Long-term follow-up of laryngeal Rhinosporidium seeberi diagnosed by PCR and treated with laser ablation and voriconazole nebulization in a retired thoroughbred polo horse.

A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an incidental finding of a granulomatous mass on the dorsal aspect of the epiglottis was made. Rhinosporidium seeberi was suspected from a histological section obtained from an initial biopsy, and the mass was removed via laser surgery for cytology and PCR. Sequencing of the PCR amplicons confirmed the diagnosis of R. seeberi. A treatment protocol of nebulized voriconazole for 10 d postoperatively was used. Long-term follow-up required 2 more laser surgeries plus oral fluconazole to resolve the remaining fungal spores. However, 2.5 y later, there was no evidence of remaining fungal spores. Key clinical message: Horses from endemic regions can potentially be exposed to R. seeberi. Based on its travel history, this horse may have contracted the infection in South America, California, or Alberta. Treatments administered, including diode laser resection, voriconazole antifungal nebulization, and oral fluconazole administration, were successful but required repeated interventions.

Suivi à long terme du Rhinosporidium seeberi laryngé diagnostiqué par PCR et traité par ablation au laser et nébulisation au voriconazole chez un cheval de polo thoroughbred pur-sang à la retraiteUn cheval thoroughbred argentin de polo retraité de 21 ans, issu d'un troupeau d'enseignement, a été présenté pour une démonstration de lavage broncho-alvéolaire de routine, au cours de laquelle une découverte fortuite d'une masse granulomateuse sur la face dorsale de l'épiglotte a été faite. Rhinosporidium seeberi a été suspecté à partir d'une coupe histologique obtenue à partir d'une biopsie initiale, et la masse a été retirée par chirurgie au laser pour cytologie et PCR. Le séquençage des amplicons PCR a confirmé le diagnostic de R. seeberi. Un protocole de traitement au voriconazole nébulisé pendant 10 jours après l'opération a été utilisé. Le suivi à long terme a nécessité 2 autres interventions chirurgicales au laser et du fluconazole oral pour éliminer les spores fongiques restantes. Cependant, 2,5 ans plus tard, il n'y avait aucune trace de spores fongiques restantes.Message clinique clé:Les chevaux des régions endémiques peuvent potentiellement être exposés à R. seeberi. D'après ses antécédents de voyage, ce cheval pourrait avoir contracté l'infection en Amérique du Sud, en Californie ou en Alberta. Les traitements administrés, notamment la résection au laser à diode, la nébulisation antifongique au voriconazole et l'administration orale de fluconazole, ont été efficaces mais ont nécessité des interventions répétées.(Traduit par Dr Serge Messier).

Clinical application of voriconazole in pediatric patients: a systematic review.

The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.

Interaction of age and CYP2C19 genotypes on voriconazole steady-state trough concentration in Chinese patients.

OBJECTIVES: Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients. METHODS: A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (C ss-min ) in overall patients and in age subgroups was analyzed. RESULTS: Voriconazole C ss-min correlated positively with age, and mean voriconazole C ss-min was significantly higher in the elderly group ( P  < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole C ss-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole C ss-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole C ss-min (>5.5 mg/l) was higher in the elderly patients. When the average C ss-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole C ss-min in the young group, while the influence of age on voriconazole C ss-min exceeded CYP2C19 genotypes in the elderly. CONCLUSION: CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients.

