* Hit Fungal Infections from Beginning Hit Fungal Infections from Beginning in ICU *An educational service provided by: Disease Burden Hit Fungal Infections from Beginning Hit Fungal Infections from Beginning Invasive fungal infections Candida species are the most common cause of IFIs and represent 70% to 90% of all invasive mycoses1 In patients with bloodstream infections, Candida species are the fourth most commonly isolated pathogens in the United States and seventh in Europe1 In ICU patients, Candida species are now the third most common cause of nosocomial bloodstream infections2 In critically ill patients, increased use of invasive procedures, intravenous catheters and intravenous hyperalimentation are risk factors for candidemia.3 Candidemia remains associated with:3 -High crude and attributable mortality rates -Increased costs of care -Prolonged hospitalization IFIs = Invasive Fungal Infections; ICU = Intensive Care Unit Nosocomially acquired non-albicans candida species was common in the ICU4 • The incidence of candidemia caused by non-albicans Candida species (52%) was higher than the incidence of candidemia caused by C albicans (48%).4 • Candidemia was nosocomially acquired in 92% of cases.4 Distribution of nosocomially acquired candida species in spain from 1991 to 2008.4 60 Incidence Rate % Breakdown of non-albicans Candida species 48% 52% 40 20 18% 14% 11% 4% 5% C C C C Non-albicans albicans Candida parapsilosis tropicalis glabrata C Other Candida krusei species Adapted from: M Ortega Jhin 77(2011) 157-161  his prospective surveillance study was conducted at hospital clinic in T Barcelona, Spain, a - 700 bed university tertiary center A blood culture surveillance program was conducted for a period of 18 years (1991–2008) Of 19,491 episodes of BSI, 529 consecutive patients were found to have candidemia, 485 of which were nosocomially acquired Patients were observed from diagnosis until 30 days of follow-up, death, or discharge.4 BSI: Bloodstream Infection Hit Fungal Infections from Beginning Candidemia associated with high 30 day mortality in the ICU5 • C glabrata and C krusei were the species associated with most life-threatening infections.5 30-day mortality associated with candida species in the ICU 100 100% Mortality Rate % 80 83.3% 60 40 57.9% 45.2% 36.4% 20 (19/42) (11/19) Non-albicans C Matched, Candida albicans Donor Related (4/11) (5/6) C C parapsilosis glabrata (2/2) C krusei Adapted from: Bassetti M PLoSONE 6(9): e24198 Impact of delayed treatment on mortality6 • The risk of hospital mortality found to be lower for patients receiving antifungal treatment within 12 h of having a positive blood sample for culture drawn than patients begun on antifungal treatment after 12 h.6 Percent Hospital Mortality Relationship between hospital mortality and the timing of the administration of antifungal treatment6 Delay in start of antifungal treatment (hours) FIG Relationship between hospital mortality and the timing of antifungal treatment The timing of antifungal therapy was determined to be from the time when the first blood sample for culture positive for fungi was drawn to the time when antifungal treatment was first administered to the patient Adapted from: Morrell M AAC 3645-49:3640;2005 Hit Fungal Infections from Beginning Early administration of antifungal therapy may reduce hospital length of stay7 In a retrospective cohort study of 169 evaluable adult patients with invasive candidiasis… Length Of Stay (LOS) after isolation of infecting organism was significantly reduced in patients who received early initiation vs delayed initiation of antifungal therapy (P=0.007).7 Early vs delayed initation of antifungal therapy on hospital los after isolation of infecting organism 20.60 days _3 days) Early Initiation (< n =107) ( (17.068) Delayed Initiation (>3 days) (n =62) 27.98 days (16.517) 20 40 _ SD Total LOS, Mean + Adapted from: Donald I JAC 2010;65: 1765-1770 This retrospective cohort study was conducted from January 2004 to December 2007 at US institutions in California: St Mary’s Medical Center; Loma Linda University Medical Center; and St Joseph Hospital A total of 282 adult patients (≥18 years) with invasive candidiasis were identified from microbiology and pharmacy drug utilization records of which 169 were evaluated for outcomes Primary outcome measures included: time to achieve clinical stability, treatment response, total LOS, LOS