Multi-site Gram-negative Surveillance Initiative

Overview

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.
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Background

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.

Surveillance Objectives

  1. To evaluate the incidence of selected resistant gram-negative bacteria, and to describe changes in incidence over time.
  2. To characterize the epidemiologic characteristics and risk factors associated with selected resistant gram-negative bacteria.
  3. To describe resistance mechanisms and strain types among selected resistant gram-negative bacteria.

Methods:

Case Definition

Cases are defined as follows:

  • CRE: carbapenem-resistant E. coli, Enterobacter cloacae complex species (i.e., E. cloacae, E. asburiae, E. bugandensis, E. cancerogenus, 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.

Table 1. Specimen sources that meet the case definition, by organism

Table 1. Culture sources that meet the case definition, by organism
Specimen source CRE CRAB CRPA ESBL
Normally sterile site* Yes Yes Yes Yes
Urine Yes Yes Yes Yes
Lower respiratory tract§ N/A Yes Yes N/A
Wound N/A Yes Yes N/A
Throat swab N/A N/A 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 specimens include: Bronchoalveolar lavage, sputum, tracheal aspirate, or other lower respiratory site

†Throat swab specimens 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.

Case Ascertainment

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 specimen results meeting the MuGSI case definitions directly from these ATI systems.

Surveillance Areas

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.

Table 2. MuGSI surveillance area, by state and county, 2011-2022

Catchment area for CRE, CRAB, and CRPA surveillance by Year
State County 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
California*† Alameda, Contra Costa, and San Francisco N/A N/A N/A N/A N/A N/A Yes 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 Yes
Connecticut† All counties N/A N/A N/A N/A N/A N/A N/A 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 Yes
Maryland Baltimore, Baltimore City, Carroll, and Howard N/A N/A Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Minnesota Hennepin and Ramsey Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
New Mexico Bernalillo N/A N/A Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
New York Monroe N/A N/A 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 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 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

Catchment area for ESBL surveillance by Year
State County 2011 2012 2013 2014 2015 2016 2017 2018 2019# 2020 2021 2022
Colorado Boulder N/A N/A N/A N/A N/A N/A N/A N/A Yes Yes Yes Yes
Georgia Clayton and Douglas N/A N/A N/A N/A N/A N/A N/A N/A Yes Yes Yes Yes
Maryland Baltimore City N/A N/A N/A N/A N/A N/A N/A N/A Yes Yes Yes Yes
New Mexico Bernalillo N/A N/A N/A N/A N/A N/A N/A N/A Yes Yes Yes Yes
New York Monroe N/A N/A N/A N/A N/A N/A N/A N/A Yes 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 Yes

#ESBL surveillance began in July 2019

Surveillance strategy

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 specimen 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 specimen collection, types of infections associated with the positive specimen, underlying medical conditions, and healthcare exposures.

Table 3. Procedures for completing case report forms, by organism

Procedures for completing case report forms, by organism
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

Laboratory Characterization

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.

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