Ivosidenib significantly reduces triazole levels in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations. Although posaconazole is a substrate of P-glycoprotein, it is metabolized primarily via UDP glucuronidation; thus, the impact of ivosidenib on posaconazole exposure is unknown. METHODS: Patients treated with ivosidenib and concomitant triazole with at least one serum trough level were included. Subtherapeutic levels were defined as posaconazole <700 ng/mL and voriconazole <1.0 µg/mL. The incidences of breakthrough invasive fungal infections and QTc prolongation were identified at least 5 days after initiation of ivosidenib with concomitant triazole. RESULTS: Seventy-eight serum triazole levels from 31 patients receiving ivosidenib-containing therapy and concomitant triazole were evaluated. Of the 78 concomitant levels, 47 (60%) were subtherapeutic (posaconazole: n = 20 of 43 [47%]; voriconazole: n = 27 of 35 [77%]). Compared to levels drawn while patients were off ivosidenib, median triazole serum levels during concomitant ivosidenib were significantly reduced. There was no apparent increase in incidence of grade 3 QTc prolongation with concomitant azole antifungal and ivosidenib 500 mg daily. CONCLUSIONS: This study demonstrated that concomitant ivosidenib significantly reduced posaconazole and voriconazole levels. Voriconazole should be avoided, empiric high-dose posaconazole (>300 mg/day) may be considered, and therapeutic drug monitoring is recommended in all patients receiving concomitant ivosidenib.

Development of a therapeutic drug-monitoring algorithm for outpatients receiving voriconazole: A multicentre retrospective study.

AIMS: Although therapeutic drug monitoring (TDM) of voriconazole is performed in outpatients to prevent treatment failure and toxicity, whether TDM should be performed in all or only selected patients remains controversial. This study evaluated the association between voriconazole trough concentrations and clinical events. METHODS: We investigated the aggravation of clinical symptoms, incidence of hepatotoxicity and visual disturbances, change in co-medications and interaction between voriconazole and co-medications in outpatients receiving voriconazole between 2017 and 2021 in three facilities. Abnormal trough concentrations were defined as <1.0 mg/L (low group) and >4.0 mg/L (high group). RESULTS: A total of 141 outpatients (578 concentration measurements) met the inclusion criteria (treatment, 37 patients, 131 values; prophylaxis, 104 patients, 447 values). The percentages of patients with abnormal concentrations were 29.0% and 31.5% in the treatment and prophylaxis groups, respectively. Abnormal concentrations showed 50% of the concentrations at the first measurement in both therapies. Aggravation of clinical symptoms was most frequently observed in the low treatment group (18.2%). Adverse events were most common in the high group for both therapies (treatment, hepatotoxicity 6.3%, visual disturbance 18.8%; prophylaxis, hepatotoxicity 27.9%). No differences were found in changes to co-medications and drug interactions. In the prophylaxis group, prescription duration in the presence of clinical events tended to be longer than in their absence (47.4 ± 23.4 days vs 39.7 ± 21.9 days, P = .1132). CONCLUSIONS: We developed an algorithm based on clinical events for appropriate implementation of TDM in outpatients. However, future interventions based on this algorithm should be validated.

Caracterización y resultados del uso de voriconazol nebulizado en un entorno real: un estudio observacional unicéntrico / Characterization and real-live results of nebulized voriconazole: A single-center observational study

Objetivo la administración de voriconazol nebulizado implica ventajas, incluyendo la optimización de la penetración pulmonar y la reducción de los efectos adversos e interacciones; sin embargo, la evidencia sobre su utilización es escasa y no existen presentaciones comerciales específicas para nebulización. Nuestro objetivo es caracterizar las soluciones de voriconazol elaboradas para nebulización y describir su uso en nuestro centro. Método estudio observacional retrospectivo incluyendo pacientes que reciben voriconazol nebulizado para el tratamiento de enfermedades pulmonares (infecciones fúngicas o colonizaciones). La solución de voriconazol se preparó a partir de los viales comerciales para la administración intravenosa. Resultados el pH y la osmolaridad de las soluciones de voriconazol fueron adecuados para su nebulización. Se incluyeron 10 pacientes, 9 adultos y un niño. La dosis fue de 40 mg en los adultos y 10 mg en el paciente pediátrico, diluido a 10 mg/ml, administrados cada 12-24 horas. La duración mediana del tratamiento fue de 139 (rango: 26-911) días. No se reportaron efectos adversos y no se detectó voriconazol en plasma cuando se administró únicamente vía nebulizada. Conclusiones la nebulización de voriconazol es bien tolerada y no se absorbe hacia la circulación sistémica. Son necesarios más estudios de investigación para evaluar su eficacia (AU)

Objective Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. Method This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. Results The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. Conclusion Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy (AU)

The importance of CYP2C19 genotype in tacrolimus dose optimization when concomitant with voriconazole in heart transplant recipients.

