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2015 fungal infection

Hit Fungal Infections from Beginning

Hit Fungal Infections
from Beginning in ICU

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Disease Burden

Infections from

Hit Fungal Infections from Beginning

Invasive fungal infections

Candida species are the most common cause of IFIs and
represent 70% to 90% of all invasive mycoses1
In patients with bloodstream infections, Candida species are
the fourth most commonly isolated pathogens in the United
States and seventh in Europe1
In ICU patients, Candida species are now the third most
common cause of nosocomial bloodstream infections2
In critically ill patients, increased use of invasive procedures,
intravenous catheters and intravenous hyperalimentation are
risk factors for candidemia.3
Candidemia remains associated with:3
-High crude and attributable mortality rates.
-Increased costs of care.
-Prolonged hospitalization.

IFIs = Invasive Fungal Infections; ICU = Intensive Care Unit

acquired non-albicans
candida species was
common in the ICU4
• The incidence of candidemia caused by non-albicans
Candida species (52%) was higher than the incidence of
candidemia caused by C. albicans (48%).4
• Candidemia was nosocomially acquired in 92% of cases.4
Distribution of nosocomially acquired candida species in
spain from 1991 to 2008.4

Incidence Rate %

Breakdown of non-albicans Candida species










C. Non-albicans
albicans Candida
parapsilosis tropicalis glabrata

Other Candida

Adapted from: M. Ortega Jhin 77(2011) 157-161
 his prospective surveillance study was conducted at hospital clinic in
Barcelona, Spain, a - 700 bed university tertiary center. A blood culture
surveillance program was conducted for a period of 18 years (1991–2008).
Of 19,491 episodes of BSI, 529 consecutive patients were found to have
candidemia, 485 of which were nosocomially acquired. Patients were
observed from diagnosis until 30 days of follow-up, death, or discharge.4
BSI: Bloodstream Infection

Hit Fungal Infections from Beginning

Candidemia associated with high 30 day
mortality in the ICU5
• C. glabrata and C. krusei were the species associated
with most life-threatening infections.5

30-day mortality associated with candida species in the ICU


Mortality Rate %










albicans Donor



parapsilosis glabrata


Adapted from: Bassetti M. PLoSONE 6(9): e24198


Impact of delayed
on mortality6

• The risk of hospital mortality found to be lower for patients receiving
antifungal treatment within 12 h of having a positive blood sample
for culture drawn than patients begun on antifungal treatment after
12 h.6

Percent Hospital Mortality

Relationship between hospital mortality and the timing
of the administration of antifungal treatment6

Delay in start of antifungal treatment (hours)

FIG. 1. Relationship between hospital mortality and the timing of antifungal
treatment. The timing of antifungal therapy was determined to be from the
time when the first blood sample for culture positive for fungi was drawn to
the time when antifungal treatment was first administered to the patient.

Adapted from: Morrell M. AAC 3645-49:3640;2005.

Hit Fungal Infections from Beginning

Early administration of antifungal therapy
may reduce hospital length of stay7
In a retrospective cohort study of 169 evaluable adult
patients with invasive candidiasis…
Length Of Stay (LOS) after isolation of infecting organism
was significantly reduced in patients who received
early initiation vs delayed initiation of antifungal therapy
Early vs delayed initation of antifungal therapy on hospital los
after isolation of infecting organism 7

20.60 days

_3 days)
Early Initiation (<


Delayed Initiation (>3 days)
(n =62)

27.98 days



_ SD
Total LOS, Mean +

Adapted from: Donald I. JAC 2010;65: 1765-1770

This retrospective cohort study was conducted from January 2004 to
December 2007 at 3 US institutions in California:
St Mary’s Medical Center; Loma Linda University Medical Center; and St
Joseph Hospital. A total of 282 adult patients (≥18 years) with invasive
candidiasis were identified from microbiology and pharmacy drug utilization
records of which 169 were evaluated for outcomes. Primary outcome
measures included: time to achieve clinical stability, treatment response, total
LOS, LOS after isolation of organism, and all-cause and infection-related inhospital mortality.7


Clinical practice guidelines for the
management of candidiasis :
2009 update by the Infectious Diseases
Society of America8
Criteria for starting empirical antifungal therapy in non
neutropenic patients remain poorly defined.8
Early initiation of antifungal therapy may reduce morbidity,
mortality, and length of stay in critically ill patients, but the
widespread use of these agents must be balanced against the
risk of toxicity, costs, and the emergence of resistance.8
Early diagnosis of invasive candidiasis remains a challenge;
thus, clinical prediction rules have been developed to identify
patients in the ICU who are at high risk of candidiasis.8

