Multi-site Gram-negative Surveillance Initiative
Gram-negative bacteria cause infections including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis in healthcare and community settings. Selected gram-negative bacteria are becoming resistant to all or nearly all antibiotics, meaning that patients with infections from these bacteria might have few or no treatment options. Infections due to highly resistant bacteria, such as carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), are mainly associated with healthcare settings and have high death rates, but some resistant bacteria, such as Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, have reportedly increased as a cause of human infection in the community. Data from this tracking project will help scientists understand illness caused by these bacteria and help shape prevention strategies to contain and prevent the spread of resistant bacteria.
In response to growing concerns about resistant gram-negative bacteria, the Emerging Infections Program’s (EIP) Healthcare-Associated Infections Community Interface (HAIC) activity started the Multi-site Gram-negative Surveillance Initiative (MuGSI) in 2011 to:
- Determine the extent of selected resistant gram-negative bacteria in the United States
- Measure trends of disease over time
- Identify people most at risk for illness from these bacteria
- In addition, the project provides infrastructure that allows future research to be done on these and other Gram-negative bacteria.
MuGSI initially conducted active population- and laboratory-based surveillance for CRE and CRAB; however, recent history has shown that new resistant bacteria emerge when new antimicrobials are developed. Therefore, public health surveillance for these resistant bacteria must be dynamic. Consequently, MuGSI expanded the bacteria under surveillance to include CRPA from August 2016 through July 2018; and, starting in July 2019, ESBL-producing Enterobacterales.
- To evaluate the incidence of selected resistant gram-negative bacteria, and to describe changes in incidence over time.
- To characterize selected resistant gram-negative bacteria cases to understand epidemiologic characteristics and risk factors in cases in the areas under surveillance.
- To describe resistance mechanisms and strain types among selected resistant gram-negative bacteria.
Cases are defined as follows:
- CRE: carbapenem-resistant E. coli, Enterobacter cloacae complex species (i.e., E. cloacae, E. asburiae, E. bugandensis, E. hormaechei, E. kobei, E. ludwigii, and E. nimipressuralis), and Klebsiella species (i.e., K. aerogenes, K. oxytoca, K. pneumoniae, and K. variicola) isolated from normally sterile sites or urine (Table 1) from a resident of the surveillance area.
- CRAB: carbapenem-resistant Acinetobacter baumannii complex (A. baumannii, A. baumannii complex, and A. calcoaceticus-baumannii complex [including A. calcoaceticus]) isolated from normally sterile sites or urine (Table 1) from a resident of the surveillance area. Starting in 2021, CRAB surveillance expanded at selected EIP sites to include specimens from the lower respiratory tract and wounds.
- CRPA: carbapenem-resistant P. aeruginosa isolated from normally sterile sites, urine, lower respiratory tract (LRT) specimens, wounds, or cystic fibrosis patient throat swabs from a resident of the surveillance area. HAIC CRPA surveillance ended mid-2018.
- ESBL-producing Enterobacterales: extended-spectrum cephalosporin-resistant E. coli, Klebsiella pneumoniae, Klebsiella variicola, or Klebsiella oxytoca isolated from normally sterile sites or urine (Table 1) from a resident of the surveillance area.
|Normally sterile site*||Yes||Yes||Yes||Yes|
|Lower respiratory tract§||N/A||Yes¶||Yes||N/A|
*Normally sterile site include the following: Blood, cerebrospinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint/synovial fluid, bone, internal body site (lymph node, brain, heart, liver spleen, vitreous fluid, kidney, pancreas, or ovary), muscle, deep tissue or other normally sterile site
§Lower respiratory tract cultures include: Bronchoalveolar lavage, sputum, tracheal aspirate, or other lower respiratory site
†Throat swab cultures include: CRPA cystic fibrosis patient only
¶Lower respiratory tract and wound cultures added for CRAB surveillance at selected EIP sites in 2021
Phenotypic case definitions: The minimum inhibitory concentration (MIC) and zone diameter interpretive criteria produced by the local clinical laboratory’s primary antibiotic testing methodology are used to classify isolates.
- For CRE surveillance, carbapenem resistance is defined as resistance to one or more carbapenems (doripenem, imipenem, meropenem, or ertapenem).
- For CRAB surveillance, carbapenem resistance is defined as resistance to one or more carbapenems (doripenem, imipenem, or meropenem).
- For CRPA surveillance, carbapenem resistance was defined as resistance to one or more carbapenems (doripenem, imipenem, or meropenem).
- For ESBL-producing Enterobacterales surveillance, resistance is defined as resistance to at least one extended-spectrum cephalosporin (ceftazidime, cefotaxime, or ceftriaxone) and non-resistant (i.e., susceptible or intermediate) to all carbapenems tested. The exclusion of carbapenem-resistant isolates ensures lack of duplication with existing MuGSI CRE surveillance.
