg once daily, the patient\'s symptoms slightly improved, and PVC frequency decreased on a 12-lead ECG; however, PVCs did not disappear. After discontinuing fluconazole, the symptoms improved, and a follow-up 12-lead electrocardiogram showed no PVCs.
UNASSIGNED: We encountered the case of frequent PVCs induced by fluconazole during the treatment of human immunodeficiency virus-related pulmonary cryptococcosis. Furthermore, it was suggested that the PVC frequency was dose-dependent for fluconazole. Careful follow-up for new-onset arrhythmias and ECG evaluations are essential before and after fluconazole administration.

Individual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug–drug interaction), concentration monitoring, and subsequent modeling of population pharmacokinetics to support treatment decisions. In a 69-year-old female patient with allogeneic hematopoietic stem cell transplantation, sirolimus concentrations were stable until she developed cerebral toxoplasmosis with tonic–clonic seizures. During treatment of this acute infection, sirolimus concentrations dropped to subtherapeutic levels and remained largely unaffected by dose increases. [Correction added on 4 May 2024, after first online publication: The word “tacrolimus concentrations” has been changed to “sirolimus concentrations” in the preceding sentence.] Only the simultaneous administration of the CYP3A4 inhibitor fluconazole and a shortening of the sirolimus dosing intervals to a (non-approved) twice-daily administration led to successful control of the concentrations, which ultimately even made a dose reduction possible. This intervention resulted in an increase of sirolimus mean trough concentration to 5.85 ng/mL, i.e., into the desired target range. Additionally, a higher ratio of sirolimus trough levels/daily dose from 26.9 to 109 ng/mL/mg/kg/day was achieved with the initiation of fluconazole. Thus, this case report describes the use of clinical pharmacological concepts and pharmacokinetic modeling to optimize treatment strategies in an individual patient. This strategy could be generalized to other CYP inhibitors and other treatment regimens.

BACKGROUND: Candida species are among the most important invasive pathogens in intensive care units (ICUs). Non-albicans species including Candida parapsilosis (C. parapsilosis) has increased in recent years. Fluconazole is the leading antifungal agent but resistance is a concern among C. parapsilosis species.
OBJECTIVE: The aim of this study was to determine the factors associated with fluconazole resistance in patients with candidemia due to C. parapsilosis in ICUs.
METHODS: This case-case study was conducted in a 750-bed, tertiary hospital between 2015 and 2021. Patients with fluconazole-resistant C. parapsilosis candidemia constituted the \'cases of interest\' group and patients with fluconazole-susceptible C. parapsilosis candidemia constituted the \'comparison cases\' group. Demographic and clinical data of the patients were recorded. Logistic regression analysis was performed using the backward elimination method to determine the independent predictors of fluconazole-resistant C. parapsilosis bloodstream infections.
RESULTS: The study included 177 patients. In the cultures of these patients, 76 (43%) fluconazole-resistant, 13 (7.3%) fluconazole-reduced susceptible, and 88 (49.7%) fluconazole-susceptible isolates were found. In the regression analysis the risk factors for fluconazole-resistant C. parapsilosis bloodstream infection, malignancy, immunosuppressive treatment, history of intra-abdominal surgery, hypoalbunemia, previous fluconazole use, and SOFA score were found to be associated in univariate analysis. In multivariate regression analysis, history of intra-abdominal surgery (OR: 2.16; 95% CI: 1.05-4.44), hypoalbuminemia (OR: 2.56; 95% CI: 1.06-6.17) and previous fluconazole use (OR: 3.35; 95% CI: 1.02-11) were found to be independent predictors.
CONCLUSIONS: In this study, a significant correlation was found between candidemia due to fluconazole-resistant C. parapsilosis in ICUs and intra-abdominal surgery, hypoalbuminemia, and previous fluconazole use. C. parapsilosis isolates and fluconazole resistance should be continuously monitored, strict infection control measures should be taken and antifungal stewardship programs should be implemented.

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast, rarely found as a causal agent of invasive fungal infection. In this study, we report a 31-year-old man infected with M. capitatus in the oral cavity, with a history of heroin and amphetamine abuse. M. capitatus was isolated through culture and microscopic analysis and identified by PCR amplification of the ITS DNA region. Based on the in vitro antifungal susceptibility test, the lowest MICs for M. capitatus were recorded for nystatin, itraconazole, and amphotericin, while higher MICs were observed for caspofungin and fluconazole. Treatment with nystatin successfully eliminated M. capitatus and relieved the clinical symptoms. This study presents the first case of M. capitatus in a patient with substance use disorder, manifesting as a plaque-like ulcer in the oral cavity.

BACKGROUND: Protothecosis is an infection of humans and animals caused by a rare conditionally pathogenic fungus (prototheca). It can occur in immunocompromised or normal patients.
OBJECTIVE: To describe the epidemiology of prototheca infection in China.
METHODS: We report a case of successful treatment of cutaneous protothecosis with fluconazole and analyzed the epidemiological characteristics, risk factors, clinical manifestations, diagnosis, treatment and prognosis of prototheca infections in China.
RESULTS: We describe this case and 29 cases of prototheca infections in China. At present, Prototheca wickerhamii (Pw) infection is the most common infection in China, and single or combined itraconazole is the preferred treatment.
CONCLUSIONS: These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of protothecosis in China.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children.
METHODS: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive.
CONCLUSIONS: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

UNASSIGNED: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications.
UNASSIGNED: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs.
UNASSIGNED: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed.
UNASSIGNED: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds.
UNASSIGNED: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.

UNASSIGNED: Endogenous fungal endophthalmitis tends to occur in immunocompromised patients, including COVID-19 infection. For high-risk populations, timely tissue biopsy, fungal culture, and susceptibility testing can facilitate early diagnosis and treatment, thereby improving the prognosis.
UNASSIGNED: While endogenous fungal endophthalmitis is a rare condition, its incidence has recently been on the rise. A 48-year-old male presented with complaints of acute visual loss in his right eye for 2 weeks. He had a history of COVID-19 infection, confirmed by a positive nucleic acid test, and was treated with intravenous antibiotics and glucocorticoids a week before the episode. A comprehensive eye examination revealed significant inflammatory cells floating in the anterior chamber and considerable cloudiness in the vitreous of the right eye, while few vitreous cells were visualized in the left eye. After pars plana vitrectomy (PPV) was performed in the right eye, a vitreous biopsy revealed an intravitreal infection of Candida albicans, which was susceptible to fluconazole. Endogenous fungal endophthalmitis occurs in patients with various underlying systemic conditions, such as those with diabetes, organ transplantation recipients, individuals undergoing chemotherapy, users of corticosteroids and immunosuppressants, AIDS patients, and those engaged in intravenous drug use. In high-risk populations associated with intravenous antibiotics, the timely identification of one or more well-defined oval yellow-white chorioretinal lesions, especially in the posterior pole of the retina, can contribute to an early diagnosis through tissue biopsy, fungal culture, and susceptibility testing. This approach enables targeted antifungal therapy, thereby improving the prognosis of visual function for the patient.