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Introduction The Need for SMART Antimicrobial Therapy • Antimicrobial resistance worldwide is a growing challenge to effective treatment. • There are few new antibiotic agents to meet the demand. 1 • To preserve their long term effectiveness, it is important to use available antibiotics wisely. • Antimicrobial surveillance is a critical tool to guide sensible treatment recommendations on an institutional or regional level 1 Boucher HW, et al. Clin Infect Dis (2009)48(1):1-12. SMART Study supports a key recommendation of the Center for Global Development’s Drug Resistance Working Group • Improve surveillance by collecting and sharing resistance information across networks of laboratories http://www.cgdev.org/content/publications/detail/1424207 What Is SMART? • Sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA, the Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance study monitoring the in vitro susceptibility of intra-abdominal aerobic and facultatively anaerobic gram- negative bacilli. The study was initiated in 2002 and is ongoing. 1,2 1 Chow JW, et al. Surg Infect (Larchmt). 2005;6(4):439–448. 2 Baquero F, et al. Surg Infect (Larchmt). 2009;10(2):99–104. 3 Badal R, et al. Trends in susceptibility of gram-negative pathogens isolated from intra-abdominal infections in Europe from 2003 to 2007—the SMART study. Poster presented at: 19th Annual European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); 16–19 May 2009; Helsinki, Finland. Study Objectives 1 • To monitor the in vitro susceptibility of clinical bacterial isolates to antimicrobials in complicated intra-abdominal infections and complicated urinary tract infections worldwide • To identify early changes in susceptibility patterns of community- or hospital- acquired organisms, including those that produce extended-spectrum β-lactamases (ESBLs) 1 Chow JW, et al. Surg Infect (Larchmt). 2005;6(4):439–448. SMART Study: 175 Global Centers (2010) Spain (11) Italy (4) Korea (1 Philippines Switzerland (1) Germany (5) Taiwan (8 China USA (25) Turkey (4) Guatemala (2) Argenna (2) Brazil (6) Peru (2) Venezuela (3) Mexico (4) Puerto Rico (2) Portugal (3) New Zealand (4) Greece (2) Israel (2) Colombia (4) Lithuania (1) Estonia (1) South Africa (4) France (4) Panama (2) United Kingdom (5) Latvia (1) Thailand Vietnam ( Malays Singapore (2) India (8) Hong Ko Dom. Rep. (1) Canada (9) Jordan (2) Ecuador (2) Romania (2) Australia (4) Saudi Arabia (2) UAE (1) Global Growth in Number of Sites: Snapshots from 2002, 2005 & 2010 0 10 20 30 40 50 60 2010 2005 2002 Asia Pacific EU, ME, Africa North America Latin America A Private Sector Approach to Surveillance of Antimicrobial Resistance: The SMART Study Walter L. Straus, MD MPH, 1 Robert E. Badal, BS 2 1 Global Center for Scientific Affairs, MSD, 2 IHMA, Inc. Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights Reserved Study Methods 1 • Isolates are identified to the species level and are shipped and tested at a central study laboratory. 1,2 • Each site contributes up to 150 (100 from IAI, 50 from UTI) isolates of facultative gram-negative bacilli (from different patients) with intra- abdominal infections – Include unique initial isolates – Urinary tract infection isolates collected since 2009 • Community-acquired and nosocomial infections defined – Isolates recovered when hospitalization was <48 hours considered community acquired – Isolates recovered after ≥48 hours of hospitalization considered hospital acquired • Micro-broth dilution method for detection – Tryptic Soy Broth with Glycerol and Chocolate Agar Slants for the storage and shipping of isolates • A centralized database of SMART study findings is maintained by International Health Management Associates, Inc, of Schaumburg, IL. 3 1 Chow JW, et al. Surg Infect (Larchmt). 2005;6(4):439–448. 2 Baquero F, et al. Surg Infect (Larchmt). 2009;10(2):99–104. 3 Badal R, et al. Trends in susceptibility of gram-negative pathogens isolated from intra-abdominal infections in Europe from 2003 to 2007—the SMART study. Poster presented at: 19th Annual European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); 16–19 May 2009; Helsinki, Finland. Organism Report Forms • Easy to use forms • Optical Character Recognition (OCR) reads the forms with high accuracy rates • Allows for rapid data reporting • Labeling system for storage and shipping media built in for convenience Antibiotics Panel 1,2,a Ampicillin/sulbactam b Imipenem/cilastatin Piperacillin/tazobactam Cefoxitin Amikacin Cefotaxime d Ciprofloxacin Ceftazidime Levofloxacin c Ceftriaxone Ertapenem Cefepime a Meropenem and tobramycin removed from test panel in 2005. b Ampicillin/sulbactam removed from test panel in 2003 and 2004. Returned to test panel in 2005 onward. c Levofloxacin added to test panel in 2003. d Cefotaxime added to test panel in 2005. 1 Chow JW, et al. Surg Infect (Larchmt). 2005;6(4):439–448. 2. Bochicchio GV, et al. Surg Infect (Larchmt). 2006;7(6): 537–545. The SMART Online Resource: www.globalsmartsite.com • Direct access to regional data • List of study publications • Webcasts for investigators • Useful resources/tools • Access to data tool for investigators The SMART e-Map: www.globalsmartsite.com • Dynamic interactive map provides instant access to: – Regional data for North America, Latin America, Middle East/Africa, Europe, and Asia/Pacific – Recent susceptibility data for Enterobacteriaceae, E coli, and K pneumoniae – ESBL-positive rates/trends SMART Study: Distribution of Enterobacteriaceae Worldwide (2009) a 4.3% 4.7% 55.5% 1.9% 2.1% 2.6% 7.1% 18.1% 3.7% E coli K pneumoniae E cloacae P mirabilis K oxytoca C freundii E aerogenes M morganii Other a In 2009, both intraabdominal infection (IAI) and urinary tract infection (UTI) isolates were collected (IAI=9173;UTI=1201). SMART Study: Prevalence of ESBL-Positive E coli Worldwide, 2002 to 2009 a 0 10 20 30 40 50 60 2002 2003 2004 2005 2006 2007 2008 2009 Percentage of ESBL-Positive E coli Europe Middle East/Africa Asia/Pacific Latin America North America Worldwide a In 2009, both intraabdominal infection (IAI) and urinary tract infection (UTI) isolates were collected. SMART Study: Susceptibility of ESBL-Positive E coli in Asia/Pacific, 2002 to 2009 0 20 40 60 80 100 ETP IMP CPE CFX CAZ CAX A/S P/T AK LVX CP Percentage of Isolates 2002 (n=49) 2003 (n=89) 2004 (n=68) 2005 (n=144) 2006 (n=264) 2007 (n=574) 2008 (n=426) 2009 (n=659) a a In 2009, both intraabdominal infection (IAI) and urinary tract infection (UTI) isolates were collected (IAI=578; UTI=81). ETP=ertapenem; IMP=imipenem; CPE=cefepime; CFX=cefoxitin; CAZ=ceftazidime; CAX=ceftriaxone; A/S=ampicillin/ sulbactam; P/T=piperacillin/tazobactam; AK=amikacin; LVX=levofloxacin; CP=ciprofloxacin. SMART Study: Susceptibility of ESBL-Positive and ESBL-Negative K pneumoniae in Asia/Pacific Region IAI, 2007 1 0 10 20 30 40 50 60 70 80 90 100 Percentage of Isolates ETP IMP AK CPE CFT CFX CAZ CAX CP LVX P/T A/S ESBL-Negave (n=339) ESBL-Posive (n=189) ETP=ertapenem; IMP=imipenem; AK=amikacin; CPE=cefepime; CFT=cefotaxime; CFX=cefoxitin; CAZ=ceftazidime; CAX=ceftriaxone; CP=ciprofloxacin; LVX=levofloxacin; P/T=piperacillin/tazobactam; A/S=ampicillin/sulbactam. 1 Hawser SP, et al. Antimicrob Agents Chemother. 2009;53(8):3280–3284. SMART Study: Frequency of ESBL-Positive Isolates by Country (Asia-Pacific Region), 2007 1 0 10 20 30 40 50 60 70 80 90 100 Percentage of ESBL-Posive Isolates India China Thailand Vietnam Singapore South Korea Hong Kong Philippines Taiwan Australia New Zealand A/P Overall E coli K pneumoniae K oxytoca a (n=1368) (n=528) (n=51) A/P = Asia/Pacific 1 Hawser SP, et al. Antimicrob Agents Chemother. 