*IDSA = Infectious Diseases Society of America



Hit Fungal Infections from Beginning

Practical approach to early
diagnosis of invasive candidiasis
in critically ill patients9
• Clinicians should combine risk factors and the dynamic
of colonization to try to identify early critically ill patients
susceptible to benefit from early empirical antifungal
Practical approach to early diagnosis of invasive candidiasis
In critically ill patients9
Patient at risk of invasive candidiasis (IC)

Colonization index
Nº sites +/Nº sites screened
2x weekly
> 0.5 or ≥0.4 corrected

Candida score
-Surgery on ICU admission
-Total parenteral nutrition
-Severe sepsis
-Candida colonization
>2.5 points

Predictive rule
≥ 4th day of ICU stay:
Sepsis + CVC + Mec.Vent.
+ 1 one of:
-TPN (day 1-3)
-Dialysis (day 1-3)
-Major surgery (within 7 days)
-Pancreatitis (within 7 days)
-Immuno sup. (within 7 days)
or steroids (within 7 days)

Start empirical antifungal treatment

Adapted from: Eggimann et al., Annals of invasive care 2011,1:37

Risk factors reported to
predispose ICU patients for invasive
candida infections10
• Neutropenia (particularly > 10
• Candida colonization (e.g.
colonization index > 0.5)
• Necrotizing pancreatitis
• Gastrointestinal perforation
• Acute Renal Failure
• Bacterial Sepsis
• Malignant hematological
• High APACHE II score
• Diabetes Mellitus
• Higher Age

Iatrogenic factors

• Immunosuppressive therapy
• Broad-spectrum antibiotic
• Total parenteral nutrition
• Central Venous Catheters
• Mechanical Ventilation
• Major Surgical procedures
(e.g. abdominal tumor
• Leaking gastrointestinal
• Antineoplastic chemotherapy
• Haemodialysis

Adapted from: A. Glo¨ckner. Mycoses 54, 420–433

APACHE II = Acute Physiology and Chronic Health Evaluation II

Risk Factors

Host factors

Hit Fungal Infections from Beginning

Many risk factors predispose patients to
invasive candidiasis infections11
Risk Factors for Invasive Candidiasis in General and
Candidemia Due to Different Candida Species 11

Candida in General
• Prior abdominal surgery
• Intravascular catheters
• Parenteral nutrition
• Use of broad-spectrum antibiotics
• Immunosuppression, including corticosteroid therapy
• Acute renal failure
• Diabetes
• Transplantation
• Hemodialysis
• Pancreatitis

C. tropicalis
• Neutropenia and bone marrow transplantation

C. krusei
• Fluconazole use
• Neutropenia and bone marrow transplantation

C. glabrata
• Fluconazole use
• Surgery
• Vascular catheters
• Cancer
• Older age

C. parapsilosis
• Parenteral nutrition and hyperalimentation
• Vascular catheters
• Being a neonate a

C. lusitaniae, C guilliermondii
• Previous polyene use

Candida rugosa
• Burns
a= Epidemics due to nosocomial horizontal transmission via hands of health personnel
have been reported
Adapted from: Mediterr J Hematol Infect Dis 3 ;2011; Open Journal System

The Candida Score12

(cut-off value of ≥2.5)
· Total parentral nutrition.......................(+1)
· Surgery on ICU admission..................(+1)
· Multifocal Candida colonization*.........(+1)
· Clinical severe sepsis..........................(+2)

*Definition of Candida colonization:

- The presence of candida species in non significant samples
obtained from the Oropharynx, stomach, urine or tracheal
- Colonization was considered unifocal when Candida species
were isolated from one focus and multifocal when Candida
species were isolated from various noncontagious foci.
- Unifocal and multifocal persistence was defined by at least
two weekly consecutive sets of Candida positive



Sensitivity 81%, Specificity 74%

Hit Fungal Infections from Beginning

Clinical prediction rule13
Patients who stay in the ICU for at least 4 days
Systemic antibiotic treatment (days 1 to 3 of ICU admission)
Indwelling central venous catheter (days 1 to 3 of ICU admission)
Mechanically ventilated for at least 48 hours
One or more of the following risk factors

