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1.
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
2.
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
3.
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
4.
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
5.
Am J Case Rep ; 20: 1378-1381, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31530795

RESUMO

BACKGROUND Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder that is part of a group of acute porphyria disorders usually found in females of reproductive age. Although clinically there is low penetrance, with 90% of genetically diagnosed individuals never experiencing an acute flair, consequences of acute flairs may lead to devastating results. Debilitating paresis, seizures, respiratory failure, and even death may result from AIP. Early detection is key in preventing these devastating manifestations. CASE REPORT A 67-year-old Hispanic man with a past medical history of pulmonary Coccidioides on fluconazole presented with bilateral thigh pain for 2 days. At baseline, the patient had no limitations, but now was limited to minimal walking due to his thigh pain subsequently progressing to diffuse weakness after the administration of IV Solumedrol. Over the next few months, EMG was notable for acute-on-chronic sensorimotor axonal denervation in upper and lower extremities, without evidence of myositis. Urine porphobilinogen was 58 mmol/L, which is 29 times the upper limit of normal. Treatment was started with hemin 4 mg/kg/day for 4 days. CONCLUSIONS Over our patient's clinical course, he was affected by a severe manifestation of repeated acute porphyria attacks, which started as anterior thigh pain and progressed to diffused weakness disproportionally affecting the muscles of the upper extremities. Although the patient was in his late 60's at the initial onset of AIP, his diffuse Coccidioides infection, use of azoles, and steroids likely contributed to his first AIP attack.


Assuntos
Antifúngicos/efeitos adversos , Coccidioidomicose/tratamento farmacológico , Fluconazol/efeitos adversos , Pneumopatias Fúngicas/tratamento farmacológico , Polineuropatias/etiologia , Porfiria Aguda Intermitente/diagnóstico , Idoso , Antifúngicos/administração & dosagem , Fluconazol/administração & dosagem , Humanos , Masculino , Porfobilinogênio/urina
6.
Transpl Infect Dis ; 21(5): e13156, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31390109

RESUMO

BACKGROUND: Invasive fungal infection (IFI) after liver transplant (LTx) is associated with extensive morbidity and mortality. Targeted prophylaxis reduces risk, but qualifying criteria, drug of choice and regimen are unclear and compliance is inconsistent. OBJECTIVE: Assess the impact of a risk factor-based fungal prophylaxis protocol (FPP) after LTx on fungal infection rates, fungal epidemiology, and transplant outcomes. METHODS: Observational cohort study of adult LTx recipients between July 1, 2009, and June 30, 2017. Patients in the FPP group were given a set dose of 400 mg fluconazole without renal adjustment on POD 1-14 via pharmacist delegation protocol. RESULTS: One hundred and eighty-nine patients met inclusion criteria; 50 in the FPP and 139 in the pre-implementation comparator group. Of those who would be considered high-risk, 22.3% received antifungal prophylaxis prior to FPP implementation vs 92% after implementation (P < .0001). There were significantly fewer fungal infections in the FPP group at 1 year (12.5% vs 26.6%, P = .03). IFI in the pre-implementation control group was due to Candida species in 95% of cases; 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates had reduced fluconazole susceptibility. Aspergillus did not account for any IFI between the groups. One-year patient and graft survival were similar between groups. In a multivariable model accounting for patient and donor age, donor type, MELD, and cold ischemic time, FPP was protective against fungal infection (HR 0.3, P = .015). FPP did not significantly impact graft survival (HR 0.4, P = .14), but trended toward improved patient survival. (HR 0.18, P = .06). CONCLUSION: Implementation of a targeted FPP utilizing static dosing of fluconazole 400 mg × 14 days to those that meet high-risk criteria significantly reduces invasive fungal infection after liver transplant. Use of this protocol did not adversely affect fungal epidemiology and may have a positive impact on allograft and patient survival. Future large prospective studies are needed to better evaluate survival impact.