AIMS: Voriconazole remains the mainstay for the treatment of invasive fungal infections in heart transplant patients and can significantly increase tacrolimus exposure because of drug-drug interaction (DDI). However, the magnitude of this DDI is highly variable and difficult to predict. The purpose of this study was to present the characteristics of the DDI between tacrolimus and voriconazole, and further identify the various predictors of tacrolimus dose modification. METHODS: We retrospectively enrolled 69 heart transplant recipients who did not use voriconazole as the control and 68 patients received voriconazole treatment in voriconazole group. CYP3A4*1G, CYP3A5*3 and CYP2C19*2 or *3 were thereafter genotyped by Sanger sequencing. The dose of tacrolimus required to achieve the therapeutic concentrations and tacrolimus dose-corrected trough concentration (C0 /D) before and after VRC administration was evaluated. RESULTS: The DDI between tacrolimus and voriconazole displayed a large interindividual variability with more than 10-fold changes in tacrolimus dose (range 1.28-13.00) and C0 /D (range 1.43-13.75). In addition, the fold changes for the tacrolimus dose were associated with CYP2C19 genotype, which was found to be significantly lower in CYP2C19 extensive metabolizers than in CYP2C19 intermediate metabolizers or poor metabolizers (4.06 ± 1.85 vs 5.49 ± 2.47, P = .0031). However, no significant difference was found in both CYP3A4 and CYP3A5 genotypes. Moreover, CYP2C19 genotype and hematocrit acted as independent predicting factors for tacrolimus dose modification after voriconazole co-therapy. CONCLUSIONS: The findings of this study have identified the various important factors to adjust tacrolimus dosage when co-administrated with voriconazole in individual patients. CYP2C19 genotype and haematocrit should be considered when tailoring tacrolimus dose.

Evaluation of efficacy and safety of oral voriconazole in the management of recalcitrant and recurrent dermatophytosis.

BACKGROUND: Dermatophytosis is a worldwide public health problem, affecting > 25% of the world's population. There has been a rampant increase in the resistant, recurrent dermatophytosis in the past few years, especially in India. Azole resistance in dermatophytes has been reported to be as high as 19% worldwide, hence evaluating the efficacy and safety of a newer oral antifungal is important. AIM: To evaluate the efficacy and safety of oral voriconazole in the management of recalcitrant and recurrent dermatophytosis. METHODS: Patients with extensive, recurring and resistant dermatophytosis. The clinical diagnosis was confirmed by potassium hydroxide staining. Patients were given a 2-week course of oral voriconazole, administered as 800 mg on Day 1, followed by two daily doses of 200 mg (total 400 mg/day) for the remaining 13 days. The patients were followed up in Week 2 to assess response and in Week 6 to assess recurrence. Patients were monitored for any adverse effects (AEs). RESULTS: In total, 40 patients completed the study. Complete clearance was seen in 90% and 75% at Weeks 2 and 6, respectively. By the end of Week 6, eight patients (20%) had partial improvement of disease without complete clearance and only 5% had recurrence. No AEs were recorded during the treatment course. CONCLUSION: Voriconazole, a novel oral antifungal that can be used for treatment of recurrent and resistant dermatophytosis, has a good efficacy and safety profile with a very low rate of recurrence.

Population pharmacokinetic model-guided optimization of intravenous voriconazole dosing regimens in critically ill patients with liver dysfunction.

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.

Voriconazole-Cyclodextrin Supramolecular Ternary Complex-Loaded Ocular Films for Management of Fungal Keratitis.