after isolation of organism, and all-cause and infection-related inhospital mortality.7 60 Clinical practice guidelines for the management of candidiasis : 2009 update by the Infectious Diseases Society of America8 Criteria for starting empirical antifungal therapy in non neutropenic patients remain poorly defined.8 Early initiation of antifungal therapy may reduce morbidity, mortality, and length of stay in critically ill patients, but the widespread use of these agents must be balanced against the risk of toxicity, costs, and the emergence of resistance.8 Early diagnosis of invasive candidiasis remains a challenge; thus, clinical prediction rules have been developed to identify patients in the ICU who are at high risk of candidiasis.8 *IDSA = Infectious Diseases Society of America Guidelines IDSA* Guidelines Hit Fungal Infections from Beginning Practical approach to early diagnosis of invasive candidiasis in critically ill patients9 • Clinicians should combine risk factors and the dynamic of colonization to try to identify early critically ill patients susceptible to benefit from early empirical antifungal treatment.9 Practical approach to early diagnosis of invasive candidiasis In critically ill patients9 Patient at risk of invasive candidiasis (IC) Colonization index Nº sites +/Nº sites screened 2x weekly > 0.5 or ≥0.4 corrected Candida score -Surgery on ICU admission -Total parenteral nutrition -Severe sepsis -Candida colonization >2.5 points Predictive rule ≥ 4th day of ICU stay: Sepsis + CVC + Mec.Vent + one of: -TPN (day 1-3) -Dialysis (day 1-3) -Major surgery (within days) -Pancreatitis (within days) -Immuno sup (within days) or steroids (within days) Start empirical antifungal treatment Adapted from: Eggimann et al., Annals of invasive care 2011,1:37 Risk factors reported to predispose ICU patients for invasive candida infections10 • Neutropenia (particularly > 10 days) • Candida colonization (e.g colonization index > 0.5) • Necrotizing pancreatitis • Gastrointestinal perforation • Acute Renal Failure • Bacterial Sepsis • Malignant hematological disease • High APACHE II score • Diabetes Mellitus • Higher Age Iatrogenic factors • Immunosuppressive therapy (Corticosteroides) • Broad-spectrum antibiotic therapy • Total parenteral nutrition • Central Venous Catheters • Mechanical Ventilation • Major Surgical procedures (e.g abdominal tumor resection) • Leaking gastrointestinal anastomosis • Antineoplastic chemotherapy • Haemodialysis Adapted from: A Gloăckner Mycoses 54, 420433 APACHE II = Acute Physiology and Chronic Health Evaluation II Risk Factors Host factors Hit Fungal Infections from Beginning Many risk factors predispose patients to invasive candidiasis infections11 Risk Factors for Invasive Candidiasis in General and Candidemia Due to Different Candida Species 11 Candida in General • Prior abdominal surgery • Intravascular catheters • Parenteral nutrition • Use of broad-spectrum antibiotics • Immunosuppression, including corticosteroid therapy • Acute renal failure • Diabetes • Transplantation • Hemodialysis • Pancreatitis C tropicalis • Neutropenia and bone marrow transplantation C krusei • Fluconazole use • Neutropenia and bone marrow transplantation C glabrata • Fluconazole use • Surgery • Vascular catheters • Cancer • Older age C parapsilosis • Parenteral nutrition and hyperalimentation • Vascular catheters • Being a neonate a C lusitaniae, C guilliermondii • Previous polyene use Candida rugosa • Burns a= Epidemics due to nosocomial horizontal transmission via hands of health personnel have been reported Adapted from: Mediterr J Hematol Infect Dis ;2011; Open Journal System The Candida Score12 (cut-off value of ≥2.5) · Total parentral nutrition .(+1) · Surgery on ICU admission (+1) · Multifocal Candida colonization* .