- The minimum inhibitory concentration (MIC) and zone diameter interpretive criteria produced by the local clinical laboratory’s primary antibiotic testing methodology is used to classify isolates.
Cases are identified based on the local clinical laboratory’s antibiotic susceptibility testing data. Most local clinical laboratories conduct antibiotic testing using an Automated Testing Instrument (ATI). Many of the clinical laboratories within the surveillance catchment area identify the culture results meeting the MuGSI case definitions directly from these ATI systems.
The MuGSI surveillance catchment area consists of selected counties in the following states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee.
|California*†||Alameda, Contra Costa, and San Francisco||N/A||N/A||N/A||N/A||N/A||N/A||Yes||Yes||Yes||Yes||Yes|
|Colorado||Adams, Arapahoe, Denver, Douglas, and Jefferson||N/A||N/A||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
|Georgia||Clayton, Cobb, Dekalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
|Maryland||Baltimore, Baltimore City, Carroll, and Howard||N/A||N/A||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
|Minnesota||Hennepin and Ramsey||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
|Oregon||Clackamas, Multnomah, and Washington||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
|Tennessee‡||Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, and Wilson||N/A||N/A||N/A||Yes||Yes||Yes||Yes||Yes||Yes||Yes||Yes|
¶CRPA surveillance began in August 2016 and ended in July 2018
*California does not participate in CRAB surveillance
†California and Connecticut did not participate in CRPA surveillance
‡CRPA surveillance catchment area in Tennessee only included Davidson county
|Georgia||Clayton and Douglas||N/A||N/A||N/A||N/A||N/A||N/A||N/A||N/A||Yes||Yes||Yes|
|Tennessee||Lewis, Marshall, Maury, and Wayne||N/A||N/A||N/A||N/A||N/A||N/A||N/A||N/A||Yes||Yes||Yes|
#ESBL surveillance began in July 2019
The first carbapenem-resistant Enterobacterales of each species, first carbapenem-resistant Acinetobacter baumannii complex, first extended-spectrum cephalosporin-resistant Enterobacterales of each species, and first carbapenem-resistant Pseudomonas aeruginosa per patient in a 30-day period is eligible for inclusion as an incident case. The date of incident specimen collection is the date the first specimen was obtained for each organism in the 30-day period. If a new specimen meeting the case definition is collected more than 30 days after the patient’s last incident case of the same organism, it is reported as an incident case and a case report form is completed, according to the procedures described in Table 3. If a culture was collected less than 30 days after the patient’s last incident case of the same organism, the case is categorized as a “non-incident” case and a case report form is not completed.
The process for completing case report forms may differ across the EIP sites but primarily consists of trained surveillance epidemiologists reviewing the patient’s medical records to gather information, such as patient demographic characteristics, location of culture collection, types of infections associated with the positive culture, underlying medical conditions, and healthcare exposures.
|Organism||A case report form will be completed for the following:|
|CRE||All incident cases|
|CRAB||All incident cases|
|ESBL||First incident case per species in a patient in a 365-day period and for all incident cases from normally sterile sites (Note: 365-day period is defined as January 1st to December 31st)|
|CRPA*||In surveillance year two, case report forms were completed for the first incident case in a patient in a 365-day period and for all incident cases from normally sterile sites (Note: 365-day period is defined as August 1st to July 31st)|
*CRPA surveillance ended on July 31, 2018
As part of MuGSI, isolates of selected resistant gram-negative bacteria that meet the MuGSI surveillance definitions will be collected by sites and submitted to CDC in order to:
- Characterize antibiotic resistance mechanisms (i.e. phenotypic carbapenemase production, phenotypic ESBL production, and the presence of antibiotic resistance genes) associated with the bacteria under surveillance
- Evaluate antimicrobial susceptibility testing results using a reference method
- Characterize the molecular epidemiology of selected resistant gram-negative bacteria
Additionally, CDC contributes some MuGSI isolates to the AR Isolate Bank.
Bower CW, Fridkin DW, Wolford HM, Slayton RB, Kubes JN, Jacob JT, Ray SM, Fridkin SK. Evaluating Movement of Patients With Carbapenem-resistant Enterobacteriaceae Infections in the Greater Atlanta Metropolitan Area Using Social Network Analysisexternal icon. Clin Infect Dis. 2020 Jan 1;70(1):75-81. doi: 10.1093/cid/ciz154.
