Phase IV assisted laboratories in detecting antimicrobial resistance through a better understanding of bacterial resistance mechanisms and through better detection methods.

The current phase, Phase V, links as well with laboratories and colleagues inside and outside the United States in a project to coordinate and strengthen global efforts to recognize new multi-drug resistant bacterial pathogens so that the impact of their anti-infective drug resistance can be assessed. A major focus of the project now is "rogue resistance determinants." As defined by Dr. Tenover (ASM News, September 2004, pages 392-3), rogue antibiotic resistance genes are those determinants that are:
• Mobile
• Compromise well-established therapeutic regimens
• Are difficult to detect in the clinical laboratory (or public health laboratory)
• Have a significant public health effect

Currently, Phase V of Project ICARE focuses on continued collection of fresh bacterial isolates, study of susceptibility testing and typing problems related to the spread of methicillin-resistant Staphylococcus aureus (MRSA) strains both in healthcare and community settings, epidemiologic analyses of integron-related and other molecular determinants of resistance, and diagnostic problems associated with multi-drug resistant gram-negative aerobic bacilli. Based on findings from these priority study areas, targeted educational programs are being developed and disseminated to help laboratories improve testing of these problem organisms The findings will be presented at national and international meetings, and published in the medical literature, as cooperative projects of CDC, Emory, and the individual participating laboratories, with appropriate joint authorship.

Study Period	2005-2006
Number of Participants	Selected U.S. hospital laboratories, Selected international laboratories
Study Objectives	Evaluate current antimicrobial resistance detection methods, focusing on newly-emerging resistant bacteria of clinical importance that represent a potential problem for laboratory testing and the reporting of antimicrobial susceptibility results. Identify for these organisms the drug/organism combinations for which the detection of resistance pose a problem for clinical and public health laboratories. For these target drug/organism combinations, Define methods of resistance and epidemiology through the use of current molecular and typing methods. Fine tune current methods, and/or develop new detection methods that are practical and affordable for clinical and public health laboratories. Provide web-based education on these procedures for clinical and public health laboratories, synchronized with other laboratory educational efforts.
Methodology	Participating laboratories collected certain bacteria selected for clinical relevance and the potential for problems in detection or reporting of antimicrobial resistance. Isolates sent to the Project ICARE Central Laboratory at RSPH where they are frozen and then tested by the NCCLS broth microdilution reference method. Molecular characterization and typing of isolates pursued at the Project ICARE Central Laboratory, CDC, or the originating laboratory. When indicated by above studies, current methods modified, or new methods are developed, to make detection and reporting of resistance more accurate, practical, and/or cost-effective. Recommended changes disseminated through targeted educational programs to help laboratories improve testing and reporting. The changes were shared with regulatory and professional societies and organizations.
Focus for Isolate Collection (2005-2006)	Staphylococcus aureus with decreased susceptibility to vancomycin, linezolid, daptomycin, or quinupristin/dalfopristin Staphylococcus aureus strains prominent in healthcare or the community. Enterobacteriaceae with decreased susceptibility to extended-spectrum cephalosporins, fluoroquinolones, or carbapenems.
Funding Sources (Januray, 2005 - present)	Unrestricted research grants to the Rollins School of Public Health of Emory University from: Abbott Laboratories. Abbott Park, IL AstraZeneca Pharmaceuticals, Wilmington, DE bioMerieux, Incorporated, Durham, NC Elan Pharmaceuticals, Inc. 3M Healthcare Markets, Medical Division, St. Paul, MN Pfizer Incorporated, New York, NY
Additional Notes	Each participating laboratory received financial assistance from Project ICARE to assist with identification, processing, and shipment of the target resistant organisms.

PHASE V OF PROJECT ICARE IS SPONSORED IN PART BY: