Reducing the Burden of Severe Sepsis and Infections in Indian ICUs J.V. Divatia Professor & Head Department of Anaesthesia, Critical Care & Pain Tata Memorial Hospital Mumbai India
Infections in the ICU Sepsis and multiple organ failure is the commonest cause of death in ICU s ICU patients are 5-10 times more prone to infection Increased nosocomial infections Infections with resistant strains
Absence of national agency to survey and report on nosocomial inffections Absence of effective national or statewide antimicrobial policy Community Hospital Widespread use of oral QN and Ceph Free availability of OTC antibiotics Self-medication by patients Availability of cheap generics of variable potency and quality Spread by crowding and poor sanitary conditions. ICU Predominance of open ICUs Failure to implement or adhere to infection control protocols Prolonged use of broad-spectrum antibiotics Inadequate staffing, especially nurses Lack of hospital-wide infection control or antibiotic policies Extensive empirical use of cephalosporins in hospitals and ICUs Prolonged use of antimicrobial prophylaxis in surgical patients Failure to restrict privileges to prescribe major antibiotics
Severe Sepsis is Increasing in Incidence Sepsis Cases (x10 3 ) 1,800 1,600 1,400 1,200 1,000 800 Severe Sepsis Cases US Population 600 500 400 300 Total US Population (million) 2001 2025 2050 Year Angus DC, et al. JAMA 2000;284:2762-70. Angus DC, et al. Crit Care Med 2001;29:1303-10.
Sepsis is a Medical Emergency Title: This is the footer Date: 13th September 2012 Slide no: 5
Severe Sepsis Incidence and Mortality Rate per 100,000 Population 300 250 200 150 100 50 0 Incidence Mortality Severe Sepsis Stroke Breast Cancer Lung Cancer * Calculated data based on information compiled from the American Heart Association, American Cancer Society, National Center for Health Statistics and the US Census Bureau (1995-1999) Severe sepsis mortality rates range from 28%-50% (79/100,000 to 141/100,000 population).
Sepsis : A neglected but common entity Title: This is the footer Date: 13th September 2012 Slide no: 7
Reducing the Global Burden of Sepsis Title: This is the footer Date: 13th September 2012 Slide no: 8
EPIC-II INDIA Total Patients 13796 533 Total ICUs 1265 39
EPIC II India 39 ICUs, 533 patients from India Infected 213 (40%) ICU Mortality 13.4% Hospital Mortality 17.2% Central and South America had the highest infection rate (60%) Africa had the lowest (46%)
Microorganisms Microorganisms (%) EPIC-II India Positive isolates 69.8 63.4 Gram-positive 46.8 23 Gram-negative 62.2 77.8 Anaerobes 4.5 0.7 Fungi 19.0 8.1 Viral/Parasitic 0.7 5.1 Other bacteria 1.5 3 Other organisms 3.9 2.2
Types of organisms Microorganisms % EPIC-II All India Gram-positive Staphylococcus aureus 20.5 10.4 MRSA 10.2 3.7 S. epidermidis 10.8 0.7 S. pneumoniae 4.1 1.5 Enterococcus 11.0 5.9 Others 6.4 5.9 Gram-negative E. coli 16.0 21.5 Enterobacter 7.0 1.5 Klebsiella spp 12.7 23.7 Pseudomonas spp 19.0 33.3 Acinetobacter spp 8.8 16.3 *P < 0.05 vs Western India
Types of organisms Microorganisms % EPIC-II All India Others 17.0 6.7 Anaerobes 4.5 0.7 Other bacteria 1.5 3 Fungi Candida 17.0 6.7 Aspergillus 1.4 2.2 Others 1.0 0.7 Parasites 0.7 1.5 Other organisms 3.9 5.9
International Nosocomial Infection Control Consortium MISSION: An International scientific community that works interactively through a network aiming at reducing healthcareassociated infections in developing countries Non Profit Organization Collects and analyses infection related data from the developing countries and prepares a report which is sent to the ICU Publishes data in high quality journals
HCAIs Indian Data 12 ICUs of 7 Indian cities Prospective surveillance from July 2004 to March 2007 10 835 patients hospitalized for 52 518 days 476 HCAIs, 4.4% or 9.06 HCAIs/1000 ICU-days CVC-BSI rate 7.92/ 1000 catheter-days Excess mortality 4% VAP rate10.46 / 1000 ventilator-days Excess mortality 19% CAUTI rate 1.41 /1000 catheter-days Excess mortality 11.6%
Antibiotic Resistance Overall 87.5% of all Staphylococcus aureus HCAIs were caused by MRSA Enterobacteriaceae resistance 71.4% resistant to ceftriaxone 26.1% to piperacillin-tazobactam Pseudomonas aeruginosa resistance 28.6% resistant to ciprofloxacin 64.9% to ceftazidime 42.0% to imipenem
Antimicrobial Resistance at TMH Pseudomonas sp
Antimicrobial Resistance at TMH E. Coli & Klebsiella sp
Indian Intensive Care Case Mix and Practice Patterns Study July 14, 2010; October 13, 2010; January 12, 2011, April 13, 2011
INDICAPS Study Design Multicenter, All-India observational, one-day prevalence study, performed on four separate days Inclusion criteria All patients present in the ICU on the second Wednesdays of July and October 2010, January and April 2011 July 14, 2010 October 13, 2010 January 12, 2011 April 13, 2011 Data of all patients in the ICU for the 24 hours starting 0800 am to 0800 am next day.
Severe Sepsis or Septic Shock Severe Sepsis / Septic Shock was diagnosed in 1144 patients (28.3%) Males 725 (63.4%), Females 419 (36.6%) Infection developed in ICU in 235 patients (20.5%) Characteristic Patients Age APACHE II SOFA ICU Mortality Severe Sepsis / Septic Shock 1144 (28.3%) 53.8 ± 17.7 20.0 ± 8.4 ** 5.9 ± 4.3** 42.1% ** No severe Sepsis 2894 (71.7%) 54.2 ± 17.7 16.9 ± 7.9 2.6 ± 2.9 17.6% ** : p=0.000
Patients with Tropical Infections vs. Others with Severe Sepsis / Septic Shock Tropical Infection N = 231 (20.2%) No Tropical Infection N=913 (79.8%) Age 46.2 ± 17.9 55.7 ±17.2** APACHE II 16.4 ± 7.5 20.9 ± 8.3 ** Acute Physiology 14.0 ± 7.0 16.1 ± 7.2** Score SOFA 6.3 ± 4.3 5.8 ± 4.3 ICU Mortality 71 (30.7%) 411 (45.0%)** ** : p=0.000
Microorganisms Identified Fungi 8 % Gm Pos 17 % Micro-organisms Cultures sent in 909 patients (79.5%) Virus 1 % Mycobact 2 % Gm Neg 69% Positive in 368 / 909 patients (40.5%) 576 organisms identified Polymicrobial cultures in 140 / 368 positive cultures (38%)
Major Microorganisms (n=576) Gram Negatives N =400 (69.4%) Gram Positives N = 98 (17%) Pseudomonas aeruginosa 92 (23%) MRSA 22 (22.4%) MSSA 17 (17.3%) Pseudomonas spp 13 (3.2%) Acinetobacter spp 89 (22.3%) Klebsiella spp 84 (21%) E. Coli 76 (19%) Fungi n=44 Candida albicans 27 (61.4%) Candida non-albicans 15 (34.1%) Enterococcus 14 (14.3%) (Vancomycin sensitive) MR-CNS 13 (13.3%) MS-CNS 9 (9.2%) Strep. pneumoniae 7 (7.1%) MR: Methicillin resistant; MS: methicillin sensitive SA: staph. aureus; CNS: coagulase negative staph.
Antibiotic use No. of antibiotics given % patients 40 35 30 25 20 15 10 5 0 0 1 2 3 4 34,6 27,4 20,5 9,8 7,8 No. of Antibiotics 1032 (90.2%) patients were receiving antibiotics on the study day Patients received a median of 2.0 (IQR 1,3) or mean of 1.9 ± 1.1 antibiotics
Antibiotics Used Tigecycline Colistin / 4% Polymixin B Quinolones 9% 14% Penicillins 24% Other 20% Macrolides 5% Linezolid 6% Antifungal 13% Carbapenems 30% Cephalosporins 27% Glycopeptide 15% Aminoglycoside 8% AntiTB 1 % Antimalarial 5% Antiviral 3% Aztreonam 2%
Antifungals (154) Major Antibiotics used Fluconazole 56%, Caspofungin13%, Amphotericin B 10% Cephalosporins (309) Ceftriaxone 34%, Cefoperazone-sulbactam 28% Penicillins (272) Piperacillin-tazobactam 72% Carbapenems (346) Meropenem 66%, Imipenem 25% Glycopeptides (177) Teicoplanin 70%, Vancomycin 30% Levofloxacin (111 / 155), 72% of Quinolones Colistin / Polymixin B (108)
Management of Severe Sepsis Antibiotics for primary infection Percutaneous or surgical drainage High-quality intensive care Modulate inflammatory response Prevent secondary infections Exogenous & endogenous
Antibiotic Therapy in Sepsis Start early, after obtaining samples for C/S Intravenous Adequate doses Broad-spectrum Initially empirical Specific therapy after C/S De-escalate whenever possible
Consequences of Overdiagnosis of Sepsis Inappropriate use of antibiotics Increases costs Risk of adverse drug reactions Selects for resistant microbial flora increase morbidity and mortality Incorrect diagnosis can engender a false sense of security Distract a clinician from finding and treating the true cause of a patient s clinical deterioration JAMA 2007; 297:1583-93
Broad-Spectrum Antibiotics Creating problems Kill harmful organisms, and several other non-pathogenic ones as well Negative culture reports Overgrowth of Cl. difficile Overgrowth of fungi Selects out resistant organisms Induces resistance
Antimicrobial Stewardship Strategies Education Clinical guidelines Antimicrobial restriction Preprescription approval Prospective audit and feedback Postprescription review Computer-based decision support Antibiotic cycling?
Optimising antimicrobial therapy Avoid prolonged Prophylactic Antibiotics Combination therapy Dose and route PK / PD principles De-escalation Duration of therapy Biomarker guided therapy : procalcitonin Patenteral to oral conversion
Concentration Cmax / MIC Cmax (Peak) AUC T >MIC Concentration dependent Time Aminoglycosides dependent B-lactams Metronidazole Carbapenems Daptomycin Linezolid Erythromycin Conc and Time Lincosamines Dependent Fluoroquinolones Glycopeptides Tigecycline MIC Time (Hours)
Barriers to De-escalation Negative blood / other cultures. 40-60% of blood cultures may be negative Positive cultures : colonization or infection? Contaminants Errors in collection of samples Quantitative instead of Non quantitative cultures No clinical improvement Clincal improvement Why change a winning team? Role of biomarkers Advanced molecular diagnostic techniques
Bundles of Care Concept of bundles developed by IHI Help health care providers more reliably deliver the best possible care for patients undergoing particular treatments with inherent risks Structured way of improving the processes of care and patient outcomes A small, straightforward set of evidencebased practices generally three to five that, when performed collectively and reliably, have been proven to improve patient outcomes
Sepsis Resuscitation Bundle 1. Serum lactate measured Goals in the first 6 hours 2. Blood cultures obtained prior to antibiotics 3. From the time of presentation, broad-spectrum antibiotics administered within 1 hour In the event of hypotension and/or lactate >4 mmol/l 4. Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent*) 5. Vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP 65 mm Hg 6. Achieve CVP of 8 mm Hg 7. Achieve ScvO 2 of 70%
