1. Dr R N CHUGH Head, Dptt. Of Medicine Safdarjung Hospital
Professor UCMS New Delhi
Personal Physician to late Prime Minister
Shri LAL BAHADUR SHASTRI

2. ICU INFECTIONS Dr A P Misra Sr. Consultant
Fortis Flt. Lt. Rajan Dhall Hospital, New Delhi

3. ICU---EPICENTRE of Infections
Extremely vulnerable population
Multiple procedure & Devices
Drugs , sedatives, muscle relaxants etc.
Highest rates of Nosocomial Infections ( 20-30% )
Prolonged stay, ↑ cost
↑ morbidity & mortality
India Overcrowding , Understaffing, ↓resources, lack
of data , not adhering to infection control program

4. PLAN of TALK GLOBAL SCENARIO INDIAN OVERVIEW COMMON PATHOGENS
COMMON INFECTIONS
PREVENTION & CONTROL

5. International Study of the Prevalence & Outcome of Infections in ICUs (EPIC II)
14414 pt., ICUs, 75 countries
1 day, prospect1ive, May 8, 2007
51% infected, 70% culture +
64% respiratory
Gram – 62%, Gram + 47%, Fungi 19%
Staph. aureus, Acinetobacter, Pseudomonas, Candida
ICU mortality % vs 11%, In-hospital mortality 33% vs 15%
Pts. With longer stay prior to study day- higher infection rate
Vincent et al JAMA2009

6. ICU Infections- Indian studies
Apollo Hospital Chennai, Jan-July 2009
401 pts (25%) + cultures
60% Gram- E coli commonest in blood & urine
Pseudomonas in respiratory secretions
CONS most common Gram +
49% E coli ESBL+, 5% carbapenem resistant
35% Pseudomonas & 92% Acinetobacter-MDR
50% Staphylococcus –MRSA
31% of culture + died in ICU
Ravi et al ,Am J Inf Dis 2013
Ravi et al Am J Inf Dis 2013

7. 679 pt. 166 pt. had 198 device associated infection
UTI % / Pseudomonas 35.7%
CLA-BSI % / Klebsiella 29.2%
VAP % / Acinetobacter 41.3%
Mortality % vs %
Datta et al, Ind J Anaesth. 2014

8. Important Pathogens in ICUs
Acinetobacter
Pseudomonas
E. coli
Klebsiella
MRSA
Enterococcus
Candida
Clostridium difficile

9. Acinetobacter in ICUs in different geographical zones
N AMERICA %
W EUROPE %
E EUROPE %
OCEANIA %
S AMERICA %
AFRICA %
ASIA %
(EPIC II), JAMA 2009

10. Acinetobacter
Commonest Respiratory pathogens in ICU , Late VAP, BSI, Wound infection, Meningitis
Wattal et al: Acinetobacter (32.16%)
Our data : Acinetobacter (25.8%)
India Carbapenem sesitivity
Gopalkrishnan %
Wattal %
Subbalaxmi %
Patwardhan et al >90% MDR, 1-4 Plasmids
JAPI 2010 , Ind J Med Res 2008

11. Acinetobacter baumannii

12. Acinetobacter problems
RESISTANCE to ANTIBIOTICS
RESISTANCE to DESICCATION
mean survival time 27 d ( d)
Bio-film formation
RESISTANCE to DISINFECTANTS
Propanol , Macetronium , Triclasan , Ethyl sulfate, Chlorhexidine , Polyvinylpyrrolidone –iodine
CONTACT TIME 30 s , PROPER DILUTION

13. Acinetobacter menace Carbapenem resistance in Acinetobacter a serious
threat CDC 2013
2-5 times that seen in Pseudomonas & Klebsiella
↑ risk of Inappropriate Initial Antibiotic Therapy
IIAT in Sepsis & Pneumonia fold ↑ in death
Escalation of Tt fails to mitigate ↑ risk
BMC Inf Dis 2014, Chest 2008, Inf Con Hosp Epidemiol. 2013

14. Resistance mechanisms
Amp C Cephalosporinase chromosomally mediated
Oxacillinases (Ambler Class D)
bla OXA 23 , → Carbapenems
Metallo β lactamases (Class B)
IMP, VIM, SIM → Carbapenems
first discovered in Edinburgh 1985
Non-enzymatic
change in outer membrane proteins

15. Resistance mechanisms (contd.)
- Multi-drug Efflux Pumps
AdeABC
- Alteration in Affinity/ Expression of PBP
Aminoglycoside modifying enzymes
↓ binding to Lipopolysaccharide ( LPS) target site
Polymyxins
Other ESBLs VEB 1 , PER 1, PER 2 , TEM 92, 116
SHV 16, CTX M2 , 43
MDR / XDR / PDR

16. Acinetobacter & Carbapenems
4 yr. surveillance of A. baumannii resistance pattern in China
Imipenem % → 90.8%
Meropenem % → 91%
J Thor. Dis. 2013, Aug
Total Carbapenem consumption is significantly correlated with resistance to IMP, MRP, β lactam, Fluoroquinolones, Aminoglycosides
J Clin Pharmacol. 2013
Doripenem Oxa 58
Discordance
Infusion time 3 hr

17. POLYMYXINS Discovered in 1947
Target lipopolysaccharide of outer membrane of gram – bacte.
Nebulized colistin
Kwa et al 86 % favourable, 5% bronchospasm
Berlana et al 71 pt. Favourable, microbiological eradication in all pt. receiving nebulized colistin
1 death after premixed CMS , not FDA approved
USE CMS IMMEDIATELY AFTER PREPARATION
Predose bronchodilation
1-3 million units in divided doses / d ( max. 6 mu/d)

18. SULBACTAM etc. Intrinsic activity against Acinetobacter Wood et al
A. baumannii VAP, Retrospective
Imipenem+ cilastin vs. Ampicillin –Sulbctam
83 % vs 93%
Equivalent efficacy in BSI
Meningitis mixed results
CSF penetration 2-32% of serum conc. Peak levels
after 1 gm. IV
Dose 6 gm/ d in divided doses , Max. 12 gm/d
RIFAMPIN , COMBINATION CHEMOTHERAPY

19. Klebsiella Global prevalence
N. America 9%, W. Europe 9.7%, Oceania 11.8% S. America 16.1%, Africa 18.5%, Asia 20.7%, E. Europe 21.3% JAMA 2009
K P C growing threat
INDIA
Wattal et al % Amp C
Carbapenem resistance 51%
Tigecycline resistance 61%
Gopalkrishnan et al
Cefperazone-sulbactam sensitive 70%
Piperacillin-tazobactam %
Carbapenem resistance ↑ 0% in 2005 to 34% in 2008
Subbalaxmi et al
CPZ-SB & Piperacillin-tazobactam sensitive 61%

20. E coli Global prevalence
W. Europe 17.1%, E. Europe 14.8%, S. America 14.3%, N. America 14.2%, Oceania 13.2%, Africa 11.1%, Asia 16.7%
INDIA
SMART study % ESBL producer
Gopalkrishnan et al %
CPZ-SB 80% & PP-TZ 70% sensitivity
5-25% combined resistance to Cephalosporins, Quinolones & Aminoglycosides in Europe
Some CTX-M ESBL may have Carbapenem resistance

21. Pseudomonas Global prevalence
W.Europe 17.1%, E.Europe28.0%, S.America 26.3%, N. America 12.9%, Oceania 14.7%, Africa 14.8%, Asia 28.7%
INDIA
Wattal et al 20% in respiratory isolates
Gopalkrishnan et al Carbapenem sensitive 50-70%
Subbalaxmi et al Carbapenem sensitivity
↓ 64% in to 35% in 2008
Patel et al Carbapenem sensitivity < 70%

22. Staphylococcus aureus & MRSA
Global prevalence
W.Europe 19.6% (8.7%), E.Europe 21.6% (10.4%), S.America 19.2% (11.0%), N.America 26.9% (17.5%), Oceania 27.5% (9.3%), Africa 29.6% (20.4%), Asia 16.1% (10.0%)
INDIA- INSAR
Isolation Rate of MRSA OPD IPD ICU Year
26310 isolates MRSA 41%
Ind J Med Res 2013 Feb

23. Staph. aureus & MRSA, Enterococcus
Glycopeptide remain mainstay of Treatment
Vancomycin intermediate strains in US
Report of VRSA in India
LINEZOLID , TIGECYCLINE & DAPTOMYCIN
Coagulase negative Staph. aureus ( CONS)
- most common CLA-BSI
-high resistance to oxacillin & Clindamycin
- colonizers / contaminants
Enterococcus -- E. fecalis , E. fecium
VRE

