RESUMEN
Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host. In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals-usually used off-label in paediatrics-to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population.
Asunto(s)
Antibacterianos , Antifúngicos , Monitoreo de Drogas , Humanos , Recién Nacido , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antifúngicos/uso terapéutico , Antifúngicos/farmacocinética , Antifúngicos/efectos adversos , Antifúngicos/administración & dosificación , Niño , Lactante , Preescolar , España , Servicio de Farmacia en HospitalRESUMEN
Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host. In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals-usually used off-label in paediatrics-to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population.
Asunto(s)
Antibacterianos , Antifúngicos , Monitoreo de Drogas , Humanos , Recién Nacido , Monitoreo de Drogas/métodos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Niño , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Lactante , PreescolarRESUMEN
Lomentospora prolificans is a rare filamentous fungus that causes invasive fungal disease (IFD) in immunocompromised patients with hematological malignancies, as well as hematopoietic cell or solid organ transplant recipients. A 75-year-old woman was diagnosed with acute myeloid leukemia, and started induction therapy with azacitidine and adjusted-dose venetoclax along with antifungal prophylaxis with fluconazole. On day 7, she became febrile and chest CT imaging showed multiple nodules in both lung fields, and the serum galactomannan antigen index became positive, indicating probable IFD. Anti-fungal therapy with liposomal amphotericin B was immediately initiated; however, the patient's condition rapidly deteriorated, and she died on day 15. L. prolificans was later identified in blood culture tests that had been repeatedly performed while she had been febrile. L. prolificans is generally resistant to most antifungal agents, which can make it fatal. As early definitive diagnosis is difficult, it may be appropriate to consider combination therapy when conventional anti-IFD therapy seems inadequate.
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Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Femenino , Azacitidina/administración & dosificación , Azacitidina/uso terapéutico , Sulfonamidas/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Resultado Fatal , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Quimioterapia de Inducción , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/diagnóstico , Micosis/tratamiento farmacológico , Micosis/diagnósticoRESUMEN
Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.
Asunto(s)
Anfotericina B , Antifúngicos , Enfermedades Hematológicas , Infecciones Fúngicas Invasoras , Terapia Recuperativa , Humanos , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Anfotericina B/uso terapéutico , Estudios Retrospectivos , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/uso terapéutico , Terapia Recuperativa/métodos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Enfermedades Hematológicas/complicaciones , Resultado del Tratamiento , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.
Asunto(s)
Anfotericina B , Antifúngicos , Broncoscopía , Mucormicosis , Aspergilosis Pulmonar , Humanos , Masculino , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Persona de Mediana Edad , Mucormicosis/tratamiento farmacológico , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Aspergilosis Pulmonar/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Coinfección/tratamiento farmacológico , Mucor/aislamiento & purificación , Tomografía Computarizada por Rayos XRESUMEN
A 6-year-old Hispanic patient presented with a 1-month history of pruritic patches on her scalp, characterized by hair loss, black dots, and dandruff-like scales. The patient was seen by her primary care physician, who prescribed ketoconazole 2% shampoo. This provided little relief for her symptoms, which prompted her admission to nearby hospital, where fluconazole was administered intravenously and mometasone lotion applied. The patient was discharged and instructed to use the ketoconazole shampoo and mometasone lotion. The previously prescribed medications failed to improve her now enlarged, inflamed, scaly, pustule-speckled lesions. Given her condition, she was admitted to the University Pediatric Hospital in San Juan, where the Dermatology Department was consulted. Cultures were taken from the lesions, revealing the presence of Trichophyton tonsurans, which led to the diagnosis of tinea capitis (ringworm of the scalp) with kerion formation. In addition, multiple nits and adult lice characteristic of Pediculus humanus capitis were observed. A 6-week course of griseofulvin, a 1-week course of permethrin solution, and a 5-day course of oral prednisolone were started, effectively cleared the patient's inflammation and fungal infection. This case highlights how there exist areas of improvement in terms of interprofessional communication between physicians, as well a need to increase awareness of the proper treatment for this common pediatric skin condition. We postulate that in doing so, similar cases could be spared the unfortunate results of untreated tinea capitis, that is, kerion formation and the possible scarring this lesion can produce.
