RESUMO
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
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.
Assuntos
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.
Assuntos
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.
Assuntos
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.
Assuntos
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.
Assuntos
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.
Assuntos
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.
Assuntos
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 SobrevidaAssuntos
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
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
A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 microg/ml; range, 0.25 to 4 microg/ml) to resistant (MIC >/= 16 microg/ml; range, 16 to >/=128 microg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of MDR. This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Fluconazol/farmacologia , Animais , Candida albicans/patogenicidade , Candidíase/tratamento farmacológico , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , VirulênciaRESUMO
We present a case of a left atrial myxoma infected with Porphyromonas asaccharolytica in a 55-year-old man, successfully treated with surgical excision and a brief course of antibiotic therapy. Infected cardiac myxomas are extremely rare, with only 39 cases previously reported. They can be difficult to diagnose due to their protean clinical manifestations, which can often be seen in uninfected myxomas as well. We suggest that blood cultures and careful pathologic examination be performed in all cases of cardiac myxoma with constitutional symptoms. However, fever and elevated sedimentation rate are significantly more common in infected tumors. Organisms responsible are similar in distribution to those causing bacterial endocarditis. Emboli, though frequent, may not be more common in infected than uninfected myxomas. Case reports have become more common since the development of better diagnostic techniques. Echocardiography, especially by the transesophageal approach, is the diagnostic procedure of choice, and sensitivity approaches 100%. Surgical excision is curative and generally has low morbidity and mortality.
Assuntos
Infecções por Bacteroidaceae/complicações , Neoplasias Cardíacas/complicações , Mixoma/complicações , Porphyromonas , Infecções por Bacteroidaceae/diagnóstico , Infecções por Bacteroidaceae/tratamento farmacológico , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/cirurgiaRESUMO
Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from =0.125 to 64 microgram/ml. Two isolates were resistant to fluconazole (MIC, 64 microgram/ml) and one strain was dose dependent susceptible (MIC, 16 microgram/ml). MICs of other azoles, including voriconazole, itraconazole, and SCH 56592, for these isolates were lower. C. dubliniensis was identified in 11 of 63 (17%) serially evaluated patients. Variability in phenotypic characteristics dictates the use of molecular and biochemical techniques to identify C. dubliniensis. This study identifies C. dubliniensis in HIV-infected patients from San Antonio, Tex., and shows that C. dubliniensis is frequently detected in those patients by using a primary CHROMagar screen.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antifúngicos/farmacologia , Candida/classificação , Candidíase Bucal/diagnóstico , Infecções por HIV/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Anfotericina B/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candida/genética , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/etiologia , Fluconazol/farmacologia , Genótipo , Humanos , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Boca/microbiologia , América do Norte , Faringe/microbiologia , Fenótipo , Pirimidinas/farmacologia , Triazóis/farmacologia , VoriconazolRESUMO
PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known. PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates. RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day. CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Fluconazol/administração & dosagem , Orofaringe/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Candidíase Bucal/prevenção & controle , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
Signs and symptoms of oropharyngeal candidiasis (OPC) were correlated with microbiology and clinical response to fluconazole in a cohort of patients with advanced human immunodeficiency virus (HIV) infection and recurrent OPC. Sixty-four HIV-infected patients with a median CD4 cell count of < 50/mm3 (range, 3-318/mm3) who presented with OPC were enrolled in a longitudinal study. Specimens for cultures were taken weekly until clinical resolution. Therapy with fluconazole was increased weekly as required to a maximum daily dose of 800 mg until resolution of symptoms and oral lesions. Resistant or dose-dependent susceptible yeasts, defined as a minimum inhibitory concentration of > or = 16 micrograms/mL, were detected in 48 (31%) of 155 episodes. Clinical resolution with fluconazole therapy occurred in 107 (100%) of 107 episodes with susceptible yeasts vs. 44 (92%) of 48 episodes with resistant or dose-dependent susceptible strains (P = .008). Patients from whom fluconazole-resistant yeasts were isolated required longer courses of therapy and higher doses of fluconazole for response, but overall, excellent responses to fluconazole were seen in patients with advanced HIV infection.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antifúngicos/uso terapêutico , Candidíase/microbiologia , Fluconazol/uso terapêutico , Doenças Faríngeas/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Candidíase/tratamento farmacológico , Candidíase/fisiopatologia , Resistência Microbiana a Medicamentos , Humanos , Estudos Longitudinais , Testes de Sensibilidade Microbiana , Orofaringe , Doenças Faríngeas/tratamento farmacológico , Doenças Faríngeas/fisiopatologiaRESUMO
A simple screening method for fluconazole susceptibility of Cryptococcus neoformans using 2% dextrose Sabouraud dextrose agar (SabDex) with fluconazole was compared to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method. By this method, fluconazole-susceptible C. neoformans isolates are significantly smaller on medium with fluconazole than on fluconazole-free medium. Isolates with decreased susceptibility have normal-size colonies on medium containing fluconazole. The 48-h NCCLS broth macrodilution MICs (NCCLS MICs) for isolates with normal-size colonies on 8- or 16-microg/ml fluconazole plates were predicted to be > or =8 or > or =16 microg/ml, respectively. On medium with 16 microg of fluconazole per ml, all strains (84 of 84) for which the NCCLS MICs were <16 microg/ml were correctly predicted, as were all isolates (7 of 7) for which the MICs were > or =16 microg/ml. Agar dilution appears to be an effective screening method for fluconazole resistance in C. neoformans.