Treatment of Invasive Candidiasis: A Narrative Review

In the paper

“Anidulafungin was associated with a higher treatment success rate than was fluconazole, but mortality rates were not significantly different [22].”

What the sources say

• Not checked yetcites [22] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N. Engl. J. Med. source

In the paper

“In point prevalence studies, Candida species account for about 1 in 5 nosocomial bloodstream infections [1,3].”

What the sources say

• Not checked yetcites [1] Magill, 2014, Multistate point-prevalence survey of health care-associated infections, N. Engl. J. Med. source
• Not checked yetcites [3] Vincent, 2009, International study of the prevalence and outcomes of infection in intensive care units, JAMA source

In the paper

“Candida species are frequent colonizers of the human alimentary tract and skin that have emerged as important nosocomial pathogens, in tandem with advances in modern medical therapeutics [1,2].”

What the sources say

• Not checked yetcites [1] Magill, 2014, Multistate point-prevalence survey of health care-associated infections, N. Engl. J. Med. source
• Not checked yetcites [2] Wisplinghoff, 2004, Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study, Clin. Infect. Dis. source

In the paper

“Prospective studies comparing echinocandins with amphotericin B for the treatment of candidiasis have shown similar efficacy of caspofungin and amphotericin B deoxycholate in the intention to treat analysis but superiority of caspofungin in the per-protocol analysis [20]”

What the sources say

• Not checked yetcites [20] Betts, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasis, N. Engl. J. Med. source

In the paper

“C. auris presents a serious challenge to healthcare systems due to its frequent resistance to multiple systemic antifungals and disinfectants and its capacity for rapid spread within healthcare facilities [15,16].”

What the sources say

• Not checked yetcites [15] Ku, 2018, Candida auris: Disinfectants and Implications for Infection Control, Front. Microbiol. source
• Not checked yetcites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source

In the paper

“Specifically, C. glabrata has become an important pathogen in North America, Europe (with the exception of Spain), and Australia, whereas C. parapsilosis is the dominant non-albicans species in South America, Japan, and Spain [8,9,10].”

What the sources say

• Not checked yetcites [8] Pfaller, 2010, Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: An assessment from the ARTEMIS DISK Global Antifungal Surveillance Program, Diagn. Microbiol. Infect. Dis. source
• Not checked yetcites [9] Arendrup, 2010, Epidemiology of invasive candidiasis, Curr. Opin. Crit. Care source
• Not checked yetcites [10] Cleveland, A.A., Harrison, L.H., Farley, M.M., Hollick, R., Stein, B., Chiller, T.M., Lockhart, S.R., and Park, B.J. (2015). Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: Results from population-based surveillance. PLoS ONE, 10. source

In the paper

“Micafungin at both doses was non-inferior to caspofungin, whereas the median time to culture negativity was 1 day longer for the micafungin 150-mg dose versus the micafungin 100-mg dose [23].”

What the sources say

• Not checked yetcites [23] Pappas, 2007, Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis, Clin. Infect. Dis. source

In the paper

“In an often cited nationwide survey, Candida species were found to be the fourth most frequent causes of bloodstream infection in hospitalized patients in the US, and were associated with the highest mortality rate among leading bloodstream isolates [2].”

What the sources say

• Not checked yetcites [2] Wisplinghoff, 2004, Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study, Clin. Infect. Dis. source

In the paper

“Deep-seated candidiasis, arising from direct inoculation or hematogenous dissemination of Candida into normally sterile body sites, is often difficult to diagnose and may affect a population as large as that of candidemia [4,5,6].”

What the sources say

• Not checked yetcites [4] Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi (Basel), 3. source
• Not checked yetcites [5] Cheng, 2014, Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses, Infect. Immun. source
• Not checked yetcites [6] Leroy, 2009, Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006), Crit. Care Med. source

In the paper

“In randomized controlled clinical trials of nonneutropenic patients with candidemia, outcomes were similar for patients treated with fluconazole versus amphotericin B, but toxicity was more frequent with amphotericin B [26,27].”

What the sources say

• Not checked yetcites [26] Rex, 1994, A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute, N. Engl. J. Med. source
• Not checked yetcites [27] Phillips, 1997, Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group, Eur. J. Clin. Microbiol. Infect. Dis. source

In the paper

“Drug efflux is the most frequent mechanism, and is mediated by transmembrane transporter molecules of either the ATP-binding cassette (ABC) or major facilitator (MFS) superfamilies [48,49].”

What the sources say

• Not checked yetcites [48] Izumikawa, 2003, Function of Candida glabrata ABC transporter gene, PDH1, Yeast source
• Not checked yetcites [49] White, 1997, Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus, Antimicrob. Agents Chemother. source

In the paper

“Breakpoints for C. albicans, C. tropicalis, and C. parapsilosis were lowered, so that MICs over 4 mg/L are considered resistant. For C. glabrata, an inherently fluconazole-tolerant species, an MIC greater than 32 mg/L is considered resistant, whereas an MIC of 32 mg/L or less is considered susceptible dose-dependent (S-DD), a term indicating that maximal drug dosage is required for optimal tre”

What the sources say

• Not checked yetcites [47] Pfaller, 2010, Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: Time for harmonization of CLSI and EUCAST broth microdilution methods, Drug. Resist. Updat. source

In the paper

“A study comparing fluconazole monotherapy with fluconazole combined with amphotericin B found a higher overall treatment success rate and a lower rate of failure to clear the bloodstream with the combination regimen [28].”

What the sources say

• Not checked yetcites [28] Rex, 2003, A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects, Clin. Infect. Dis. source

In the paper

“This effect is more pronounced with caspofungin than with other echinocandins, is unrelated to MIC, appears to be most common with C. albicans and C. dubliniensis, and is strikingly absent in C. glabrata [37,38,39].”

What the sources say

• Not checked yetcites [37] Chamilos, 2007, Paradoxical effect of Echinocandins across Candida species in vitro: Evidence for echinocandin-specific and candida species-related differences, Antimicrob. Agents Chemother. source
• Not checked yetcites [38] Fleischhacker, 2008, Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis, Eur. J. Clin. Microbiol. Infect. Dis. source
• Not checked yetcites [39] Shields, 2011, Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum, Antimicrob. Agents Chemother. source

In the paper

“Contrary to echinocandin resistance, fluconazole-resistance does not incur a significant fitness cost, and may in fact be associated with enhanced virulence [55].”

What the sources say

• Not checked yetcites [55] Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5. source

In the paper

“Perhaps related to their reduced fitness, Candida species carrying FKS hotspot mutations are almost invariably recovered from patients with extensive recent exposure to echinocandins, and usually after more than 3 weeks of treatment [45].”

What the sources say

• Not checked yetcites [45] Dannaoui, 2012, Candida spp. with acquired echinocandin resistance, France, 2004-2010, Emerg. Infect. Dis. source

In the paper

“Overall, acute kidney injury occurs in 30% of adults treated with amphotericin B, and is associated with significantly increased mortality rates, length of hospital stay, and costs [30].”

What the sources say

• Not checked yetcites [30] Bates, 2001, Mortality and costs of acute renal failure associated with amphotericin B therapy, Clin. Infect. Dis. source

In the paper

“Acquired echinocandin resistance has been described in all major Candida species, but is most frequently encountered in C. glabrata, where an association with echinocandin treatment failure has been described [14,42].”

What the sources say

• Not checked yetcites [14] Alexander, 2013, Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations, Clin. Infect. Dis. source
• Not checked yetcites [42] Shields, 2013, Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure, Antimicrob. Agents Chemother. source

In the paper

“The paradoxical effect is abolished by testing in 50% human serum and in the presence of the chitin synthase inhibitor nikkomycin Z and calcineurin inhibitors, suggesting that cell-wall stress response pathways are involved [39].”

What the sources say

• Not checked yetcites [39] Shields, 2011, Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum, Antimicrob. Agents Chemother. source

In the paper

“Of the major pathogenic Candida species, C. glabrata is the most prone to acquire fluconazole resistance, usually associated with upregulation of the ABC efflux pumps CDR1 and CDR2 [51,52].”

