Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

https://www.easy-immune-health.com/support-files/clin_practice_guidelines_candidiasis.pdf

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

BACKGROUND Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. METHODS We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. RESULTS A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). CONCLUSION A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

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Time to Initiation of Fluconazole Therapy Impacts Mortality in Patients with Candidemia: A Multi-Institutional Study

Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods. Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. Results. The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P = .002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.

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Epidemiology and Outcomes of Candidemia in 2019 Patients: Data from the Prospective Antifungal Therapy Alliance Registry

Objective:To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices.Design:Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset.Results:We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization (22,000, respectively) and the length of stay (3 to 13 days).Conclusion:Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment (Infect Control Hosp Epidemiol 2005;26:540-547).

Excess Mortality, Hospital Stay, and Cost Due to Candidemia: A Case-Control Study Using Data From Population-Based Candidemia Surveillance

Background:Nosocomial bloodstream infections are associated with increased hospital costs in adult and pediatric patients. Candida is an increasingly important nosocomial pathogen within intensive care nurseries. The purpose of this study was to determine the attributable cost of candidemia in neona

Excess costs of hospital care associated with neonatal candidemia.

BACKGROUND Almost one-third of patients with bloodstream infections with Candida species (candidemia) have onset of disease that occurs outside of the hospital or < or = 2 days after hospital admission (i.e., community-onset candidemia). We compared the characteristics of patients who developed candidemia by the timing of onset of infection. METHODS Incident episodes of candidemia were identified through active, population-based surveillance in Connecticut and in Baltimore and Baltimore County, Maryland, during 1 October 1998-30 September 2000. The molecular subtypes of a sample of 45 Candida parapsilosis isolates were evaluated using Southern blots hybridized with the complex probe Cp3-13. RESULTS Overall, 356 (31%) of the 1143 incident episodes of candidemia were classified as community-onset disease (occurring < or = 2 days after hospital admission), and 132 (37%) were caused by Candida albicans, 89 (25%) were caused by Candida glabrata, 57 (16%) were caused by C. parapsilosis, and 53 (15%) were caused by Candida tropicalis. Community-onset disease was less likely to be associated with concurrent immunosuppressive therapy, recent surgery, or use of a central venous catheter, compared with inpatient disease. Among patients with community-onset disease, the median time from blood culture to initiation of antifungal treatment was 2.7 days, the 30-day case-fatality rate was 26%, and 262 patients (75%) had been hospitalized at least once in the previous 3 months. Although there were few differences between patients with very recent hospitalization (in the previous 1 month), less recent hospitalization (previous 1-3 months), and no documented past hospitalization, C. parapsilosis was more frequently associated with community-onset disease as hospitalization became more distant. C. parapsilosis strains tended to be unique to the patient, with little similarity found between strain types, on the basis of epidemiologic classification of patients. CONCLUSION We report that community-onset candidemia is common and occurs in patients with extensive contact with the health care system. Disease caused by C. parapsilosis tends to involve unique strains.

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Epidemiology of community-onset candidemia in Connecticut and Maryland.

Hepatitis C (HCV) is a leading cause of chronic liver disease in the United States. Connecticut has a registry of laboratory reported cases of HCV. These reports include limited patient-level information. Using a one-page abstraction instrument, we used this registry to contact providers by fax to obtain contact, epidemiologic, and clinical information on Waterbury residents with newly reported HCV. We offered to perform the data abstraction if desired by the physician. In 2004, 376 new cases of HCV were reported. Eighty-eight percent of abstraction instruments were returned; most were completed by physician office staff. These included detailed information on age, race, gender, risk factors for acquisition of infection, clinical status, and confirmatory testing. Many patients appear to not have adequate follow-up for the management of this infection. Fax-back surveillance in the case of HCV is feasible and provides much-needed patient-level information.

Sharon Huie-White

Papers

Excess Mortality, Hospital Stay, and Cost Due to Candidemia: A Case-Control Study Using Data From Population-Based Candidemia Surveillance

Excess costs of hospital care associated with neonatal candidemia.

Epidemiology of community-onset candidemia in Connecticut and Maryland.

Use of fax-back surveillance to determine epidemiologic and clinical characteristics of patients diagnosed with hepatitis C in Waterbury, Connecticut.