RESUMO
Objective: To evaluate an in vitro antiplatelet effect of generic ticagrelor 90 mg (ticaspan) alone and in combination with aspirin 75 mg as compared to the innovator formulation of ticagrelor alone and in combination with aspirin among healthy Indian volunteers. Methods: 18 volunteers were enrolled and platelet viability was tested using lactate dehydrogenase (LDH) assay in six of 18 volunteers. In 12 volunteers, maximum platelet aggregation (MPA) and percentage inhibition of platelet aggregation (PI) were assessed using a platelet aggregometer in six study groups. Results: There was no significant increase in LDH levels when platelets were incubated with an innovator or generic drug alone and in combination with aspirin as compared to the dimethyl sulfoxide [DMSO] group. All five study groups showed a significant reduction in the MPA values compared to the DMSO group (P < 0.01). The extent of decrease in MPA observed with the generic drug was not significantly different from the innovator drug (P = 0.325). Similarly, the MPA observed with the two combination groups did not differ from each other (P = 1.000), but it was significantly different from the MPA observed with aspirin (P = 0.039, each). The PI of platelet aggregation was significantly more in four study groups [generic drug alone; innovator alone; generic drug + aspirin; and innovator drug + aspirin] (P < 0.01) as compared to the aspirin group. Conclusion: The generic ticagrelor and its combination with aspirin demonstrated an antiplatelet effect equivalent to the innovator drug and its combination with aspirin.
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OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.
Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Terbinafina/uso terapêutico , Voriconazol/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Infecções Fúngicas Invasivas/sangue , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Scedosporium/efeitos dos fármacos , Resultado do TratamentoRESUMO
We report the presentation and management of 17 cases of Exophiala dermatitidis and Rhodotorula mucilaginosa bloodstream infections caused by a compounded parenteral medication at an oncology clinic. Twelve patients were asymptomatic. All central venous catheters were removed and antifungal therapy, primarily voriconazole, was administered to patients. Three patients died.
Assuntos
Gerenciamento Clínico , Surtos de Doenças , Contaminação de Medicamentos , Fungemia/tratamento farmacológico , Feoifomicose/tratamento farmacológico , Idoso , Instituições de Assistência Ambulatorial , Antifúngicos/uso terapêutico , Infecções Assintomáticas , Exophiala/efeitos dos fármacos , Exophiala/isolamento & purificação , Feminino , Fungemia/mortalidade , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Serviço Hospitalar de Oncologia , Pacientes Ambulatoriais , Feoifomicose/mortalidade , Rhodotorula/efeitos dos fármacos , Rhodotorula/isolamento & purificaçãoRESUMO
Cryptococcal meningitis is a relatively common invasive fungal infection in immunocompromised patients, especially in solid organ transplant recipients. Clinical presentation typically includes fever, headache, photophobia, neck stiffness, and/or altered mental status. Unusual presentations may delay diagnosis. Therapy is challenging in renal transplant patients because of the nephrotoxicity associated with amphotericin B, the recommended treatment. We present a case of cryptococcal meningitis in a renal transplant recipient presenting as acute sinusitis with successful treatment using fluconazole as primary therapy.
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Antifúngicos/uso terapêutico , Cryptococcus neoformans/isolamento & purificação , Fluconazol/uso terapêutico , Transplante de Rim/efeitos adversos , Meningite Criptocócica/diagnóstico , Sinusite/diagnóstico , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Hospedeiro Imunocomprometido , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/microbiologia , Pessoa de Meia-Idade , Sinusite/tratamento farmacológico , Sinusite/microbiologiaRESUMO
Candiduria is commonly encountered in hospitalized patients, particularly those with indwelling urinary catheters. While risk factors and therapy are well described in previous studies, little is known about long-term outcomes and recurrence rates of candiduria. We studied 188 patients with candiduria in a retrospective chart review at a single institution from January 1999 to December 2000. Data were collected regarding risk factors and underlying disease, therapy, follow-up cultures until December 2003, and mortality. Ninety-one patients with at least one follow-up culture >1 month after the initial culture (range 2-48) were available for further study. In this group, patients receiving antifungal therapy for asymptomatic candiduria were paradoxically more likely to have subsequent positive urine cultures than patients who never received antifungal therapy. Six patients developed candidemia during follow-up, although in none was this considered to represent a consequence of candiduria. Mortality rate at the end of the follow-up period (mean of 18 months) was 43%, including one death attributed to candidemia. Therapy for candiduria does not appear to reduce candiduria recurrence rates through 48 months of follow-up and little evidence of treatment benefit was identified.
