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1.
Dermatol Surg ; 46(1): 78-85, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807385

RESUMO

BACKGROUND: The study proposes a novel protocol for targeting the jowls using deoxycholic acid (DCA) injections, with emphasis on safety and feasibility of the procedure. METHODS: This prospective study was conducted at a cosmetic practice between June 2016 and May 2017. Twelve consecutive patients seeking reduction/improvement in mild/moderate jowl fat were injected with DCA subcutaneously in a predefined circular area 1.0 cm above the mandibular border. Treatment response was assessed using physician-evaluated Global Aesthetic Improvement Scale (GAIS) and Subject GAIS. RESULTS: Twelve patients (11 women and 1 man) with mild (n = 8) or moderate (n = 4) jowls were treated. After the first treatment, GAIS responses for 24 jowls showed 5 jowls with vast improvement, 15 with moderate improvement, and 4 with no change. After the second session for 5 jowls in 3 patients, GAIS responses showed vast improvement in 4 jowls and moderate improvement in 1. Adverse events included induration (n = 4), bruising (n = 6), numbness (n = 2), pain (n = 5), redness (n = 3), edema (n = 9), and dysphagia (n = 1). CONCLUSION: Results of this early experience showed that DCA injections were safe and effective for nonsurgical jowl reduction.


Assuntos
Queixo , Colagogos e Coleréticos/uso terapêutico , Técnicas Cosméticas , Ácido Desoxicólico/uso terapêutico , Idoso , Estudos de Viabilidade , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
BMC Infect Dis ; 19(1): 1034, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805893

RESUMO

BACKGROUND: The incidence of Taralomyces marneffei infection in HIV-infected individuals has been decreasing, whereas its rate is rising among non-HIV immunodeficient persons, particularly patients with anti-interferon-gamma autoantibodies. T. marneffei usually causes invasive and disseminated infections, including fungemia. T. marneffei oro-pharyngo-laryngitis is an unusual manifestation of talaromycosis. CASE PRESENTATION: A 52-year-old Thai woman had been diagnosed anti-IFNÉ£ autoantibodies for 4 years. She had a sore throat, odynophagia, and hoarseness for 3 weeks. She also had febrile symptoms and lost 5 kg in weight. Physical examination revealed marked swelling and hyperemia of both sides of the tonsils, the uvula and palatal arches including a swelling of the epiglottis, and arytenoid. The right tonsillar biopsy exhibited a few intracellular oval and elongated yeast-like organisms with some central transverse septum seen, which subsequently grew a few colonies of T. marneffei on fungal cultures. The patient received amphotericin B deoxycholate 45 mg/dayfor 1 weeks, followed by oral itraconazole 400 mg/day for several months. Her symptoms completely resolved without complication. CONCLUSION: In patients with anti-IFN-É£ autoantibodies, T. marneffei can rarely cause a local infection involving oropharynx and larynx. Fungal culture and pathological examination are warranted for diagnosis T. marneffei oro-pharyngo-laryngitis. This condition requires a long term antifungal therapy.


Assuntos
Antifúngicos/uso terapêutico , Laringite/tratamento farmacológico , Micoses/tratamento farmacológico , Faringite/tratamento farmacológico , Talaromyces/patogenicidade , Anfotericina B/uso terapêutico , Autoanticorpos/sangue , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Interferon gama/imunologia , Itraconazol/uso terapêutico , Laringite/microbiologia , Laringite/patologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/patogenicidade , Micoses/etiologia , Micoses/microbiologia , Faringite/microbiologia , Faringite/patologia , Tailândia
3.
Mycoses ; 62(11): 1049-1055, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479538

