Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

Fernández‐Ruiz, Mario; Aguado, José María; Almirante, Benito; Lora-Pablos, David; Padilla, Belén; Puig-Asensio, Mireia; Montejo, Miguel; García-Rodríguez, Julio; Pemán, Javier; Pipaón, Maite Ruiz Pérez de; Cuenca‐Estrella, Manuel; Reipi,

doi:10.1093/cid/ciu158

Cited by 107 publications

(68 citation statements)

References 36 publications

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“…1,5 Exclusion of these patients is appropriate given our clinical question of whether choice of definitive therapy affects 30 day mortality, though the reduced event rate resulted in a relatively wide confidence interval around the point estimate (OR 0.82, 95% CI 0.33 -2.07). As the lower and upper bounds of the confidence interval range from 0.33 and 2.07 we cannot completely exclude the possibility that echinocandins are either superior or inferior to fluconazole for C. parapsilosis.…”

Section: Discussionmentioning

confidence: 99%

“…2 Consequently, there has been concern about the use of echinocandins as primary therapy for C. parapsilosis, and prior versions of the IDSA candidiasis treatment guidelines recommended fluconazole over an echinocandin for this reason. 4 However, a recent observational cohort study of 103 nonneonatal candidiasis episodes did not find a difference in clinical failure between initial treatment with an azole versus an 5 Based on these new data, considered in context of existing data, 1,6,7 the 2016 IDSA invasive candidiasis guidelines no longer clearly support fluconazole over echinocandin, though a paucity of clinical data precludes a more definitive statement of equivalence. 8 We therefore aimed to compare the effectiveness of fluconazole with echinocandins in a US cohort of adults with C. parapsilosis candidaemia to provide additional clinical data to guide the choice of a definitive therapeutic agent in this clinical setting.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis : a retrospective observational cohort study of the Mycoses Study Group (MSG-12): Table 1.

Chiotos

Vendetti

Zaoutis

et al. 2016

J. Antimicrob. Chemother.

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Objectives: A polymorphism in the gene encoding b-1,3-glucan synthase, the target of the echinocandin class of antifungals, results in increased in vitro MICs of the echinocandins. This has resulted in controversy surrounding use of the echinocandins for treatment of Candida parapsilosis candidaemia. We aimed to compare 30 day mortality in adults with C. parapsilosis candidaemia treated with echinocandins versus fluconazole.Methods: This is a retrospective observational cohort study. We used the Premier Perspective Database to identify adult patients with C. parapsilosis candidaemia treated with only fluconazole or only an echinocandin as definitive therapy. The primary outcome was 30 day mortality. Propensity scores were derived to estimate the probability the patient would have received either an echinocandin or fluconazole. Inverse probability of treatment weighting (IPTW) was used in a weighted logistic regression to calculate odds of 30 day mortality.Results: There were 307 unique patients with C. parapsilosis candidaemia. One hundred and twenty-six (41%) received fluconazole and 181 (59%) received an echinocandin. Age, gender, race, year of admission, need for ICU resources in the week prior to candidaemia onset, and receipt of vasopressors on the day of candidaemia onset were included in the propensity score model used to calculate inverse probability of treatment weights. Weighted logistic regression demonstrated no difference in 30 day mortality between patients receiving an echinocandin as compared with fluconazole (OR 0.82, 95% CI 0.33 -2.07).Conclusions: Our result supports the 2016 IDSA invasive candidiasis guidelines, which no longer clearly favour treatment with fluconazole over an echinocandin for C. parapsilosis candidaemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis : a retrospective observational cohort study of the Mycoses Study Group (MSG-12): Table 1.

Chiotos

Vendetti

Zaoutis

et al. 2016

J. Antimicrob. Chemother.

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“…The notable exceptions are C. parapsilosis complex ( Candida parapsilosis sensu stricto , C. orthopsilosis , and C. metapsilosis ) and C. guilliermondii, which display higher echinocandin antifungal MIC values relative to other highly susceptible Candida species [29–31] [32–34] and is reflected in higher breakpoints [35]. Intrinsic reduced susceptibility has an unclear clinical significance as patients are often successfully treated with echinocandin drugs [36–38] [39], although clinical efficacy may vary with patient population [40–42]. Since first reported in 2005, susceptible Candida spp.…”

Section: Epidemiology Of Echinocandin Resistancementioning

confidence: 99%

Echinocandin Resistance, Susceptibility Testing and Prophylaxis: Implications for Patient Management

Perlin

2014

Drugs

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This article addresses the emergence of echinocandin resistance among Candida species, mechanisms of resistance, factors that promote resistance and confounding issues surrounding standard susceptibility testing. Fungal infections remain a significant cause of global morbidity and mortality, especially among patients with underlying immunosupression. Antifungal therapy is a critical component of patient management for acute and chronic diseases. Yet, therapeutic choices are limited due to only a few drug classes available to treat systemic disease. Moreover, the problem is exacerbated by the emergence of antifungal resistance, which has resulted in difficult to manage multidrug resistant strains. Echinocandin drugs are now the preferred choice to treat a range of candidiasis. These drugs target and inhibit the fungal-specific enzyme glucan synthase, which is responsible for the biosynthesis of a key cell wall polymer. Therapeutic failures involving acquisition of resistance among susceptible organisms like Candida albicans is largely a rare event. However, in recent years, there is an alarming trend of increased resistance among strains of Candida glabrata, which in many cases are also resistant to azole drugs. Echinocandin resistance is always acquired during therapy and the mechanism of resistance is well established to involve amino acid changes in “hot-spot regions of the Fks subunits carrying the catalytic portion of glucan synthase. These changes significantly decrease the sensitivity of the enzyme to drug resulting in higher MIC values. A range of drug responses, from complete to partial refractory response, is observed depending on the nature of the amino acid substitution, and clinical responses are recapitulated in pharmacodynamic models of infection. The cellular processes promoting the formation of resistant Fks strains involve complex stress response pathways, which yield a variety of adaptive compensatory genetic responses. Stress-adapted cells become drug tolerant and can form stable drug resistant FKS mutations with continued drug exposure. A major concern for resistance detection is that classical broth microdilution techniques show significant variability among clinical microbiology laboratories for certain echinocandin drugs and Candida species. The consequence is that susceptible strains are misclassified according to established clinical breakpoints, and this has led to confusion in the field. Clinical factors that appear to promote echinocandin resistance include the expanding use of antifungal agents for empiric therapy and prophylaxis. Furthermore, host reservoirs such as biofilms in the gastrointestinal tract or intra-abdominal infections can seed development of resistant organisms during therapy. A fundamental understanding of the primary molecular resistance mechanism, along with cellular and clinical factors that promote resistance emergence, is critical to develop better diagnostic tools and therapeutic strategies to overcome and prevent echinocandin resistance.

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“…53 A comparative trial of caspofungin at standard doses and micafungin at doses of 100 or 150 mg daily had similar clinical and microbiological outcomes across the three treatment arms in the primary intention-to-treat analysis, as well as similar safety and tolerability. 52 C. parapsilosis has comparatively higher MICs to echinocandins than other Candida species, but studies 54 suggest echinocandin treatment may be successfully used to treat C. parapsilosis infections (level III evidence, grade C recommendation). In children with IC, there have been only two RCTs published comparing an echinocandin with another class of antifungal drug.…”

Section: Echinocandinsmentioning

confidence: 99%

Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014

Chen

Sorrell

Chang

et al. 2014

Internal Medicine Journal

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Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the Candida spp., Cryptococcus spp., Pneumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'preemptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of Pneumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement).

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Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

Abstract: The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Cited by 107 publications

References 36 publications

Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis : a retrospective observational cohort study of the Mycoses Study Group (MSG-12): Table 1.

Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis : a retrospective observational cohort study of the Mycoses Study Group (MSG-12): Table 1.

Echinocandin Resistance, Susceptibility Testing and Prophylaxis: Implications for Patient Management

Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014

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