La terapia empirica nelle infezioni micotiche

Spinello Antinori

Dipartimento di Scienze Biomediche e Cliniche “Luigi Sacco”

Castellanza, 5 ottobre 2013

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 !

Azie N et al. Diagn Microbiol Infect Dis 2012;73:293-

300

Distribution of most commonly observed IFIs by patient category

Risk factors for candidemia in ICU patients

Allou N et al. Curr Infect Dis Rep 2011; 13:426-32

Empiric antifungal therapy: why employ it?

Infections/diseases associated with high mortality when diagnosis/therapy is delayed

low sensitivity of traditional microbiologic diagnosis

and/or

and/or

Lack of appropriate health care/diagnostic facilities

Empiric antifungal therapy: when employ it? Category Risk factors Lab & Clin

parameters

Symptoms Diagnosis

HIV infection

Oral thrush

Interstitial

pneumonia

CD4< 200/L

Dysphagia

Fever, cough,

dyspnea

Candida

esophagitis

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

Long ICU stay

Parenteral

nutrition

Surgery

Candida colon

Shock/MOF

APACHE

Fever/Sepsis

Fever/

Pneumonia

Candidemia

IA

Empiric antifungal therapy: pitfalls

Overtreatment

High costs

Side effects

Resistance selection

and

What are we treating and for how long?

Empiric antifungal therapy: Candida spp.

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

0

5

10

15

20

25

30

35

<12 12 to 24 24 to 48 >48

Relationship between hospital mortality and the timing of antifungal treatment

Delay in start of antifungal treatment (hours)

Morrel M et al. Antimicrob Agents Chemother

2005;49:3640-45

0

5

10

15

20

25

30

35

40

45

day 0 day 1 day 2 day>3

Garey et al. Clin Infect Dis 2006; 43:25-31

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

0

10

20

30

40

50

60

70

80

90

100

P<.001

Hospital mortality according to whether or not patients received antifungal therapy and

adequate source control within 24 hours of the onset of septic shock

Treatment within 24 hours: + + - -

Adequate source control : + - + -

Kollef M et al. Clin Infect Dis 2012;54:1739-46

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)

Severe sepsis & septic shock: role of Candida spp.

Days in the intensive care unit (ICU) in the extended prevalence in the

ICU Study (EPIC) II study day by pathogen

Kett DH et al. Crit Care Med 2011;39:665-70

Crit Care Med

2009; 37.1612-9

Variable Proven

Candidal

infection %

P Value Crude Odd

ratio (95% CI)

Adjusted

Odds ratio

(95% CI)

Surgery on ICU

admission

No

Yes

6.9

16.5

<.001

2.69 (1.76-4.10)

2.71 (1.45-5.06)

Total parenteral

nutrition

No

yes

2.8

15.5

<.001

6.46 (3.48-11.98)

2.48 (1.16-5.31)

Severe sepsis

No

Yes

4.5

28.8

<.001

8.63 (5.49-13.56)

7.68 (4.14-14.22)

Candida spp.

colonization

No

Yes

4.2

12.3

<.001

3.20 (1.85-5.53)

3.04 (1.45-6.39)

Leon et al. Crit Care Med 2006; 34:730-7

Risk factors for proven candidal infection in 1,669 adult patients:multivariate analysis

88 cases and 264 controls (1:3)

Incidence of invasive candidiasis= 2,3% with

at least 4 days of ICU stay

Clin Infect Dis 2013; 56:1284-92

Sensitivity 38 %

Clin Infect Dis 2011;52:770-90

•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

Clin Infect Dis 2012; 54:1240-8

Distribution of isolated yeast

species Nov 2009-March 2011

56,4%

19,9%

9,2% 7,5% 2,3% 2,9%

J Clin Microbiol 2012; 50:176-9

J Clin Microbiol 2012; 50:176-9

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

Int J Antimicrob Agents 2013;

42:294-300

Clin Microbiol Infect 2011;17 Suppl5:1-12

Clin Microbiol Infect 2011;17 Suppl5:1-12

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

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

Eur J Cancer 2008;44:2192-2203

Clin Infect Dis 2009; 48:1042-51

Haematologica 2011;96:1366-70

Lancet Infect Dis 2013;13:519-28

Lancet Infect Dis 2013;13:519-28

Lancet Infect Dis 2013;13:519-28

Lancet Infect Dis 2013;13:519-28

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

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

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