RESUMO

Antifungal treatment options for allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) are largely limited to itraconazole based on the outcome of randomised controlled trials. It is unclear if nebulised amphotericin B deoxycholate (Fungizone® ) is a viable therapeutic option. We evaluated the safety and efficacy of nebulised Fungizone® in the long-term treatment of various forms of pulmonary aspergillosis. We assessed the records of 177 patients with various forms of pulmonary aspergillosis attending the National Aspergillosis Centre in Manchester who had received Fungizone® . Patients first received a challenge test with nebulised Fungizone® in hospital with spirometry pre/post-Fungizone® and nebulised salbutamol given pre-Fungizone® . Tolerability and changes in Aspergillus IgE, Aspergillus IgG and total IgE were evaluated. Sixty-six per cent (117/177) were able to tolerate the test dose of Fungizone® and in all cases, the reason for discontinuation of the first test dose was worsening breathlessness. Twenty six (21%) stopped therapy within 4-6 weeks, and the commonest reason cited for discontinuation of therapy was increased breathlessness, hoarseness and cough. Eighteen (10.2%) patients continued the Fungizone® for >3 months of which 5 (27.8%) recorded an improvement in total IgE, Aspergillus-specific IgE and Aspergillus IgG. Eleven had ABPA, four had SAFS, two had Aspergillus bronchitis and one had Aspergillus sensitisation with cavitating nodules. Among these 18 patients, sputum fungal culture results went from positive to negative in five patients, became positive in one patient, remained positive in three patients, and remained negative in seven patients. Nebulised Fungizone® appears to be a poorly tolerated treatment for pulmonary Aspergillosis with high dropout rates. There appears to be both clinical and serological benefits following sustained treatment with nebulised Fungizone® in some patients.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ácido Desoxicólico/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Nebulizadores e Vaporizadores , Aspergilose Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/efeitos adversos , Anticorpos Antifúngicos/sangue , Antifúngicos/efeitos adversos , Aspergillus/efeitos dos fármacos , Ácido Desoxicólico/efeitos adversos , Vias de Administração de Medicamentos , Combinação de Medicamentos , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido , Adulto Jovem
4.
PLoS One ; 14(7): e0214705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276498

RESUMO

Despite reducing the prevalent foodborne pathogen Campylobacter jejuni in chickens decreases campylobacteriosis, few effective approaches are available. The aim of this study was to use microbial metabolic product bile acids to reduce C. jejuni chicken colonization. Broiler chicks were fed with deoxycholic acid (DCA), lithocholic acid (LCA), or ursodeoxycholic acid (UDCA). The birds were also transplanted with DCA modulated anaerobes (DCA-Anaero) or aerobes (DCA-Aero). The birds were infected with human clinical isolate C. jejuni 81-176 or chicken isolate C. jejuni AR101. Notably, C. jejuni 81-176 was readily colonized intestinal tract at d16 and reached an almost plateau at d21. Remarkably, DCA excluded C. jejuni cecal colonization below the limit of detection at 16 and 28 days of age. Neither chicken ages of infection nor LCA or UDCA altered C. jejuni AR101 chicken colonization level, while DCA reduced 91% of the bacterium in chickens at d28. Notably, DCA diet reduced phylum Firmicutes but increased Bacteroidetes compared to infected control birds. Importantly, DCA-Anaero attenuated 93% of C. jejuni colonization at d28 compared to control infected birds. In conclusion, DCA shapes microbiota composition against C. jejuni colonization in chickens, suggesting a bidirectional interaction between microbiota and microbial metabolites.


Assuntos
Infecções por Campylobacter/veterinária , Campylobacter jejuni/fisiologia , Galinhas/microbiologia , Ácido Desoxicólico/uso terapêutico , Doenças das Aves Domésticas/prevenção & controle , Substâncias Protetoras/uso terapêutico , Animais , Infecções por Campylobacter/metabolismo , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/prevenção & controle , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/isolamento & purificação , Galinhas/metabolismo , Ácido Desoxicólico/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/microbiologia , Substâncias Protetoras/metabolismo
5.
Facial Plast Surg ; 35(3): 274-277, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31189201

RESUMO

There has been an increasing interest in addressing the issue of submental fat (SMF) when it comes to cosmetic medicine. With the rise of social media, video calls, and the now almost omnipresent accessibility of cameras, there is perhaps now more than ever an emphasis on the facial image. Although invasive procedures such as liposuction and neck lift still play a significant role in reducing SMF, the trend toward minimally invasive methods has finally given rise to a single Food and Drug Administration-approved injectable that is both safe and effective: ATX-101, also known as Kybella in the United States.


Assuntos
Ácido Desoxicólico/uso terapêutico , Queixo , Técnicas Cosméticas , Injeções Subcutâneas , Gordura Subcutânea
6.
PLoS One ; 14(6): e0218786, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242231

RESUMO

BACKGROUND: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. METHODS: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. RESULTS: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78-13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09-0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). CONCLUSION: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML.


Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis , Leishmaniose Mucocutânea/tratamento farmacológico , Lesão Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/efeitos adversos , Antimônio/efeitos adversos , Antimônio/uso terapêutico , Antiprotozoários/efeitos adversos , Brasil , Estudos de Coortes , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Itraconazol/efeitos adversos , Itraconazol/uso terapêutico , Lipossomos , Masculino , Pessoa de Meia-Idade , Pentamidina/efeitos adversos , Pentamidina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Mycoses ; 62(8): 686-691, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31120606

RESUMO

Cryptococcal meningitis (CM) carries a high risk of mortality with increasing incidences in immune competent hosts. Current treatments are not well tolerated, and evaluation of other treatments is needed. Fluconazole and 5-flucytosine in treating immune competent hosts have not been characterised. To evaluate the efficacy of fluconazole and 5-flucytosine in treating non-HIV- and non-transplant-associated CM. We performed a retrospective cohort study of the outcomes in immune competent patients with CM treated with fluconazole and 5-flucytosine or deoxycholate-amphotericin B and 5-flucytosine. The primary outcome was treatment response evaluated at the 12th week after initiation of antifungal therapy. A total of 43 and 47 patients received amphotericin B deoxycholate and 5-flucytosine or fluconazole and 5-flucytosine, respectively. A total of 38 (88.4%) patients cannot tolerate recommended doses of amphotericin B deoxycholate and 5-flucytosine (patients needed dose reduction during the treatment). Patients given fluconazole and 5-flucytosine had higher baseline cryptococcal burdens (median 3632 versus 900 cryptococci/mL, P = 0.008). No significant differences were seen in cryptococcus clearance (74.4% vs 70.2%, P = 0.814), treatment time (39 days, 20-69 days vs 21 days, 7-63 days, P = 0.107) and successful response (including complete and partial responses) rates (69.7% vs 72.3%, P = 0.820). Fluconazole and 5-flucytosine treatment had lower total adverse events (19.1% vs 90.7%, P < 0.001). Fluconazole and 5-flucytosine had relatively high efficacy with few adverse events in treating CM. Fluconazole and 5-flucytosine therapy is promising in patients that do not tolerate or are not suited for amphotericin B deoxycholate treatment.


Assuntos
Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Adulto , Anfotericina B/uso terapêutico , Cryptococcus/efeitos dos fármacos , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV , Humanos , Imunocompetência , Masculino , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Transplante de Órgãos , Estudos Retrospectivos , Resultado do Tratamento
8.
mBio ; 10(3)2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138748

RESUMO

Cryptococcus neoformans is an encapsulated yeast responsible for approximately a quarter of a million deaths worldwide annually despite therapy, and upwards of 11% of HIV/AIDS-related deaths, rivaling the impact of tuberculosis and malaria. However, the most effective antifungal agent, amphotericin B, requires intravenous delivery and has significant renal and hematopoietic toxicity, making it difficult to utilize, especially in resource-limited settings. The present studies describe a new nanoparticle crystal encapsulated formulation of amphotericin B known as encochleated amphotericin B (CAmB) that seeks to provide an oral formulation that is low in toxicity and cost. Using a 3-day delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A C. neoformans, CAmB, in combination with flucytosine, was found to have efficacy equivalent to parental amphotericin B deoxycholate with flucytosine and superior to oral fluconazole without untoward toxicity. Transport of fluorescent CAmB particles to brain as well as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of mice treated with conventional amphotericin B. Additional toxicity studies using a standardized rat model showed negligible toxicity after a 28-day treatment schedule. These studies thus offer the potential for an efficacious oral formulation of a known fungicidal drug against intrathecal cryptococcal disease.IMPORTANCE Cryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Administração Oral , Anfotericina B/química , Animais , Antifúngicos/química , Cryptococcus neoformans/efeitos dos fármacos , Ácido Desoxicólico/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Composição de Medicamentos , Quimioterapia Combinada , Feminino , Flucitosina/uso terapêutico , Lipídeos/química , Masculino , Meningoencefalite/microbiologia , Camundongos , Nanopartículas/química , Ratos , Ratos Sprague-Dawley
9.
Am J Health Syst Pharm ; 76(11): 810-813, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30994894

