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We extracted data using the standard methods of the CNRG. Two review authors independently assessed the relevance and risk of bias of the retrieved records. We expressed our dichotomous results using risk ratio (RR) with their 95% confidence intervals (CIs). We assessed for heterogeneity using the I(2) statistic.
The relationship between fluconazole concentrations and preventive effectiveness was poor. Together with the rather large inter-occasion variability in fluconazole clearance, this suggests no role of therapeutic drug monitoring in optimising fluconazole treatment for secondary prevention.
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Candida is present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, and corticosteroid use. In most people, untreated candidiasis persists for months or years unless associated risk factors are treated or eliminated. In neonates, spontaneous cure of oropharyngeal candidiasis usually occurs after 3-8 weeks.
A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town.
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We report the case of a 52-year-old man with HIV-AIDS, non-complaint with highly active antiretroviral therapy, who presented with long-standing dysphagia. He was treated for three episodes of severe Candida esophagitis with fluconazole and later caspofungin due to poor response. In spite of the prolonged treatment courses the patient did not report an improvement in his symptoms. He was also concomitantly being treated for other opportunistic infections including cytomegalovirus (CMV) retinitis with i.v. foscarnet for almost 2 months prior to the index presentation. Upper esophagogastroduodenoscopy revealed multiple superficial ulcers with stricturing. Bougie dilatation was attempted but failed. The biopsy specimens revealed multiple intracellular inclusion bodies pathognomonic of CMV infection. We aim to highlight the increasing resistance of CMV to conventional first-line antiviral agents such as foscarnet.
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Drug-drug interactions are a recurring problem in immunocompromised patients treated with triazole antifungals. While the introduction of new antifungals has expanded opportunities for lowering drug toxicity, virtually all antifungal regimens carry the risk of pharmacokinetic and pharmacodynamic interaction. This review presents the published data on molecular determinants (enzymes, transporters, orphan nuclear receptors) of systemic triazole pharmacokinetics in humans, including itraconazole, fluconazole, voriconazole and posaconazole. Systemic triazoles are inhibitors of cytochrome P450 (CYP) isozymes, such as CYP3A4, CYP2C9 and CYP2C19, to varying degrees. In addition, some are substrates and/or inhibitors of drug transporters such as multidrug resistance-1 gene product, P-glycoprotein, or breast cancer resistance protein. The interactions of triazole antifungals can be divided into the following categories: modifications of antifungal pharmacokinetics by other drugs, modifications of other drug pharmacokinetics by antifungals, and two-way interactions. These features are the basis of most interactions that occur during triazole therapy.
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The aim of this study was to evaluate the use of one of the molecular typing methods such as PCR (polymerase chain reaction) following by RFLP (restriction fragment length polymorphism) analysis in the identification of Candida species and then to differentiate the identified azole susceptible and resistant Candida albicans strains by using AP-PCR (arbitrarily primed-polymerase chain reaction). The identification of Candida species by PCR and RFLP analysis was based on the size and primary structural variation of rDNA intergenic spacer regions (ITS). Forty-four clinical Candida isolates comprising 5 species were included to the study. The amplification products were digested individually with 3 different restriction enzymes: HaeIII, DdeI, and BfaI. All the isolates tested yielded the expected band patterns by PCR and RFLP analysis. The results obtained from this study demonstrate that Candida species can be differentiated as C. albicans and non-C. albicans strains only by using HaeIII restriction enzyme and BfaI maintains the differentiation of these non-C. albicans species. After identification Candida species with RFLP analysis, C. albicans strains were included to the AP-PCR test. By using AP-PCR, fluconazole susceptible and resistant strains were differentiated. Nine fluconazole susceptible and 24 fluconazole resistant C. albicans were included to the study. Fluconazole resistant strains had more bands when evaluating with the agarose gel electrophoresis but there were no specific discriminatory band patterns to warrant the differentiation of the resistance. The identification of Candida species with the amplification of intergenic spacer region and RFLP analysis is a practical, short, and a reliable method when comparing to the conventional time-consuming Candida species identification methods. The fluconazole susceptibility testing with AP-PCR seems to be a promising method but further studies must be performed for more specific results.
