Candida tropicalis isolates obtained from veterinary sources show resistance to azoles and produce virulence factors
Rossana de Aguiar CordeiroJonathas Sales de OliveiraDébora de Souza Collares Maia Castelo‐BrancoCarlos Eduardo Cordeiro TeixeiraFrancisca Jakelyne de Farias MarquesPaula Vago BittencourtVítor Luz CarvalhoTereza de Jesus Pinheiro Gomes BandeiraRaimunda Sâmia Nogueira BrilhanteJosé Luciano Bezerra MoreiraWaldemiro de Aquino Pereira‐NetoJosé Júlio Costa SidrimMarcos Fábio Gadelha Rocha
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Candida tropicalis has been associated with invasive candidiasis, being the first or second most common non-Candida albicans Candida species isolated in humans with candidemia and candiduria, as well as being frequently isolated from healthy animals. This study aimed to characterize C. tropicalis isolates (n = 64) obtained from several animal species regarding antifungal susceptibility and production of virulence factors. The isolates were obtained from the microbiota of healthy animals (goats, n = 25; sheep, n = 6; psittacines, n = 14; rheas, n = 6; horses, n = 2; sirenians, n = 5; shrimp, n = 1), as well as from aquatic mammals found dead in the environment (cetaceans, n = 5). The isolates were subjected to in vitro susceptibility testing by broth microdilution according to the CLSI M27-A3 protocol against amphotericin B, caspofungin, itraconazole, and fluconazole. We also evaluated the virulence attributes, such as proteases and phospholipases, as well as biofilm formation. Resistance to itraconazole (n = 29) and fluconazole (n = 30) was detected among isolates from every source; resistance to both azoles was detected in 24 isolates, but none of them were resistant to amphotericin B and caspofungin. Protease production was detected in the majority of the isolates (n = 59), but phospholipase was produced by only a few of them (n = 6). The isolates showed different patterns in biofilm production, being considered strong producers (n = 41), moderate producers (n = 11), weak producers (n = 9) or non-producers (n = 3). In summary, C. tropicalis isolated from animals showed high rate of resistance to azoles, expressed virulence factors and therefore may represent a potential threat to human and animal health.Keywords:
Broth microdilution
Objective To compare the efficacy and safety of itraconazole with those of fluconazole as earlier empirical antifungal therapy in ICU. Methods In a randomized,controlled,open trial,40 patients with risk factors of systemic fungal infections and unexplained fever that did not respond to broad-spectrum antibiotic therapy for 3-7 days were randomly divided into itraconazole group(20 patients) and fluconazole group(20 patients).Intravenous itraconazole,200 mg,was administered by infusion every 12 hours for the first 48 hours,followed by 200 mg daily from days 3 to 7.From day 8,oral itraconazole solution,200 mg twice daily,replaced intravenous itraconazole for another 14 days.Fluconazole was infused intravenously at a daily dose of 400 mg for 21 days.Body temperature,fungal infection,drug-related adverse events,and the efficacy were investigated. Results For itraconazole and fluconazole,the overall effective rates were 65.0% and 50.0%,and the adverse reactions rates were 30.0% and 5.0% respectively.But there were no significant differences in the overall effective rates and the adverse reactions rates between two groups.Two patients developed deep fungal infections in fluconazole group during the therapy. Conclusion Nowadays,itraconazole and fluconazole are effective and safe as the first-line drugs in earlier empirical therapy in ICU.However,itraconazole appears better in efficacy.
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Background: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. Objective: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. Design: Randomized, double-blind, placebo-controlled trial. Setting: 7 treatment centers in California, Arizona, and Texas. Patients: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. Measurements: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. Results: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, −2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. Conclusions: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.
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Ninety patients with tinea versicolor were randomly assigned to treatment with either a single 450‐mg dose of fluconazole, two 300‐mg doses of fluconazole given 1 week apart, or itraconazole 200 mg daily for 7 days. At the end of treatment, the cure rate for itraconazole (20%) was significantly higher ( P = 0.024) than that for fluconazole 450 mg (0%). When cure plus improvement was considered, response rates among the three treatment groups were comparable (97, 100, and 97% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively). Failure rates at the end of treatment were low (0–3%). Clinical response rates achieved at the end of treatment generally were maintained at 1 month, but tended to decrease at 2 months. Eradication at the end of treatment was not significantly different among the treatment groups (17, 33, and 38% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively). At 1 month, the eradication rate was significantly higher ( P = 0.012) for the two‐dose than the single‐dose fluconazole treatment group (97 and 70%, respectively). At 2 months, reinfection rates were 21, 20, and 4% for fluconazole 450 mg, fluconazole 300 mg, and itraconazole, respectively. No clinical adverse events occured, and no patients were withdrawn for laboratory abnormalities.
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To compare the efficiency and safety of itraconazole oral solution with those of fluconazole to prevent invasive fungal infections (IFI) in postoperative patients receiving orthotopic liver transplantation (OLT).In a randomized, controlled, open trial, 60 patients receiving OLT were randomized into itraconazole treatment group (n = 30) and fluconazole treatment group (n = 30). The patients in itraconazole treatment group were given itraconazole oral solution in a dose of 20 ml once a day for 15 days and the patients in the fluconazole treatment group were given fluconazole in a dose of 150 mg once a day also for 15 days. The incidences of fungal infections after liver transplantation and the resistance to drugs were recorded.There were three patients in the itraconazole treatment group getting IFI; the infection rate was 10.0%. One patient had confirmed diagnosis and two other patients were diagnosed clinically. In the fluconazole treatment group there were 10 patients getting IFI, the infection rate was 33.3%. Two patients had confirmed diagnosis, six patients were diagnosed clinically and the remaining two were diagnosed tentatively. There was a significant difference between the two groups (P < 0.05).Compared with fluconazole, itraconazole oral solution is more effective in the treatment of invasive fungal infections in postoperative patients receiving OLT.
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Objective: To compare the efficacy and safety of caspofungin and itraconazole in the treatment of invasive pulmonary fungal infection(IPFI).Methods: A retrospective analysis was applied to collect the data about the basic characteristics and signs of patients,clinical manifestation and adverse events in invasive pulmonary fungal infection patients in pneumology department from Sep 2010 to Aug 2011.And the clinical efficacy and the incidence of adverse reactions were compared and statistically analyzed between caspofungin and itraconazole group.Results: Caspofungin group had 36 cases and itraconazole group had 31 cases.The overall effective rates of caspofungin group and itraconazole group were 58.3% and 38.7%,with significant difference between two groups(P 0.05).The overall incidences of adverse reaction in caspofungin group and itraconazole group were 22.2% and 54.8%,respectively.There was significant difference in drug withdrawal after toxicity reaction between two groups(P 0.05),four patients changed to other medicines because of toxicity reaction in itraconazole group,while that did not occur in caspofungin group.Conclusion: Caspofungin was associated with better clinical outcomes(higher cure and fewer adverse effects) than itraconazole in the treatment of invasive pulmonary fungal infections,it should be used rationally in order to reduce the emergence of resistant strains.
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This multicenter, randomized, double-blind study compared the efficacy and safety of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. One hundred twenty-six immunocompromised patients with esophageal candidiasis were treated with itraconazole oral solution or fluconazole tablets (both at 100–200 mg) once daily for 3–8 weeks, for 2 weeks beyond the resolution of symptoms, and were then followed for 4 more weeks. Severity of symptoms was assessed weekly during treatment and every 2 weeks during follow-up. Patients treated with itraconazole oral solution had a rate of clinical response (cured or improved) comparable to that of patients treated with fluconazole (94% vs. 91%). The mycologic eradication rate was 92% for itraconazole and 78% for fluconazole. Both treatments were well tolerated. Results from treatment with once-daily itraconazole oral solution was clinically comparable to those with fluconazole and is an alternative for the treatment of esophageal candidiasis in immunocompromised patients.
