The relevance of Gram-negative pathogens for public health situation in India

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1 The relevance of Gram-negative pathogens for public health situation in India Dr. Sanjay Bhattacharya MD, DNB, DipRCPath, FRCPath, CCT (UK) Consultant Microbiologist Tata Medical Center Rudolf Schulke Foundation Nov 2015, Hamburg, Germany

2 Overview WHO country statistics ESBL-carba R- North India ESBL- South India Carba-R- West India Stool surveil- East India Pediatric oncol infect Carba R in BSI Mortality in carba R GNB- BSI Colistin R Klebsiella Water quality monitoring GNB in hospital water Cost of Antibiotics in India Hospital cleaning monitoring in India Infection Vectors Hand Hygiene- historical legacy

3 WHO: Country statistics Germany India USA Population 82.7 million 1.25 billion 320 million GNI/capita (PPP) $ 44,540 $ 5,350 $ 53,960 Life expectancy (M/F) 79/83 yrs 65/68 yrs 76/81 yrs Healthy Life Expectancy Total expenditure on health per capita Total exp on health as % of GDP 71 years 57 years 70 years $4812 $215 $ % 4% 17.1%

4 WHO: Country statistics Germany India USA Doctors/ Nurses/ Access to improved water Access to improved sanitation Hospital beds/ Age standardized mortality rate by cause/100,000 Communicable diseases

5 ESBL and carbapenem resistance Gangaram Hospital, New Delhi (North India): ESBL E. coli in BSI (Blood Stream Infections) increased from 40% in 2002 to 61% in 2009 Carbapenem resistance in BSI increased from 2.4% in 2002 to 52% in Klebsiella pneumoniae Datta S et al. Indian J Med Res 135, June 2012, pp

6 ESBL South India 131 bacteremic patients (62.6% nosocomially acquired), ESBL production was detected in 73.28% of the isolates of E. coli and Klebsiella spp. The commonest source of bacteremia was the urinary tract (45.04%). The 14-day mortality rate was 23.6% J Assoc Physicians India Dec;58 Suppl:13-7.

7 Mumbai (West India): Molecular characterization of carbapenemresistant Enterobacteriaceae bla NDM-1 was the most prevalent carbapenemase and accounted for % (85/113) of the isolates. This was followed by bla OXA [4.42 % (n = 5)] % (21/113) of the isolates possessed dual carbapenemase genes. Eur J Clin Microbiol Infect Dis Mar;34(3):

8 Bhattacharya S.

9

10 Surveillance culture for MDRO detection Stool/ rectal swab- For MDRO GNB/ VRE Throat swab/ sputum- For MDRO- GNB/MRSA Nose swab/ groin swab/ Ulcer or wound swab- For MRSA Principle: culture of bacteria under antibiotic pressure Cefpodoxime Cefoxitin Vancomycin+ meropenem Meropenem ESBL detection MRSA and AmpC detection VRE detection Carbapenemase detection IQC- using CLSI criteria Bacteriology Quality Assurance EQAS- IAMM

11 Infections in Pediatric Oncology: Kolkata, East India In press. Bhattacharyya A. Indian Journal of Cancer

12 Data from Pediatric Blood Stream Infections: Jan 2015-Oct 2015 Tata Medical Center, Kolkata, India

13 Profile of organisms causing blood stream infections Acinetobacter 7% No. of isolates Other GNB 9% Enterococcus 5% Staph aureus 3% Other GPC 31% Candida 2% E. coli 18% Klebsiella 16% Pseudomonas 9% Acinetobacter E. coli Klebsiella Pseudomonas Candida Staph aureus Enterococcus Other GNB Other GPC N= 235; TMC; Dec 2014 to May 2015

14 Carbapenem Resistant Gram Negative Bacilli in Blood stream Infections blood cultures 235- positive BC (13%) 52 BC with carba R GNB (22%) Carba R- 2.9% of all Blood cultures Carba R E. coli Klebsiella Pseudomonas Acinetobacter Total numbers: E. coli= 45 Klebsiella= 41 Pseudomonas= 23 Acinetobacter= 18 Tata Medical Center, Kolkata, India; Dec 2014 to May 2015

15 Antibiotic sensitivity in Gram Negative Bacilli: blood stream infection data E. coli Klebsiella Pseudomonas Acinetobacter Amikacin Pip-taz Meropenem Colistin Tigecy Hospital antibiogram: Tata Medical Center, Kolkata, India : Dec 2014-May 2015

16 Antibiotic sensitivity in Gram Negative Bacilli: blood stream infection data Amikacin Gentamicin Cipro Ceftaz Meropenem E. coli Klebsiella Pseudomonas Acinetobacter Hospital antibiogram: Tata Medical Center, Kolkata, India : Dec 2014-May 2015