Asunto(s)
Antifúngicos , Tiña del Cuero Cabelludo , Humanos , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/microbiología , Femenino , Niño , Antifúngicos/administración & dosificación , Factores de Tiempo , Griseofulvina/administración & dosificación , Retraso del TratamientoRESUMEN
Chronic pulmonary aspergillosis (CPA) represents a spectrum of lung disorders caused by local proliferation of Aspergillus hyphae in individuals with non-systemic or mildly systemic immunodepression or altered pulmonary integrity due to underlying disease. While long-term systemic antifungal treatment is still the mainstay for management, surgery is considered mainly in rarer invasive disease manifestations such as sinusitis and osteomyelitis. Optimal application of existing antifungal agents with suitable pharmacokinetic properties is important for the treatment of diseases such as CPA, which requires long-term use. Appropriate management of side effects by therapeutic drug monitoring, maintenance of adherence, and assessment of drug resistance to Aspergillus can provide safe and effective treatment in the future. Most available antifungal agents for the management of mycoses in humans have disadvantages that can limit their use in clinical practice. By contrast, second generation antifungals such as triazoles have advantages of extended antifungal spectrum and availability in both oral and intravenous formulations. Isavuconazole, a new extended spectrum triazole, has been shown to be effective against Aspergillus. The safety profile and excellent pharmacokinetic characteristics of isavuconazole make it an attractive option for treatment of invasive fungal infections including CPA. With this drug now available in Japan, new evidence is expected to expand treatment options. This review focuses on the selection of antifungal agents based on national and international guidelines and the characteristics of each agent for their appropriate use in CPA.
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Antifúngicos , Aspergilosis Pulmonar , Triazoles , Humanos , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Aspergilosis Pulmonar/tratamiento farmacológico , Enfermedad Crónica , Triazoles/farmacocinética , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Aspergillus/efectos de los fármacos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/farmacocinética , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Nitrilos/farmacocinética , Farmacorresistencia FúngicaAsunto(s)
Antifúngicos , Nitrilos , Piridinas , Triazoles , Humanos , Triazoles/farmacocinética , Triazoles/administración & dosificación , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Piridinas/farmacocinética , Piridinas/administración & dosificación , Nitrilos/farmacocinética , Nitrilos/administración & dosificación , Infusiones Intravenosas , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Voluntarios SanosRESUMEN
Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA , Antifúngicos , Histoplasma , Histoplasmosis , Humanos , Masculino , Adulto , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Histoplasma/aislamiento & purificación , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Huésped InmunocomprometidoRESUMEN
Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.
Asunto(s)
Anfotericina B , Antifúngicos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Enfermedades Pulmonares Fúngicas , Mucormicosis , Humanos , Anfotericina B/administración & dosificación , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Antifúngicos/administración & dosificación , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Resultado del Tratamiento , Inyecciones Intralesiones , Persona de Mediana Edad , BroncoscopíaRESUMEN
INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.
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Infecciones Oportunistas Relacionadas con el SIDA , Síndrome de Inmunodeficiencia Adquirida , Anfotericina B , Antifúngicos , Ácido Desoxicólico , Histoplasmosis , Humanos , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/inmunología , Masculino , Femenino , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Adulto , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Persona de Mediana Edad , Ácido Desoxicólico/uso terapéutico , Ácido Desoxicólico/administración & dosificación , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Recuento de Linfocito CD4 , Brasil/epidemiología , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Reconstitución Inmune , Combinación de Medicamentos , Quimioterapia de Consolidación , Estudios Retrospectivos , Cumplimiento de la Medicación/estadística & datos numéricos , Recurrencia , Duración de la Terapia , Resultado del Tratamiento , Estudios de Seguimiento , Terapia Antirretroviral Altamente ActivaRESUMEN
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.
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Antifúngicos , Trasplante de Células Madre Hematopoyéticas , Triazoles , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración Oral , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , China , Pueblos del Este de Asia , Modelos Biológicos , Estudios Retrospectivos , Suspensiones , Triazoles/farmacocinética , Triazoles/administración & dosificaciónRESUMEN
BACKGROUND: Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. METHODS: A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. RESULTS: A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. CONCLUSIONS: Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients.
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Antifúngicos , Micosis , Infecciones Relacionadas con Prótesis , Humanos , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/terapia , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Micosis/terapia , Micosis/cirugía , Factores de Riesgo , Resultado del TratamientoRESUMEN
The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.
