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1.
BMC Infect Dis ; 21(1): 375, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882845

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. METHOD: This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7-1.0 mg/kg) and oral fluconazole (800 mg orally/day). RESULTS: Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. CONCLUSION: Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Cryptococcus neoformans/imunologia , Ácido Desoxicólico/administração & dosagem , Fluconazol/administração & dosagem , HIV , Meningite Criptocócica/complicações , Meningite Criptocócica/tratamento farmacológico , Atenção Primária à Saúde , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Administração Intravenosa , Administração Oral , Adolescente , Adulto , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Cryptococcus neoformans/isolamento & purificação , Ácido Desoxicólico/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Fluconazol/efeitos adversos , Humanos , Masculino , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Mianmar/epidemiologia , Flebite/induzido quimicamente , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Isr Med Assoc J ; 23(2): 116-120, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33595218

RESUMO

BACKGROUND: Extremely preterm infants are at high risk for mortality and morbidity including neurodevelopmental impairment from invasive Candida infections. Prophylactic antifungal therapy has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants. Prophylactic treatment should be started in the first 48 to 72 hours after birth to extremely low birth weight (ELBW) infants (weighing ≤ 1000 grams at birth) or below 27 weeks gestation age with risk factors, or in any NICU with moderate (5-10%) or high (≥ 10%) rates of invasive candidiasis. Studies demonstrated the benefits of fluconazole prophylaxis regarding its safety of the short-term and long-term without the development of fungal resistance. Empiric antifungal therapy may lower mortality and improve outcomes.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Invasiva/prevenção & controle , Doenças do Prematuro/prevenção & controle , Antifúngicos/efeitos adversos , Candidíase Invasiva/mortalidade , Farmacorresistência Fúngica , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/microbiologia , Doenças do Prematuro/mortalidade , Unidades de Terapia Intensiva Neonatal , Seleção de Pacientes
3.
Drug Dev Ind Pharm ; 47(2): 246-258, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33416006

RESUMO

The aim of this work was to prepare and optimize mucoadhesive nanostructured lipid carrier (NLC) impregnated with fluconazole for better management of oral candidiasis. The NLCs were fabricated using an emulsification/sonication technique. The nanoparticles consisted of stearic acid, oleic acid, Pluronic F127, and lecithin. Box-Behnken design, artificial neural networking, and variable weight desirability were employed to optimize the joint effect of drug concentration in the drug/lipid mixture, solid lipid concentration in the solid/liquid lipid mixture, and surfactant concentration in the total mixture on size and entrapment. The optimized NLCs were coated with chitosan. The nanoparticles were characterized by surface charge, spectroscopic, thermal, morphological, mucoadhesion, release, histopathological, and antifungal properties. The nanoparticles are characterized by a particle size of 335 ± 13.5 nm, entrapment efficiency of 73.1 ± 4.9%, sustained release, minor histopathological effects on rabbit oral mucosa, and higher fungal inhibition efficiency for an extended period of time compared with fluconazole solution. Coating the nanoparticles with chitosan increased its adhesion to rabbit oral buccal mucosa and improved its anti-candidiasis activity. It is concluded that mucoadhesive lipid-based nanoparticles amplify the effect of fluconazole on Candida albicans in vitro. This finding warrants pre-clinical and clinical studies in oral candidiasis disease models to corroborate in vitro findings.


Assuntos
Candidíase Bucal , Fluconazol/farmacologia , Lipídeos/química , Nanopartículas , Nanoestruturas , Animais , Candidíase Bucal/tratamento farmacológico , Portadores de Fármacos , Fluconazol/administração & dosagem , Fluconazol/química , Aprendizado de Máquina , Tamanho da Partícula , Coelhos
4.
J Card Surg ; 35(10): 2672-2678, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32678965

RESUMO

BACKGROUND: Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. METHODS: A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. RESULTS: We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. CONCLUSIONS: Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Coração Auxiliar/efeitos adversos , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Inquéritos e Questionários , Aztreonam/administração & dosagem , Cefalosporinas/administração & dosagem , Estudos Transversais , Quimioterapia Combinada , Fluconazol/administração & dosagem , Humanos , Levofloxacino/administração & dosagem , Infecções Relacionadas à Prótese/etiologia , Rifampina/administração & dosagem , Infecção da Ferida Cirúrgica/etiologia , Vancomicina/administração & dosagem
5.
BMC Infect Dis ; 20(1): 377, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460728

RESUMO

BACKGROUND: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases. CASE PRESENTATION: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 µg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements. CONCLUSION: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.


