Role of Posaconazole Drug in the Treatment of Invasive Fungal Disease: A Review.

Posaconazole is an antifungal medication used primarily to treat invasive fungal in-fections caused by various organisms, such as Aspergillus, Candida, and certain molds. It be-longs to the class of drugs known as triazole antifungals. Clinical studies have reported posaconazole to be effective in treating various invasive fungal infections, especially in patients who are immunocompromised, such as those with weakened immune systems due to conditions like HIV/AIDS, undergoing chemotherapy, or having received an organ transplant. It has ef-fectively treated invasive candidiasis, aspergillosis, zygomycosis, and other serious fungal in-fections. The effectiveness of the drug varies based on factors, such as the type of infection, the patient's immune status, and the site of infection. This review describes the types of infection, the drug's safety profile, the development of resistance to posaconazole, and strategies to man-age or prevent resistance.

Usage of Antifungal Agents in Pediatric Patients Versus Adults: Knowledge and Gaps.

Invasive fungal infections (IFIs) present significant challenges in managing hospitalized and immunocompromised pediatric patients, contributing to high morbidity and mortality. Despite advancements in diagnostics and treatment, outcomes remain suboptimal due to unique clinical epidemiology, lack of pediatric-specific trials, and varied pharmacokinetics. The emergence of new antifungal classes and agents has expanded our options for preventing and treating IFIs in children, enhancing the safety and effectiveness of antifungal therapy. The oral formulations of ibrexafungerp, fosmanogepix and olorofim along with the extended dosing intervals of rezafungin show promising features for effective antifungal treatment in pediatrics. Despite the promising potential of novel antifungal drugs, their performance in heavily immunosuppressed patients remains unstudied. Until then, dedicated antifungal stewardship programs for high-risk patients are essential to optimize therapeutic outcomes, improve patient care, and limit the emergence of resistance.

Aspergillus calidoustus and Talaromyces columbinus infections in chronic graft-versus-host disease.

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents.

Approaches for posaconazole therapeutic drug monitoring and their clinical benefits.

OBJECTIVE: This review examines the progress of research on posaconazole therapeutic drug monitoring (TDM) that has focused on differences in the TDM of posaconazole after clinical application in different formulations and in different populations, the factors that affect posaconazole concentrations, the advantages of posaconazole TDM in terms of clinical efficacy and cost savings, and measurement methods. METHODS: A literature search (2006 to 2024) was performed in PubMed and Embase with the following search terms: noxafil, posaconazole hydrate, posaconazole, drug monitoring, therapeutic drug monitoring, and TDM. Abstracts of review articles, prospective studies, and retrospective studies were reviewed. RESULTS: TDM should be implemented earlier for posaconazole tablets and injections than for oral posaconazole suspensions. Posaconazole TDM is beneficial for improving clinical efficacy, and the incidence of breakthrough invasive fungal infections (IFIs) can be significantly reduced by gradually adjusting the posaconazole dose in response to TDM in patients with inadequate trough concentrations. Early TDM allows more patients to achieve target therapeutic posaconazole concentrations. TDM can also facilitate dose adjustments, which reduce the cost of this expensive drug. Different assay techniques, including chromatography, microbiological detection, chemofluorimetry, paper spray mass spectrometry, and capillary electrophoresis, can be used for posaconazole TDM. CONCLUSIONS: Posaconazole TDM has potential clinical utility and cost-saving benefits and could improve the outcomes of IFI treatment.

Mucormycosis in an Immunocompetent Patient Recovering From Dengue Fever.

Mucormycosis is a rare yet aggressive fungal infection. Despite its rarity, India has experienced a surge in cases during the post-COVID-19 era. The high mortality rate associated with this infection necessitates early diagnosis, intervention, and aggressive treatment. Typically, it is observed in immunocompromised patients, where the disease progresses rapidly and leads to unfavorable outcomes. However, occurrences in previously healthy individuals are not uncommon. Dengue has been occasionally associated with mucormycosis in the post-recovery phase. This case report highlights the importance of heightened clinical suspicion and early intervention in patients with recent dengue infections and chronic sinus conditions. It explores potential risk factors, such as dengue-related immune alterations, environmental exposures, and anatomical alterations that may contribute to the development of mucormycosis in otherwise healthy individuals.