Assuntos
Antifúngicos/administração & dosagem , Protocolos Clínicos , Fluconazol/administração & dosagem , Infecções Fúngicas Invasivas/prevenção & controle , Transplante de Fígado/efeitos adversos , Idoso , Esquema de Medicação , Feminino , Humanos , Infecções Fúngicas Invasivas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento
7.
BMC Infect Dis ; 19(1): 710, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405376

RESUMO

BACKGROUND: Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy. CASE PRESENTATION: A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates. CONCLUSION: PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in pulmonary cryptococcal infections may occur. The incidence of false positive 18FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.


Assuntos
Criptococose/diagnóstico por imagem , Criptococose/microbiologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Derrame Pleural/microbiologia , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Masculino , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Tomografia por Emissão de Pósitrons
8.
BMJ Case Rep ; 12(8)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401574

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory syndrome characterised by unregulated macrophage and T-lymphocyte activation, resulting in cytokine overproduction and subsequent histiocytic phagocytosis. Here we report a case of pulmonary cryptococcosis, in a 59-year-old diabetic patient, with no other risk factors whose clinical course was complicated by secondary hemophagocytosis. Even after addressing the primary underlying illness (pulmonary cryptococcosis), his clinical condition continued to worsen. After excluding the other causes of HLH and possible reasons of his clinical worsening, glucocorticoids were added following which the patient experienced a remarkable improvement in his clinical and laboratory parameters. To our knowledge, this is the first case report of HLH being caused by pulmonary cryptococcosis and only second case report of cryptococcosis being complicated with HLH (previous report being associated with meningoencephalitic cryptococcosis).


Assuntos
Criptococose/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Antifúngicos/administração & dosagem , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/isolamento & purificação , Dexametasona/administração & dosagem , Fluconazol/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
9.
BJOG ; 126(13): 1546-1552, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31446677

RESUMO

BACKGROUND: Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole. OBJECTIVES: To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy. SEARCH STRATEGY: A systematic literature search was conducted to identify relevant studies published from inception until April 2019. SELECTION CRITERIA: Relevant English-language citations using the terms oral fluconazole and pregnancy in humans. DATA COLLECTION: Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS: Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [OR] 1.09, 95% CI 0.99-1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high-dose users (>150 mg) (OR 1. 19, 95% CI 1.01-1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09-1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1-1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71-6.74, P < 0.001; n = 2) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (OR 1.99, 95% CI 1.38-2.88, P < 0.001; n = 3). CONCLUSIONS: Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven. TWEETABLE ABSTRACT: Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Anormalidades Craniofaciais/induzido quimicamente , Fluconazol/administração & dosagem , Anormalidades Induzidas por Medicamentos , Administração Oral , Antifúngicos/efeitos adversos , Feminino , Fluconazol/efeitos adversos , Humanos , Segurança do Paciente , Gravidez , Primeiro Trimestre da Gravidez
10.
BMJ Case Rep ; 12(8)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451456

RESUMO

We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Criptococose , Cryptococcus neoformans/isolamento & purificação , Fluconazol/administração & dosagem , Doenças Pulmonares Intersticiais , Pulmão , Lúpus Eritematoso Sistêmico , Antifúngicos/administração & dosagem , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Eur J Clin Microbiol Infect Dis ; 38(9): 1773-1780, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197619

RESUMO

To evaluate the association between fluconazole exposure parameters and clinical outcomes in patients with candidemia. We retrospectively included all adults with candidemia in a single center from January 2009 to December 2017, treated initially with fluconazole for fluconazole-susceptible candidemia. We assessed the association between fluconazole exposure parameters and 30-day mortality or 14-day clinical failure, a composite of mortality at day 14 or persistent candidemia ≥ 72 h, in all patients and in patients with C. glabrata candidemia. During the study period, 158 patients fulfilled the inclusion criteria. Main species were C. albicans 66 (41.8%), C. glabrata 35 (22.2%), and C. parapsilosis 31 (19.6%). Sixty patients (38%) died within 30 days. Sixty-one patients (38.6%) experienced 14-day failure. In 30-day survivors, the median AUC24/MIC was 2279 [398, 5989] versus 1764 [238, 6714] h in non-survivors, p = 0.75. Median fluconazole MIC was 0.75 [0.25, 4] and 1 [0.22, 5.50] mg/L, p = 0.54, respectively. Similar non-significant differences were found for other fluconazole exposure parameters and in the 14-day clinical failure analysis. For C. glabrata, a higher AUC24/MIC was observed among 30-day survivors with a median of 230 [77, 539] compared to 96 [75, 164] h in non-survivors, p = 0.008, in parallel with a trend for lower MIC values (median 7 [1, 2] versus 16 [8, 24] mg/L, p = 0.06, respectively). Currently used fluconazole dosing has no association with clinical outcome in Candida with low MIC values. For Candida species with high MICs, attention to dosing is needed.