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OBJECTIVE:To compare the efficacy and safety between caspofungin and fluconazole in the treatment of severe pulmonary fungal infection in intensive care unit. METHODS:36 patients with systemic fungal infections in intensive care unit were randomly assigned to receive caspofungin 50 mg·d-1 which was added into 250 mL normal saline and infused in no less than 1h for 14 days after initial dose of 70 mg(caspofungin group,n=18) or fluconazole 400 mg·d-1 for 14 days by iv gtt (fluconazole group,n=18). The curative efficacy and adverse events in the two groups were observed. RESULTS:The effective rate was 100.0% in caspofungin group versus 66.7% in fluconazole group. The incidence rates were 22.2% and 72.2%,respectively. There were significant differences in the overall effective rate between two groups(P0.05),and the incidence of adverse reactions in caspofungin group was significantly lower than in fluconazole group(P0.05). CONCLUSION:Caspofungin is superior to fluconazole in both efficacy and safety in the treatment of severe pulmonary fungal infection in intensive care unit.
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The manifestations of histoplasmosis in 20 patients with the acquired immunodeficiency syndrome are presented. In this series, patients were treated with either itraconazole or fluconazole. Twelve patients received treatment with itraconazole at 400 mg/day, including two patients who had not responded to treatment with fluconazole at 100 mg/day. Of the responses, seven were classified as remissions (mean treatment duration of 24 months), two as improvements, and three as failures. Ten patients received fluconazole. Of the responses, three were classified as remissions (mean treatment duration of 12 months), one as improvement, and six as failures. Of the 10 patients treated with fluconazole, five received doses of 100 mg/day, and five were given doses of 400 or 800 mg/day. The differences in outcome among the five patients receiving the lower dose of fluconazole (one remission, one improvement, and three failures) and the five patients given the higher doses of fluconazole (two remissions and three failures) were negligible. One other patient showed signs of histoplasmosis while receiving fluconazole at 50 mg/day for treatment of thrush. Three failures (two treated with itraconazole and one with fluconazole) followed lapses in azole therapy because of associated conditions. Azole therapy was well tolerated. The treatment responses in this pilot series appear promising in comparison with those reported in the literature with amphotericin B or ketoconazole.
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In cryptococcosis, fluconazole is a standard prophylactic, therapeutic and maintenance option, particularly in the expanding HIV/AIDS group. However, its excessive use may lead to resistance in Cryptococcus neoformans. Variations in clinical response to fluconazole have already been noted elsewhere, and cases of post-therapy relapse are not uncommon. To assess azole antifungal susceptibility profiles of clinical cryptococcal isolates in India, the All India Institute of Medical Sciences (AIIMS) has recently initiated preliminary studies using NCCLS M27-A.Twenty-eight randomly chosen AIIMS clinical isolates (spanning 1997-2000), 16 isolates from other institutions in North India, and six reference strains of C. neoformans were subjected to susceptibility testing to fluconazole and itraconazole.Among clinical isolates, susceptibilities to fluconazole and itraconazole were 84.1% and 93.2%, respectively. MICs for all clinical isolates were 0.25-32 mg/L for fluconazole and <0.03-0.25 mg/L for itraconazole. MIC50 and MIC90 values for fluconazole were 4 and 16 mg/L, respectively, and those for itraconazole were 0.032 and 0.125 mg/L, respectively. Out of 28 AIIMS clinical isolates, 22 had minimum fungicidal concentrations (MFCs) of fluconazole at 128 mg/L. Moderately high fluconazole MICs (16-32 mg/L) were observed in 16% of clinical isolates--probably the first such report from India. MIC/MFC ratios for fluconazole and itraconazole were 1:32 or more in 16 AIIMS clinical isolates, indicating possible azole tolerance. There was good agreement between MIC values obtained by the micro- and macro-broth dilution techniques of M27-A compared in this study.The observed MIC data warrant continued surveillance of susceptibility values of clinical cryptococcal isolates in India.
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