Candida krusei Arthritis in a Patient with Hematologic Malignancy: Successful Treatment with Voriconazole

Abstract Background Candida krusei (CK) candidemia is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. We analyzed factors associated with C. krusei candidemia and its outcomes. Methods A retrospective analysis of hospitalized patients with candidemia was conducted at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and labs. Univariable logistic and Cox regression were used to identify potential risk factors associated with CK and mortality, respectively. Multivariable analyses were then constructed parsimoniously from these variables. Results Of 1,873 candidemia events, 59 were due to CK. In multivariable analysis, CK candidemia was predicted by hematologic malignancy (OR 8.9, 95% CI [4.1, 19.7]), stomach cancer (OR 14.6, 95% CI [2.9, 72.5]), absolute neutrophil count (OR 2.4, 95% CI [1.2, 4.8]), and the use of prophylactic azole antifungals (OR 2.2, 95% CI [1.1, 4.3]), monoclonal antibodies (OR 5.7, 95% CI [2.0, 15.8]), and penicillin β-lactamase inhibitors (OR 2.5, 95% CI [1.3, 4.8]). The C-statistic was 0.86 (95% CI [0.81, 0.91]). The crude mortality rates were 86.4% for CK candidemia and 63.6% for non-CK candidemia. Although CK was associated with higher mortality in univariable Cox regression (Figure 1, HR 1.8, 95% CI [1.3, 2.4]), this relationship was no longer significant (HR 1.2, 95% CI [0.8, 1.7]) with the addition of the following confounders: hematologic malignancy (HR 0.9, 95% CI [0.7, 1.1]), absolute neutrophil count (HR 1.7, 95% CI [1.4, 2.2]), stomach cancer (HR 1.0, 95% CI [0.5, 1.9]), coagulopathy (HR 1.0, 95% CI [0.9, 1.2], and prophylactic corticosteroids (HR 1.4, 95% CI [1.2, 1.7] (Figure 2). Conclusion A similar set of patient characteristics is associated with both CK infection and increased mortality, suggesting that patients with CK candidemia are at higher risk of mortality due to underlying illness rather than organism-specific mechanisms. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant Gilead: Scientific Advisor, Consulting fee Astellas: Grant Investigator, Research grant A. Spec, Astellas Pharma US, Inc.: Grant Investigator, Research grant

Download Full-text

Update on Candida krusei, a potential multidrug-resistant pathogen

Medical Mycology ◽

10.1093/mmy/myaa031 ◽

2020 ◽

Vol 59 (1) ◽

pp. 14-30 ◽

Cited By ~ 2

Author(s):

A T Jamiu ◽

J Albertyn ◽

O M Sebolai ◽

C H Pohl

Keyword(s):

Water Solubility ◽

Fungal Infections ◽

Current Knowledge ◽

Hematologic Malignancy ◽

Multidrug Resistant ◽

Candida Krusei ◽

Antifungal Resistance ◽

Antifungal Drugs ◽

Antifungal Drug ◽

Intrinsic Resistance

Abstract Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

Download Full-text

Successful treatment of Candida krusei infection with caspofungin acetate: A new antifungal agent

Critical Care Medicine ◽

10.1097/01.ccm.0000063145.15336.31 ◽

2003 ◽

Vol 31 (5) ◽

pp. 1577-1578 ◽

Cited By ~ 12

Author(s):

William T. McGee ◽

Gary J. Tereso

Keyword(s):

Successful Treatment ◽

Antifungal Agent ◽

Candida Krusei

Download Full-text

Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx253 ◽

2018 ◽

Vol 5 (2) ◽

Cited By ~ 3

Author(s):

Ryan Kronen ◽

Kevin Hsueh ◽

Charlotte Lin ◽

William G Powderly ◽

Andrej Spec

Keyword(s):

Clinical Decision Making ◽

Cox Regression ◽

Hematologic Malignancy ◽

Vital Signs ◽

Bloodstream Infections ◽

Patient Characteristics ◽

Clinical Decision ◽

Mortality Rates ◽

Candida Krusei ◽

Crude Mortality

Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics.

Download Full-text