Walters MS, Grass JE, Bulens SN, Hancock EB, Phipps EC, Muleta D, Mounsey J, Kainer MA, Concannon C, Dumyati G, Bower C, Jacob J, Cassidy PM, Beldavs Z, Culbreath K, Phillips WE Jr, Hardy DJ, Vargas RL, Oethinger M, Ansari U, Stanton R, Albrecht V, Halpin AL, Karlsson M, Rasheed JK, Kallen A. Carbapenem-Resistant Pseudomonas aeruginosa at US Emerging Infections Program Sites, 2015external icon. Emerg Infec Dis. 2019 Jul;25(7):1281-1288. doi: 10.3201/eid2507.181200.
Karlsson M, Stanton RA, Ansari U, McAllister G, Chan MY, Sula E, Grass JE, Duffy N, Anacker ML, Witwer ML, Rasheed JK, Elkins CA, Halpin AL. Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniae Isolate in the United Statesexternal icon. Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00519-19. doi: 10.1128/AAC.00519-19.
Bulens SN, Yi SH, Walters MS, Jacob JT, Bower C, Reno J, Wilson L, Vaeth E, Bamberg W, Janelle SJ, Lynfield R, Vagnone PS, Shaw K, Kainer M, Muleta D, Mounsey J, Dumyati G, Concannon C, Beldavs Z, Cassidy PM, Phipps EC, Kenslow N, Hancock EB, Kallen AJ. Carbapenem-Nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012-2015external icon. Emerg Infec Dis. 2018 Apr;24(4):727-34. doi: 10.3201/eid2404.171461.
Guh A, Bulens SN, Mu Y, Jacob JT, Reno J, Scott J, Wilson LE, Vaeth E, Lynfield R, Shaw KM, Vagnone PM, Bamberg WM, Janelle SJ, Dumyati G, Concannon C, Beldavs Z, Cunningham M, Cassidy PM, Phipp EC, Kenslow N, Travis T, Lonsway D, Rasheed JK, Limbago BM, Kallen AJ. Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013external icon. JAMA. 2015 Oct 13;314(14):1479-87. doi: 10.1001/jama.2015.12480.
Chea N, Bulens SN, Kongphet-Tran T, Lynfield R, Shaw KM, Vagnone PS, Kainer MA, Muleta DB, Wilson L, Vaeth E, Dumyati G, Concannon C, Phipps EC, Culbreath K, Janelle SJ, Bamberg WM, Guh AY, Limbago B, Kallen AJ. Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae. Emerg Infect Dis. 2015 Sep;21(9):1611-1615. doi: https://dx.doi.org/10.3201/eid2109.150198.
Reno J, Schenck C, Scott J, Clark LA, Wang YF, Ray S, Vagnone P, Jacob JT. Querying automated antibiotic susceptibility testing instruments: a novel population-based active surveillance method for multidrug-resistant gram-negative bacilliexternal icon. Infect Control Hosp Epidemiol. 2014 Apr;35(4):336-41. doi: 10.1086/675608.
Shaw KM, Harper JE, Vagnone PS, Lynfield R. Establishing Surveillance for Carbapenem-resistant Enterobacteriaceae in Minnesota, 2012external icon. Infect Control Hosp Epidemiol. 2014 Apr;35(4):451-3. doi: 10.1086/675615.
Pereira EC, Shaw KM, Vagnone PM, Harper JE, Kallen AJ, Limbago BM, Lynfield R. Thirty-day laboratory-based surveillance for carbapenem-resistant Enterobacteriaceae in the Minneapolis-St. Paul metropolitan areaexternal icon. Infect Control Hosp Epidemiol. 2014 Apr;35(4):423-5. doi: 10.1086/675602.
Pfeiffer CD, Cunningham MC, Poissant T, Furuno JP, Townes JM, Leitz A, Thomas A, Buser GL, Arao RF, Beldavs ZG. Establishment of a statewide network for carbapenem-resistant Enterobacteriaceae prevention in a low-incidence regionexternal icon. Infect Control Hosp Epidemiol. 2014 Apr;35(4):356-61. doi: 10.1086/675605.
CDC. Vital signs: Carbapenem-Resistant Enterobacteriaceae. Morb Mortal Wkly Rep. 2013 Mar 5;62(9):1-6.
- Antibiotic/Antimicrobial Resistance
- Antibiotic Prescribing and Use
- Be Antibiotics Aware
- World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistanceexternal icon
- Transatlantic Taskforce on Antimicrobial Resistance
- European Committee on Antimicrobial Susceptibility Testingexternal icon
- Canadian Integrated Program for Antimicrobial Resistance Surveillanceexternal icon
- Carbapenem-resistant Enterobacterales in Healthcare Settings
- General information about CRE
- Tracking CRE
- AHRQ CRE Control and Prevention Toolkitexternal icon