Fungal keratitis is one of the leading causes of ophthalmic mycosis affecting the vision due to corneal scarring. Voriconazole (VRC) is the most preferred azole antifungal agent for treating ocular mycotic infections. Ocular drug delivery is challenging due to the shorter corneal residence time of the formulation requiring frequent administration, leading to poor patient compliance. The present study aimed at improving the solubility, transcorneal permeation, and efficacy of voriconazole via the formation of cyclodextrin-based ternary complexes and incorporation of the complex into mucoadhesive films. A phase solubility study suggested a ∼14-fold improvement in VRC solubility, whereas physicochemical characterization confirmed the inclusion of VRC in the cyclodextrin inner cavity. In silico docking studies were performed to predict the docking conformation and stability of the inclusion complex. Complex-loaded films showed sustained release of voriconazole from the films and improved transcorneal permeation by ∼4-fold with an improved flux of 8.36 µg/(cm2 h) for ternary complex-loaded films compared to 1.86 µg/(cm2 h) for the pure VRC film. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and hen's egg-chorioallantoic membrane test (HET-CAM) assays confirmed that the complexes and ocular films were nonirritant and safe for ocular administration. The antifungal study performed using Aspergillus fumigatus and Fusarium oxysporum suggested improved antifungal activity compared to the pure drug film. In conclusion, the supramolecular cyclodextrin ternary complex proved to be a promising strategy for enhancing the solubility and permeability and augmenting the antifungal activity of voriconazole in the management of fungal keratitis.

Impact of an electronic alert on prescription patterns of meropenem, voriconazole and caspofungin.

BACKGROUND: Antimicrobial stewardship programs promote the appropriate use of antimicrobial substances through the implementation of evidence-based, active and passive interventions. We analyzed the effect of a computer-assisted intervention on antimicrobial use in a tertiary care hospital. METHODS: Between 2011 and 2016 we introduced an electronic alert for patients being prescribed meropenem, voriconazole and caspofungin. At prescription and at day 3 of treatment, physicians were informed about the risk related to these antimicrobial substances by an electronic alert in the medical records. Physicians were invited to revoke or confirm the prescription and to contact the infectious disease (ID) team. Using interrupted time series regression, the days of therapy (DOTs) and the number of prescriptions before and after the intervention were compared. RESULTS: We counted 64,281 DOTs for 5549 prescriptions during 4100 hospital stays. Overall, the DOTs decreased continuously over time. An additional benefit of the alert could not be observed. Similarly, the number of prescriptions decreased over time, without significant effect of the intervention. When considering the three drugs separately, the alert impacted the duration (change in slope of DOTs/1000 bed days; P = 0.0017) as well as the number of prescriptions (change in slope of prescriptions/1000 bed days; P < 0.001) of voriconazole only. CONCLUSIONS: The introduction of the alert lowered prescriptions of voriconazole only. Thus, self-stewardship alone seems to have a limited impact on electronic prescriptions of anti-infective substances. Additional measures such as face-to-face prompting with ID physicians or audit and feedback are indispensable to optimize antimicrobial use.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

Formulation, optimization, and nephrotoxicity evaluation of an antifungal in situ nasal gel loaded with voriconazole‒clove oil transferosomal nanoparticles.