- Total Parenteral Nutrition (TPN) ----------------------------(1 to 3 days)
- Any type of dialysis------------------------------------------(1 to 3 days)
- Any major surgery -------------(within 7 days prior to ICU admission)
- Pancreatitis ---------------------(within 7 days prior to ICU admission)
- Steroid --------------------------(within 7 days prior to ICU admission)
- Other immunosuppressive agents --(within 7 days prior to ICU admission)

Sensitivity 50%, Specificity of 83%

Candida colonization

Colonization =
index (CI)14

No.of nonblood (dbs)* colonized
by candida spp
Total No. of body sites cultured

colonization = CI x

No.of heavy growth (dbs)*
Total growing Candida (dbs)*

(CI ≥0.5)**

(CCI ≥0.4)**

• 2 to 3 samples were obtained weekly***.

* Distinct Body Sites
** All infected patients reached the threshold values (CI ≥0.5 and CCI ≥0.4) before the time of infection.
*** For the microbiologic surveillance in this prospective cohort study, two to three samples were obtained
weekly from oropharynx or trachea and stomach.

Specificity 100%, Sensitivity 100%



Hit Fungal Infections from Beginning

Patients at risk of Invasive
Candidiasis (IC)9




Start empirical antifungal treatment

The proportion of people with the disease who are correctly
identified by a positive test result (“true positive rate”).15

The proportion of people free of the disease who are
correctly identified by a negative test result
(“true negative rate”).15


1- Leroy O, et al. Epidemiology, management, and risk factors for
death of invasive Candida infections in critical care: A multicenter,
prospective, observational study in France (2005–2006). Crit Care
Med. 2009;37(5):1612-1618.
2- Bougnoux ME, et al. Candidemia and candiduria in critically
ill patients admitted to intensive care units in France: incidence,
molecular diversity, management and outcome. Intensive Care
Med. 2008;34:292–299.
3 - Horn DL, et al. Epidemiology and Outcomes of Candidemia
in 2019 Patients: Data from the Prospective Antifungal Therapy
Alliance Registry.
Clin Infect Dis. 2009;48:1695-1703.
4 - Ortega M. et al. Candida species bloodstream infection:
epidemiology and outcome in a single institution from 1991 to
2008, Journal of Hospital Infection 77 (2011) 157-161
5 - Matteo Bassetti et al. Epidemiology, Species Distribution,
Antifungal Susceptibility and Outcome of Nosocomial Candidemia
in a Tertiary Care Hospital in Italy . PLoS One. 2011;6.9):e24198.
6 - Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment
of Candida bloodstream infection until positive blood culture results
are obtained: a potential risk factor for hospital mortality. Antimicrob
Agents Chemother 2005;49: 3640–5.
7 - Donald I. Hsu et al. A multicentre study to evaluate the impact
of timing of caspofungin administration on outcomes of invasive
candidiasis in non-immunocompromised adult patients . J
Antimicrob Chemother 2010; 65: 1765–1770

Hit Fungal Infections from Beginning

8 - Clinical Practice Guidelines for the Management of Candidiasis:
2009 Update by the Infectious Diseases Society of America . CID
9 - Eggimann et al. Diagnosis of invasive candidiasis in the ICU.
Annals of Intensive Care 2011, 1:37
10 - A. Glöckner et al.Current aspects of invasive candidiasis
and aspergillosis in adult intensive care patients. Mycosts.
11 - Mikulska M, Bassetti M, Ratto S. et al.lnvasive candidiasis
in non-hematological patients . Mediterr J Hematol lnfect Dis.
12 - Cristóbal León et al. A bedside scoring system (“Candida
score”) for early antifungal treatment in nonneutropenic critically ill
patients with Candida colonization. Crit Care Med 2006 Vol. 34, No. 3
13 - L. Ostrosky-Zeichner et al. Improvement of a clinical prediction
rule for clinical trials on prophylaxis for invasive candidiasis in the
intensive care unit. Blackwell Verlag GmbH 2009 • Mycoses 54,
14 - Didier Pittet, etal. Candida Colonization and Subsequent
Infections in Critically Ill Surgical Patients ANNALS OF SURGERY
Vol. 220, No. 6, 751-758 page 752 C) 1994 J. B. Lippincott
15 - Daniel Pewsner et al. Ruling a diagnosis in or out with “SpPIn”
and “SnNOut”: a note of caution. BMJ. Jul 24, 2004; 329(7459):

May 2016 AINF-1000664-0000

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