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Candida/isolamento & purificação , Candidíase/microbiologia , Candidíase/patologia , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Candidíase/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Infecções Urinárias/mortalidade , Urina/microbiologiaRESUMO
OBJECTIVES: Zygomycosis is an uncommon but devastating disease with few therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. They are known to demonstrate synergy with triazoles against certain fungi, though limited data exist about their activity against zygomycetes. Our aim was to study the in vitro interaction of posaconazole with calcineurin inhibitors and sirolimus against zygomycetes. METHODS: Drug interactions were assessed with chequerboard dilution for posaconazole with calcineurin inhibitors and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty-eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae, Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed in duplicate. Mean fractional inhibitory concentration indices were calculated. RESULTS: Posaconazole with calcineurin inhibitors demonstrated consistent synergy against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no interaction was primarily observed against R. arrhizus, R. microsporus, R. pusillus and Mucor. Antagonism was seen with the combination of posaconazole and sirolimus. Strain variability was noted among the same species. CONCLUSIONS: The clinical significance of these findings is unclear, but further studies are warranted given the potential for concomitant use of these agents in transplant patients treated for zygomycosis.
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Antifúngicos/farmacologia , Calcineurina/farmacologia , Mucorales/efeitos dos fármacos , Sirolimo/farmacologia , Triazóis/farmacologia , Ciclosporina/farmacologia , Interações Medicamentosas , Humanos , Tacrolimo/farmacologiaRESUMO
STUDY DESIGN: Prospective data collection. OBJECTIVES: To evaluate occurrence and characteristics of candiduria in a population of individuals with spinal cord injury (SCI) or multiple sclerosis (MS) and chronic catheter usage. Candiduria, or presence of Candida species in the urine, is a common clinical problem. It is most frequently seen in patients with indwelling urinary catheters. Many patients have these catheters in place chronically. Previous studies have shown that despite therapy, most patients with candiduria will develop the infection again and that complications such as invasive candidiasis are rare. However, there are no studies that specifically examine the role of candiduria in patients with SCI and long-term catheter use. SETTING: Inpatients and outpatients in a US Veterans Affairs spinal cord injury center. METHODS: Urinalysis, culture, patient demographic and clinical characteristics through chart review. RESULTS: Of 100 total patients, 52 had paraplegia, 45 tetraplegia and 3 MS. Overall, 17 (17%) patients had candiduria, which was observed in urine culture. Antibiotic use was associated with an increased risk of developing candiduria. Indwelling catheter (urethral or suprapubic) usage was also significantly associated with candiduria; only one person on intermittent catheterization developed candiduria, which was not associated with adverse clinical outcomes. CONCLUSIONS: Antibiotic usage and indwelling catheterization were associated with candiduria. No participant in our study population developed invasive candidiasis, and persistence of candiduria was not frequent.
Assuntos
Candidíase/etiologia , Traumatismos da Medula Espinal/terapia , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidíase/epidemiologia , Candidíase/terapia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/terapia , Quadriplegia/terapia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Estados Unidos/epidemiologia , VeteranosRESUMO
Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.
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Antifúngicos/uso terapêutico , Triazóis/uso terapêutico , Zigomicose/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Criança , Feminino , Fungos/efeitos dos fármacos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/farmacocinética , Triazóis/farmacologia , Zigomicose/microbiologiaRESUMO
The ergosterol pathway in fungal pathogens is an attractive antimicrobial target because it is unique from the major sterol (cholesterol) producing pathway in humans. Lanosterol 14alpha-demethylase is the target for a major class of antifungals, the azoles. In this study we have isolated the gene for this enzyme from Cryptococcus neoformans. The gene, ERG11, was recovered using degenerate PCR with primers designed with a novel algorithm called CODEHOP. Sequence analysis of Erg11p identified a highly conserved region typical of the cytochrome P450 class of mono-oxygenases. The gene was present in single copy in the genome and mapped to one end of the largest chromosome. Comparison of the protein sequence to a number of major human fungal pathogen Erg11p homologs revealed that the C. neoformans protein was highly conserved, and most closely related to the Erg11p homologs from other basidiomycetes. Functional studies demonstrated that the gene could complement a Saccharomyces cerevisiae erg11 mutant, which confirmed the identity of the C. neoformans gene.
