La terapia empirica nelle infezioni micotiche

Transcription

1 La terapia empirica nelle infezioni micotiche Spinello Antinori Dipartimento di Scienze Biomediche e Cliniche Luigi Sacco Castellanza, 5 ottobre 2013

2 Empiric antifungal therapy: definition The receipt of an effective antimicrobial regimen early in the workup of a patient with suspected fungal infection, before the availability of culture results Generally based on the association of high risk patients/risk factors, and signs & symptoms: low sensitivity and specificity!

3 Distribution of most commonly observed IFIs by patient category Azie N et al. Diagn Microbiol Infect Dis 2012;73:

4 Risk factors for candidemia in ICU patients Allou N et al. Curr Infect Dis Rep 2011; 13:426-32

5 Empiric antifungal therapy: why employ it? Infections/diseases associated with high mortality when diagnosis/therapy is delayed and/or low sensitivity of traditional microbiologic diagnosis and/or Lack of appropriate health care/diagnostic facilities

6 Empiric antifungal therapy: when employ it? Category Risk factors Lab & Clin parameters Symptoms Diagnosis HIV infection Oral thrush CD4< 200/ L Dysphagia Candida esophagitis Interstitial pneumonia Fever, cough, dyspnea PCP Hematology With uncontrolled underlying disease Undergoing treatment Allogenic HSCT Previous Mold Inf Neutropenia Fever unresponsive to antibacterial Invasive aspergillosis, mucormycosis Candidiasis fusariosis Extremely low birth weight CV line Enteral feeding Antibiotics? Sepsis, meningitis Invasive candidiasis (meningitis; candidemia) ICU patients CV line Shock/MOF Fever/Sepsis Candidemia Long ICU stay APACHE Parenteral nutrition Surgery Fever/ Pneumonia IA Candida colon

7 Empiric antifungal therapy: pitfalls Overtreatment High costs Side effects Resistance selection and What are we treating and for how long?

8 Empiric antifungal therapy: Candida spp. Clin Microbiol Infect 2012; 18 (suppl:7): 19-37

9 Morrel M et al. Antimicrob Agents Chemother 2005;49: Relationship between hospital mortality and the timing of antifungal treatment <12 12 to to 48 >48 Delay in start of antifungal treatment (hours)

10 Relationship between hospital mortality and the number of days to initiation of fluconazole therapy Delay of antifungal administration from the time a positive blood culture was drawn day 0 day 1 day 2 day>3 Garey et al. Clin Infect Dis 2006; 43:25-31

11 Hospital mortality according to whether or not patients received antifungal therapy and adequate source control within 24 hours of the onset of septic shock P< Treatment within 24 hours: Adequate source control : Kollef M et al. Clin Infect Dis 2012;54:

12 Severe sepsis & septic shock: role of Candida spp. In the EPIC II study (comprising 7087 infected ICU patients in 75 countries) Candida spp. were the third most frequent organism cultured accounting for 17 % of all isolates. ( Vincent JL et al. JAMA 2009; 302:2323-9) Candida species are the most important fungi reported in the context of severe sepsis and septic shock (Wisplinghoff H et al. Clin Infect Dis 2004; 39:309-17) In case of severe sepsis fungal infection is a risk factor for inappropriate antimicrobial therapy (Harbarth S et al. Am J Med 2003;115:529-35)

13 Days in the intensive care unit (ICU) in the extended prevalence in the ICU Study (EPIC) II study day by pathogen Crit Care Med 2009; Kett DH et al. Crit Care Med 2011;39:665-70

14 Risk factors for proven candidal infection in 1,669 adult patients:multivariate analysis Variable Proven Candidal infection % P Value Crude Odd ratio (95% CI) Adjusted Odds ratio (95% CI) Surgery on ICU admission No Yes Total parenteral nutrition No yes Severe sepsis No Yes Candida spp. colonization No Yes < ( ) 2.71 ( ) < ( ) 2.48 ( ) < ( ) 7.68 ( ) < ( ) 3.04 ( ) Leon et al. Crit Care Med 2006; 34:730-7

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16 88 cases and 264 controls (1:3) Incidence of invasive candidiasis= 2,3% with at least 4 days of ICU stay

17 Clin Infect Dis 2013; 56: Sensitivity 38 %

18 Clin Infect Dis 2011;52:770-90

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20 Provided that the hospital lab is able to provide results to clinicians within 12 to 24 hours, BG antigenemia would prompt the start of pre-emptive antifungal therapy Alternatively, empirical antifungal therapy may be discontinued as soon as negative BG and blood culture results are available However,demonstration of the reproducibility of this sound and appealing unprecedented observation in different hospitals and patient settings is needed

21 Clin Infect Dis 2012; 54:1240-8

22 Nov 2009-March ,4% Distribution of isolated yeast species 19,9% 9,2% 7,5% 2,9% 2,3% J Clin Microbiol 2012; 50:176-9

23 J Clin Microbiol 2012; 50:176-9

24 Clin Microbiol Infect 2012; 18 (suppl:7): 19-37

25 Int J Antimicrob Agents 2013; 42:

26 Clin Microbiol Infect 2011;17 Suppl5:1-12

27 Clin Microbiol Infect 2011;17 Suppl5:1-12

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30 Clin Microbiol Infect 2012; 18 (Suppl 7): 53-67

31 J Antimicrob Chemother 2011;66 Suppl 1 :i37-43

32 Eur J Cancer 2008;44:

33 Clin Infect Dis 2009; 48:

34 Haematologica 2011;96:

35 Lancet Infect Dis 2013;13:519-28

36 Lancet Infect Dis 2013;13:519-28

37 Lancet Infect Dis 2013;13:519-28

38 Lancet Infect Dis 2013;13:519-28

39 Clin Microbiol Infect 2012; 18 (Suppl 7): 53-67

40 Empirico, Enciclopedia Treccani In contrapposizione a sistematico, che risulta immediatamente dall esperienza e non si deduce da altra legge o proprietà conosciuta: criteri empirici; norme empiriche; spiegazioni empiriche; con significato peggiorativo, che è il risultato di osservazioni superficiale, priva di principi e norme metodiche: metodo empirico, medicina empirica; medico empirico; rimedi empirici, tratti dalla comune esperienza, non scientifici