RESUMO

PURPOSE: We describe the use of liposomal amphotericin B and amphotericin B deoxycholate in a critically ill patient with pulmonary blastomycosis receiving both venovenous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). SUMMARY: A 50-year-old African American man presented for dyspnea and cough and was noted to have blastomycosis on bronchoscopy. He developed respiratory failure and acute kidney injury, requiring mechanical ventilation, ECMO, and CRRT. After 4 days of liposomal amphotericin, the transmembrane pressure gradient on the membrane oxygenator increased dramatically without visualization of a clot, requiring a circuit exchange. A trough amphotericin B level taken the day before the exchange was undetectable for amphotericin B. After the circuit exchange, the patient was switched to amphotericin B deoxycholate. A subsequent trough level was 3.8 µg/mL. The patient improved and was able to be decannulated. However, he did require tracheostomy and long-term hemodialysis. CONCLUSION: In our case we believe that liposomal amphotericin B was significantly removed by ECMO and was responsible for the failure of the ECMO circuit. We would suggest amphotericin B deoxycholate be used in such patients preferentially and that serum levels of the drug be assessed when possible.


Assuntos
Anfotericina B/farmacologia , Blastomicose/terapia , Ácido Desoxicólico/farmacologia , Oxigenação por Membrana Extracorpórea/instrumentação , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Anfotericina B/química , Anfotericina B/uso terapêutico , Área Sob a Curva , Blastomicose/sangue , Blastomicose/complicações , Terapia Combinada/métodos , Estado Terminal/terapia , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Substituição de Medicamentos , Falha de Equipamento , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenadores de Membrana/efeitos adversos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Resultado do Tratamento
10.
Transpl Infect Dis ; 21(3): e13075, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868691

RESUMO

Pleurostomophora richardsiae is a dematiaceous mold that causes subcutaneous cystic phaeohyphomycosis. Few cases of invasive P richardsiae infection have been reported. Hepatic artery thrombosis following organ transplantation caused by a fungal organism is also very rare. We present here a 57-year-old man with refractory ascites and liver failure following liver transplantation for treatment of hepatocellular carcinoma. Abdominal computed tomography demonstrated total occlusion of hepatic artery and blood clot in the portal vein and inferior vena cava. P richardsiae was isolated from blood culture and the blood clot in his liver. The patient was treated successfully with a 4-week course of amphotericin B deoxycholate and liver retransplantation.


Assuntos
Ascomicetos/patogenicidade , Artéria Hepática/microbiologia , Transplante de Fígado/efeitos adversos , Feoifomicose/sangue , Veia Porta/microbiologia , Trombose/microbiologia , Abdome/diagnóstico por imagem , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Humanos , Fígado/microbiologia , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Feoifomicose/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
BMC Infect Dis ; 19(1): 220, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832607

RESUMO

BACKGROUND: Cryptococcosis is a common opportunistic infection in patients infected by Human Immunodeficiency Virus (HIV) and is the second leading cause of mortality in Acquired Immunodeficiency Syndrome (AIDS) patients worldwide. The most frequent presentation of cryptococcal infection is subacute meningitis, especially in patients with a CD4+ T Lymphocytes count below 100 cells/µL. However, in severely immunosuppressed individuals Cryptococcus neoformans can infect virtually any human organ, including the bone marrow, which is a rare presentation of cryptococcosis. CASE PRESENTATION: A 45-year-old HIV-infected male patient with a CD4+ T lymphocyte count of 26 cells/µL who presented to the emergency department with fever and pancytopenia. Throughout the diagnostic evaluation, the bone marrow aspirate culture yielded encapsulated yeasts in budding, identified as Cryptococcus sp. The bone marrow biopsy revealed a hypocellularity for age and absence of fibrosis. It was observed presence of loosely formed granuloma composed of multinucleated giant cells encompassing rounded yeast like organisms stained with mucicarmine, compatible with Cryptococcus sp. Then, the patient underwent a lumbar puncture to investigate meningitis, although he had no neurological symptoms and neurological examination was normal. The cerebrospinal fluid culture yielded Cryptococcus sp. The species and genotype identification step showed the infection was caused by Cryptococcus neoformans var. grubii (genotype VNI). The patient was initially treated with amphotericin B deoxycholate plus fluconazole for disseminated cryptococcosis, according to guideline recommendations. However, the patient developed acute kidney injury and the treatment was switched for fluconazole monotherapy. The symptoms disappeared completely with recovery of white blood cells and platelets counts. Cerebrospinal fluid cultures for fungi at one and two-weeks of treatment were negative. CONCLUSIONS: Bone marrow infection caused by Cryptococcus neoformans is a rare presentation of cryptococcosis. The cryptococcal infection should be included for differential diagnosis in HIV-infected patients with fever and cytopenias, especially when CD4+ T lymphocytes count is below 100 cells/µL.


