Combination Therapy Of Voriconazole Research Articles

A Rare Clinical Form of Candidaemia: A Pediatric Case of Leukemia with Skin Involvement

Cutaneous involvement is seen in very few patients with candidemia. Cutaneous involvement of candidemia is usually seen in immunocompromised patients with hematologic-oncologic diseases. Lesions may be maculopapular or nodular. In this case report, cutaneous lesions due to disseminated candidemia in an eight-year-old child with leukemia and febrile neutropenia are presented. The general condition of the patient was quite poor. Blood and port cultures grew resistant Candida. The diagnosis was made clinically. The patient was given amphotericin B and voriconazole combination therapy. The lesions disappeared. Today, Candida spp. infections are becoming more common, and the rate of skin involvement is also increasing. However, the diagnosis of Candida skin involvement may be difficult. Histopathology can be used in the diagnosis. Skin involvement is more common in candidemia patients with risk factors, especially in patients with Candida tropicalis growth.

Distribution and antifungal susceptibility of clinical Trichosporon spp. isolates: 10 years of single-center experience

Purpose: The genus Trichosporon, which is a yeast-like basidiomycete, is ubiquitous in nature and a part of human microbiota. It’s an oppurtunistic fungal pathogen, which was once rare, but increasing dramatically recently, leading to fatal infections. The aim of this study was to determine the prevalence, and antifungal susceptibility of clinical Trichosporon spp. isolates, and to determine whether there was a change in incidence during the COVID-19 Pandemic. 
 Materials and Methods: This was a retrospective cross-sectional descriptive study, conducted between January 1, 2013 and February 5, 2023. Cultures which Trichosporon spp. isolated (n=125) were screened, and those met the eligibility criteria were included (n=77). Identification, antifungal susceptibility test results, age, gender records were identified from Microbiology Laboratory Information Management System. 
 Results: 97.4% of the isolates were Trichosporon asahii, and 2.6% were Trichosporon mucoides. The most frequent isolation period was the 2016 and 2019 year group (71.4%), not during the COVID-19 Pandemics (19.5%). The most common sample type was urine (58.4%), of whom predominantly (58.4%) hospitalized in the Intensive Care Unit. Amphotericin B MICs were ≤1µg/ml in 68.9% of the isolates. Fluconazole and voriconazole MICs were ≤1µg/ml in 20.0% and 94.8%, respectively. 59.7% of the isolates had a MIC of ≥4µg/ml for flucytosine. Micafungin and caspofungin MICs were ≥4µg/ml in 88.3% and 92.2% of the isolates, respectively. Voriconazole had the strongest in vitro activity, and amphotericin B had lower MICs than expected. The combination therapy of voriconazole and amphotericin B could be a therapeutic option in this setting, as well as monotherapy of voriconazole.
 Conclusion: Trichosporon spp. isolated in clinical specimens and their antifungal susceptibility depend on the geographic region and the anatomic site. Identifying local data will contribute to both the management of these patients, and surveillance studies.

Invasive Trichoderma spp. infections: clinical presentation and outcome of cases from the literature and the FungiScope® registry.

Background Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients.ObjectivesTo analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections.MethodsA systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies’ references. Cases from the FungiScope® registry were added to a combined analysis.ResultsWe identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived.ConclusionsDespite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.

Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major

IntroductionThe aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy. Methods: For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days. Results: According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups. Conclusions: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.

Managing invasive aspergillosis in haematological patients in the era of resistance polymerase chain reaction and increasing triazole resistance: A modelling study of different strategies

Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known. A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events. Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5-20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates. Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics.

Invasive Scopulariopsis alboflavescens infection in patient with acute myeloid leukemia

Scopulariopsis alboflavescens is a soil saprophyte that is widely distributed in nature. Recently, there have been increasing number of reports of invasive infections with Scopulariopsis species in immunocompromised patients. In this report, we described an adult woman with acute myeloid leukemia and who developed S. alboflavescens pneumonia. Liposomal amphotericin B and voriconazole combination therapy was unsuccessful and the patient died because of pneumonia. Scopulariopsis is highly resistant to available antifungal agents and almost invariably fatal. This case report should alert clinicians to the importance of listing Scopulariopsis as a pathogenic fungus in immunocompromised patients.

Dose optimization of voriconazole/anidulafungin combination against Aspergillus fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response surface analysis: clinical implications for azole-resistant aspergillosis.

Combination therapy of voriconazole with an echinocandin is often employed in order to increase the efficacy of voriconazole monotherapy. Four clinical Aspergillus fumigatus isolates with different in vitro susceptibilities to voriconazole (MIC 0.125-2 mg/L) and anidulafungin (MEC 0.008-0.016 mg/L) were tested in an in vitro pharmacokinetic/pharmacodynamic model simulating human serum concentrations of standard dosages of voriconazole and anidulafungin. Fungal growth was assessed using galactomannan production and quantitative PCR. Drug concentrations were determined with bioassays. Pharmacodynamic interactions were assessed using Bliss independence analysis (BI) and Loewe additivity-based canonical mixture response-surface non-linear regression analysis (LA). Probability of target attainment (PTA) was estimated with Monte Carlo analysis for different doses of anidulafungin (25, 50 and 100 mg) and azole resistance rates (5%-25%). Synergy [BI 51% (8%-80%), LA 0.63 (0.38-0.79)] was found at low anidulafungin (fCmax/MEC <10) and voriconazole (fAUC/MIC <10) exposures, whereas antagonism [BI 12% (5%-18%, LA 1.12 (1.04-4.6)] was found at higher drug exposures. The largest increase in PTA was found with 25 mg of anidulafungin and voriconazole MIC distributions with high (>10%) resistance rates. PTAs for isolates with voriconazole MICs of 1, 2 and 4 mg/L was 78%, 12% and 0% with voriconazole monotherapy and 96%-100%, 68%-82% and 9%-20% with combination therapy, respectively. Optimal activity was associated with a voriconazole tCmin/MIC ratio of 1.5 for monotherapy and 0.75 for combination therapy. The present study indicated that the combination of voriconazole with low-dose anidulafungin may increase the efficacy and reduce the cost and potential toxicity of antifungal therapy, particularly against azole-resistant A. fumigatus isolates and in patients with subtherapeutic serum levels. This hypothesis warrants further in vivo verification.

Combination therapy of voriconazole and terbinafine for disseminated fusariosis: case report and literature review

Fusarium spp. cause a broad spectrum of infection and are relatively resistant to most antifungal agents, leading to unfavorable prognosis, especially in immunocompromised patients. Several reports have shown synergism among amphotericin B, voriconazole (VRC), terbinafine (TRB), and other antifungal agents in vitro, but the most efficacious combination remains to be elucidated. We report the first case of disseminated Fusarium solani infection successfully treated by combination therapy of VRC and TRB accompanied by surgical resection of endocardial lesions. We also review 15 case reports of combination antifungal therapy for fusariosis and 6 case reports of Fusarium endocarditis.

A Case of Aspergillus Empyema Successfully Treated with Combination Therapy of Voriconazole and Micafungin: Excellent Penetration of Voriconazole and Micafungin into Pleural Fluid

A 62-year-old man with empyema caused by Aspergillus fumigatus was successfully treated with a combination of voriconazole (VRCZ) and micafungin (MCFG). Data regarding the penetration of antifungal agents into pleural fluid are limited. Thus, we measured the concentration of VRCZ and MCFG in his plasma and pleural fluid. Penetration of VRCZ and MCFG into the pleural fluid was excellent. Therefore, the combination therapy using VRCZ and MCFG may contribute to successful management of Aspergillus empyema.