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Antifúngicos , Biopelículas , Candida albicans , Ciclosporina , Sinergismo Farmacológico , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Voriconazol , Voriconazol/administración & dosificación , Voriconazol/farmacología , Voriconazol/química , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antifúngicos/química , Candida albicans/efectos de los fármacos , Nanopartículas/química , Ciclosporina/administración & dosificación , Ciclosporina/farmacología , Ciclosporina/química , Biopelículas/efectos de los fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Portadores de Fármacos/química , Polietilenglicoles/química , Pruebas de Sensibilidad Microbiana , Ácido Láctico/químicaRESUMEN
Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of â¼ 68.96â¯% and extra fine particle fraction of â¼ 36.87â¯%, equivalently â¼ 4.60â¯mg and â¼ 2.46â¯mg could reach the lung and alveoli, respectively, when inhaling 10â¯mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.
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Sistemas de Liberación de Medicamentos , Itraconazol , Pulmón , Tamaño de la Partícula , Itraconazol/química , Itraconazol/administración & dosificación , Itraconazol/farmacocinética , Pulmón/metabolismo , Administración por Inhalación , Taraxacum/química , Polvos/química , Liofilización , Aerosoles/química , Nanopartículas/química , Propiedades de Superficie , Antifúngicos/química , Antifúngicos/administración & dosificación , Vitamina ERESUMEN
Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 FFDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.
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Adenocarcinoma del Pulmón , Criptococosis , Enfermedades Pulmonares Fúngicas , Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Persona de Mediana Edad , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Antifúngicos/administración & dosificación , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/patología , Criptococosis/terapia , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Pulmón/patología , Pulmón/cirugía , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/terapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Cirugía Torácica Asistida por Video , Tomografía Computarizada por Rayos XRESUMEN
Mucormycosis is a rare opportunistic infection caused by Mucorales fungi. Cutaneous mucormycosis typically present as chronic indolent infection, whereas rhino-orbital mucormycosis is rapidly progressive disease often invade the adjacent cerebral tissue associated with high mortality. This case represents the atypical clinical history of rhino-orbital-cutaneous mucormycosis. The patient was presented with a right orbital cellulitis associated with an extensive multiple suppurative deep cutaneous infection and worsening headache. The skin lesion was initiated from a localized abscess at the right periorbital area nine months before admission. Suspicion of fungal infection was raised after weeks of non-responsive antibiotics treatment. Aggressive treatment with exoneration of the right eye and surgical debridement was undertaken. Periodic acid Schiff staining from healthy periorbital tissue revealed ribbon-like hyphae with pauciseptate and 90° branching identified as Mucoraceaefamily. The resolution was seen after four weeks of antifungal treatment with Amphotericin B.
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Anfotericina B , Antifúngicos , Desbridamiento , Mucormicosis , Humanos , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Masculino , Desbridamiento/métodos , Dermatomicosis/diagnóstico , Dermatomicosis/microbiología , Dermatomicosis/tratamiento farmacológico , Inmunocompetencia , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/microbiología , Enfermedades Orbitales/terapia , Mucorales/aislamiento & purificación , Persona de Mediana Edad , Cefalea/etiologíaRESUMEN
In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.
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Antifúngicos , Candidiasis Bucal , Liberación de Fármacos , Miconazol , Impresión Tridimensional , Miconazol/administración & dosificación , Miconazol/química , Miconazol/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/química , Antifúngicos/farmacocinética , Administración Bucal , Candidiasis Bucal/tratamiento farmacológico , Humanos , Zeína/química , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiología , Povidona/química , Permeabilidad , Sistemas de Liberación de Medicamentos/métodos , Animales , Química Farmacéutica/métodos , NiñoRESUMEN
Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.
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Antifúngicos , Candida albicans , Candidiasis Vulvovaginal , Celulosa , Clotrimazol , Nanopartículas , Clotrimazol/administración & dosificación , Clotrimazol/farmacología , Candidiasis Vulvovaginal/tratamiento farmacológico , Nanopartículas/química , Candida albicans/efectos de los fármacos , Femenino , Celulosa/química , Celulosa/análogos & derivados , Antifúngicos/farmacología , Antifúngicos/administración & dosificación , Polímeros/química , Tamaño de la Partícula , Pruebas de Sensibilidad Microbiana/métodos , Liberación de FármacosRESUMEN
OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.