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Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.
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Three vertically HIV-infected children showed, in addition to oral candidiasis, HIV-gingivitis, which healed on antimycotic treatment. The intense linear gingival erythema of a fourth child was also clinically evaluated as a possible form of erythematous oral candidiasis. Direct microscopic examination of material from the gingival lesions of the latter disclosed yeast cells and hyphae. Subsequent culture, biochemical and serological tests identified the yeast as Candida dubliniensis. As the patient was on long-term prophylaxis with fluconazole, ketoconazole was administered and led to a good clinical response. This is the first report implicating this new Candida species as a pathogen in linear gingival erythema in a HIV-positive individual. The case reports presented provide evidence that linear gingival erythema may be of candidal origin. Further clinical and laboratory observations are required to establish whether this condition constitutes a variant of erythematous candidiasis associated with paediatric HIV infection.
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Pharmacists moderately agreed (5.78 ± 1.33 [mean ± SD]) that introducing a BTC category of medication would advance the profession's goals of providing more pharmacist-directed patient care. Pharmacists also moderately agreed (6.09 ± 1.71) that patient counseling should be mandatory before providing any medications in a BTC category. At their current practice site, pharmacists moderately agreed (5.65 ± 1.62) that they would participate in providing BTC medications; however, they felt the largest issue pertaining to a BTC category of medications was the added amount of time that would be spent with patients (5.34 ± 1.53). On the other hand, pharmacists moderately agreed (5.82 ± 1.26) that they would take the time to counsel patients on BTC medications. Prescription prenatal vitamins (1 mg folic acid), triamcinolone cream, silver sulfadiazine cream, mometasone nasal inhalation, fluconazole 150 mg, epinephrine injection, promethazine, and mebendazole were considered the most appropriate for a BTC category of medications.
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Cross-sectional study conducted in the public healthcare system of Maringá, Paraná, Brazil.
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This article reported the identification of heat shock protein 90 (hsp90) homologues by immunoblot in Cryptococcus neoformans. Mycograb, a genetically recombinant antibody against hsp90, was evaluated against 8 clinical isolates and the National External Quality Assessment Service for Microbiology strain of C. neoformans alone and in combination with amphotericin B, caspofungin, and fluconazole by checkerboard assay. At the end point of an optically clear well, the minimum inhibitory concentration (MIC) 0's ranged from 256 to 1024 microg/mL for Mycograb, from 0.5 to 1 microg/mL for amphotericin B, and from 16 to 32 microg/mL for caspofungin. The combination of Mycograb and amphotericin B produced a fractional inhibitory concentration index from 0.27 to 0.56, indicating a mainly synergistic effect, whereas for caspofungin, it varied from 0.5 to 2. At an end point of > or =50% inhibition, the MIC-2s varied from 16 to 128 microg/mL for Mycograb and from 0.125 to 16 microg/mL for fluconazole. The fractional inhibitory concentration index classified the combination as indifferent for 5 isolates, additive for 3 more isolates, and synergistic in a single isolate. Time-kill analysis on 2 isolates (F/7844 and F/10156), which had synergistic and additive results with amphotericin B, respectively, on checkerboard was performed with 4-16 microg/mL of Mycograb, 2-8 microg/mL of fluconazole, and 0.0625-2 microg/mL of amphotericin B. This demonstrated an increasingly static effect with augmenting concentrations of fluconazole and an initial static effect with amphotericin B at lower concentrations, which became fungicidal as the level of drug increased. The addition of either 4 or 8 microg/mL of Mycograb to 0.5 microg/mL of amphotericin B with C. neoformans F/7844 changed a static effect to a fungicidal effect at 8 h with an increased killing of 1.2 logs at 48 h. With C. neoformans F/10156, the addition of 16 microg/mL of Mycograb to 0.25 microg/mL of amphotericin B produced a difference in killing from 1 logarithm after 4 h to 1.5 logarithms after 48 h. These data suggest that the combination of amphotericin B and Mycograb would be worth exploring in the treatment of infection due to C. neoformans.