Assuntos
Antifúngicos/administração & dosagem , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Fluconazol/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Candida/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Farmacorresistência Fúngica , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
12.
Appl Microbiol Biotechnol ; 103(16): 6701-6709, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201451

RESUMO

Candida albicans causes a high mortality rate in immunocompromised individuals, but the increased drug resistance challenges the current antifungal therapeutics. Fluphenazine (FPZ), a commonly used antipsychotic medication, can induce the expression of drug efflux pumps in C. albicans and, thus, may interfere with the therapeutic efficacy of antifungals, such as fluconazole (FLC) and amphotericin B (AmB). Here, we investigated the combined effects of FLC/FPZ and AmB/FPZ against C. albicans in vitro and in a systemic candidiasis mouse model. The antifungal activity of FLC was significantly reduced when supplemented with FPZ. The inhibitory effects of FLC on the expression of the Candida virulence-related genes ALS3 and HWP1 were antagonized by FPZ. However, FPZ enhanced the susceptibility of C. albicans to AmB and further downregulated the expression of ALS3 and HWP1 in a synergistic manner with AmB. FPZ also enhanced the gene expression of ERG11, a key gene of the ergosterol biosynthesis pathway that has been associated with the activities of both FLC and AmB. In our mammalian infection model, mice treated with FLC/FPZ showed notably poor living status and increased fungal burden in their kidneys and brains compared with those treated with FLC alone. Conversely, the combined application of AmB/FPZ significantly improved the survival rate, attenuated the weight loss and reduced the organ fungal burdens of the infected mice. These data suggest that FPZ antagonized the therapeutic efficacy of FLC but enhanced the antifungal activity of AmB in the treatment of candidiasis.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Antipsicóticos/farmacologia , Candida albicans/efeitos dos fármacos , Interações Medicamentosas , Fluconazol/farmacologia , Flufenazina/farmacologia , Anfotericina B/administração & dosagem , Estruturas Animais , Animais , Antifúngicos/administração & dosagem , Antipsicóticos/administração & dosagem , Candidíase/tratamento farmacológico , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Fluconazol/administração & dosagem , Flufenazina/administração & dosagem , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Camundongos , Resultado do Tratamento
15.
BMJ Case Rep ; 12(6)2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31229985

RESUMO

Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in mortality. To the best of our knowledge, we identified the first case of K. ohmeri keratitis following an injury with vegetative material. A 57-year-old woman with underlying, poorly controlled diabetes mellitus was gardening when a tree leaf accidentally poked her in the eye. Two weeks later, the patient presented with right eye pain, redness and progressive blurring of vision due to a traumatised right cornea. Slit-lamp examination showed a small inferior paracentral corneal stromal infiltrate with overlying epithelial defect. A corneal scraping sample yielded K. ohmeri from Analytical Profile Index (API) 20C yeast identification system. She was treated with intensive topical amphotericin B and fluconazole. After 6 weeks of treatment, the keratitis resolved with faint scar tissue, and her visual acuity improved.