24. Healthcare Associated Pneumonia (HAP) & Ventilator Associated Pneumonia (VAP)
Prevalence HAP 10-65%, VAP 25%
Mehta et al VAP /1000 ventilated days
Chawla et al HAP 53.9% , VAP 8.95/1000 ventilator days
Joseph et al H influenzae, S pneumoniae, S aureus, Enterobacteriaceae---EARLY VAP
Acinetobacter, Pseudomonas ---LATE VAP
Clinical criteria to diagnose VAP Sensitivity 69% , Specificity 75%
J Hosp. Inf Oct, Thorax 1999

25. Clinical Pulmonary Infection Score System

26. PROMPT, APPROPRIATE ANTIBIOTIC ↓ MORTALITY
INITIAL Choice of COMBINATION ANTIBIOTICS for HAP/ VAP
MDR Pathogens
Antibiotics
Pseudomonas
Acinetobacter
Klebsiella
3rd/4th generation Cephalosporins + β lactam inhibitors Or
Piperacillin + Tazobactum +Ciprofloxacin / Levofloxacin
Imipenem / Meropenem
Amikacin / Tobramycin / Gentamycin
plus
MRSA
Linezolid / Vancomycin

27. HAP & VAP (contd.) Diagnosis-quantitative culture BAL/pBAL/PSB/TBA
Biomarkers- CRP, PCT, Strem-1
Margarita R Carbrera-Cancio
↓ VAP rates from 6.18/1000 in 1998 to 0.44/1000 in 2010
Protocol- ↑ of head by 30⁰, twice weekly body bath with chlorhexidine, mupirocine on nares, hand washing, tracheostomy by day 7, staff adherence, infection control campaign
Respiratory Care 2012 June

28. Blood Stream Infection
Central Line Associated Blood Stream Infections (CLABSI) in US every year
Mehta et al 7.92/1000 catheter days→ 4% excess mortality in ICUs in India
Chopdekar et al 9.26/1000 c.d. ( 27.02/1000 c.d .in NICU)
Incidence of BSI ↑ duration of catheterization, no. of ports, no. of manipulations
Prevention Training , Avoid femoral vein for CVC, Use of CVC with minimum no. of ports, Maximal sterile barrier precautions
J Hosp. Inf Oct, Ind J Med Microbiology 2011

29. Catheter Associated Urinary Tract Infection (CAUTI)
Most common HAI
NNIS 3.38/1000 patient days in ICU
Mehta et al 1.21/ ↑ mortality of 11.6%
Rosenthal et al 8.9/1000 in 55 ICUs in 8 developing countries
Pathogens – E coli, Candida most common
Prevention - Use only when necessary, Sterile techniques, Closed drainage, Remove as soon as possible, Silicone catheters
Publ. Health Rep. 2007, J Hosp. Inf. 2007

30. Surgical Site Infection (SSI)
NNIS 0.95/1000 patient days in accounted to 11% deaths
Suchitra et al – 1125 surgeries, prospective - 12% SSI S. aureus (33%) & Enterococcus (33%) commonest
MRSA & Gram – bacteria
Elderly, Diabetics, Malnourished, obese, Immuno-compromised
Prevention – Adequately treating pre-existent infections, Good anti-septic practices, Good diabetic control, Antibiotics before surgery
Afr. J Microbiol. R. 2009
Pub Health Report 2007
Public Health Report 2007

31. Clostridium difficile Associated Diarrhea
Diarrhea, pain in abdomen
Complications- ileus, toxic megacolon
Risk factors- previous exposure to various antibiotics, length of hospital stay, Age >64 yr
Diagnosis –CD antigen A & B enzyme immunoassay –rapid, less sensitive
PCR- more sensitive & specific
Treatment – i/v Metronidazole , oral Vancomycin
Fidoxamicin , Fecal transplant

32. Fungal infections Considerable increase Candida most common
Wattal et al % non-albicans Candida in ICU
C tropicalis 18.3%, C albicans 13.2%, C haemulonii 9.5%, C glabrata 6.2%, C krusei 3.1%
C albicans- sensitive to Fluconazole & Voriconazole
C haemulonii sensitive to Capsofungin, resistant to Amphotericin B & Flucytosine
C tropicalis & C glabrata resistant to Fluconazole
JAPI 2010 Dec