What the sources say

• Not checked yetcites [51] Sanglard, 1999, The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents, Antimicrob. Agents Chemother. source
• Not checked yetcites [52] Miyazaki, 1998, Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata, Antimicrob. Agents Chemother. source

In the paper

“Treatment failure occurred most frequently with C. albicans [26].”

What the sources say

• Not checked yetcites [26] Rex, 1994, A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute, N. Engl. J. Med. source

In the paper

“C. auris is intrinsically resistant to fluconazole, and cannot reliably be treated with other azoles [16,58,59].”

What the sources say

• Not checked yetcites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source
• Not checked yetcites [58] Berman, 2017, Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel, Emerg. Infect. Dis.
• Not checked yetcites [59] Chowdhary, A., Sharma, C., and Meis, J.F. (2017). Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog., 13. source

In the paper

“Real-life use of this prediction rule in the intensive care setting reveals a high negative predictive value (80% to 97%) but modest positive predictive value (57% to 70%) [77,78].”

What the sources say

• Not checked yetcites [77] Bruyere, R., Quenot, J.P., Prin, S., Dalle, F., Vigneron, C., Aho, S., Leon, C., and Charles, P.E. (2014). Empirical antifungal therapy with an echinocandin in critically-ill patients: Prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect. Dis., 14. source
• Not checked yetcites [78] Posteraro, 2011, Early diagnosis of candidemia in intensive care unit patients with sepsis: A prospective comparison of (1-->3)-beta-d-glucan assay, Candida score, and colonization index, Crit. Care source

In the paper

“Lipid formulations of amphotericin B are associated with similar rates of treatment success as echinocandins but higher rates of nephrotoxicity [21].”

What the sources say

• Not checked yetcites [21] Kuse, 2007, Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: A phase III randomised double-blind trial, Lancet source

In the paper

“Not only does C. glabrata have higher median MICs of fluconazole compared with other common Candida species, but treatment failure and the emergence of fluconazole-resistant strains occur frequently during treatment of initially susceptible isolates [52].”

What the sources say

• Not checked yetcites [52] Miyazaki, 1998, Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata, Antimicrob. Agents Chemother. source

In the paper

“Moreover, the median time to blood culture positivity is 2–3 days, and may be as long as 8 days. Again, median time to detection is longer for C. glabrata versus other species [75].”

What the sources say

• Not checked yetcites [75] Pfeiffer, 2011, Quantitation of Candida CFU in initial positive blood cultures, J. Clin. Microbiol. source

In the paper

“Heteroresistance, specifically to fluconazole, was also shown to be highly frequent among clinical C. glabrata strains, and is associated with failure of fluconazole to clear C. glabrata from tissues of experimentally infected immunocompetent mice [68].”

What the sources say

• Not checked yetcites [68] Zimmerman, 2016, Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence, mBio source

In the paper

“Finally, PCR assays that detect Candida DNA in full blood or serum are both sensitive and specific [82].”

What the sources say

• Not checked yetcites [82] Avni, 2011, PCR diagnosis of invasive candidiasis: Systematic review and meta-analysis, J. Clin. Microbiol. source

In the paper

“Candida strains resistant to amphotericin B were found to harbor mutations in ERG2, ERG3, ERG5, and ERG11, and were co-resistant to fluconazole [63,64,65,66].”

What the sources say

• Not checked yetcites [63] Martel, 2010, Identification and characterization of four azole-resistant erg3 mutants of Candida albicans, Antimicrob. Agents Chemother. source
• Not checked yetcites [64] Martel, 2010, A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B, Antimicrob. Agents Chemother. source
• Not checked yetcites [65] Sanglard, 2003, Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents, Antimicrob. Agents Chemother. source
• Not checked yetcites [66] Jensen, 2015, Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations, J. Antimicrob. Chemother. source

In the paper

“Specific mutations in the DNA mismatch repair gene MSH2 lead to a hyper-mutable phenotype and were found to be highly prevalent in clinical C. glabrata isolates [67].”

What the sources say

• Not checked yetcites [67] Healey, 2016, Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance, Nat. Commun. source

In the paper

“Acquired resistance is also rare, and involves reduced ergosterol biosynthesis and the production of alternative sterols to which amphotericin B has low affinity.”

What the sources say

• Not checked yetcites [63] Martel, 2010, Identification and characterization of four azole-resistant erg3 mutants of Candida albicans, Antimicrob. Agents Chemother. source
• Not checked yetcites [64] Martel, 2010, A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B, Antimicrob. Agents Chemother. source
• Not checked yetcites [65] Sanglard, 2003, Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents, Antimicrob. Agents Chemother. source
• Not checked yetcites [66] Jensen, 2015, Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations, J. Antimicrob. Chemother. source

In the paper

“Heteroresistance to fluconazole is associated with up-regulation of ABC-type drug transporters, and may be detected and quantified using population analysis profiling [68], a method not routinely used by clinical microbiological laboratories.”

What the sources say

• Not checked yetcites [68] Zimmerman, 2016, Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence, mBio source

In the paper

“A total score of 3 or more has 81% sensitivity and 74% specificity for the diagnosis of invasive candidiasis, and a 7.7-fold greater risk of candidiasis [76].”

What the sources say

• Not checked yetcites [76] Leon, 2006, A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization, Crit. Care Med. source

In the paper

“A differential time to positivity of greater than 2 h is associated with Candida CVC infection, but is not useful in cases of C. glabrata bloodstream infection [99].”

What the sources say

• Not checked yetcites [99] Park, 2014, Diagnostic usefulness of differential time to positivity for catheter-related candidemia, J. Clin. Microbiol. source

In the paper

“Clinical trials have shown numerically more cases of treatment failure for C. parapsilosis with anidulafungin versus fluconazole [22] and with caspofungin versus amphotericin B [20], although these differences were not statistically significant.”

What the sources say

• Not checked yetcites [22] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N. Engl. J. Med. source
• Not checked yetcites [20] Betts, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasis, N. Engl. J. Med. source

In the paper

“Exposure to echinocandins was consistently found to be a risk factor for infection with C. auris, and breakthrough infection on echinocandins has been noted [16,90,91].”

What the sources say

• Not checked yetcites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source
• Not checked yetcites [90] Ruiz-Gaitan, A., Moret, A.M., Tasias-Pitarch, M., Aleixandre-Lopez, A.I., Martinez-Morel, H., Calabuig, E., Salavert-Lleti, M., Ramirez, P., Lopez-Hontangas, J.L., and Hagen, F. (2018). An outbreak due to Candida auris with prolonged colonization and candidemia in a tertiary care European hospital. Mycoses. source
• Not checked yetcites [91] Rudramurthy, 2017, Candida auris candidaemia in Indian ICUs: Analysis of risk factors, J. Antimicrob. Chemother. source

In the paper

“Peripheral blood time to positivity alone may also be of value, as a value greater than 30 h is associated with a significantly lower likelihood of CVC infection [100]. For the slow growing C. glabrata, a breakpoint of 48 h may be used [101].”

What the sources say

• Not checked yetcites [100] Weinberger, 2008, Time to blood culture positivity as a marker for catheter-related candidemia, J. Clin. Microbiol. source
• Not checked yetcites [101] Stempel, 2016, Time-to-reporting of blood culture positivity and central venous catheter-associated Candida glabrata fungemia in cancer patients, Diagn Microbiol. Infect. Dis. source

In the paper

“De-escalation to oral fluconazole may reduce exposure to echinocandins, limit the emergence of resistance to this important drug class, shorten hospital stays, and limit costs.”

What the sources say

• Not checked yetcites [94] Vazquez, J., Reboli, A.C., Pappas, P.G., Patterson, T.F., Reinhardt, J., Chin-Hong, P., Tobin, E., Kett, D.H., Biswas, P., and Swanson, R. (2014). Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: Results from an open-label trial. BMC Infect. Dis., 14. source

In the paper

“However, because subclinical vitritis may be present, treatment with antifungals that achieve therapeutic concentrations within the vitreous is preferred.”