Assuntos
Medula Óssea/microbiologia , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Infecções por HIV/patologia , Lesão Renal Aguda/etiologia , Anfotericina B/efeitos adversos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Medula Óssea/patologia , Linfócitos T CD4-Positivos/citologia , Líquido Cefalorraquidiano/microbiologia , Criptococose/complicações , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/farmacologia , Ácido Desoxicólico/uso terapêutico , Diagnóstico Diferencial , Combinação de Medicamentos , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Genótipo , Infecções por HIV/complicações , Humanos , Masculino , Meningite/complicações , Meningite/diagnóstico , Pessoa de Meia-Idade
13.
Artigo em Inglês | MEDLINE | ID: mdl-30420478

RESUMO

Amphotericin B deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known about the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were obtained from 78 patients; among them, 55 patients had serial fungal CFU counts in blood also available for analysis. A population pharmacokinetic-pharmacodynamic model was fitted to the data. The relationships between the area under the concentration-time curve (AUC)/MIC and the time to blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variability in the average AUC, with a mean ± standard deviation of 11.51 ± 3.39 mg·h/liter. The maximal rate of drug-induced kill was 0.133 log10 CFU/ml/h, and the plasma concentration of the DAmB that induced the half-maximal rate of kill was 0.02 mg/liter. Fifty percent of patients sterilized their bloodstreams by 83.16 h (range, 13 to 264 h). A higher initial fungal burden was associated with a longer time to sterilization (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.36 to 0.70; P < 0.001). There was a weak relationship between AUC/MIC and the time to sterilization, although this did not reach statistical significance (HR, 1.03; 95% CI, 1.00 to 1.06, P = 0.091). Furthermore, there was no relationship between the AUC/MIC and time to death (HR, 0.97; 95% CI, 0.88 to 1.08; P = 0.607) or early fungicidal activity {slope = log[(0.500 - 0.003·(AUC/MIC)]; P = 0.319} adjusted for the initial fungal burden. The population pharmacokinetics of DAmB are surprisingly consistent. The time to sterilization of the bloodstream may be a useful pharmacodynamic endpoint for future studies. (This study has been registered at the ISRCTN registry under no. ISRCTN59144167.).


Assuntos
Antifúngicos/uso terapêutico , Talaromyces/patogenicidade , Adulto , Anfotericina B/farmacocinética , Anfotericina B/uso terapêutico , Antifúngicos/farmacocinética , Área Sob a Curva , Ácido Desoxicólico/farmacocinética , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Penicillium/efeitos dos fármacos , Penicillium/patogenicidade , Talaromyces/efeitos dos fármacos
14.
Dermatol Ther ; 32(4): e12623, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30182495

RESUMO

Aesthetic dermatology (AD) is a rapidly growing subspecialty of dermatology. The acceptance of AD in scientific community and the society is associated with its competence, efficiency, and seriousness. This review highlights some recent developments toward new tools, techniques, and understanding in the field of AD. Analyzing the specific needs of patients and assessing the effect by objective measurements is important for further progress. For long time ignored, white adipose tissue has gained increasing interest in biology and rejuvenation. Characterization of dermal and subcutaneous white adipose tissue has made progress. The interaction of hyaluronic acid and calcium hydroxyl apatite (CaHA) fillers with adipocytes could be responsible for clinical efficacy. New developments of oral collagen treatment and highly diluted CaHA to contour the body outside the face will be discussed. Submental contouring using purified desoxycholic acid is another new development.


Assuntos
Técnicas Cosméticas , Dermatologia , Estética , Tecido Adiposo/citologia , Colágeno/uso terapêutico , Ácido Desoxicólico/uso terapêutico , Humanos , Ácido Hialurônico/uso terapêutico , Hidroxiapatitas/uso terapêutico , Rejuvenescimento
15.
Pediatr Infect Dis J ; 38(1): 42-49, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29596219

