fungal icu infections in india” -...

“Fungal ICU Infections in India”

Dr Bansidhar Tarai, MDSr Consultant Microbiology

Max Super Specialty Hospital , Saket, New Delhi

Infection in ICU

• ICU occupied with immunocompromised patients

• Broad-spectrum antibiotic usage, restricted and multiple no

• Longer ICU stay

• Multiple Invasive procedure

• Infection control practices and hand hygiene

• More prone to HAI i.e MDR pathogens

• ICU occupied with immunocompromised patients

• Broad-spectrum antibiotic usage, restricted and multiple no

• Longer ICU stay

• Multiple Invasive procedure

• Infection control practices and hand hygiene

• More prone to HAI i.e MDR pathogens

Fungal ICU infection

• High mortality rate 35-75%, so early antifungal is essential forsurvival

• ICU acquired fungal infection patients characteristically haveseveral underlying medical and surgical risk factors andfrequently exposed to high-risk medications

• Mainly Candidemia in ICU and rarely mold infections

• Rising trend of non-albicans Candida species

• Few multicentric studies on Candidemia from Asian countries

• High mortality rate 35-75%, so early antifungal is essential forsurvival

• ICU acquired fungal infection patients characteristically haveseveral underlying medical and surgical risk factors andfrequently exposed to high-risk medications

• Mainly Candidemia in ICU and rarely mold infections

• Rising trend of non-albicans Candida species

• Few multicentric studies on Candidemia from Asian countries

Study:

215,112 patients admitted

27 intensive care units

North -11, East -3, West-3Central- 4, South – 6

11 public sector and 16private/corporate hospitals

Adult ICU > 18 years

ICU acquired Candidemiaafter 48 hrs ICU admission

SIHAM Candidemia Network(April 2011 – September 30, 2012)

Study:

215,112 patients admitted

27 intensive care units

North -11, East -3, West-3Central- 4, South – 6

11 public sector and 16private/corporate hospitals

Adult ICU > 18 years

ICU acquired Candidemiaafter 48 hrs ICU admission

Chakrabarti et al, Intensive Care Medicine 2015

ICU acquired candidemia in India

• Incidence of candidemia = 6.51/1000 ICU admission

• Highest burden in north India (8.95/1,000) and lowest fromwest (3.61/1000 admissions)

• 65.2% were adults with median age of 50 years

• Median duration of onset of candidemia in ICU – 8 days

• Majority were non-neutropenic (98.7%)

• Median APACHE II score of 17.0 at admission

• Incidence of candidemia = 6.51/1000 ICU admission

• Highest burden in north India (8.95/1,000) and lowest fromwest (3.61/1000 admissions)

• 65.2% were adults with median age of 50 years

• Median duration of onset of candidemia in ICU – 8 days

• Majority were non-neutropenic (98.7%)

• Median APACHE II score of 17.0 at admission

Underlying disease and risk factors

• Underlying respiratory illness (25.0%)– Pneumonia (32.9%)– ARDS (17.9%)– COPD (15.4%)

• Underlying renal disease (22.9%)– Acute (61.2%) or chronic renal failure (30.1%)

• Malignancy (12.8%)– Solid organ (82.9%) and haematological (17.1%)– 47.9% gastrointestinal, 60.7% were intraperitoneal

• Surgical procedure (37.3%) within 30 days– Gastrointestinal, hepat-obilliary and pancreatic surgeries (48.4%)

• Underlying respiratory illness (25.0%)– Pneumonia (32.9%)– ARDS (17.9%)– COPD (15.4%)

• Underlying renal disease (22.9%)– Acute (61.2%) or chronic renal failure (30.1%)

• Malignancy (12.8%)– Solid organ (82.9%) and haematological (17.1%)– 47.9% gastrointestinal, 60.7% were intraperitoneal

• Surgical procedure (37.3%) within 30 days– Gastrointestinal, hepat-obilliary and pancreatic surgeries (48.4%)

Risk factor analysis ICU

Risk Factors Percentage

Central venous catheterization* 74.0

Urethral Catheterisation* 75.9

Invasive Mechanical Ventilation* 52.9

Antibiotic therapy

•Broad spectrum agents

• median duration 16 days , 11 days

93.0

92.3

Antibiotic therapy

•Broad spectrum agents

• median duration 16 days , 11 days

93.0

92.3

Patient on dialysis 17.3

Total parentral nutrition 13.4

Corticosteroids (50mg / day)

