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[This corrects the article DOI: 10.1371/journal.pone.0048369.].

Globally, cryptococcal meningitis is a leading cause of mortality among people with AIDS, despite the availability of effective amphotericin B–based therapy. In this trial in sub-Saharan Africa, the efficacy of two simpler treatment regimens was assessed.

Background. The treatment of cutaneous leishmaniasis (CL) caused by leishmania braziliensis in Brazil with pentavalent antimony (Sb) is associated with a high rate of failure, up to 45% of cases. In addition, Sb can only administered parenterally and has important toxic effect. An effective, safe, and oral treatment for CL is required. Methods. A randomized controlled clinical trial was conducted to compare the efficacy and safety of high-dosage oral fluconazole (6.5–8.0 mg/kg/d for 28 days) versus a standard Sb protocol (20 mg/kg/d for 20 days) for the treatment of CL in Bahia, Brazil. Results. A total of 53 subjects were included in the trial; 26 were treated with Sb, and 27 with fluconazole. Intention-to-treat analysis showed initial cure rates (2 months after treatment) of 22.2% (6 of 27) in the fluconazole and 53.8% (14 of 26) in the Sb group (P = .04). Six months after treatment, the final cure rate remained the same in both groups, without any replaces. The frequencies of adverse effects in the Sb and fluconazole groups were similar, 34.6% versus 37% respectively. One patient treated with fluconazole discontinued treatment owing to malaise, headache, and moderate dizziness (Common Terminology Criteria for Adverse Events grade 2). Conclusions. Oral fluconazole at a dosage of 6.5–8 mg/kg/d for 28 days should not be considered an effective treatment for CL caused by L. braziliensis. Clinical Trials Registration. NCT01953744.

Background. Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)–associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day, but mortality rates remain unacceptably high. Therefore, we examined the effect of adding oral flucytosine to fluconazole. Methods. From 13 February through 2 December 2008, HIV-seropositive, antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up. The primary end point was early fungicidal activity, derived from quantitative cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were safety and 2- and 10-week mortality. Results. Forty-one patients were analyzed. Baseline mental status, cryptococcal burden, opening pressure, CD4+ cell count, and HIV load were similar between groups. Combination therapy was more fungicidal than fluconazole alone (mean early fungicidal activity ± standard deviation, −0.28±0.17 log colony-forming units [CFU]/mL per day vs −0.11±0.09 log CFU/mL per day; P<.001). The combination arm had fewer deaths by 2 weeks (10% vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia with combination therapy (5 vs 1, within the first 2 weeks; P=.20), but there was no increase in infection-related adverse events. Conclusions. The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan ® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between −21 and −33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan ® cream.

Background. Cryptococcosis is a life-threatening infection among patients with human immunodeficientcy virus (HIV) infection. Therapeutic options for the treatment of central nervous system cryptococcosis are limited, especially in resource-limited settings. Methods. We conducted a randomized, open-label, phase II trial in Thailand and the United States that compared the safety and efficacy of intravenous amphotericin B deoxycholate (AmB) 0.7 mg/kg (the standard therapy) with that of AmB 0.7 mg/kg plus fluconazole 400 mg (the low-dosage combination) or AmB 0.7 mg/kg plus fluconazole 800 mg (the high-dosage combination) administered daily for 14 days, followed by fluconazole alone at the randomized dosage (400 or 800 mg per day) for 56 days. The primary safety end point was the number of severe or life-threatening treatment-related toxicities; the primary efficacy end point was a composite of survival, neurologic stability, and negative cerebrospinal fluid culture results after 14 days of therapy. Results. A total of 143 patients were enrolled. There were no differences in treatment-related toxicities among the 3 arms. Toxicity was predictable and was most often related to AmB, and it included electrolyte abnormalities, anemia, nephrotoxicity, and infusion-related events. At day 14, 41%, 27%, and 54% of patients in the standard therapy, low-dosage combination, and high-dosage combination therapy arms, respectively, demonstrated successful outcomes. A trend towards better outcomes in the combination therapy arms was seen at days 42 and 70. Conclusions. AmB plus fluconazole administered at a dosage of 800 mg for 14 days, followed by fluconazole administered at a dosage of 800 mg daily for 56 days, is well-tolerated and efficacious among HIV-positive patients with central nervous system cryptococcosis. These results have significant treatment implications and should be validated in a randomized phase III trial. Clinical trials registration. This clinical trial is registered in the National Library of Medicine's registry (http://www.clinicaltrials.gov) under the registration number NCT00145249.

