Development of echinocandin‐resistant Candida albicans candidemia following brief prophylactic exposure to micafungin therapy

Empiric antifungal coverage is indicated in patients with graft‐versus‐host disease (GVHD) following a stem cell transplant (SCT) who are febrile and neutropenic for extended periods of time. Empiric antifungal coverage is indicated for patients with hematologic malignancies who have persistent fever and neutropenia as well as patients who have GVHD following SCT. Although the prophylactic use of antifungals is a cornerstone of the care for such patients, the selection of the particular antifungal is at the discretion of the clinician. We report a patient case whose surveillance blood cultures obtained 14 days after the switch from voriconazole to micafungin were positive for the growth of Candida albicans. Clinicians prescribing echinocandin therapy for antifungal prophylaxis must be aware of the risks of echinocandin resistance and possible breakthrough candidemia with C. albicans.     

犹他游动放线菌中酰胺水解酶基因拷贝数增加对转化棘白菌素B效率的影响

目的:利用ΦC31整合酶介导的位点特异性重组方法,构建棘白菌素B酰胺水解酶基因拷贝数增加的犹他游动放线菌重组菌株。方法:构建含有棘白菌素B酰胺水解酶基因的基因整合型质粒pYGCQ-03-13,通过属间接合转移的方法将该基因片段转入犹他游动放线菌SIPI-T2001中;利用静息细胞转化法,考察其对转化效率的影响。结果:筛选得到的阳性重组菌株SIPI-GE.T2001,对棘白菌素B的转化效率最高达到61.7%。结论:增加棘白菌素B酰胺水解酶基因拷贝数,有效地提高了犹他游动放线菌对棘白菌素B的转化效率。     

Micafungin for the prophylaxis and treatment of Candida infections

Invasive fungal infection is a significant cause of morbidity and mortality worldwide. The incidence of these infections is steadily increasing. In addition, strains resistant to many commonly used antifungal agents are becoming more prevalent. Many new antifungals have become commercially available in recent years, which have vastly improved the ability to treat these infections effectively. Micafungin is one of three commercially available echinocandins available for use in the USA. This class of agents possess a unique mechanism of action that helps to reduce toxicity while maintaining potent antifungal activity. Micafungin is currently approved for the treatment of esophageal candidiasis in adults and is the only in its class approved for the prophylaxis of Candida infection in patients who have undergone hematopoietic stem cell transplantation. It was also recently approved in the USA for the treatment of candidemia and other forms of invasive candiaisis (acute disseminated candiaisis, Candida peritonitis and abscess). In general, micafungin is well tolerated and has favorable safety and drug-interaction profiles.     

Safety and tolerability of caspofungin acetate in the treatment of fungal infections

Abstract Caspofungin acetate is the first member of the novel echinocandin class of antifungal drugs to be marketed in the United States. It has recently been approved for use in patients with invasive aspergillosis who are refractory to or intolerant of conventional therapy. Accordingly, its safety profile is particularly important to review. The safety and tolerability of caspofungin have been examined in 623 persons, including 295 patients who received ≥ 50 mg/day for at least one week in clinical studies. In the 263 patients, given caspofungin in randomized double-blind active-control trials to date, there have been no serious clinical or laboratory drug-related adverse events; caspofungin was discontinued in only 2% of these patients because of drug-related adverse experiences. Caspofungin may have potentially important drug interactions with cyclosporine and tacrolimus.     

Candida glabrata – unique features and challenges in the clinical management of invasive infections

Candida glabrata is a pathogenic yeast with several unique biological features. This article provides an up‐to‐date review on current data and reasoning aspects of this clinically problematic organism. Haploidy, absence of pseudohyphae, facultative anaerobe growth of C. glabrata, as well as its intrinsically low susceptibility to azole antifungals require specific consideration in diagnosis and treatment approaches. As C. glabrata today represents a sizeable percentage of pathogens in candidaemia, the use of azole antifungals in upfront therapy of invasive yeast infections is discouraged by recent guidelines. While the selection of C. glabrata mutants with impaired susceptibility to echinocandins has been described, analyses of several clinical studies indicate an association of improved outcomes with the use of echinocandins as the primary treatment for invasive yeast infections with potential or documented involvement of C. glabrata.     

Candidemia in the cancer patient: diagnosis,treatment, and future directions

ABSTRACT

Introduction: The presence of Candida species in the blood is known as candidemia and may constitute a medical emergency for patients with cancer. Despite advances in diagnosis and treatment of this fungal infection, mortality remains unacceptably high.

Areas covered: This paper reviews recent advances in molecular diagnostics to detect species of Candida as well as novel antifungal agents that have been developed to address candidiasis. We also review prophylaxis strategies to prevent candidiasis in high-risk cancer patients.

Expert commentary: We draw from our own experiences treating candidemia in the cancer patient and review novel diagnostic strategies involving molecular resonance and mass spectroscopy. We also explore novel chemoprophylaxis and treatment options, including new drugs such as rezafungin and SCY-078. We also look ahead, to examine how this condition will be managed in the years ahead.     

Micafungin: A brief review of pharmacology,safety, and antifungal efficacy in pediatric patients

Invasive fungal infections are a major cause of morbidity and mortality in children with hematological malignancies and those undergoing allogeneic hematopoietic stem‐cell transplantation (HSCT). Although several new antifungal compounds recently became available, some are not yet approved for the use in the pediatric population. Among the new class of echinocandins, micafungin has been licensed in Europe and Japan for children including neonates. Because micafungin is well tolerated and exhibits few clinical relevant drug–drug interactions, the compound is of particular interest for prophylaxis and treatment of invasive mycoses in pediatric patients with cancer or following allogeneic HSCT. This review will focus on the currently available pediatric data of micafungin with emphasis on pharmacokinetics, efficacy, and safety. Pediatr Blood Cancer. 2010;55:229–232. © 2010 Wiley–Liss, Inc.     

Cell wall active antifungal agents

The recent American approval of Cancidas^?, a semi-synthetic echinocandin, for salvage treatment of aspergillosis has demonstrated that the cell wall is a clinically viable target for treating fungal infections. Recently, a variety of new, sulfated members of the echinocandin lipopeptide family have been reported, which, like other echinocandins, are glucan synthesis inhibitors. In addition, two new classes of lipopeptide glucan synthesis inhibitors, the aerothricin lipopeptidolactones and the Sankyo lipopeptides, have been identified, as well as a novel member of the papulacandin family of liposaccharide glucan synthesis inhibitors. The first new structural class of glucan synthesis inhibitors discovered in over 20 years, the so-called sterol glycosides, is reviewed. Five different structural types within this class have been characterised. Finally, several novel compounds with cell wall antifungal activity based on inhibition of chitin synthase are reviewed.     

The echinocandin micafungin: a review of the pharmacology,spectrum of activity,clinical efficacy and safety

Micafungin is a relatively broad-spectrum antifungal agent available for clinical use in the US and Japan. By inhibiting the production of β-1,3-glucan, an essential fungal cell wall component, micafungin has reduced toxicity to mammalian cells while maintaining potent antifungal activity against many pathogenic fungi including polyene- and azole-resistant isolates. Indeed, micafungin has been shown to be efficacious in the treatment of infections caused by Candida and Aspergillus species in clinical trials without the associated toxicities of amphotericin B formulations and drug interactions that occur with the azoles. In this review, the pharmacology, spectrum of activity, clinical efficacy and safety profile of micafungin are discussed.     

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig

Introduction  

Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig.