Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

Lepak, Alexander J.; Zhao, Miao; Berkow, Elizabeth L.; Lockhart, Shawn R.; Andes, David R.

doi:10.1128/aac.00791-17

Cited by 78 publications

(78 citation statements)

References 32 publications

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“…Due to the relatively low resistance to echinocandins, it is recommended that an echinocandin empirical therapy be initiated in patients suspected to have C. auris infections prior to antifungal susceptibility testing of collected strains (Lee et al., ; Todd, ). The echinocandins can then be maintained or changed based on the susceptibility results (Lepak et al., ; Todd, ); it should, however, be noted that some patients have died even while on echinocandins (Azar et al., ; Ruiz Gaitán et al., ; Schelenz et al., ). Early initiation of echinocandin therapy has been advised to cut down on C. auris‐ mediated mortalities (Chowdhary et al., ; Lee et al., ).…”

Section: Resistance Profiles Rates and Mechanismsmentioning

confidence: 99%

“…An official management protocol for C. auris infections is yet to be concluded, an optimal antifungal agent(s) or dosing regimen for C. auris infections is not defined and CLSI/EUCAST breakpoints for this pathogen is wanting (Lepak et al., ), making researchers resort to that established for closely related species of Candida (Arendrup et al., ; Lockhart et al., ). Interestingly, the efficacy of this approach was recently established by Lepak et al.…”

Section: Management and Clinical Outcomes (Mortalities)mentioning

confidence: 99%

“…Candida haemulonii was first isolated from the gut of a blue‐striped grunt fish ( Haemulon scirus ), and later from the blood of a renal failure patient (Cendejas‐Bueno et al., ). The closer phylogenetic relationship between C. auris and Candida krusei, C. lusitaniae, C. haemulonii, C. pseudohaemulonii, and C. duobushaemulonii, which are inherently multidrug resistant to amphotericin B (polyenes) and azoles, has been cited as a reason for the similarly higher resistance of C. auris to these two drug classes (Cendejas‐Bueno et al., ; Lepak, Zhao, Berkow, Lockhart, & Andes, ).…”

Section: Introductionmentioning

confidence: 99%

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Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

2018

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From 2009, Candida auris has emerged as a multidrug‐resistant ascomycete yeast pathogen with the capacity for easy transmission between patients and hospitals, as well as persistence on environmental surfaces. Its association with high mortalities, breakthrough and persistent candidaemia, inconsistencies in susceptibility testing results, misidentification by available commercial identification systems and treatment failure, complicates its management and detection. Within the last nine years, C. auris has been increasingly reported from far‐Eastern Asia, the Middle East, Africa, Europe, South and North America with substantial fatalities and misidentification. Herein, I provide a systematic and thorough review of this emerging pathogen. Meta‐analysis showed that at least 742 C. auris isolates have been reported in 16 countries, with most of these being from India (≥243), USA (≥232) and UK (≥103) (p‐value = .0355) within 2013–2017. Most isolates were from males (64.76%) (p‐value = .0329) and blood (67.48%) (p‐value < .0001), with substantial crude mortality (29.75%) (p‐value = .0488). Affected patients presented with other comorbidities: diabetes (≥52), sepsis (≥48), lung diseases (≥39), kidney diseases (≥32) etc. (p‐value < .0001). Resistance to fluconazole (44.29%), amphotericin B (15.46%), voriconazole (12.67%), caspofungin (3.48%) etc. were common (p‐value = .0059). Commonly used diagnostic tools included PCR (30.38%), Bruker MALDI‐TOF MS (14.00%), Vitek 2 YST ID (11.93%), AFLP (11.55%) and WGS (10.04%) (p‐value = .002). Multidrug resistance, high attributable mortality and persistence are associated with C. auris infections. Two novel drugs, SCY‐078 and VT‐1598, are currently in the pipeline. Contact precautions, strict infection control, periodic surveillance and cleaning with chlorine‐based detergents, efficient, faster and cheaper detection tools are necessary for prevention, containment and early diagnosis of C. auris infections.

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Section: Resistance Profiles Rates and Mechanismsmentioning

confidence: 99%

Section: Management and Clinical Outcomes (Mortalities)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

2018

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“…27 28 Micafungin showed increased efficacy in a murine study of C. auris candidaemia compared with fluconazole and amphotericin B. 32 For the paediatric population, micafungin and caspofungin can be used while awaiting susceptibility testing results. 33 34 Depending on the site of infection, alternative choices might be considered.…”

Section: Clinical Managementmentioning

confidence: 99%

Candida auris, what do paediatricians need to know?

Warris

2018

Arch Dis Child

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The newly recognised and emerging fungal species, Candida auris, has caused worldwide invasive infections and has been implicated in difficult to control hospital outbreaks. Challenges are encountered in the correct identification of this fungus as commonly used phenotypic and biochemical methods fail to differentiate C. auris from other Candida species. Its resistance profile, over 90% of isolates are fluconazole resistant and 35% are resistant to amphotericin, confronts clinicians with the restricted arsenal of antifungals and concerns about optimal treatment. The very first C. auris isolate was recovered from a paediatric patient in retrospect. Although infections with the more antifungal-resistant Candida species are less frequently observed in paediatric patients, this seems to be different for C. auris infections.

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“…In vitro studies demonstrate synergy between micafungin and voriconazole; and sulfamethoxazole with azole antifungals; for selected strains. Animal‐model data imply that micafungin‐based combination therapies are promising …”

Section: Clinical Managementmentioning

confidence: 99%

Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases

Ong

Chen

Clark

et al. 2019

Internal Medicine Journal

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Candida auris is an emerging drug‐resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30–60%. Acquisition is generally healthcare‐associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix‐assisted laser desorption ionisation time‐of‐flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first‐line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre‐emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.

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Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

Cited by 78 publications

References 32 publications

Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

Candida auris, what do paediatricians need to know?

Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases

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