OBJECTIVETo evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).

METHODSA retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.

RESULTSOverall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.

CONCLUSIONFor IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; microbiology ; Humans ; Mycoses ; drug therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Humans ; Invasive Pulmonary Aspergillosis ; complications ; drug therapy ; Lipopeptides ; Liver Failure ; complications ; drug therapy ; microbiology ; Male ; Middle Aged ; Voriconazole ; administration & dosage ; therapeutic use

BACKGROUNDNowadays, there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB). However, these studies have a modest sample size and convey inconclusive results. The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs), compared with L-AmB.

METHODSElectronic databases (up to July 31, 2013) PubMed and Embase databases, the Cochrane Library, and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB. Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed by χ(2)-test and the I(2)-statistic.

RESULTSThree trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients. The results showed that caspofungin produced equal efficacy in favorable overall response (RR = 1.02, 95% CI 0.88-1.18; P = 0.81) and mortality rate (RR = 1.53, 95% CI 0.38-6.27, P = 0.55), safer in clinical adverse events (RR = 0.20, 95% CI 0.08-0.54; P = 0.001), laboratory adverse events (RR = 0.69, 95% CI 0. 57-0.84; P = 0.0002), and discontinuation rate (RR = 0.26, 95% CI 0.08-0.83, P = 0.02), compared with L-AmB in the treatment of patients with IFIs.

CONCLUSIONBased on the results of this meta-analysis, it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.

Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Echinocandins ; therapeutic use ; Febrile Neutropenia ; drug therapy ; Humans ; Lipopeptides ; Mycoses ; drug therapy

Antifungal Agents ; administration & dosage ; therapeutic use ; Candidiasis ; complications ; diagnosis ; drug therapy ; Child ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; complications ; Humans ; Lipopeptides ; Mycoses ; complications ; diagnosis ; drug therapy ; Neoplasms ; complications ; Pediatrics ; Practice Guidelines as Topic ; Voriconazole ; administration & dosage ; therapeutic use

Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized recently. We present a case of breakthrough trichosporonosis with acute viral myocarditis while receiving caspofungin therapy. Trichosporon infection should be considered in patients, who have risk factors for invasive fungal infection and develop unexplained clinical manifestations of infection despite treatment with echinocandins.
Adult ; Antifungal Agents ; therapeutic use ; Echinocandins ; therapeutic use ; Female ; Humans ; Lipopeptides ; Treatment Outcome ; Trichosporonosis ; drug therapy ; microbiology

Aged, 80 and over ; Echinocandins ; adverse effects ; therapeutic use ; Humans ; Lipopeptides ; Liver ; drug effects ; Liver Function Tests ; Mycoses ; drug therapy ; Retrospective Studies

BACKGROUNDIn our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA). In this study we analyzed the clinical data from patients with PNTA, so as to guide the diagnosis and treatment of the disease.

METHODSA total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009. Their clinical data, including the demographic information, clinical symptoms, imaging findings, bronchoscopy findings, treatment strategies and efficacy, and prognosis, were retrospectively analyzed.

RESULTSAll 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focal airways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors, 5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors, and 2/16 (12.5%) had lung transplantation. The most common causes of PNTA included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%) and recurrent intervention therapy by bronchoscope (4/16, 25.0%). Aspergillus fumigatus was the most frequent pathogen (62.5%, 10/16). The main clinical manifestations included progressive dyspnea (14/16, 87.5%) and irritable cough (12/16, 75.0%). The trachea was involved in 9/16 patients (56.3%), right main bronchus in 10/16 (62.5%). All 16 patients were treated with systemic anti-aspergillosis agents, local anti-aspergillosis agents with amphotericin B inhalation and direct perfusion of amphotericin B by bronchoscope, and interventional treatment by bronchoscope to ensure an unobstructed airway. The total efficiency was 31.3%.

CONCLUSIONSPNTA is an infectious disease caused by aspergillus and it mainly involves the trachea, primary bronchus and segmental bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe clinical threat and often occurs after systemic immunodeficiency and/or local airway damage, with the main symptoms including dyspnea and irritable cough. Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment of PNTA is difficult and requires a long course. Systemic and local anti-aspergillosis agents plus bronchoscopy debridement can improve the prognosis of the disease.

Adult ; Aged ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Aspergillosis ; diagnosis ; drug therapy ; Bronchoscopy ; Echinocandins ; therapeutic use ; Female ; Humans ; Itraconazole ; therapeutic use ; Lipopeptides ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Voriconazole

BACKGROUNDInvasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients. Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus. We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.

METHODSWe did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection. Seven trials involving 2913 patients were included in this analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.

RESULTSMicafungin was associated with significantly better treatment success compared with the comparator antifungal agents (modified intention to treat, 2851 patients; random-effects model, OR 1.20, 95%CI 1.00 - 1.45, P = 0.0487). In addition, micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation (OR 1.47, 95%CI 1.08 - 2.00, P = 0.01). Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects (OR 0.94, 95%CI 0.77 - 1.11), fewer patients treated with micafungin withdrew from the studies because of adverse events (OR 0.64, 95%CI 0.44 - 0.94).

CONCLUSIONSMicafungin has a good safety and tolerability profile, with an efficacy at least comparable to the other antifungal agents. Micafungin offers advantages over other agents for antifungal prophylaxis. Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

Antifungal Agents ; adverse effects ; therapeutic use ; Candidiasis, Invasive ; drug therapy ; Echinocandins ; adverse effects ; therapeutic use ; Humans ; Lipopeptides ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

INTRODUCTIONBecause invasive fungal infections cause significant morbidity and mortality in liver transplant recipients, the use of antifungal prophylaxis, and the early empirical use of antifungal agents, is widespread on liver transplant units. The new-generation azoles such as voriconazole and the echinocandins have been welcome additions to the antifungal armamentarium. These agents have become the leading options for prophylaxis in liver transplant units, despite the absence of strong data for their efficacy in this setting.

CLINICAL PICTUREWe report two recipients of living-donor liver transplants who became infected/colonised with fungi resistant to an echinocandin and the azoles after exposure to these agents. One patient developed trichosporonosis while on caspofungin and the other became infected/ colonised with Candida glabrata that was resistant to voriconazole and posaconazole.

CONCLUSIONWe report these to highlight some of the consequences of using the newer antifungal agents.

Adult ; Antifungal Agents ; therapeutic use ; Drug Resistance, Fungal ; Echinocandins ; therapeutic use ; Fatal Outcome ; Female ; Fluconazole ; therapeutic use ; Humans ; Lipopeptides ; Liver Transplantation ; adverse effects ; immunology ; Male ; Middle Aged ; Mycoses ; drug therapy ; prevention & control ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Trichosporonosis ; drug therapy ; prevention & control ; Voriconazole ; Young Adult

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Female ; Hematologic Neoplasms ; drug therapy ; microbiology ; Humans ; Lipopeptides ; Male ; Middle Aged ; Mycoses ; drug therapy ; Pyrimidines ; administration & dosage ; therapeutic use ; Treatment Outcome ; Triazoles ; administration & dosage ; therapeutic use ; Voriconazole ; Young Adult