17 Organism Mortality from Carba resistant Gram Negative Bacilli Median age (years) Mortality Time to mortality after positive blood culture Time to mortality (Median) E. coli % NA NA Klebsiella pneumoniae Pseudomonas aeruginosa Acinetobacter baumanii Cumulative figures % 3-8 days 4.5 days % 1-5 days 1 day % 1-30 days 4.5 days %; Hemat: 43%; Solid: 26% 1-30 days 3 days N= 40; Tata Medical Center, Kolkata, India : Dec May 2015 data

18 Tata Medical Center, Kolkata, India The number of patients previously receiving colistin before isolation of CRK was 15 (62.5%) of 24. In total, 18 patients survived and 6 died (all cause mortality, 25%). The mean duration of hospital stay after detection of CRK was 17.9 days. Two patients received outpatient care only. The clinical infection types noted included: Sepsis/blood stream infection in 15 patients, pneumonia in 4 patients, Urosepsis in 1 patient, and soft-tissue infection in 1 patient. Three patients had asymptomatic colonization. Twenty (83.3%) of 24 patients had cases that came under the category of HCAI Ten (41.7%) of 24 patients had previous carbapenamase-producing Klebsiella isolated from 1 or more specimens before detection of CRK.

19 Klebsiella and antibiotic resistance: Figures Feb 4 th 2014-Oct 5 th 2015; Tata Medical Center, Kolkata, India Total no of Klebsiella isolated from all cultures-948 No of Klebsiella isolated from blood cultures-173 No of carbapenamase Klebsiella from blood cultures-97 No of colistin resistant Klebsiella isolated-15 No of colistin resistant Klebsiella from blood cultures-3

20 Colistin Resistant Klebsiella: Experience fromtata Medical Center, East India Previous Study June 2013 to Feb 2014 No:- 24 Previous Carbapenamase isolates-41.7% Previous colistin use- 62.5% All cause mortality- 25% This Study Feb 2014 to Oct 2015 No:-15 Previous Carbapenamase isolates % Previous Colistin use- 53.3% All cause mortality-46% Colistin-Resistant Klebsiella pneumoniae: Report of a Cluster of 24 Cases from a New Oncology Center in Eastern India- Gaurav Goel, Lalawmpuia Hmar, Maitrayee Sarkar De, Sanjay Bhattacharya, Mammen Chandy, infection control and hospital epidemiology august 2014, vol. 35, no. 8

21 What is India doing Greater awareness about issues related to antibiotic resistance: Chennai Declaration- IJC; 2013: 50, IJMM;2014: 32 Indian Council of Medical Research: IJMR; 2011: 134 Greater awareness about Infection Control issues especially in Private Hospitals NABH accreditation: Need for better sanitation, water hygiene and notification of GNB associated morbidity and mortality

22 Water quality monitoring Water chlorine level- Colorimeter O-toluidine/ Electronic Target: ppm Ref: WHO Water TDStotal dissolved salt- Conductivity meter; CSSD target<10 mg/l Source: Aesculap Water microbiology Membrane filtration Target: Coliforms- 0/100 ml Pseudomonas- 0/100 ml Ref: WHO, HPA (UK)

23 I n d i a n J o u r n a l o f P a t h o l o g y a n d M i c r o b i o l o g y ( 3 ), J u l y - S e p t

24 Cost of antimicrobial therapy in India Antibiotic Per day cost (adult) 10 day cost (adult) Cefoperazone-sulbactam Rs. 1,492 Rs. 14,920 Piperacillin-tazobactam Rs. 2,028 to Rs. 2,880 Rs. 20,280 to Rs. 28,880 Meropenem Rs. 2,697 to Rs. 7,488 Rs. 26,970 to Rs. 74,880 Colistin Rs. 3,000 to Rs. 5,670 Rs. 30,000 to Rs. 56,700 Tigecycline Rs. 5,600 to Rs. 5,980 Rs. 56,000 to Rs. 59,800 Per capita Gross National Income (PPP, 2013), WHO India $5350 Rs. 3,21,000 Bangladesh $2810 Rs. 168,600 Bhutan $7210 Rs. 7,32,600 Source: ( )

25 Assessment of cleaning Visual observation Ultra-violet light Microbiological assessment Swab culture PCR ATP bioluminescence

26 Infection vectors

27

28

29

30 Conclusion Gram negative pathogens represent a major public health problem in India There are many factors responsible for this problem The areas to focus for improvement: Hygiene and sanitation Proper waste disposal- biomedical and general waste Efficient data collection and its dissemination Regulation on the use of antibiotics Indian J Med Res 134, September 2011, pp

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