Echinocandins are emerging as important new therapeutic agents for the treatment of candida infections. In this randomized, double-blind, international, multicenter study, anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. In this study, anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. Invasive candidiasis is an important cause of complications and death in hospitalized patients. 1 – 4 Current choices for treatment include fluconazole, caspofungin, voriconazole, and amphotericin B. 5 – 8 These agents were developed through prospective, randomized trials in which amphotericin B deoxycholate was used as the comparison agent. 6 – 9 Although caspofungin has been shown to be noninferior to amphotericin B, dose-limiting nephrotoxicity contributed to a worse outcome in the amphotericin B group. 7 Echinocandins have emerged as important agents for the treatment of invasive candidiasis. 9 , 10 Fluconazole and echinocandins have favorable safety profiles. 11 – 13 Anidulafungin, a new echinocandin with activity against candida species, 14 – . . .

Background Invasive fungal infections (IFIs), particularly Candida infections, are a significant cause of morbidity and mortality in patients with acute leukemia. While fluconazole is widely used for prophylaxis, the optimal dosing regimen remains uncertain. This study aimed to evaluate the efficacy of low‐dose fluconazole for primary prophylaxis against invasive Candida infections in patients with acute leukemia receiving intensive chemotherapy. Methods A double‐blind, randomized clinical trial was conducted with patients diagnosed with acute leukemia. Patients were assigned to receive either low‐dose (150 mg/day) or standard high‐dose (400 mg/day) fluconazole for primary prophylaxis against invasive Candida infections during intensive chemotherapy. The primary outcomes were the efficacy of antifungal prophylaxis and the safety profile. Results A total of 120 patients (60 per group) were enrolled. The overall incidence of Candida infections was similar between the groups (p = 0.615). Candida colonization was higher in the low‐dose fluconazole group during the first week, particularly with non‐albicans Candida at oral and subaxillary sites (p < 0.001). However, by the third week, both groups showed a significant decline in colonization, with the reduction in the oral cavity being statistically significant (p = 0.03). Aspergillosis occurred in 38.3% of patients, with no significant difference between groups (p > 0.99). Adverse events were similar in both groups (p > 0.05). Conclusion Low‐dose fluconazole is an effective alternative to high‐dose regimens for preventing Candida infections in acute leukemia patients, with similar efficacy and safety. The rising threat of aspergillosis highlights the need for targeted prophylaxis. Further research is needed to refine strategies for high‐risk patients. Trial Registration Iranian Registry of Clinical Trials (IRCT) number: IRCT20140818018842N37

Cryptococcal meningitis is a major complication of HIV infection. In this phase 3, randomized, controlled trial in sub-Saharan Africa, a single dose of liposomal amphotericin B induction therapy combined with fluconazole and flucytosine for cryptococcal meningitis was shown to be noninferior to standard induction therapy with amphotericin B deoxycholate and was associated with fewer adverse events.

In this randomized trial of patients undergoing treatment for acute myelogenous leukemia or the myelodysplastic syndrome, prophylaxis with posaconazole resulted in fewer fungal infections and longer survival than did prophylaxis with fluconazole or itraconazole. The difference was primarily due to a lower rate of invasive aspergillosis in the posaconazole group. In patients undergoing treatment for acute myelogenous leukemia or the myelodysplastic syndrome, prophylaxis with posaconazole resulted in fewer fungal infections and longer survival than did prophylaxis with fluconazole or itraconazole. Invasive fungal infections remain a major cause of illness and death in patients with neutropenia who have hematologic cancers, despite the availability of new antifungal agents. The incidence of proven or probable mold and yeast infections can reach 24% among patients with leukemia. 1 , 2 Reported mortality from candidiasis or aspergillosis ranges from 40 to 50%, and mortality from fusariosis or zygomycosis is 70% or more. 3 – 8 Prophylaxis is a commonly used treatment strategy, because the diagnosis of fungal infection is often delayed or difficult to establish with certainty, and a delay in antifungal treatment increases mortality. 9 – 11 Antifungal prophylaxis with . . .