Breaking the mold: Insights into the clinical management and outcomes of rhinocerebral mucormycosis in adults.

Background: Rhinocerebral mucormycosis is a rare, life-threatening fungal infection that affects the sinuses, nasal passages, and brain. Its management remains challenging owing to high mortality rates. Combination antifungal therapy is an area of ongoing research aimed at improving outcomes. We aimed to describe the clinical management and outcomes of patients with rhinocerebral mucormycosis who were treated with antifungal combination therapy. Methods: This retrospective case series included 10 patients diagnosed with rhinocerebral mucormycosis at two academic medical centers between January 2008 and July 2023 who received initial antifungal therapy with liposomal amphotericin B (L-AmB), alone or in combination, within 24 h of diagnosis. Clinical data were extracted from the medical records. Results: Most patients were males (70 %) with uncontrolled diabetes (71.4 %). L-AmB was used as the initial therapy in all patients, either as monotherapy (n = 4) or combination therapy (n = 6), followed by posaconazole maintenance. The combinations included L-AmB with posaconazole (n = 4), L-AmB with micafungin (n = 3), or both (n = 3). The overall mortality rate was 50 %. Survivors had high morbidity, with median 31-day hospitalizations and 50 % readmission rate. Conclusions: Despite aggressive management, rhinocerebral mucormycosis has high mortality and morbidity rates. While combination antifungal therapy aims to improve cure rates, our case series showed higher mortality rates than monotherapy. Additional research is warranted to optimize management approaches for this devastating infection.

Individualized regimen of Posaconazole oral suspension in Chinese HSCT patients based on population pharmacokinetic model.

To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60-90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30-60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.

Hard Gelatin Capsules with Alginate-Hypromellose Microparticles as a Multicompartment Drug Delivery System for Sustained Posaconazole Release.

Microparticles as a multicompartment drug delivery system are beneficial for poorly soluble drugs. Mucoadhesive polymers applied in microparticle technology prolong the contact of the drug with the mucosa surface enhancing drug bioavailability and extending drug activity. Sodium alginate (ALG) and hydroxypropyl methylcellulose (hypromellose, HPMC) are polymers of a natural or semi-synthetic origin, respectively. They are characterized by mucoadhesive properties and are applied in microparticle technology. Spray drying is a technology employed in microparticle preparation, consisting of the atomization of liquid in a stream of gas. In this study, the pharmaceutical properties of spray-dried ALG/HPMC microparticles with posaconazole were compared with the properties of physical mixtures of powders with equal qualitative and quantitative compositions. Posaconazole (POS) as a relatively novel antifungal was utilized as a model poorly water-soluble drug, and hard gelatin capsules were applied as a reservoir for designed formulations. A release study in 0.1 M HCl showed significantly prolonged POS release from microparticles compared to a mixture of powders. Such a relationship was not followed in simulated vaginal fluid (SVF). Microparticles were also characterized by stronger mucoadhesive properties, an increased swelling ratio, and prolonged residence time compared to physical mixtures of powders. The obtained results indicated that the pharmaceutical properties of hard gelatin capsules filled with microparticles were significantly different from hard gelatin capsules with mixtures of powders.

Optimizing Ni-Cr patterned boron-doped diamond band electrodes: Doping effects on electrochemical efficiency and posaconazole sensing performance.

There is growing interest in developing diamond electrodes with defined geometries such as, for example, micrometer-sized electrode arrays to acquire signals for electroanalysis. For electroanalytical sensing applications, it is essential to achieve precise conductive patterns on the insulating surface. This work provides a novel approach to boron-doped diamond patterning using nichrome masking for selective seeding on an oxidized silicon substrate. The optimized process involves nichrome deposition, sonication, chemical etching, seeding, and tailored chemical vapor deposition of boron-doped diamond with an intrinsic layer to suppress boron diffusion. Through a systematic investigation, it was determined that isolated boron-doped diamond band electrodes can be efficiently produced on non-conductive silica. Additionally, the influence of boron doping on electrochemical performance was studied, with higher doping enhancing the electrochemical response of band electrodes. To demonstrate sensing capabilities, boron-doped diamond bands were used to detect posaconazole, an antifungal drug, exploiting its electroactive behaviour. A linear correlation between posaconazole concentration and oxidation peak current was observed over 1.43 × 10-8 - 5.71 × 10-6 M with a 1.4 × 10-8 M detection limit. The developed boron-doped diamond microbands could significantly impact the field of electroanalysis, facilitating detection of diverse biologically relevant molecules. Overall, this diamond patterning approach overcomes major challenges towards all-diamond electrochemical sensor chips.