Assuntos
Infecção Hospitalar/microbiologia , Fungemia/microbiologia , Antibacterianos , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candida/fisiologia , Cateteres Venosos Centrais , Infecção Hospitalar/tratamento farmacológico , DNA Ribossômico/genética , Feminino , Fluconazol/administração & dosagem , Fungemia/tratamento farmacológico , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Nutrição Parenteral Total
6.
Int J Pharm ; 578: 119096, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32006626

RESUMO

In contrast to the plethora of antibacterial agents, only a handful of antifungals are currently available to treat Candida albicans biofilm-associated infections. Additional novel antibiofilm strategies to eliminate C. albicans biofilm infections are needed. This study aims to improve the efficacy of a widely used azole, fluconazole by co-delivering it with a Pseudomonas aeruginosa quorum sensing molecule (QSM), N-3-oxo-dodecanoyl-L-homoserine lactone (C12AHL) in a liposomal formulation. C12AHL is known to inhibit C. albicans' morphological transition and biofilm formation. Four different formulations of liposomes with fluconazole (L-F), with C12AHL (L-H), with fluconazole and C12AHL (L-HF), and a drug-free control (L-C) were prepared using a thin-film hydration followed by extrusion method, and characterised. The effect of liposomes on colonising (90 min-24 h) and preformed (24 h) C. albicans biofilms were assessed using a standard biofilm assay. Biofilm viability (XTT reduction assay), biomass (Safranin-O staining) and architecture (confocal laser scanning microscopy, CLSM) were determined. Similar efficiencies of fluconazole entrapment were noticed in L-HF and L-F (11.74% vs 10.2%), however, L-HF released greater quantities of fluconazole compared to L-F during 24 h (4.27% vs 0.97%, P < 0.05). The entrapment and release of C12AHL was similar for L-H and L-HF liposomes (33.3% vs 33% and 88.9% vs 92.3% respectively). L-HF treated colonising, and preformed biofilms exhibited >80%, and 60% reduction in their respective viabilities at a fluconazole concentration as low as 5.5 µg/mL compared to 12% and 36%, respective reductions observed in L-F treated biofilms (P < 0.05). CLSM confirmed biofilm disruption, lack of hyphae, and reduction in biomass when treated with L-HF compared to other liposomal preparations. Liposomal co-delivery of C12AHL and fluconazole appears to suppress C. albicans biofilms through efficacious disruption of the biofilm, killing of constituent yeasts, and diminishing their virulence at a significantly lower antifungal dose. Therefore, liposomal co-formulation of C12AHL and fluconazole appears to be a promising approach to improve the efficacy of this common triazole against biofilm-mediated candidal infections.


Assuntos
4-Butirolactona/análogos & derivados , Antifúngicos/administração & dosagem , Candida albicans/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Fluconazol/administração & dosagem , Homosserina/análogos & derivados , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum , 4-Butirolactona/administração & dosagem , 4-Butirolactona/química , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Candida albicans/fisiologia , Liberação Controlada de Fármacos , Fluconazol/química , Homosserina/administração & dosagem , Homosserina/química , Lipossomos
7.
Artigo em Inglês | MEDLINE | ID: mdl-31967211

RESUMO

Cryptococcosis is an opportunistic fungal infection causes significant disease predominantly in immunocompromised patients. Here we present an excepcional case of disseminated cryptococcosis with pulmonary and cerebral involvement in an immunocompetent patient with no apparent predisposing factors at the time of hospital admission. We described a case of an apparently immunocompetent 66-years old man admitted to hospital with a one-month history of cough, fever and vertigo. During hospitalization, thorax imaging was suggestive of lung metastasis, therefore, he went through several investigations. During hospitalization, he developed neurological symptoms and subsequently underwent a lumbar puncture. Cerebrospinal fluid (CSF) culture was positive for Cryptococcus spp. isolated on Sabouraud's dextrose agar and bird seed agar. In addition, the direct microscopy examination was positive for the India ink test, as well as with the latex agglutination test for cryptococcal polysaccharide antigen (CrAg) in CSF, while serum CrAg was negative. Despite the absence of classic immunocompromising features, he was treated with amphotericin B and fluconazole due to suspected disseminated cryptococcal infection. Later, he was diagnosed with prostatic adenocarcinoma. Upon successful completion of treatment for disseminated cryptococcosis, the patient underwent radical prostate ablation surgery as a treatment forprostatic adenocarcinoma. This exceptional case emphasizes the high degree of suspicion of atypical infections, and in these cases, it is particularly important to consider fungal infections in hitherto healthy patients with no apparent predisposing factors. Although Cryptococcus spp. is predominantly reported in patients with hematological malignancies, cryptococcosis investigation should also be considered as part of the initial workup of patients with a new diagnosis of a solid tumour prior to chemotherapy or radiotherapy.