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Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/genética , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Oxirredutases/química , Oxirredutases/genética , Algoritmos , Sequência de Aminoácidos , Antifúngicos/farmacologia , Clonagem Molecular , Primers do DNA/química , DNA Complementar/metabolismo , Genes Fúngicos , Teste de Complementação Genética , Íntrons , Dados de Sequência Molecular , Mutação , Filogenia , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase , RNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Esterol 14-DesmetilaseRESUMO
Fungi have become increasingly important causes of nosocomial bloodstream infections. The major cause of nosocomial fungemia has been Candida spp, but increasingly molds and other yeasts have caused disease. Exophiala jeanselmei and members of the genus Rhinocladiella are dematiaceous moulds, which have been infrequently associated with systemic infection and have not been described as causes of fungemia. In this paper, the occurrence of 23 cases of fungemia due to these organisms over a 10-month period is reported and the clinical characteristics of patients and outcomes are described. The majority of patients were immunosuppressed; 21 of 23 (91%) had received blood products and 78% had a central venous catheter. All patients had at least one manifestation of fever, but only one patient had signs or symptoms suggesting deep-seated infection. Antifungal therapy was given to 19 of the 23 patients; of those who did not receive therapy, 3 died prior to the culture result and 1 had been discharged without therapy. Antifungal susceptibility of the organisms showed activity of amphotericin B, itraconazole, and the new triazole antifungals voriconazole and posaconazole. E. jeanselmei and Rhinocladiella species are potential causes of nosocomial fungemia and may be associated with systemic infection.
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Ascomicetos/isolamento & purificação , Infecção Hospitalar/microbiologia , Fungemia/diagnóstico , Micoses/diagnóstico , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ascomicetos/classificação , Cateterismo Venoso Central/efeitos adversos , Criança , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Feminino , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/etiologia , Resultado do TratamentoRESUMO
OBJECTIVES: To report our experience with disseminated Mycobacterium simiae disease in patients with AIDS, and review other cases reported in the literature. METHODS: We retrospectively reviewed all cases of M. simiae that were isolated from sterile body sites over a 9-year period at the University Health System Hospital at San Antonio, Texas, U.S.A. Data included patient demographics, clinical features, other accompanying opportunistic infections, in vitro susceptibility, therapy and outcome. RESULTS: Ten cases of M. simiae disseminated disease were identified. All of them were inpatients with AIDS. Another nine cases of disseminated infection in AIDS patients were reported in the literature. Advanced AIDS with absolute CD4 counts of less than 50 and an associated AIDS-defining illness characterized all cases. Persistent fever and debilitation without localizing signs were the most common clinical features. Our patients responded poorly to antimycobacterial drugs and died within 6 months of diagnosis. The only reported successful therapy was in patients who responded well to highly active antiretroviral therapy and antimycobacterial regimens containing clarithromycin, ethambutol and ciprofloxacin. CONCLUSIONS: Clinical presentation of M. simiae infection mimics Mycobacterium avium complex, with fever and progressive debilitation, but is less responsive to therapy. Immuno-reconstitution with potent antiretroviral therapy may be the best therapy for such resistant disease.
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Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções por Mycobacterium/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Humanos , Masculino , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/microbiologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVE: To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. METHODS: A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. RESULTS: The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. CONCLUSION: Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand.
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Clonazepam/administração & dosagem , Clonazepam/farmacocinética , Administração Oral , Adulto , Análise de Variância , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Sensibilidade e Especificidade , ComprimidosAssuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Coleta de Amostras Sanguíneas/métodos , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Criptococose/microbiologia , Humanos , Masculino , Técnicas de Tipagem Micológica/métodosRESUMO
OBJECTIVE: To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. DESIGN: A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. RESULTS: The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. CONCLUSION: Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.