Sepsis Management Bundle Goals over 24 hours Low-dose steroids administered for refractory septic shock not responding to fluids and vasopressor therapy Glucose control maintained lower limit of normal, but < 180 mg/dl Inspiratory plateau pressures maintained < 30 cm H 2 O for mechanically ventilated patients
Management of Sepsis in Indian ICUs Indian Data from the MOSAICS Study Management of Sepsis in Asia s Intensive Care Units India Co-ordinator : JV Divatia BMJ 2011;342:d3245
MOSAICS Study Prospective, observational non-interventional study 1285 patients recruited, 16 countries, 148 ICUs All consecutive patients with severe sepsis in July 2009 Excluded patients < 21yrs Transferred from another hospital or from another ICU Previously admitted to the ICU for severe sepsis Primary Outcome Compliance with the 6-hour and 24-hour bundles Secondary Outcome All-cause in-hospital mortality
MOSAICS Study Asia India No. Of ICUs 150 17 No. of Patients 1285 162 APACHE II 22.8 ± 8.7 21.9 ± 8.4 Hospital mortality 44.9% 38.3%
Overall Bundle Compliance India % Compliance 100 90 80 70 60 50 40 30 20 10 0 Resus Bundle 6,8 8 Management Bundle 13 Mx Bundle without apc 2,5 Both (without apc)
Compliance with Sepsis Bundles Asia Compliance (%) 20 18 16 14 12 10 8 6 4 2 8.5 2.6 8.5 6-hr bundle 24-hr bundle 24-hr bundle less apc 13.7 13 8 6.8 4.9 1 7.5 4.2 10.8 18 3.1 14.8 11.4 11.8 10.9 2.4 2.7 2.1 0 China Hong Kong India Malaysia Singapore South Korea Others
INICC - Process Surveillence Hand Hygeine Care to prevent Nosocomial Pneumonia Vascular Catheter Care Urinary Catheter Care
Care to Prevent Nosocomial Pneumonia Elevation of the Head of the Bed (30-45 degrees) Tubings / Water traps free of fluid and secretions Absent air leak around cuff Smooth enteric nutrition Aseptic Aspiration technique
Care to prevent CLABSI Date of Catheter Insertion Correct condition of dressing Sterile Dressings for peripheral lines Use needleless intravascular catheter access systems avoid stopcocks. Closed catheter access systems should be preferred to open systems.
Process Surveillance Forms Vascular Catheter Care Correct condition of dressing - well coated - clean - no fluid collection Date of Catheter Insertion
Process Surveillance Forms Urinary Catheter Care Catheter over thigh Level of the urine bag below level of the bladder Urine bag should not have floor contact
Effectiveness of a multidimensional approach for prevention of VAP in adult ICUs from 14 developing countries of 4 continents: INICC findings 55,507 patients in 44 ICUs in 38 hospitals Before and after study Intervention: bundle of infection-control interventions Education outcome surveillance process surveillance feedback of VAP rates performance feedback of infection-control practices. Crit Care Med 2012
INICC Multidimensional aproach to prevent VAP Results Phase 1 VAP rate 22.0 per 1,000 mechanical ventilator days Phase 2 VAP Rate 17.2 per 1,000 mechanical ventilator days 55.83% reduction in the rate of VAP after the intervention Crit Care Med 2012
Research Opportunities Diagnosis of Sepsis Empirical Antibiotics Optimal Dosing Deescalation Differentiate non-infectious conditions: Biomarkers (procalcitonin) Rapid accurate diagnosis incl fungi, viruses Rapid culture, Molecular / PCR, microarrays, other Identify resistant patterns ESBL +ve, carabapenemase, MBL, MRSA, VRE, New drugs! Therapeutic drug monitroing Point of care tests Rapid drug assays Diagnosis of absence of infection Biomarkers
Research Opportunities Develop effective strategies for communication, dissemination and implementation of guidelines Develop simple effective strategies to prevent nosocomial infections Bundles INICC strategy Nationwide surveillance of antimicrobial therapy, AMR Nationwide Process surveillance Hand hygiene Monitoring and feedback