2009;53(8):3280–3284. SMART Study: Susceptibility of Community- and Hospital-Acquired ESBL-Positive K pneumoniae in China IAI, 2007 1 0 10 20 30 40 50 60 70 80 90 100 Percentage of Isolates AK A/S CPE CFT CFX CAZ CAX CP ETP IMP LVX P/T Community- Acquired (n=21) Hospital- Acquired (n=18) a a Drugs with statistically significant differences (P<0.05). AK=amikacin; A/S=ampicillin/sulbactam; CPE=cefepime; CFT=cefotaxime; CFX=cefoxitin; CAZ=ceftazidime; CAX=ceftriaxone; CP=ciprofloxacin; ETP=ertapenem; IMP=imipenem; LVX=levofloxacin; P/T=piperacillin/tazobactam. 1 Badal R, et al. Comparison of ESBL rates and antimicrobial susceptibility in Escherichia coli and Klebsiella pneumoniae isolated from community- and hospital-onset intra-abdominal infections in China and India—SMART 2007. Poster presented at: 7th International Symposium on Antimicrobial Agents and Resistance (ISAAR);18–20 March 2009; Bangkok, Thailand. Strengths • Global scope (>40 countries) • Large number of sites (>200) • Systematic sample • Centralized laboratory processing (since 2008) • Results well-disseminated (~20 published manuscripts, and ~45 posters) • User-friendly internet database provides flexible real-time data analysis • Clinical Laboratory Standards Institute (CLSI) used SMART findings to revise susceptibility thresholds for ertapenem with Enterobacteriaceae infections • Recent addition of molecular characterization offers insight into meechanisms of resistance Limitations • Until 2008, susceptibility testing was performed by participating labs using common protocol and microbroth dilution test panels (vs. a single central study laboratory) • Some regions (Africa) and countries are under-represented – Small number of sites in these countries limits generalizability • Not all sites contribute 100 IAI isolates/year – Similar to most laboratory surveillance systems, success is dependent on the level of interest, capability, and volume at the site level The Value of SMART • In-depth analysis of susceptibility patterns by pathogen. – Allows for local/worldwide analysis. – Identifies differences in community- vs hospital-acquired infections. • Timely, comprehensive data promote informed, evidence-based choices. – An important adjunct to local institutional antibiogram data. – May help identify the best options when facing resistance. • Insight into the local and regional distribution of gram-negative pathogens. – Allows tracking of prominent pathogens over time. Summary • Merck/MSD has supported development of one of world’s largest surveillance studies of antimicrobial resistance • Has provided country, regional, and global data to inform guideline development and clinical decision-making • Open platform provides significant research opportunity for local investigators Acknowledgments Thanks to the SMART investigators around the world, whose efforts make this program possible. Selected references In vitro susceptibilities of aerobic and facultative anaerobic gram-negative bacilli isolated from patients with intra-abdominal infections at a medical center in Taiwan: results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) 2002-2006. Chen W-Y, Jang T-N, Huang C-H, Hsueh P-R. J Microbiol Immunol Infect. 2009;42(4):317-323. In vitro susceptibilities of aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Hsueh P-R, Snyder TA, DiNubile MJ, et al; 2004 Asia-Pacific SMART Team. Int J Antimicrob Agents. 2006;28(3):238-243. Evolution of antimicrobial susceptibility patterns of aerobic and facultative gram-negative bacilli causing intra-abdominal infections: results from the SMART studies 2003-2007. Guembe M, Cercenado E, Alcalá L, et al. Rev Esp Quimioter. 2008;21(3):166–173. In vitro susceptibilities of aerobic and facultatively anaerobic gram-negative bacilli isolated from patients with intra- abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Rossi F, Baquero F, Hsueh P-R, et al. J Antimicrob Chemother. 2006;58(1)205-210. Results