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A total of 17 939 women were included in the final analysis. Trimethoprim/sulfamethoxazole was associated with significantly increased risks for preterm birth (aOR 1.51, 95% CI 1.10, 2.08) and low birth weight (aOR 1.67, 95% CI 1.14, 2.46). Exposure to non anti-infective FDA category C, D and X drugs was also associated with increased risks for preterm birth (aOR 1.17, 95% CI 1.09, 1.31) and low birth weight (aOR 1.14, 95% CI 0.92, 1.42), but to a lesser degree. Other FDA C and D anti-infectives were not (statistically) significantly associated with increased risks for preterm birth (aOR 0.93, 95% CI 0.49, 1.77) or low birth weight (aOR 0.65, 95% CI 0.27, 1.60).
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The prognosis of T-cell lymphoma is poor. To explore the addition of the monoclonal antibody alemtuzumab, we studied the efficacy and tolerability of an intensified alemtuzumab-chemotherapy combination for aggressive T-cell lymphoma in a phase II study by Dutch-Belgian Hemato-Oncology Group (HOVON).
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Follow-up study, neted case-control group.
C. fistula fruit pulp and seed extract possessed anticandidal activity. The result was significantly correlated between the MICs, cytotoxicity and ergosterol inhibition. It was concluded that the crude extract is a promising source for anticandidal compounds.
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The antifungal activity of catechin was pH dependent. The concentration of epigallocatechin gallate (EGCg) causing 90% growth inhibition of tested strains of C. albicans was 2000 mg/L at pH 6.0, 500-1000 mg/L at pH 6.5 and 15.6-250 mg/L at pH 7.0. Among catechins, pyrogallol catechin showed stronger antifungal activity against C. albicans than catechol catechin. The addition of 6.25-25 or 3.12-12.5 mg/L EGCg to amphotericin B 0.125 or 0.25 mg/L (below MIC) at pH 7.0 resulted in enhancement, respectively, of the antifungal effect of amphotericin B against amphotericin B-susceptible or -resistant C. albicans. Combined treatment with 3.12-12.5 mg/L EGCg plus amphotericin B 0.5 mg/L (below MIC) markedly decreased the growth of amphotericin B-resistant C. albicans. When fluconazole-susceptible C. albicans was treated with 25-50 mg/L EGCg and fluconazole 0.125-0.25 mg/L (below MIC), its growth was inhibited by 93.0%-99.4% compared with its growth in the presence of fluconazole alone. The combined use of 12.5 mg/L EGCg and fluconazole 10-50 mg/L (below MIC) inhibited the growth of fluconazole-resistant C. albicans by 98.5%-99.7%.
Blastomycosis is an endemic mycosis caused by the dimorphic fungus Blastomyces dermatitidis. Although this disease primarily involves the lungs, the clinical spectrum of blastomycosis can range from subclinical infection to extrapulmonary dissemination. The central nervous system (CNS) form of blastomycosis is primarily treated with an amphotericin B formulation, but associated toxicities of this agent preclude its use in some patients. Voriconazole is a broad-spectrum triazole antifungal that has emerged as a potential treatment option for CNS blastomycosis because of its excellent penetration into the cerebrospinal fluid and brain tissue.
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Invasive fungal infections (IFIs) remain an important cause of morbidity and mortality in patients with acute or chronic leukemia. Advances in the pharmacotherapy of fungal infections and a shift in the epidemiological characteristics of fungal pathogens toward fluconazole-resistant Candida species and saprophytic molds have placed a greater emphasis on selection of broader-spectrum agents for empirical therapy of IFIs in this high-risk population. Newer diagnostic modalities, such as the Aspergillus galactomannan test, the 1,3-beta-d-glucan test, and polymerase chain reaction detection of fungal DNA, may facilitate the earlier diagnosis of IFIs, but their role in detecting breakthrough infection and their usefulness as a marker to withhold antifungal therapy in high-risk leukemia patients with IFI are less obvious, especially in patients who are receiving antifungal prophylaxis. Only 2 strategies have been shown in prospective studies to improve survival from mold infection in patients with acute myelogenous leukemia or myelodysplastic syndrome: (1) preemptive initiation of antifungal therapy at first sign of invasive aspergillosis on computed tomography (CT) scan and (2) antifungal prophylaxis with posaconazole. CT-guided treatment decisions are more complex in patients with advanced leukemia, however, because of concomitant infection or relapsing malignancy. Similarly, posaconazole is often not a viable prophylaxis or treatment option in patients with poor oral intake, gastrointestinal dysfunction, or possible drug interaction (eg, proton pump inhibitor prophylaxis in patients on high-dose glucocorticosteroids). As a result, the management of IFI in patients with leukemia demands an individualized treatment plan.