Assuntos
Adenocarcinoma/diagnóstico , Criptococose/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Idoso , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Criptococose/tratamento farmacológico , Criptococose/imunologia , Fluconazol/administração & dosagem , Humanos , Hospedeiro Imunocomprometido , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/cirurgia
8.
Ann Pharmacother ; 54(7): 676-683, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31893943

RESUMO

Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.


Assuntos
Antifúngicos/farmacologia , Ciclofosfamida/farmacocinética , Fluconazol/farmacologia , Itraconazol/farmacologia , Cetoconazol/farmacologia , Modelos Biológicos , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/sangue , Interações Medicamentosas , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Cetoconazol/administração & dosagem , Cetoconazol/uso terapêutico
10.
Mol Pharm ; 17(1): 145-154, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31800255

RESUMO

Cryptococcus neoformans (C. neoformans) is one of the most well-known zoonotic fungal pathogens. Cryptococcal encephalitis remains a major cause of morbidity and mortality in immunocompromised hosts. Effective and targeting killing of C. neoformans in the brain is an essential approach to prevent and treat cryptococcal encephalitis. In this study, a fluorescent polypyridyl ruthenium complex RC-7, {[phen2Ru(bpy-dinonyl)](PF6)2 (phen = 1,10-phenanthroline, bpy-dinonyl = 4,4'-dinonyl-2,2'-bipyridine)}, was screened out, which showed a highly fungicidal effect on C. neoformans. The values of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) in antifungal activities were significantly lower than fluconazole as the control. Moreover, RC-7 was prepared as a brain-targeting nanoliposome (RDP-liposome; RDP is a peptide derived from rabies virus glycoprotein) for in vivo application. The results revealed that the liposomes could accumulate in the encephalitis brain and play an antifungal role. Compared with the cryptococcal encephalitis model mice, the RDP-liposomes remarkably prolonged the survival days of the encephalitis-bearing mice from 10 days to 24 days. Here, we introduce a polypyridyl ruthenium complex that could be used as a novel antifungal agent, and this study may have a broad impact on the development of targeted delivery based on ruthenium complex-loaded liposomes for theranostics of cryptococcal encephalitis.


Assuntos
Antifúngicos/administração & dosagem , Encéfalo/efeitos dos fármacos , Criptococose/tratamento farmacológico , Cryptococcus neoformans/efeitos dos fármacos , Encefalite Infecciosa/tratamento farmacológico , Lipossomos/administração & dosagem , Nanocápsulas/administração & dosagem , Compostos de Rutênio/administração & dosagem , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/uso terapêutico , Encéfalo/microbiologia , Encéfalo/patologia , Células Cultivadas , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus neoformans/metabolismo , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Glicoproteínas/química , Encefalite Infecciosa/microbiologia , Encefalite Infecciosa/mortalidade , Lipossomos/síntese química , Lipossomos/química , Lipossomos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/química , Compostos de Rutênio/química , Compostos de Rutênio/uso terapêutico , Nanomedicina Teranóstica , Distribuição Tecidual , Proteínas Virais/química
11.
J Mycol Med ; 30(1): 100916, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31843296

RESUMO

Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs.


Assuntos
Infecções Relacionadas a Cateter/diagnóstico , Infecções por HIV/complicações , Neutropenia/complicações , Tricosporonose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Anfotericina B/administração & dosagem , Antituberculosos/administração & dosagem , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/complicações , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Quimioterapia Combinada , Feminino , Fluconazol/administração & dosagem , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/microbiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Neutropenia/diagnóstico , Neutropenia/microbiologia , Neutropenia/virologia , Trichosporon/isolamento & purificação , Tricosporonose/tratamento farmacológico , Tricosporonose/etiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
12.
J Low Genit Tract Dis ; 24(1): 48-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31860575