Posaconazole gastro-resistant tablets for preventing invasive fungal disease after haematopoietic stem cell transplantation: a propensity-matched cohort study.

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DISCUSSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

AQbD-guided development and validation of an innovative extraction procedure and stability-indicating RP-HPLC method for quantification of posaconazole in tablet formulation.

OBJECTIVE: The objective of this work is to develop a stability-indicating HPLC method for the quantification of posaconazole (PCZ) in tablet formulation using an Analytical Quality by Design (AQbD) approach. MATERIALS AND METHODS: The development process involved the Design of Experiments (DOE) utilizing distinctive constraints mixture design for mobile phase ratio optimization and a 2-level factorial design for selection of extraction diluent compositions. Key responses measured included % assay and system suitability parameters. Method operable design regions (MODR) were determined, and final optimum conditions were selected. Forced degradation studies were conducted to assess method stability. RESULTS: The optimized HPLC method employed a Zorbax C18 column with a mobile phase consisting of pH 3.5 10mM phosphate buffer, acetonitrile, and methanol in a ratio of 30:53:17% v/v/v. The method demonstrated stability-indicating capabilities, with PCZ degradation observed in acidic and oxidative environments, while remaining stable in alkali. Peak purity analysis from Empower software confirmed the absence of interaction with degradants. Validation according to ICH Q2 (R2) guidelines showed precision, linearity over the range of 0.25 to 376µg/mL, and accuracy demonstrated through recovery studies from 50 to 150%. CONCLUSION: The developed HPLC method utilizing AQbD approach is specific, robust, precise, and accurate for the quantification of PCZ in tablet formulations, thus suitable for routine analysis.

Posaconazole-hemp seed oil loaded nanomicelles for invasive fungal disease.

Invasive fungal infections (IFI) pose a significant health burden, leading to high morbidity, mortality, and treatment costs. This study aims to develop and characterize nanomicelles for the codelivery of posaconazole and hemp seed oil for IFI via the oral route. The nanomicelles were prepared using a nanoprecipitation method and optimized through the Box Behnken design. The optimized nanomicelles resulted in satisfactory results for zeta potential, size, PDI, entrapment efficiency, TEM, and stability studies. FTIR and DSC results confirm the compatibility and amorphous state of the prepared nanomicelles. Confocal laser scanning microscopy showed that the optimized nanomicelles penetrated the tissue more deeply (44.9µm) than the suspension (25µm). The drug-loaded nanomicelles exhibited sustained cumulative drug release of 95.48 ± 3.27% for 24 h. The nanomicelles showed significant inhibition against Aspergillus niger and Candida albicans (22.4 ± 0.21 and 32.2 ± 0.46 mm, respectively). The pharmacokinetic study on Wistar rats exhibited a 1.8-fold increase in relative bioavailability for the nanomicelles compared to the suspension. These results confirm their therapeutic efficacy and lay the groundwork for future research and clinical applications, providing a promising synergistic antifungal nanomicelles approach for treating IFIs.

Antifungal Susceptibility and Genotypic Analysis of cyp51A Mutations in Aspergillus fumigatus Isolates in Malaysia.

Purpose: Azole resistance in Aspergillus fumigatus poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and cyp51A mutation profiles of A. fumigatus isolates in Malaysia. Patients and Methods: Sixty clinical A. fumigatus isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC50/MIC90 for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against A. fumigatus in non-invasive cases and invasive cases were calculated. In addition, the presence of cyp51A mutations was also identified. Results: The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various cyp51A mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance. Conclusion: The majority of clinical Aspergillus fumigatus isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, cyp51A mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.

Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis.

INTRODUCTION: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies. AREAS COVERED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals. EXPERT OPINION: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.

Plasma Venetoclax Concentrations in Patients with Acute Myeloid Leukemia Treated with CYP3A4 Inhibitors.

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.

An Update on Breakthrough Invasive Mold Infections.

The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.