Assuntos
Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Ceratite/microbiologia , Administração Tópica , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Córnea/patologia , Lesões da Córnea/complicações , Substância Própria/patologia , Feminino , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Ceratite/patologia , Pessoa de Meia-Idade , Pichia/isolamento & purificação , Folhas de Planta/efeitos adversos , Folhas de Planta/microbiologia , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
16.
Transpl Infect Dis ; 21(4): e13113, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31106504

RESUMO

BACKGROUND: Fluconazole represents a common antifungal option for the treatment of Candida infections in liver transplant recipients. Although adequate antifungal exposure is known to correlate with favorable outcomes in patients with invasive candidiasis, therapeutic drug monitoring (TDM) of fluconazole is currently not recommended. METHODS: We conducted a retrospective study including adult liver transplant recipients receiving fluconazole for invasive candidiasis and undergoing TDM. We assessed the correlation between clinical variables, fluconazole trough plasma levels (Cmin ), and outcome. RESULTS: Twenty-seven patients (74% males; median age 57 years) were included. Abdominal candidiasis was the most frequent infection (56%). Median duration of fluconazole therapy was 17 days (IQR 9-21). Fluconazole median Cmin was 11.0 mg/L (range 2.4-30.6 mg/L). Five (19%) patients required TDM-guided fluconazole dose increase. All-cause in hospital mortality was 33%. Fluconazole Cmin >11 mg/L significantly correlated with clinical success (OR 8.78, 95% CI 1.13-67.8, P = 0.04). CONCLUSIONS: Our study identified decreased fluconazole Cmin as a factor associated with negative outcomes in liver transplant recipients with Candida infection. TDM of fluconazole may be advisable in this patient population.


Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Monitoramento de Medicamentos , Fluconazol/administração & dosagem , Transplante de Fígado/efeitos adversos , Transplantados , Antifúngicos/sangue , Candidíase Invasiva/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Fluconazol/sangue , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária
17.
Minerva Ginecol ; 71(4): 321-328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31106557

RESUMO

Recurrent vulvovaginal candidiasis (RVVC) is an important pathological and infectious condition that can greatly impact a woman's health and quality of life. Clinical and epidemiological studies show that different types of therapies are able to eliminate the signs and symptoms of mycotic vaginitis in the acute phase, but so far none of these has proved able to significantly reduce the risk of long-term recurrence. In this review, based on the available literature and original data from a preliminary in-vitro microbiological study on the compatibility between fluconazole, clotrimazole and metronidazole a new therapeutic approach to RVVC is discussed and presented. The treatment proposed is a combined scheme using both systemic antimicrobial drug therapy with oral fluconazole 200 mg and topical drug therapy using the association metronidazole 500 mg and clotrimazole 100 mg (vaginal ovules) with adjuvant oral probiotic therapy. In detail, at the time of diagnosis in the acute symptom phase, we propose the following treatment scheme: fluconazole 200 mg on day 1, 4, 11, 26, then 1 dose/month for 3 months at the end of the menstrual cycle; plus metronidazole/clotrimazole ovules 1/day for 6 days the first week, then 1 ovule/day for 3 days the week before the menstrual cycle for 3 months; plus probiotic 1 dose/day for 10 days for 3 months starting from the second month to the end of the menstrual cycle. This scheme aims to address the recurrent infection aggressively from the outset by attempting not only to treat acute symptoms, but also to prevent a new event by countering many of the potential risk factors of recurrence, such as the intestinal Candida reservoir, the mycotic biorhythm, the formation of biofilm, the phenotype switching and the presence of infections complicated by the presence of C. non albicans or G. Vaginalis, without interfering, but rather favoring the restoration of the vaginal lactobacillus species. Future clinical studies will be useful to confirm the proposed scheme.


Assuntos
Candidíase Vulvovaginal/tratamento farmacológico , Clotrimazol/administração & dosagem , Fluconazol/administração & dosagem , Metronidazol/administração & dosagem , Administração Oral , Administração Tópica , Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/prevenção & controle , Quimioterapia Combinada , Feminino , Humanos , Probióticos/administração & dosagem , Recidiva
18.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142492

RESUMO

Cryptococcal meningitis is an opportunistic infection predominantly affecting immunocompromised patients but rarely can affect the immunocompetent. We describe a 53-year-old Caucasian man who presented complaining of a 2-week history of severe bilateral eye pain and diplopia. His only known risk factor was that he lived in a horse farm and recently shot bats and pigeons in his barn. He visited an outside hospital during this time without a diagnosis established. After further deliberation, we obtained a lumbar puncture (LP) which revealed an opening pressure (OP) of 27 cm H2O. Cerebrospinal fluid (CSF) and fungal cultures confirmed the presence of Cryptococcus neoformans The patient was diagnosed with C. neoformans-mediated meningoencephalitis and was initiated on the appropriate induction anti-fungal therapy. This case emphasises the need for clinicians to remain vigilant and consider cryptococcal meningitis in immunocompetent individuals even when classic symptoms of meningitis are absent.


Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Imunocompetência/fisiologia , Meningite Criptocócica/diagnóstico , Meningoencefalite/diagnóstico , Doenças dos Trabalhadores Agrícolas/tratamento farmacológico , Doenças dos Trabalhadores Agrícolas/microbiologia , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Cryptococcus neoformans , Diplopia/microbiologia , Quimioterapia Combinada , Dor Ocular/microbiologia , Fluconazol/administração & dosagem , Humanos , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/microbiologia , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Doenças Raras
19.
BMJ Case Rep ; 12(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30967448

RESUMO

Skull base osteomyelitis (SBO) is a serious and rare condition most commonly seen in elderly diabetic or immunocompromised patients as a complication of otitis externa. We present the case of a previously healthy 3-year-old girl who presented to the paediatric emergency department with vomiting, fever, lethargy, headache and left-sided facial nerve palsy. The initial CT head revealed left-sided otitis media with otomastoiditis and she was managed with intravenous antibiotics and myringotomy with grommet insertion with initial improvement. Two weeks later she re-presented having deteriorated and a dedicated mastoid CT and temporal bone MRI showed SBO. She underwent urgent cortical mastoidectomy where microbiological analysis of the cultures and specimen grew Candida albicans She was subsequently treated with long-term antifungals and antibiotics, and eventually recovered with good effect. The diagnostic dilemma and the empirical treatment of such a rare case are discussed.


Assuntos
Antifúngicos/administração & dosagem , Candidíase/terapia , Fluconazol/administração & dosagem , Mastoidectomia/métodos , Osteomielite/terapia , Administração Intravenosa , Antibacterianos/administração & dosagem , Candida albicans/isolamento & purificação , Candidíase/diagnóstico , Candidíase/microbiologia , Ceftriaxona/administração & dosagem , Pré-Escolar , Paralisia Facial/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Processo Mastoide/diagnóstico por imagem , Processo Mastoide/microbiologia , Processo Mastoide/cirurgia , Metronidazol/administração & dosagem , Osteomielite/complicações , Osteomielite/diagnóstico , Osteomielite/microbiologia , Base do Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
BMJ Case Rep ; 12(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30967449

RESUMO

A 51-year-old man with a medical history of coronary artery disease and dyslipidaemia presented with acute myocardial infarction resulting in cardiogenic shock, necessitating intra-aortic balloon pump placement and extracorporeal membrane oxygenation (ECMO). His hospital course was complicated by several infectious complications including ECMO circuit Pseudomonas aeruginosa bloodstream infection and presumed infected right atrial thrombus. He subsequently underwent urgent left ventricular assist device placement and had a prolonged hospital stay. On day 100 of admission, he developed acute hypoxic respiratory distress with new pulmonary infiltrates. Sputum cultures grew Cryptococcus neoformans Blood culture also grew C. neoformans after 96 hours of incubation and cryptococcal serum antigen was elevated at 1:20. Cerebrospinal fluid studies from a lumbar puncture were normal. He was treated with 2 weeks of combination antifungal therapy followed by life-long fluconazole suppression.


Assuntos
Criptococose/microbiologia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Coração Auxiliar/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Choque Séptico/microbiologia , Anfotericina B/administração & dosagem , Antibacterianos , Antifúngicos/administração & dosagem , Ciprofloxacino/administração & dosagem , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Cryptococcus neoformans/isolamento & purificação , Fluconazol/administração & dosagem , Flucitosina/administração & dosagem , Humanos , Imunocompetência , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Choque Séptico/sangue , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
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