RESUMO

OBJECTIVES: This study evaluated use of long-term fluconazole beyond an initial 6-month course of weekly fluconazole in premenopausal patients with idiopathic recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans. MATERIALS AND METHODS: A retrospective chart review was performed of women seen in Wayne State University Vaginitis Clinic with culture-confirmed idiopathic RVVC due to Candida albicans during a 10-year period (January 2006 to December 2015). Only patients without risk factors for secondary VVC and who initiated a 6-month course of weekly fluconazole therapy were selected. Data included long-term use of fluconazole therapy, treatment efficacy, and development of fluconazole resistance. Questionnaires were mailed to evaluate patient's experience after fluconazole therapy. RESULTS: Of 883 patients with RVVC based on clinical records, 191 with culture positive idiopathic RVVC due to C. albicans were started on the maintenance fluconazole regimen, and 147 (77.0%) completed 6 months of therapy. Of these, 107 (72.8%) continued or received maintenance past 6 months. The most common reason for additional fluconazole therapy was culture-confirmed VVC recurrence (55.1%), unconfirmed but possible VVC recurrence (16.8%), and patient preference (10.3%). The mean duration of fluconazole maintenance was 35.7 (range = 7-288) months. Fluconazole resistance emerged in 7.5% completing 6-month therapy. Upon questionnaire follow-up, 93.6% of 51 respondents reported benefit during maintenance regimen; however, 80.9% described relapse after discontinuing weekly therapy. CONCLUSIONS: Fluconazole suppression therapy was highly effective in preventing VVC symptoms but was rarely curative and VVC relapse occurred frequently after discontinuation of maintenance therapy. The development of drug resistance in C. albicans isolates after long-term fluconazole maintenance therapy although uncommon is a previously unrecognized complication.


Assuntos
Antifúngicos/administração & dosagem , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Fluconazol/administração & dosagem , Adolescente , Adulto , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Farmacorresistência Fúngica , Feminino , Humanos , Michigan , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
Int J Antimicrob Agents ; 55(1): 105804, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605727

RESUMO

The incidence of fungal infections has increased continuously in recent years, and drug resistance, especially resistance to fluconazole (FLC), has emerged. To overcome this challenge, research on the antifungal activities of non-antifungal agents has gained more attention. In this study, we determined the anti-Candida activity of ribavirin (RBV), an antiviral drug commonly used in the clinic, and found that RBV displayed potent antifungal activity when used alone or in combination with FLC in vitro and in vivo. In vitro, the MIC80 values of RBV were 2-4 µg/mL for FLC-susceptible Candida albicans and 8 µg/mL for FLC-resistant C. albicans. When RBV at a dose of 1 µg/mL was combined with FLC, significant synergistic effects were exhibited against FLC-resistant C. albicans, and the MICs of FLC decreased from >512 µg/mL to 0.25-1 µg/mL. Synergism was also exhibited against C. albicans biofilms. In vivo, RBV plus FLC significantly improved the survival of infected Galleria mellonella larvae compared with the FLC-treated group over a 4-day period and attenuated the damage of FLC-resistant C. albicans to G. mellonella larvae tissue. Furthermore, mechanistic studies indicated that the antifungal effects of RBV used alone or in combination with FLC might be associated with inhibition of biofilm formation, reduced extracellular phospholipase activity and inhibition of hyphal growth, but is not related to promotion of FLC uptake and inhibition of FLC efflux. These results provide a promising direction for overcoming drug resistance and for expanding the clinical application of existing drugs.


Assuntos
Antifúngicos/administração & dosagem , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Fluconazol/administração & dosagem , Ribavirina/administração & dosagem , Animais , Antifúngicos/farmacologia , Candida albicans/patogenicidade , Candidíase/microbiologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Humanos , Larva , Mariposas , Ribavirina/farmacologia , Virulência
15.
BMC Infect Dis ; 19(1): 1051, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830905

RESUMO

BACKGROUND: Cryptococcal prostatitis is a rare clinical disease and has never been reported in China. CASE PRESENTATION: We report on a male HIV-infected patient with pulmonary and prostate cryptococcosis that was misdiagnosed (as tuberculosis) and delayed diagnosed. Although the patients accepted anti-fungal treatment and anti-retroviral treatment finally, the physician's mistakes reflect the rarity of this condition in China. CONCLUSION: Cryptococcal prostatitis is a rare disease that unusually presents in immunodeficient patients. Physicians should have a heightened awareness of this particular infection in the immunodeficient population.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Prostatite/diagnóstico , Retenção Urinária/diagnóstico , Retenção Urinária/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , China , Criptococose/complicações , Criptococose/tratamento farmacológico , Diagnóstico Tardio , Erros de Diagnóstico , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Flucitosina/administração & dosagem , Flucitosina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/microbiologia , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Resultado do Tratamento , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico
16.
BMC Infect Dis ; 19(1): 1003, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775716

RESUMO

BACKGROUND: Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis. CASE PRESENTATION: We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient's treatment, but unfortunately, he died three days later. Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy. CONCLUSIONS: Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.