33. Bacteria---Fungal Interactions
↑ incidence of Gram — infection after Anti-fungal Prophylaxis
BMC Anesthesiology 2015
FARNESOL a Sesquiterpene molecule from C. albicans
inhibits production of virulence factors in P. aeruginosa
inhibits viability of A. baumannii in Bio-films
can ↑ susceptibility of E. coli & S. aureus to common antibiotics
Mol Microbiology 2007
Aspergillosmine A , natural fungal product can restore sensitivity of Carbapenens to NDM-1 & VIM-2 ( Metallo-betalactamases)
Nature 2014

35. 5 essential steps for Cross Transmission
Organisms from patients→ inanimate objects
Transfer to hands of Health Care Worker
Surviving on HCW’s hands
Inadequate hand washing or hand antisepsis
Contact with another patient

36. Bacterial Survival time on Hands
Acinetobacter min
E. coli min ( mean)
Klebsiella min (mean)
VRE min
Pseudomonas min; 180 min in sputum
Rotavirus % survive 20 min,
2% survive 60 min

37. Ignaz Semmelweiss 1847, Oliver Holmes, John Snow
Discovered that healthcare provider s could transmit disease
↑ maternal mortality Obstetricians & Medical students
vs. Midwives
A Pathologist die of SEPSIS after getting a scalpel wound while performing Autopsy in a patient with PUERPERIAL SEPSIS, Pathologist’s clinical illness mimicked that of woman with Puerperial sepsis
introduced CHLORINATED LIME Hand washing in clinics --- ↓ Maternal mortality rates from % to 1.27% in 2 yr.
HIS THEORIES WERE DISMISSED BY MOST OF MEDICAL ESTABLISHMENT till – Koch gave Germ Theory

38. Hand washing compliance rates
Nurse %
Physician %
Nursing assistant %
Other %
Pittet et al Ann Int Med 1999

39. HAND WASHING with Soap & Water and not with Alcohol based cleaners
Clostridium difficile Spores resistant to Alcohol
Nora & other related viruses

40. Prevention & Control of ICU Infections
Hospital Infection Control Committee
Surveillance of Infecting Organisms & Drug Resistance
Antibiotic Policy
Prescription Auditing
Infection Control Measures
Proper Use of Devices

41. THANK YOU

42. Respiratory samples- Fortis Jessa Ram data, 1-1-2011 to 31-12-2013
Total no. of samples—961
Culture + samples
No %
Acinetobacter
Klebsiella sp
Pseudomonas sp
E coli
Candida

43. Urine samples 1-1-2013 to 30-12-2013 Fortis Jessa Ram Hospital, New Delhi
Total no
Culture
No. of organisms isolated
E coli
Klebsiella
Pseudomonas
Candida
Proteus
Enterococcus

44. Blood samples 1-1-2013 to 30-12-2013 Fortis Jessa Ram Hospital, New Delhi
Total no
Culture
No. of organisms isolated
Staphylococcus aureus
Staphylococcus hemolyticus
Staphylococcus epidermidis
Staphylococcus hominis
E coli
Klebsiella
Acinetobacter baumanii
Providencia stuartae
Acinobacillus ureae

45. ICU Infections—Indian studies
Eastern India, 242 Pt., 2012
NI /1000 Pt. d.
Pneumonia /1000
VAP 26.6/1000 Vent. d.
UTI 7.44/1000 Cath. d.
BSI 2.46/1000 CVC d.
IJCCM, 2015
Western India, 487 pt
72.3% recovered, % died, % palliative care
↑ mortality – A. baumannii K pneumoniae, P aeruginosa
Recovery- direct admission, lower APACHE 2 score, shorter ICU stay
Lung India, 2015

46. Prospective,multicentric,observational 27 Indian ICUs, Apr. 2011-Aug
1400 Candidemia (6.51 / 1000 ICU admissions)
65.2% adults
Acquisition early (median 8 d., range 4-15 d.)
31 Candida sp., C. tropicalis 41.6%
Azole & Multi-drug resistance in 11.8% & 1.9%
PSU hospitals more resistant strains
30 d. Crude & attributable mortality rates % and 19.6%
A. Chakrabarti et al , Int. Care Medicine, 2014
Prophylaxis & Pre-emptive therapy