Evaluation of Posaconazole Serum Concentrations Achieved With Delayed-release Tablets and Oral Suspension in Patients Undergoing Intensive Chemotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Data on posaconazole serum levels of patients on prophylaxis with delayed-release tablets or oral suspension during intensive chemotherapy for acute myeloid leukemia and myelodysplastic syndrome are scarce. In this analysis, the proportion of patients with acute myeloid leukemia/myelodysplastic syndrome achieving posaconazole target concentrations with delayed-release tablets was higher than with oral suspension.

Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and in vivo evaluation.

OBJECTIVE: Posaconazole (PCZ) is an antifungal drug, which acts by inhibiting the lanosterol-14α-demethylase enzyme. It is a biopharmaceutical classification system class II drug with its bioavailability being limited by poor aqueous solubility. The aim of this study was to improve the oral bioavailability of PCZ by preparing nanocrystalline solid dispersion (NCS). METHODS: PCZ-NCS was prepared by a combination of precipitation and high-pressure homogenization followed by freeze-drying. Several different surfactants and polymers were screened to produce NCS with smaller particle size and higher stability. RESULTS: The optimized NCS formulation containing 0.2% Eudragit S100 and 0.2% SLS was found to provide the average particle size of 73.31 ± 4.7 nm with a polydispersity index of 0.23 ± 0.03. Scanning electron microscopy revealed the preparation of homogeneous and rounded particles. Differential scanning calorimetry and X-ray diffraction confirmed crystalline nature of NCS. Nanonization increased the saturation solubility of PCZ by about 18-fold in comparison with the neat drug. Intrinsic dissolution study showed 93% dissolution of PCZ within the first 10 min. In vivo pharmacokinetic study in Wistar rats showed that Cmax and AUCtotal of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation. CONCLUSION: PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.

Breakthrough Invasive Fungal Infections in Patients With High-Risk Hematological Disorders Receiving Voriconazole and Posaconazole Prophylaxis: A Systematic Review.

BACKGROUND: Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis. METHODS: We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023. RESULTS: We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%. CONCLUSIONS: In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management.

Management of disseminated histoplasmosis in a high-complexity clinic in Cali, Colombia.

Histoplasmosis presents a substantial clinical challenge globally, with a particular prevalence in South America, especially among patients with concurrent Human Immunodeficiency Virus (HIV) infection. Despite itraconazole's established efficacy, investigating alternative therapeutic approaches remains imperative. This is the largest study in our region to date, assessing the effectiveness of the less explored posaconazole treatment. This observational study, conducted at Fundación Valle del Lili (FVL) from 2016 to 2022, encompassed adults with disseminated histoplasmosis. Patients (n = 31) were treated with liposomal amphotericin B as an initial treatment, followed by consolidation treatment with posaconazole or itraconazole. Patients with single-organ cases, those lacking microbiological diagnosis, those who received initial treatment with antifungals other than liposomal Amphotericin B and those with < 6 months follow-up were excluded (Figure 1). Analyses considered population characteristics, treatments, and outcomes. Patients (average age: 45.6; 58.1% female) had common comorbidities (HIV 38.7%, solid organ transplantation 29% and oncologic disease 12.9%). Lungs (48.4%) and lymph nodes (16.1%) were commonly affected. Biopsy (64.5%) was the primary diagnostic method. Initial treatment with liposomal amphotericin B (100%) was given for 14 days on average. Follow-up indicated 71% completion with 19.4% requiring treatment modifications. Notably, 70.9% completed a posaconazole consolidation regimen over 350 days on average. Drug interactions during consolidation (80.6%) were common. No relapses occurred, and three deaths unrelated to histoplasmosis were reported. Traditionally, itraconazole has been the prevalent initial treatment; however, in our cohort, 55.9% of patients received posaconazole as the primary option. Encouragingly, posaconazole showed favorable tolerance and infection resolution, suggesting its potential as an effective and well-tolerated alternative for consolidation treatment. This finding prompts further exploration of posaconazole, potentially leading to more effective patient care and better outcomes.

Histoplasmosis is a critical concern in South America, notably among human immunodeficiency virus patients, leading to high mortality rates. This study, the largest in our region, investigates the effectiveness of posaconazole as an alternative treatment to itraconazole. The results offer the potential for enhanced patient care and improved outcomes.