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Les infections fongiques sont une cause majeure de mortalité chez les brûlés et en augmente significativement le coût de prise en charge. Cette étude a pour buts de déterminer l’épidémiologie et d’analyser les facteurs de risque de leur survenue dans le centre national des brûlés de l’hôpital Ibn-Roch de Casablanca. Il s’agit d’une revue rétrospective des patients hospitalisés entre 2011 et 2014 ayant eu des cultures fongiques positives. Les critères de définition d’une infection fongique nosocomiale (IFN) étaient ceux du CDC d’Atlanta de 1988, révisés en 1992 et 2004. La surveillance microbiologique était journalière. Les données démographiques, la surface atteinte, le type et le (les) sites de l’infection, l’espèce, le nombre de cultures positives on été colligés. Les facteurs de risque de survenue d’une IFN ont été analysés. L’âge était de 25,4 +/- 27,3 ans, 63% des patients étaient des femmes. La surface brûlée était de 30,7 +/- 23,4% dont 21,7 +/- 20,1% profond. Les brûlures par flammes étaient les plus fréquentes (82%), suivies des ébouillantements et des brûlures par contact. L’incidence des IFN était de 10%. Candida albicans y était l’espèce la plus largement représentée (65,7%), suivie par 18,6% de « Candida non albicans ». Aspergillus spp étaient retrouvés dans 3,9% des cas et clairement associés à la mortalité et la morbidité. Les facteurs de risque étaient essentiellement la surface brûlée et l’antibiothérapie à large spectre prolongée. Ils étaient associés à un plus grand nombre de cultures positives multiples et à une surmortalité (21,6%). L’amphotéricine B et le fluconazole étaient les antifongiques les plus prescrits. Les champignons devenant des agents fréquents d’infections nosocomiales, il est nécessaire d’y songer rapidement et de limiter les prescriptions d’antibiotiques.
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Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07-0.36), fluconazole use (HR 0.34; CI 0.18-0.64), and co-trimoxazole use (HR 0.41; CI 0.20-0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death.
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Disseminated histoplasmosis is the first AIDS-defining infection in French Guiana. A retrospective cohort study studied predictive factors of disseminated histoplasmosis in HIV-infected patients between 1996 and 2008. Cox proportional hazards models were used. The variables studied were age, sex, last CD4/CD8 count, CD4 nadir, herpes or pneumocystosis, cotrimoxazole and fluconazole use, antiretroviral treatment and the notion of recent initiation of HAART. A total of 1404 patients were followed for 6833 person-years. The variables independently associated with increased incidence of disseminated histoplasmosis were CD4 count<50 per mm3, CD4 count between 50 and 200 per mm3, a CD4 nadir <50 per mm3, CD8 count in the lowest quartile, herpes infection, and recent antiretroviral treatment initiation (less than 6 months). The variables associated with decreased incidence of histoplasmosis were antiretroviral treatment for more than 6 months, fluconazole treatment, and pneumocystosis. There were 13.5% of deaths at 1 month, 17.5% at 3 months, and 22.5% at 6 months after the date of diagnosis of histoplasmosis. The most important predictive factors for death within 6 months of diagnosis were CD4 counts and antiretroviral treatment. The present study did not study environmental/occupational factors but provides predictive factors for disseminated histoplasmosis and its outcome in HIV patients in an Amazonian environment during the HAART era.