In the paper

“However, there are no clinical data to support this recommendation, and there is evidence that C. auris is tolerant to echinocandins.”

What the sources say

• Not checked yetcites [89] Centers for Disease Control (2018, May 23). Recommendations for Treatment of Candida auris, Available online: https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html.
• Not checked yetcites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source
• Not checked yetcites [90] Ruiz-Gaitan, A., Moret, A.M., Tasias-Pitarch, M., Aleixandre-Lopez, A.I., Martinez-Morel, H., Calabuig, E., Salavert-Lleti, M., Ramirez, P., Lopez-Hontangas, J.L., and Hagen, F. (2018). An outbreak due to Candida auris with prolonged colonization and candidemia in a tertiary care European hospital. Mycoses. source
• Not checked yetcites [91] Rudramurthy, 2017, Candida auris candidaemia in Indian ICUs: Analysis of risk factors, J. Antimicrob. Chemother. source

In the paper

“There is compelling evidence that CVC removal is associated with higher rates of treatment success and lower mortality rates as compared with CVC retention [73,84,88,96,97].”

What the sources say

• Not checked yetcites [73] Kollef, 2012, Septic shock attributed to Candida infection: Importance of empiric therapy and source control, Clin. Infect. Dis. source
• Not checked yetcites [84] Andes, 2012, Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: A patient-level quantitative review of randomized trials, Clin. Infect. Dis. source
• Not checked yetcites [88] Aguado, 2014, Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: A propensity score analysis, Clin. Infect. Dis. source
• Not checked yetcites [96] Liu, 2009, Candidemia in cancer patients: Impact of early removal of non-tunneled central venous catheters on outcome, J. Infect. source
• Not checked yetcites [97] Nguyen, 1995, Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study, Arch. Intern. Med. source

In the paper

“Intra-abdominal candidiasis tends to progress to abscesses that are persistent and recalcitrant, and if undrained may predispose for the development of drug-resistance [5,104].”

What the sources say

• Not checked yetcites [5] Cheng, 2014, Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses, Infect. Immun. source
• Not checked yetcites [104] Shields, 2014, Abdominal candidiasis is a hidden reservoir of echinocandin resistance, Antimicrob. Agents Chemother. source

In the paper

“However, other groups have reported much lower incidence rates of endocarditis, suggesting that a more selective strategy may be reasonable [12].”

What the sources say

• Not checked yetcites [12] Pappas, 2016, Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America, Clin. Infect. Dis. source

In the paper

“C. parapsilosis is particularly frequent as a cause of CVC infection, and neutropenic patients are relatively more likely than non-neutropenic patients to have Candida bloodstream infection that originates in the gut [88].”

What the sources say

• Not checked yetcites [88] Aguado, 2014, Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: A propensity score analysis, Clin. Infect. Dis. source

In the paper

“Importantly, endocarditis was clinically unsuspected in a third of the cases, prompting a recommendation for TEE in all patients with candidemia [11].”

What the sources say

• Not checked yetcites [11] Cornely, 2012, ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients, Clin. Microbiol. Infect. source

In the paper

“Treatment options for drug-resistant C. glabrata and C. auris are poorly defined”

In the paper

“Treatment of invasive candidiasis is changing.”

In the paper

“Ibrexafungerp (SCY-078, Scynexis, Jersey City, NJ, USA) is a first-in-class oral glucan synthase inhibitor that has shown fungicidal activity against a wide range of Candida species in in vitro assays and animal models [111].”

What the sources say

• Not checked yetcites [111] Schell, W.A., Jones, A.M., Borroto-Esoda, K., and Alexander, B.D. (2017). Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species. Antimicrob. Agents Chemother., 61. source

In the paper

“Sensitive molecular diagnostics have the potential to shift treatment strategies from current, risk-based empirical therapy to early targeted treatments.”

In the paper

“and has fewer off-target effects and drug-drug interactions compared with other azoles.”

In the paper

“their widespread use is leading to rising rates of resistance in Candida isolates at some hospitals.”

In the paper

“Echinocandins have transformed the care of patients with invasive candidiasis”