initial antifungal therapy for critical ill patients when and which ?
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Initial Antifungal Therapy for Critical Ill Patients When and Which ?. 2012-02-21. 林口長庚 胸腔內科 林鴻銓 Lin, Horng-Chyuan Division of Pulmonary Infectious & Immunological Disease Department of Thoracic Medicine Chang Gung Memorial Hospital Chang Gung University. Fungal Infections in the ICU. - PowerPoint PPT PresentationTRANSCRIPT
Initial Antifungal Therapy for Critical Ill Patients
When and Which ?
林口長庚 胸腔內科林鴻銓
Lin, Horng-ChyuanDivision of Pulmonary Infectious & Immunological Disease
Department of Thoracic MedicineChang Gung Memorial Hospital
Chang Gung University
2012-02-21
Fungal Infections in the ICU
Impact of invasive fungal infection on outcomes of severe sepsis:a multicenter matched cohort study in critically ill surgical patients, Critical Care 2008, 12:R5
Characteristics of fungal infection
Aspergillus and Candida (75%)
Caus
e of
infe
ction
(%)
CoNS Staph Entero-coccus
Candida Pseudo-monas
Candida - the Third Most Common Cause of BSI in the ICU
BSI=Blood stream infection.ICU=Intensive care unit.Wisplinghoff H et al. Clin Infect Dis. 2004;39:309-317.
Cause of nosocomial BSI in the ICU (US; 1995-2002)40
30
25
20
15
10
5
0
35
35.9%
16.8%
9.8%10.1%
4.7%
US(1992-2001; N=3683)
More than 50% of Systemic Candida Infection - Caused by Candida albicans
Europe
(1992-2001; N=775)
Pfaller MA et al. Clin Microbiol Infect. 2004;10(suppl 1):11-23.
13% C glabrata 18%
14% C parapsilosis 13%
8% C tropicalis 10%
5% Other spp 2%
3% C krusei 2%
C albicans58% C albicans
54%
Consensus Statement on the Management of Invasive Candidiasis in ICU in the Asia-Pacific Region
Distribution of Candida spp. associated with candidaemia in selected Asian countries
International Journal of Antimicrobial Agents 34 (2009) 205–209
Risk Factors for Invasive Candidiasis
Use of antibacterials
Neutropenia
Colonization
Damaged mucosa
The catheter
Underlying Diseases
Host factors
Medical interventions
Candida colonization
Risk Factors for Invasive Candidiasis
Host factors
Medical interventions
Candida colonization
1. Extremes of age2. Neutropenia3. Renal failure4. Higher APACHE II score5. Trauma/burns6. Bowel perforation
1. Chemotherapy2. Dialysis3. Central venous catheters4. Antibiotic use (risk increases with each
additional antibiotic)5. Parenteral nutrition6. Prior surgery (especially abdominal)7. Length of ICU stay of 7 days8. Nasogastric tubes9. Gastric acid suppression
Diagnostic Tests for Invasive Candidiasis
CultureHistologyAntigenAntibody
Enolase mannan
PCR1-3-β-D-glucan
C-reactive protein (CRP)Procalcitonin (PCT)Interleukin-6 (IL-6)
Colonization
Infection Invasion
Early Antifungal Intervention Strategies in ICU Patients
• Risk factors without evidence for colonization
Prophylaxis
• Risk factors and colonization with Candida in the absence of symptoms
Preemptive therapy • Symptoms suggesting
sepsis and risk factors before the documentation of infection
Empirical therapy
Antifungal therapy
Crit Care Med 2010; 38[Suppl.]:S380 –S387
1950~ 1970~80 1997~ 2002~ 2004
Early Azoles ClotrimazoleMiconazole
Ketoconazole
Lipid Amphotericin BAmbisone
AbelcetAmphocil
2nd Tri-azole: VfendEchinocandins: Cancidas
PolyenesNystatin
Amphotericin B
1st Tri-azolesFluconazoleitraconazole
Micafungin
Posaconazole
1990~
Development of Anti-fungal Agents
Invasive AspergillosisChronic
NecrotizingAspergillosis
AspergillomasABPA
allergicsinusitis
Diseases caused by Aspergillus infection
Immune Response
PreexistingFibrocavitatory lung diseases
Structural lung diseaseGeneral debilitation
NeutropeniaHematopoietic Stem Cell TransplantationSolid Organ TransplantationAIDSChronic Granulomatous Disease
AsthmaBronchiectasisCystic fibrosis
Patients in MICUs ?
“Halo Sign” Is an Early Indicator of Invasive Pulmonary Aspergillosis
Halo SignHalo Sign
Greene RE, et al. Clin Infect Dis. 2007; 44:373-379.Greene RE, et al. Clin Infect Dis. 2007; 44:373-379.VFE-M-0804007
Invasive Pulmonary Aspergillosis in Non-neutropenic Critically Ill Patients
Risk factor
COPD in combination
with prolonged
corticosteroid use High-dose
systemic corticosteroids
>3weeks (prednisone
equivalent >20 mg/day)
Chronic renal failure with
renal replacement
therapy
Diabetes mellitus
Near-drowning
Liver cirrhosis/
acute hepatic failure
Intensive Care Med (2007) 33:1694–1703
Antifungal Drugs for Invasive Pulmonary Aspergillosis in Critically Ill Patients in ICU
Alternatives
Liposomal amphotericin B 3-5 mg/kg/day i. v.
Amphotericin B deoxycholate 1 mg/kg/day i. v.
Caspofungin 70mg i.v. on day 1, then 50 mg/day i. v.
First choiceVoriconazole 6mg/kg q 12 h i.v. on day 1, then
4mg/kg q 12 h i.v.Voriconazole 400 mg q 12 h oral on day 1, then
200 mg q 12 h oral
Primary therapy of IPA
Intensive Care Med (2007) 33:1694–1703