(+1) · Clinical severe sepsis (+2) *Definition of Candida colonization: - The presence of candida species in non significant samples obtained from the Oropharynx, stomach, urine or tracheal aspirates - Colonization was considered unifocal when Candida species were isolated from one focus and multifocal when Candida species were isolated from various noncontagious foci - Unifocal and multifocal persistence was defined by at least two weekly consecutive sets of Candida positive Scores cultures Sensitivity 81%, Specificity 74% Hit Fungal Infections from Beginning Clinical prediction rule13 Patients who stay in the ICU for at least days Systemic antibiotic treatment (days to of ICU admission) Plus Indwelling central venous catheter (days to of ICU admission) Plus Mechanically ventilated for at least 48 hours Plus One or more of the following risk factors - Total Parenteral Nutrition (TPN) (1 to days) - Any type of dialysis (1 to days) - Any major surgery -(within days prior to ICU admission) - Pancreatitis -(within days prior to ICU admission) - Steroid (within days prior to ICU admission) - Other immunosuppressive agents (within days prior to ICU admission) Sensitivity 50%, Specificity of 83% Candida colonization index14 Colonization = index (CI)14 No.of nonblood (dbs)* colonized by candida spp Total No of body sites cultured Corrected colonization = CI x index14 No.of heavy growth (dbs)* Total growing Candida (dbs)* (CI ≥0.5)** (CCI ≥0.4)** • to samples were obtained weekly*** * Distinct Body Sites ** All infected patients reached the threshold values (CI ≥0.5 and CCI ≥0.4) before the time of infection *** For the microbiologic surveillance in this prospective cohort study, two to three samples were obtained weekly from oropharynx or trachea and stomach Specificity 100%, Sensitivity 100% Conclusion9 Conclusion Hit Fungal Infections from Beginning Patients at risk of Invasive Candidiasis (IC)9 Colonization Index Candida Score Predictive Rule Start empirical antifungal treatment Definitions Sensitivity The proportion of people with the disease who are correctly identified by a positive test result (“true positive rate”).15 Specificity The proportion of people free of the disease who are correctly identified by a negative test result (“true negative rate”).15 References 1- Leroy O, et al 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 2009;37(5):1612-1618 2- Bougnoux ME, et al Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome Intensive Care Med 2008;34:292–299 - Horn DL, et al Epidemiology and Outcomes of Candidemia in 2019 Patients: Data from the Prospective Antifungal Therapy Alliance Registry Clin Infect Dis 2009;48:1695-1703 - Ortega M et al Candida species bloodstream infection: epidemiology and outcome in a single institution from 1991 to 2008, Journal of Hospital Infection 77 (2011) 157-161 - Matteo Bassetti et al Epidemiology, Species Distribution, Antifungal Susceptibility and Outcome of Nosocomial Candidemia in a Tertiary Care Hospital in Italy PLoS One 2011;6.9):e24198 - Morrell M, Fraser VJ, Kollef MH Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality Antimicrob Agents Chemother 2005;49: 3640–5 - Donald I Hsu et al A multicentre study to evaluate the impact of timing of caspofungin administration on outcomes of invasive candidiasis in non-immunocompromised adult patients J Antimicrob Chemother 2010; 65: 1765–1770 Hit Fungal Infections from Beginning - Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America CID 2009:48 - Eggimann et al Diagnosis of invasive candidiasis in the ICU Annals of Intensive Care 2011, 1:37 10 - A Glöckner et al.Current aspects of invasive candidiasis and aspergillosis in adult intensive care patients Mycosts 2011;54(5):420-433 11 - Mikulska M, Bassetti M, Ratto S et al.lnvasive candidiasis in non-hematological patients Mediterr J Hematol lnfect Dis 2011;3(1):e2011007 12 - Cristóbal León et al A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization Crit Care Med 2006 Vol 34, No 13 - L Ostrosky-Zeichner et al Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit Blackwell Verlag GmbH 2009 • Mycoses 54, 46–51 14 - Didier Pittet, etal Candida Colonization and Subsequent Infections in Critically Ill Surgical Patients ANNALS OF SURGERY Vol 220, No 6, 751-758 page 752 C) 1994 J B Lippincott Company 15 - Daniel Pewsner et al Ruling a diagnosis in or out with “SpPIn” and “SnNOut”: a note of caution BMJ Jul 24, 2004; 329(7459): 209–213 May 2016 AINF-1000664-0000 ...Disease Burden Hit Fungal Infections from Beginning Hit Fungal Infections from Beginning Invasive fungal infections Candida species are the most common cause... Infection Hit Fungal Infections from Beginning Candidemia associated with high 30 day mortality in the ICU5 • C glabrata and C krusei were the species associated with most life-threatening infections.5... administration of antifungal treatment6 Delay in start of antifungal treatment (hours) FIG Relationship between hospital mortality and the timing of antifungal treatment The timing of antifungal therapy