RESUMO

BACKGROUND: Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC. METHODS: PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized controlled trials that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients. The primary outcome was treatment success with resolution of symptoms and signs, and absence of IC. In the meta-analysis a random effects model was used, and the odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Four randomized clinical trials (324 patients), 2 confirmed IC (micafungin vs. liposomal amphotericin B (L-AmB) and caspofungin vs. L-AmB) and 2 empirical therapy trials (caspofungin vs. deoxycholate amphotericin B and caspofungin vs. L-AmB) were included. There was no significant difference between echinocandins and comparator in terms of treatment success (OR = 1.61, 95% CI: 0.74-3.50) and incidence of treatment-related adverse events (OR = 0.70, 95% CI: 0.39-1.26). However, fewer children treated with echinocandins discontinued treatment because of adverse events than amphotericin B formulations (OR = 0.26, 95% CI: 0.08-0.82, P = 0.02). CONCLUSIONS: In the treatment of IC in children, echinocandins show non-inferior efficacy compared with amphotericin B formulations with fewer discontinuations than in comparator arm.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Invasiva/tratamento farmacológico , Equinocandinas/uso terapêutico , Adolescente , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/efeitos adversos , Caspofungina/efeitos adversos , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Equinocandinas/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Lipopeptídeos/efeitos adversos , Lipopeptídeos/uso terapêutico , Masculino , Micafungina/efeitos adversos , Micafungina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Rev Chilena Infectol ; 35(4): 420-423, 2018 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-30534929

RESUMO

BACKGROUND: Cryptococcosis is a severe opportunistic mycotic infection, caused mainly by Cryptococcus neoformans. It can present as meningitis, pneumonia or cryptococcemia. AIM: To characterize patients with Cryptococcus infection between January 1°, 2013 and June 30, 2016, in Hospital Carlos van Buren, Valparaíso, Chile. METHODS: We identified retrospectively those cultures with Cryptococcus sp. growth, and then obtained their clinical files which were analyzed by two independent reviewers. RESULTS: We were able to obtain data from 13 of 15 patients who presented with Cryptococcus neoformans infection. Out of all, 11 (84.6%) were males, with a median age of 35 years old. 11 (84,6%) were HIV positive, 1 (7,7%) had chronic lymphocytic leukemia, and 1 (7,7%) refered alcohol abuse. Out of the 15 episodes, 9 (60%) had meningeal infection; 5 (33.3%) were cryptococcemia without meningeal involvement and 1 (6.6%) presented as a pulmonary infection. Eight patients were deceased at one year follow up. CONCLUSIONS: Cryptococcus sp. infection must be suspected in patients with cellular immunodeficiencies. Meningeal involvement is the most frequent form of clinical presentation. It still has a high mortality rate.


Assuntos
Criptococose/diagnóstico , Adulto , Linfócitos T CD4-Positivos , Chile , Criptococose/tratamento farmacológico , Cryptococcus neoformans/isolamento & purificação , Ácido Desoxicólico/uso terapêutico , Feminino , Fluconazol/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos
20.
J Wound Care ; 27(11): 735-742, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30398934

RESUMO

Most fungal infections found in wounds are secondary or superadded, and are generally benign in their clinical course in healthy individuals, with the exception of mucormycosis. This is a life-threatening infection caused by fungi of the order Mucorales. Primary cutaneous disease may occur following traumatic implantation of spores, or use of contaminated bandages, or as a complication of extensive burns, diabetic acidosis and other specific immunocompromised conditions. The clinical spectrum is highly non-specific and is often triggered by seemingly innocuous trauma. The superficial vesicles or patchy erythema rapidly degrade to haemorrhagic necrosis and rapidly progressive gangrenous lesion. The problem with diagnosing mucormycosis remains, therefore, that the condition has poor clinical indicators and requires reliance on microscopy and fungal culture. Management starts with a clinical suspicion, taking into account the risk factors and lack of response to first-line agents, as well as an aggressive clinical course. Treatment is multimodal, with medical correction of the risk factors and optimisation of limiting factors, such as diabetes, neutropenia and immunosuppressants. Treatment generally involves radical and repetitive surgical debridement, intravenous amphotericin B with monitoring of the nephrotoxicity, along with adjuvant modalities, such as hyperbaric oxygen therapy, colony stimulating factor, interferons gamma and white blood cell transfusion. Successful courses of therapy typically last 4-6 weeks and require cumulative doses that are equivalent to >2g of amphotericin B deoxycholate.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Desbridamento/métodos , Ácido Desoxicólico/uso terapêutico , Oxigenação Hiperbárica/métodos , Mucorales/efeitos dos fármacos , Mucormicose/terapia , Infecção dos Ferimentos/tratamento farmacológico , Adulto , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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