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Antibióticos Antituberculose/farmacocinética , Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Rifampina/farmacocinética , Adolescente , Adulto , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/sangue , Antituberculosos/administração & dosagem , Antituberculosos/sangue , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Isoniazida/administração & dosagem , Isoniazida/sangue , Masculino , Valores de Referência , Rifampina/administração & dosagem , Rifampina/sangue , Equivalência TerapêuticaRESUMO
Amphotericin B therapy continues to be the "gold standard" in the treatment of invasive aspergillosis in the immunocompromised host. Although Aspergillus fumigatus and Aspergillus flavus constitute the major species, several reports have described invasive pulmonary or disseminated disease due to the less common Aspergillus terreus and dismal clinical outcomes with high-dose amphotericin B. We therefore evaluated 101 clinical isolates of A. terreus for their susceptibility to amphotericin B and the investigational triazole voriconazole by using the National Committee for Clinical Laboratory Standards M27-A method modified for mould testing. Forty-eight-hour MICs indicated 98 and 0% resistance to amphotericin B and voriconazole, respectively. We conclude that A. terreus should be added to the list of etiologic agents refractory to conventional amphotericin B therapy and suggest the potential clinical utility of voriconazole in aspergillosis due to this species.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Pirimidinas/farmacologia , Triazóis/farmacologia , Anfotericina B/farmacocinética , Anfotericina B/uso terapêutico , Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Pirimidinas/farmacocinética , Resultado do Tratamento , Triazóis/farmacocinética , VoriconazolRESUMO
Metarrhizium anisopliae is a common pathogen of insects and has even been used to control insect populations. It is rarely isolated from human or animal sources, but recently, there have been three reported cases of disease, two in humans and one in a cat. We present our experience with five isolates from human sources, including two that were the apparent causes of two cases of sinusitis in immunocompetent hosts. The first patient was a 36-year-old male with frontal and ethmoid sinusitis, and the second was a 79-year-old female with chronic sinusitis. Both patients underwent surgery, and pathology of the surgical specimens revealed branching hyphae. Cultures grew only Metarrhizium species. Neither patient received antifungal therapy, and both did well postoperatively. The other three isolates were cultured from bronchoalveolar lavage specimens but were not felt to be clinically significant. Antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards macrobroth method revealed that all isolates were resistant to amphotericin B, 5-flucytosine, and fluconazole. Itraconazole and newer azole compounds were more active. Metarrhizium species may cause disease in humans, even those without evidence of immunosuppression, and are apparently highly resistant to amphotericin B in vitro.
Assuntos
Fungos Mitospóricos , Micoses/microbiologia , Sinusite/microbiologia , Adulto , Idoso , Antifúngicos/farmacologia , Feminino , Humanos , Imunocompetência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fungos Mitospóricos/efeitos dos fármacos , Fungos Mitospóricos/isolamento & purificação , Fungos Mitospóricos/patogenicidade , Micoses/imunologia , Sinusite/imunologiaRESUMO
OBJECTIVE: To assess the bioavailability of carbamazepine from two brands of carbamazepine--Tegretol 200 and Zen-200. METHODS: A two-way randomised cross-over bioavailability of carbamazepine was carried out in twelve healthy male volunteers. Coded plasma samples were analysed for levels of carbamazepine by high performance liquid chromatography (HPLC) method. Tegretol 200 and Zen-200 were tested for in-vitro dissolution profiles. RESULTS: The mean Cmax, Tmax and t1/2a for Tegretol 200 were: 2.17 +/- 0.42 mcg/mL, 11.67 +/- 6.37 h and 2.72 +/- 1.87 h; for Zen-200 were 3.10 +/- 0.05 mcg/mL, 3.50 +/- 2.11 h and 0.76 +/- 0.76 h respectively. These values were statistically significant. However AUC (0-96 h) value of 150.16 +/- 27.13 mcg/ml.h after Zen-200 was not statistically significant as compared to 128.68 +/- 20.22 mcg/ml.h after Tegretol 200. The in-vitro dissolution profiles of the two formulations were dissimilar. The fluctuations in CBZ levels after Tegretol 200 was significantly less as compared to Zen-200. The absorption profile as judged by parameter 'A' was 50.44 +/- 10.95 for Tegretol 200 and 42.49 +/- 18.89 for Zen-200. CONCLUSION: Based on parameter 'A' and other pharmacokinetic parameters, the marketed generic carbamazepine product, Zen-200 is not bioequivalent to Tegretol 200.