• Median duration 7 days

18.0%

Antifungal exposure 15.7%

Species No. of cases Percentage

C. tropicalis 382 41.6

C. albicans 192 20.9

C. parapsilosis 100 10.9

C. glabrata 65 7.08

C. auris 52 5.6

C. rugosa 29 3.15

Candida Species = 918 isolates

C. rugosa 29 3.15

C. kruseii 16 1.74

C. guilliermondii 16 1.74

Others* 66 7.1

•Majority had single episode of Candidemia (93.6%)•31 species, 8 species caused 92.8 %•Non – albicans Candida infections 79.1 %•C.tropicalis is higher in private / corporate ICUs• C.auris & C.rugosa more common in public sector ICUs

Susceptibility of all yeasts

Antifungal Susceptible SDD orintermediate

Resistant

Amphotericin B 97.9 - 2.1Fluconazole 82.8 11.0 6.2Voriconazole 71.5 22.9 5.6Voriconazole 71.5 22.9 5.6Itraconazole 89.5 9.3 1.2Caspofungin 84.3 10.1 5.6Anidulafungin 96.7 1.6 1.7

Micafungin 96.1 2.2 1.7

Antifungal resistant

• Amphotericin B resistant – 2.1%

• Azoles – 11.8 %

• Echinocandins – 6.9%

• MDR is 1.9% (17 isolates)

• Pan-resistant 0.3% (three isolates resistant to all)

• Common MDR isolates are– C.tropicalis (4), C.auris (4), C.krusei (3)

• Amphotericin B resistant – 2.1%

• Azoles – 11.8 %

• Echinocandins – 6.9%

• MDR is 1.9% (17 isolates)

• Pan-resistant 0.3% (three isolates resistant to all)

• Common MDR isolates are– C.tropicalis (4), C.auris (4), C.krusei (3)

Treatment practice in ICU patients

• Azoles – 72.0%• Echinocandins – 18.3%• Amphotericin B – 14.4%

• Ampho B deoxycholate more used in public sector ICUs

• Azoles & echinocandin more common in private / corporatehospitals

• Antifungals was altered in 14.8%

• CVP was removed from 32.1% (majority within 48hrs)

• Azoles – 72.0%• Echinocandins – 18.3%• Amphotericin B – 14.4%

• Ampho B deoxycholate more used in public sector ICUs

• Azoles & echinocandin more common in private / corporatehospitals

• Antifungals was altered in 14.8%

• CVP was removed from 32.1% (majority within 48hrs)

Outcome and mortality predictors

Significant survival only when treated with antifungal agents with simultaneousremoval of catheter within 48 hours

Outcome and mortalitypredictors

• Survival was poor inpatients with publicsector hospitals withrespirator and renaldisease, invasiveventilation, CVC,dialysis, corticosteroidand polymyxin therapy

• Survival was poor inpatients with publicsector hospitals withrespirator and renaldisease, invasiveventilation, CVC,dialysis, corticosteroidand polymyxin therapy

Chakrabarti et al, Intensive Care Medicine 2015

Few Indian studies

ICU infections

Few outbreak in India ICU - a review

Max hospitals

• A tertiary care super speciality hospitals – 520 bedded(private / corporate hospital)

• 17 ICUs with 165 bed

• Medical ICU– Medicine, Medical Onco, Respiratory, Cardiac, stroke

• Surgical ICU– General surgery, Neuro surgery, onco surgery, CTVS surgery

• Paediatric– PICU, NICU

• A tertiary care super speciality hospitals – 520 bedded(private / corporate hospital)

• 17 ICUs with 165 bed

• Medical ICU– Medicine, Medical Onco, Respiratory, Cardiac, stroke

• Surgical ICU– General surgery, Neuro surgery, onco surgery, CTVS surgery

• Paediatric– PICU, NICU

Fungal blood stream infectionNovember 2010 to Feb 2015

30

40

50

60

Medical ICU, n= 223

0

10

20

10

15

20

25

30 Surgical ICU, n=79


0

5

10

PICU (8 beded)

Organism Number

C.tropicalis 3

C.albicans 2

NICU (14 beded)

Organism NumberC.tropicalis 3C.albicans 6C.glabrata 1


C.albicans 2

C.parapsilopsis 1

C.rugosa 3

C.lipolytica 1

Total 10

C.glabrata 1C.haemuloni 1C.parapsilopsis 6C.famata 1C.krusei 1

Candida species 1Total 20

Mold infection – ICU patientsNovember 2010 – Feb 2015, n=86

34

25

1110

15

20

25

30

35

40

1 1 2 1

5

1 1 1 2 10

5

10

Mold Infection: ICU patientsLast 6 months in max hospitals

No Age sex ICU Sample Smear Culture isolate

1 76 M Stroke ICU BAL Septate H Aspergillus flavus

2 71 F Onco SICU Sputum Septate H Fusarium sp *

3 56 F Stroke ICU BAL Aseptate H Rhizopus sp*

4 78 M MICU BAL Septate H Aspergillus fumigatus

5 27 M Surgical ICU ET secretion Aseptate H Rhizopus sp*5 27 M Surgical ICU ET secretion Aseptate H Rhizopus sp*

6 52 M Neuro SICU Blood ------------ Alternaria alternata*

7 59 F MICU ET secretion Septate H Aspergillus flavus

8 4M M PICU ET & BAL Septate H Scedosporium apiospermum*

9 63 M CTVS ICU ET & BAL Septate H Aspergillus flavus

10 5M M PICU ET secretion Septate H Aspergillus fumigatus

* Death

ICU candidemia in India vs other countries

India Other countriesIncidence /1000 ICUadmission

6.51 cases 0.24 – 6.9 cases for Australia, France ,Germany34.3 cases for Spain and Argentina

Candidemia pts Younger (49.7years )

59.0 – 66.2 years

ICU – acquiredcandidemia

Earlier (8 days) 11-15 daysEarlier onset in Australia & France

ICU – acquiredcandidemia

11-15 daysEarlier onset in Australia & France

APACHE II score lower mean(17.2)

Higher score in Spain (20.1), Argentina(20.1) & USA(18.6)

C.tropicalis 41.6% Less common (5.6 – 12.0%) in developedC.glabrata 7.1% C.albicans(45.0-74.0)

C.glabrata(16.7-22.6)


India Other countriesFluconazole resistant• C.tropicalis•C.albicans•C.parapsilosis•C.glabrata

•2.6%•5.2%•4.0%•1.5%

• 4.5 – 14.3%•1.4 – 4.4%•2.7-10.5%•5.9 – 93.8%

Voriconazole Resistant 5.6% 1.2-5.9%

Itraconazole 1.2% 4.7%Echinocandins 6.01% 0.3 – 2.2%

Antifungal therapy 59.9% 74.5-94.1%Crude mortality rate 44.7% 35-75%


India Other countriesUnderlying respiratory,Renal, gastrointestinal

Significant Significant

Diabetes, cardivascular ,neurological

Less common0.1%, 15.1%, 19.5%

Sizable proportion10.7-28.0%, 15.8-48.3%, 13.2%

Underlying malignancy 12.8% 24.6 – 36.1%Underlying malignancy 12.8% 24.6 – 36.1%HIV/AIDSNeutropenia

0.4%1.3%

4.0-6.0%6.6 – 19.7%

Recent surgery , Gatro 37.3%, 18.1% 44.7 – 66.1%, 17.1- 31.6%CVP 74.0% 88.5-100%Mechanical ventilation 52.9% 72.1 – 97.4%Urinary catheterisation 75.9% 86.7-97.4%Haemodialysis 17.3% 17.5-32.5%Total parenteral nutrition 13.4% 43.7-71.1

• Early onset candidemia after ICU admission

•Younger and comparatively less serious patients acquiring candidemia

•No significant difference between Candida species and onset of candidemia

• No exact reason of higher incidence of C.tropicalis in India. No significanteffect of prior antifungal exposure, azole or Fluconazole therapy on higherincidence of C.tropicalis.? Healthcare providers – hands carriage

•MDR C.auris in the majority of ICUs is a matter of concern and significantlymore common in CVP and urinary catheter

• Prior antifungal exposure significantly increased in non albicans Candidainfection, azole resistant Candida infections, high prevalence of C.auris,C.krusei. however no significant gain in C.glabrata infection and not higherresistant.

Summary / Challenges / Unanswered queries

34

• Early onset candidemia after ICU admission

•Younger and comparatively less serious patients acquiring candidemia

•No significant difference between Candida species and onset of candidemia

• No exact reason of higher incidence of C.tropicalis in India. No significanteffect of prior antifungal exposure, azole or Fluconazole therapy on higherincidence of C.tropicalis.? Healthcare providers – hands carriage

•MDR C.auris in the majority of ICUs is a matter of concern and significantlymore common in CVP and urinary catheter

• Prior antifungal exposure significantly increased in non albicans Candidainfection, azole resistant Candida infections, high prevalence of C.auris,C.krusei. however no significant gain in C.glabrata infection and not higherresistant.

THANK YOU

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fungal icu infections in india” -...

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