Critical Care and Solid Organ Transplant

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Critical Care and Solid Organ Transplant
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Invasive Fungal Infections in Surgical Patients

• Candidiasis is the most common invasive fungal
  infection in surgical patients
• Aspergillosis, cryptococcosis, and zygomycoses
  occur rarely outside of hematological
  malignancies or transplant patients
• Incidence of candidal BSIs in SICU .98/1000
  patient-days, and 1.42/1000 SICU days with a
  central venous catheter1

BSIblood stream infection 1. Blumberg HM, et al.
Clin Infect Dis. 200133177-186.
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Candida
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Nosocomial Bloodstream Infections in US
Hospitals 1995-2002
BSIblood stream infection CoNScoagulase-negativ
e staphylococci Surveillance and Control of
Pathogens of Epidemiologic Importance (SCOPE)
study Wisplinghoff H, et al. Clin Infect Dis.
200439309-317.
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Common Candida Pathogens

• Candida albicans
• Most common, frequently aggressive
• Generally susceptible to fluconazole
• 47 mortality in adults, 29 in children
• Candida glabrata
• Increasing in prevalence, second most common
  isolate in adults
• Variably susceptible to fluconazole in adults
• Frequently resistant
• 43 mortality in adults, 13 in children

Hospitalized patients NIH/NIAID Mycoses Study
Group 34, study conducted from Feb 1995 Nov
1997. Pappas PG, et al. Clin Infect Dis.
200337634-643. Consensus of Front-Line
Faculty.
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Common Candida Pathogens

• Candida parapsilosis
• major concern outside the United States
• Second most common infection in infants and
  children
• 24 mortality in adults, 15 in children
• Candida tropicalis
• Prevalent in leukemia patients, potentially
  aggressive
• Generally susceptible to fluconazole
• 48 mortality in adults, 18 in children

Hospitalized patients NIH/NIAID Mycoses Study
Group 34, study conducted from Feb 1995 Nov
1997. Pappas PG, et al. Clin Infect Dis.
200337634-643. Consensus of Front-Line
Faculty.
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Incidence of Candida parapsilosis and C.
glabrata by Patient Age
Data from University of Michigan,
1988-1999. Malani PN, et al. Mycoses.
200144446-449.
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Risk for Invasive Candidiasis Is a Continuum

• If candidemia develops
• 40 die
• 60 survive

• High-risk patients
• Surgery
• Leukopenia
• Burns
• Premature infants

• Exposures
• ICU gt7 days
• CVCs
• Antibiotics
• TPN
• Colonization

Rex JH, et al. Adv Intern Med. 199843321-369. Pa
ppas PG, et al. Clin Infect Dis. 200337634-643.
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Which SICU Patients Are at High Risk for
Candidemia?
Risk Factors in SICU Patients gt48 hour
(Protective)
ARF Acute renal failure TPN total parenteral
nutrition. Relative risk based on multivariate
analysis. Blumberg HM, et al. Clin Infect Dis.
200133177-186.
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Candida Colonization Frequently Precedes
Infection in ICU Patients

• 85 of patients are colonized at gt1 site with
  Candida
• 40 of patients with Candida-colonized IV
  catheters develop infection

Petri MG, et al. Intensive Care Med.
199723317-325. Anaissie EJ, et al. Am J
Med.1998104235-245. Kuhn DM, et al. Emerg
Infect Dis. 2004101074-1081.
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Candidemia Percent Metastatic Involvement
Consensus of Front-Line Faculty.
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Does Candida Colonization Predict Infection in
ICU?

• Surveillance cultures do not have high positive
  predictive value
• Butfungal burden is significantly associated
  with infection (Plt.05)

Pelz RK, et al. Surg Infect. 20001273-281.
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Does Candida Colonization Predict Infection in
ICU?

• Site
• Noncontiguous sites
• Number of positive cultures
• Colonization density
• Species

Factors Affecting Predictive Value of an Isolate
Munoz P, et al. Int J Antimicrob Agents.
20001583-90.
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Consider Starting Antifungal Therapy in ICU
Patients When

• Candida recovered from
• Blood cultures
• Usually sterile body fluids
• Abscesses or wounds in burn patients

Munoz P, et al. Int J Antimicrob Agents.
20001583-90.
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Biofilm and Virulence

• Biofilm formation greatly increases antifungal
  drug resistance1
• Indwelling medical devices can act as substrates
  for biofilm growth2
• Clinical C. albicans2 and C. parapsilosis2-4
  isolates have produced biofilm

• Jabra-Rizk MA, et al. Emerg Infect Dis.
  20041014-19.
• Kuhn DM, et al. Infect Immun. 200270878-888.
• Kuhn DM, et al. Emerg Infect Dis.
  2004101074-1081.
• Shin JH, et al. J Clin Microbiol.
  2002401244-1248.