Assuntos
Síndrome de Imunodeficiência Adquirida/microbiologia , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Infecções Oportunistas/microbiologia , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Administração Oral , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Antígenos de Fungos/imunologia , China , Criptococose/microbiologia , Feminino , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Masculino , Meningite/microbiologia , Pessoa de Meia-Idade , Infecções Oportunistas/tratamento farmacológico , Resultado do Tratamento
17.
Pan Afr Med J ; 33: 249, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692764

RESUMO

Neuromeningeal cryptococcosis is a common and severe opportunistic fungal infection caused by the encapsulated yeast Cryptococcus neoformans. It commonly occurs in immunocompromised patients, in particular in subjects with advanced stage HIV while it is rare in immunocompetent patients. We report 40 cases of neuromeningeal cryptococcosis (NMC) diagnosed at the Mycology-Parasitology Department of the Ibn Sina hospital in Rabat, over a 21-year period (1993-2014). The diagnosis was based on nested-PCR-based assay for the detection of Cryptococcus neoformans after staining with China ink and culture on Sabouraud agar without actidione as well as on the identification of soluble cryptococcal antigens. Thirty-five patients had HIV infection, 2 patients were apparently immunocompetent and 3 were immunocompromised patients without HIV (30 men and 10 women). The average age of patients was 38 years; neuromeningeal cryptococcosis was indicative of HIV infection in 13 cases. In 22 cases it was a complication of AIDS. Twenty-seven patients of our series were treated with fluconazole monotherapy. Amphotericin B was used in 13 patients. Outcome was favorable in 13 patients (32.5%) while 3 patients had complications (7.5%). Eighteen patients died (45%) and 6 were lost to follow-up (15%). The tests to diagnose a Cryptococcus neoformans infection should be performed systematically in patients with neurological signs for early diagnosis.


Assuntos
Antifúngicos/administração & dosagem , Infecções por HIV/epidemiologia , Hospedeiro Imunocomprometido , Meningite Criptocócica/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Idoso , Anfotericina B/administração & dosagem , Cryptococcus neoformans/isolamento & purificação , Feminino , Fluconazol/administração & dosagem , Infecções por HIV/complicações , Humanos , Masculino , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Pessoa de Meia-Idade , Marrocos , Adulto Jovem
20.
Br J Clin Pharmacol ; 85(12): 2824-2837, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31475367

RESUMO

AIMS: To characterize the population pharmacokinetics (PK) of sildenafil and its active metabolite, N-desmethyl sildenafil (DMS), in premature infants. METHODS: We performed a multicentre, open-label trial to characterize the PK of sildenafil in infants ≤28 weeks gestation and < 365 postnatal days (cohort 1) or < 32 weeks gestation and 3-42 postnatal days (cohort 2). In cohort 1, we obtained PK samples from infants receiving sildenafil as ordered per the local standard of care (intravenous [IV] or enteral). In cohort 2, we administered a single IV dose of sildenafil and performed PK sampling. We performed a population PK analysis and dose-exposure simulations using the software NONMEM®. RESULTS: We enrolled 34 infants (cohort 1 n = 25; cohort 2 n = 9) and collected 109 plasma PK samples. Sildenafil was given enterally (0.42-2.09 mg/kg) in 24 infants in cohort 1 and via IV (0.125 or 0.25 mg/kg) in all infants in cohort 2. A 2-compartment PK model for sildenafil and 1-compartment model for DMS, with presystemic conversion of sildenafil to DMS, characterized the data well. Coadministration of fluconazole (n = 4), a CYP3A inhibitor, resulted in an estimated 59% decrease in sildenafil clearance. IV doses of 0.125, 0.5 and 1 mg/kg every 8 hours (in the absence of fluconazole) resulted in steady-state maximum sildenafil concentrations that were generally within the range of those reported to inhibit phosphodiesterase type 5 activity in vitro. CONCLUSIONS: We successfully characterized the PK of sildenafil and DMS in premature infants and applied the model to inform dosing for a follow-up, phase II study.


Assuntos
Recém-Nascido Prematuro/sangue , Modelos Biológicos , Inibidores da Fosfodiesterase 5/farmacocinética , Citrato de Sildenafila/farmacocinética , Administração Oral , Estudos de Coortes , Citocromo P-450 CYP3A/sangue , Citocromo P-450 CYP3A/genética , Fluconazol/administração & dosagem , Fluconazol/farmacocinética , Idade Gestacional , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Lactente , Recém-Nascido , Doenças do Prematuro/sangue , Doenças do Prematuro/tratamento farmacológico , Injeções Intravenosas , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/sangue , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/sangue , Citrato de Sildenafila/uso terapêutico
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