The incidence of the species Candida albicans and non-albicans Candida was evaluated in a Brazilian Tertiary Hospital from the environment and health practitioners. In a 12-month period we had a total positivity of 19.65% of Candida spp. The most recurring non-albicans Candida species was C. glabrata (37.62%), generally considered a species of low virulence, but with a higher mortality rate than C. albicans. Subsequently, C. parapsilosis (25.74%) and C. tropicalis (16.86%) were the second and third most commonly isolated species. Considering the total samples collected from the emergency room and from the inpatient and the pediatric sector, 19.10% were positive for Candida spp., with the predominance of non-albicans Candida species (89.42%). The high percentage of positivity occurred in the hands (24.32%) and the lab coats (21.88%) of the health care assistants. No sample of C. albicans presented a profile of resistance to the drugs. All the non-albicans Candida species presented a decreased susceptibility to miconazole and itraconazole, but they were susceptible to nystatin. Most of the isolates were susceptible to fluconazole and amphotericin B. As expected, a high resistance rate was observed in C. glabrata and C. krusei, which are intrinsically less susceptible to this antifungal agent. The contamination of environmental surfaces by Candida spp. through hand touching may facilitate the occurrence of Candida infections predominantly in immunocompromised patients. In addition to that, the antifungal agents used should be carefully evaluated considering local epidemiologic trends in Candida spp. infections, so that therapeutic choices may be better guided.
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Of the three antifungals tested, terbinafine had the most potent in vitro antifungal activity against dermatophytes. Antifungal susceptibility tests would be useful to screen antifungal-resistant dermatophyte strains.
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We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using risk ratio and risk difference.
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There was no statistically significant difference in EFA between AmB in combination with fluconazole and AmB plus 5-FC for the treatment of HIV-associated cryptococcal meningitis. AmB plus fluconazole (800-1200 mg/day) represents an immediately implementable alternative to AmB plus 5-FC. AmB plus voriconazole is an effective alternative combination in patients not receiving interacting medications.
Cryptococcal pneumonia usually occurs in immunocompromised patients with malignancy, acquired immune deficiency syndrome, organ transplantations, immunosuppressive chemotherapies, catheter insertion, or dialysis. It can be diagnosed by gaining tissues in lung parenchyma or detecting antigen in blood or bronchoalveolar lavage fluid. Here we report an immunocompetent 32-year-old male patient with diabetes mellitus diagnosed with cryptococcal pneumonia after a ultrasound-guided percutaneous supraclavicular lymph node core needle biopsy. We treated him with fluconazole at 400 mg/day for 9 months according to the guideline. This is the first case that cryptococcal pneumonia was diagnosed from a percutaneous lymph node biopsy in South Korea.
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Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Patients with PCM show a wide spectrum of clinical and pathological manifestations depending on both host and pathogen factors. Two clinical forms of the disease are recognized: the acute or juvenile form and the chronic or adult form. The major antigenic component of the parasite is a glycoprotein of 43 kDa (gp43). All patient sera present antibodies against gp43 (anti-gp43) and, as demonstrated before by our group, spontaneous anti-idiotypic (anti-Id) antibodies (Ab2) can be detected in patient sera with high titers of anti-gp43. Since it has been postulated that anti-Id antibodies may have a modulating function, we decided to purify and characterize anti-Id antibodies in this system. The possible correlation of Ab2 titers with different clinical forms of disease was also verified. Results showed that purified human anti-Id antibodies (human Ab2) recognized specifically the idiotype of some murine monoclonal anti-gp43 (17c and 3e) but not others (40.d7, 27a, and 8a). Spontaneous anti-Id antibodies were found in all clinical forms of disease. The majority of patients (88%, n = 8) with the acute form of PCM had high titers of Ab2. However, among patients with the multifocal chronic form of the disease, only 29% (n = 14) had high titers of Ab2; 70% (n = 10) of patients with the unifocal chronic form had low titers of Ab2. A correlation between Ab2 titers and anti-gp43 titers was observed before and during antimycotic treatment. Our results suggest that titers of anti-Id antibodies correlate with the severity of PCM in humans.
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Cases were identified prospectively through the British Ophthalmologic Surveillance Unit (BOSU) from December 2003 to November 2005. Questionnaire data were requested at diagnosis and at 6 months follow-up. Inclusion criteria were a positive culture or microsopic proof from a scraping or biopsy, and a normal residence in the United Kingdom.