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