Fungal infections of the paranasal cavity are among the most widely spread illnesses nowadays. The aim of the current study was to estimate the effectiveness of an in situ gel loaded with voriconazole‒clove oil nano-transferosomes (VRC-CO-NT) in enhancing the activity of voriconazole against Aspergillus flavus, which causes rhinosinusitis. The nephrotoxic side effects of voriconazole may be reduced through the incorporation of the clove oil, which has antioxidant activity that protects tissue. The Box‒Behnken design was applied to formulate the VRC-CO-NT. The particle size, entrapment efficiency, antifungal inhibition zone, and serum creatinine concentration were considered dependent variables, and the soybean lecithin, VRC, and CO concentrations were considered independent ones. The final optimized formulation was loaded into a deacetylated gellan gum base and evaluated for its gelation, rheological properties, drug release profile, permeation capabilities, and in vivo nephrotoxicity. The optimum formulation was determined to be composed of 50 mg/mL lecithin, 18 mg/mL VRC, and 75 mg/mL CO, with a minimum particle size of 102.96 nm, an entrapment efficiency of 71.70%, an inhibition zone of 21.76 mm, and a serum creatinine level of 0.119 mmol/L. The optimized loaded in situ gel released 82.5% VRC after 12 hours and resulted in a 5.4-fold increase in drug permeation. The in vivo results obtained using rabbits resulted in a nonsignificant differentiation among the renal function parameters compared with the negative control group. In conclusion, nasal in situ gel loaded with VRC-CO-NT is considered an efficient novel carrier with enhanced antifungal properties with no signs of nephrotoxicity.

Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia.

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0-18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Spinal epidural abscess caused by Aspergillus spp masquerading as spinal tuberculosis in a person with HIV.

Spinal epidural abscess caused by Aspergillus spp is a debilitating form of invasive aspergillosis that can easily be misdiagnosed as spinal tuberculosis due to shared risk factors and clinical features. In this Grand Round, we describe a case of thoracic aspergillus spinal epidural abscess in a patient with underlying HIV infection. The initial diagnostic consideration was that of spinal tuberculosis. Consequently, despite positive microbiological cultures of Aspergillus fumigatus, antifungal therapy was delayed until histopathological evaluation of the affected tissue confirmed the presence of fungal hyphae. The patient showed an initial favourable response after surgical removal of the infected focus, but unfortunately never returned to premorbid functioning. This case highlights the importance of early diagnosis, urgent surgery, and prompt antifungal therapy for the management of aspergillus spinal epidural abscesses. Associated morbidity and mortality can be substantially increased if physicians fail to recognise this condition and do not institute appropriate and timely surgical and medical treatment.

Tailoring thixotropic mixed-lipid nanoconstructs of voriconazole for the management of Vulvovaginal candidiasis: Formulation, statistical optimization, in vitro characterization and in vivo assessment.

Vulvovaginal candidiasis is a pervasive gynecological condition among women worldwide due to infection recurrence and resistance to conventional drugs. This calls for a novel formulation of alternative medication and with enhanced efficacy. This study aimed to fabricate mixed-lipid nanoconstructs (MLNCs) of voriconazole (VCZ) with a low concentration of lipids applying high shear homogenization and ultrasonication to form a semisolid formulation. Tefose 63 and Gelot 64 were employed as emulsifiers that are specified for vaginal preparations; as per their mucoadhesive properties and their texture enhancing characters, although usually used as lipids in different lipid carriers. A 24 factorial design was established and the optimized formulation was prepared using 10% total lipids, in which solid lipids (Sterotex NF: Glyceryl monostearate) ratio was 1.92:1 and the oils percentage was 30% (Maisine: Glyceryl monooleate, in the ratio of 1:1), and the emulsifiers mixture (Tefose 63: Gelot 64) ratio was 1:1, as 10% of total formulation weight. The optimized formulation with a viscosity of 964.49 ± 57.99 cp showed spherical nanoparticles (322.72 ± 15.11 nm) that entrapped 67.16 ± 3.45% of VCZ and exhibited release of 70.08 ± 2.87% in 8 h. The optimized formulation with high bioadhesive potentials significantly reduced the fungal burden in female Wistar rats infected with vaginal candidiasis, compared to the aqueous VCZ suspension (p < .05). Furthermore, in vivo histopathological findings proved the effectiveness and the safety of the optimized MLNCs formulation after vaginal application. Inclusively, MLNCs formulation could be a promising vaginal delivery system of VCZ for the treatment of vulvovaginal candidiasis.