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Infection Control Recommendations

• Hand-washing!
• Healthcare worker transmission linked to largest
  reported C. parapsilosis blood stream infection
  outbreak among adults1
• Remove catheter from infected patients
• Biofilm-associated Candida demonstrates high
  levels of antifungal resistance2
• 78 of candidemia patients have a central venous
  catheter3

• Clark TA, et al. J Clin Microbiol.
  2004424468-4472.
• Kuhn DM, et al. Infect Immun. 200270878-888.
• Hajjeh RA, et al. J Clin Microbiol.
  2004421519-1527.

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Fluconazole Susceptibility Over 12 Years
1992-2003
SSusceptible SDD Susceptible (dose
dependent) RResistant.
Pfaller MA, Diekema DJ. Clin Microbiol Infect.
200410(Suppl 1)11-23.
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Distribution of Candida species in US Hospitals
SENTRY 1997-2000
54 C. albicans
16 C. glabrata
15 C. parapsilosis
10 C. tropicalis
3 Other
2 C. krusei
N2,047 bloodstream isolates
Pfaller MA, et al. J Clin Microbiol.
2002403551-3557.
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Factors Associated With C. glabrata Infection

• Emergence of C. glabrata as an important blood
  stream pathogen may not be a simple matter of
  selection via drug pressure
• Patient age
• Underlying disease
• Geographic location
• Other unknown factors

Pfaller MA, Diekema DF. J Clin Microbiol.
2004424419-4431.
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Percentage of Candidemias due to Candida glabrata
by Age Group, EIEIO 1998-2001
Percent of candidemias

P.02 for trend of increased frequency of C.
glabrata with increasing age.
EIEIO Emerging Infections and the Epidemiology
of Iowa Organisms survey. Pfaller MA, Diekema DJ.
J Clin Microbiol. 2002403551-3557.
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Rare Candida Species

• More than 17 different species of Candida known
  to cause BSIs
• 95 due to 4 species
• C. albicans, C. glabrata, C. parapsilosis, C.
  tropicalis
• 12 to 14 remaining species account for 5 of BSI
• Several of the rare species known to occur in
  nosocomial clusters and/or to exhibit innate or
  acquired resistance to one or more established
  antifungal agents
• C. krusei C. rugosa
• C. lusitaniae C. dubliniensis
• C. guilliermondii

Pfaller, Diekema. J Clin Microbiol.
2004424419-4431.
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C. krusei

• The incidence of C. krusei infection has steadily
  increased in recent years
• Emerges when fluconazole is used for prophylaxis
• Resistant to fluconazole
• Susceptible to posaconazole, voriconazole, and
• caspofungin

Pfaller MA, Diekema DJ. J Clin Microbiol.
2004424419-4431.
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Risk Factors for Death Among 1447 Candidemia
Patients
NIH/NIAID Mycoses Study Group Study 34, Data
collected Feb 1995 Nov 1997. Excludes
children lt13 years old. Pappas PG, et al. Clin
Infect Dis. 200337634-643.
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APACHE II Scores Associated With Risk of Death in
Candidemia
90
APACHE II score gt18 significantly associated with
death within 3 months of first blood culture of
Candida spp. on multivariate analysis
80
70
60
50
Mortality at 3 months, of patients
40
30
20
10
0
0-11
12-18
19-24
³25
Apache II score
NIH/NIAID Mycoses Study Group Study 34, Data
collected Feb 1995 Nov 1997. Excludes children
lt13 years old. Pappas PG, et al. Clin Infect Dis.
200337634-643.
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Is Amphotericin Uniformly Active Against Candida
spp?

• C. albicans S
• C. tropicalis S
• C. parapsilosis S
• C. glabrata S-I
• C. krusei S-I
• C. lusitaniae S-R

S susceptible I intermediate R
resistant. Consensus of Front-Line Faculty.
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Are the Newer Azoles Active Against
Fluconazole-Resistant Candida?
N 6268 susceptible, 463 susceptible
dose-dependent, and 239 resistant. Pfaller MA, et
al. Antimicrob Agents Chemother.
2002461723-1727.
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Candida Epidemiology Summary

• Common bloodstream pathogen
• High morbidity and costs
• 4th most common pathogen in hospitalized patients
• Medical practices/prophylaxis affect the
  frequency and spectrum of nosocomial candidiasis
• Growing concerns about azole-resistant C.
  glabrata
• Independent risk factor for failure of antifungal
  therapy?
• Increasing emphasis on up-front use of more
  potent, broader-spectrum agents, especially in
  critically ill patients

Consensus of Front-Line Faculty.
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Prevention and Prophylaxis for Invasive Fungal
Infection in Transplant

• Many centers use prophylaxis, especially in lung
  and heart transplant without sufficient data
• Literature contains a number of small studies
  with numerous limitations
• Two liver transplant studies showed a benefit,
  but occurred pre technical changes
• A study by MSG in liver transplant post technical
  changes could not enroll enough high-risk
  patients
• Attempt by MSG to study lung transplantbut a
  targeted antifungal prophylactic approach may not
  be feasible

MSG mycosis study group. Singh N. Clin Infect
Dis. 200439(Suppl 4)S200-S206.