De-escalation of antifungal treatment

46 Pages·2017·1.78 MB·English

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When and where antifungal

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deescalation is possible and safe?
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CJean-François Tim sit MD PhD
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Medical and Infectious Diseases ICU
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Bichat Hospital
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Inserm© UMR 1137 IAME

Paris-Diderot University

Paris FRANCE

ESCMID Vienna April 2017
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Conflicts of interest
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• Research grants: Astellas, Pfizer, Gileadr,
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Merck

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• Scientific Boards: Merck, 3M, Paratek,
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thermoFisher, ICUREsearch, Bayer,
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Gilead, PCharma
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• Participation in symposia: Astellas, Gilead,
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Merck, Pfizer ©
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Major rules of antifungal treatment
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• Start early r
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EARLY

• With adequate druDgs h
ADEQUATE
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• Source control
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• Stop earlC y useless therap y
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DEESCALATION
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• Deescalate if possible
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But in pr actice it is not so easy
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We are helpless and confused…
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1- New drugs are safe and very effective BUT
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30day mortality of candidaemia increased with time1
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60
ICU
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50
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% 40 I u
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M Solid tumor
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2002 21003 22004 3 2005 4 2006 5 2007 6 2008 7 2009 8 2010
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Year
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2- Antifungal use increases the proportion of resistant

strains in subsequent infections and modifies fungal

distribution and MICs of fungi in ICUs2,3

1- Lortholary et al. Intens Care Med sept 2014; 2- Lortholary O et al AAC 2011; 55:532; 3- Bailly S et al- J Infect.
2016 Jan;72(1):103-11
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Antifungal pressure evidence r
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Treatment is started according to recommendations
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AMARCAND 2 study: Oct. 2012 to Oct. 2013
835 patients (87 ICUs) treated for proven or suspected candidiasis
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Exclusion: neutropenia/ transplant recipients
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Documented infections empiric secondary
(n=291) documentetd
34.8% I infections(un=112)
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13.5%
122 candidemia
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113 IAI *
19 candidemia
32 Other deep seated
C 64 IAI*
infections*
29 other deep seated infections
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Not documented infection
Early treatment
(n=432)

51.7% 28% of proven infections
in survivors: Treatment 13% of candidemia
prolonged for 12 ± 10 d
(*) more thanone per patient
(Med 10)
13.5% of AFT

Leroy et al –Ann I ntens care 2016
Bailly et al – Intens care med 2015; 1931
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Physicians are reluctant to stop empiricalr therapy
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because the diagnosis of IFI is difficult
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 who need to be treated??
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•Prolonged neutropenia with persistent fever
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• Fever or sepsis in High Risk (>25%) of invasive candidiasis only in abdominal

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surgery patients with anastomotic leDakage or necrotising pancreatitis 5
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•Cancer patients with new sepIsis of unknown origin u
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•Severe in ICU ventilated patients with sepsis 1, 2-4
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•Diagnostic tests: b
-Blood cultures are specific but delayed
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- uncontaminated tissue sa© mple not always performed
- (1-3) BD glucan is sensitive but not specific with many false positive

results and weak repeatability.

- new PCR or m olecular biology are promising but not available in routine

1-Leon et al - Crit Care Med 2009; 37:1624 –1633; 2- Schuster MG, et al. Ann Intern Med 2008;149:83–90 3:

Knitsch W et al - Clin Infect Dis 2015 Aug 13 4-Ostrosky-Zeichner et al - Clin Infect Dis 2014;58(9):1219–26 ; 5-
Tissot F, et al. - Am J Respir Crit Care Med. 2013;188:1100-1109.; 6- Clancy & Nguyen Clin Infect Dis 2013;
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First rule: In order to be confident with da eescalation
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Perform all the diagnostic tests before therapy
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• Perform blood cultures BEFORE treatment
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– > 2, preferably 3 bottles (aerobes/anaerobes

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with resins, specific bottles)
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– Low inoculuMm  10 ml of blood per bottle
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• BiomarkerCs and molecular bi ology
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– No magic bullets butb may help to stop early
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• Suspected infectio©us sites:

– direct puncture/operative room

• Colonization sites
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Second rule: In order to be confident with deescalration
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Perform all the exams to rule out alternate
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diagnoses b
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• Other infectious sources
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– Oriented by a good clinical examination
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– CT scan / US examination…
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• Fever of non infectious causes
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• OtherS infectious agents
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– Bacteria+++
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– Viruses

– Other fungi
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Third rule: In order to be confident with deesacalation
Evaluate the risks of failure/relapsre
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• Probably more important if
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– The immune system is not efficient

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• Neutropenia
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• Immunosuppressive agents and high dose CS
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• Organ transplant recipients
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• Other: usual dose of CS? / post shock immune
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paralysis?? b
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– The primary/secondary focus of infections have not
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been properly evaluated

• inapprop riate source control

• Implantable devices or catheters are still in place