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. Author manuscript; available in PMC: 2025 Apr 9.
Published in final edited form as: Am J Infect Control. 2024 Apr 29;52(9):1035–1042. doi: 10.1016/j.ajic.2024.04.184

Carbapenem-resistant Acinetobacter baumannii complex in the United States – an epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019

Sandra N Bulens 1, Davina Campbell 1, Susannah L McKay 1, Nicholas Vlachos 1, Alex Burgin 1, Mark Burroughs 1, Jasmine Padila 1, Julian E Grass 1, Jesse T Jacob 2,3, Gillian Smith 2,3,4, Daniel B Muleta 5, Meghan Maloney 6, Bobbie Macierowski 6, Lucy E Wilson 7,8, Elisabeth Vaeth 7, Ruth Lynfield 9, Sean O’Malley 9, Paula M Snippes Vagnone 9, Jennifer Dale 9, Sarah J Janelle 10, Christopher A Czaja 10, Helen Johnson 10, Erin C Phipps 11,12, Kristina G Flores 11,12, Ghinwa Dumyati 13, Rebecca Tsay 13, Zintars G Beldavs 14, P Maureen Cassidy 14, Amanda Hall 1, Maroya S Walters 1, Alice Y Guh 1, Shelley S Magill 1, Joseph D Lutgring 1
PMCID: PMC11979794  NIHMSID: NIHMS2061634  PMID: 38692307

Abstract

Background:

Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response.

Methods:

Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing.

Results:

Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible).

Conclusions:

Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

Keywords: antimicrobial drug resistance, carbapenem-resistant, surveillance, molecular epidemiology, Acinetobacter baumannii, Emerging Infections Program

Background

Acinetobacter baumannii complex predominantly causes infections among patients with frequent healthcare exposure 1–7. Common A. baumannii infections include bacteremia, urinary, wound, and respiratory tract infections 4–6,8–10. Carbapenem-resistant A. baumannii (CRAB) is considered an urgent threat by the Centers for Disease Control and Prevention (CDC) because it causes difficult-to-treat infections with mortality rates ranging from 17.9% to 61.6% 6,9,11–13.

Resistance to carbapenem antibiotics in A. baumannii can be conferred in several ways 10,14,15. Of greatest concern is the acquisition of carbapenemase genes present on mobile genetic elements, such as blaOXA-23 or blaNDM, which enable their spread via horizontal transmission 7,9,10,14. Other contributing carbapenem resistance mechanisms include low outer membrane permeability and overexpression of blaOXA-51-like due to the presence of insertion sequence Aba1 10,14,16.

Understanding the epidemiology of CRAB and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. We sought to describe the epidemiological and molecular characteristics of isolates collected from cases infected with CRAB identified through the Emerging Infections Program’s (EIP’s) Multi-site Gram-negative Surveillance Initiative (MuGSI) 6. MuGSI is a laboratory and population-based surveillance program that aims to describe the extent of select resistant gram-negative bacteria, to measure trends of these organisms over time, to identify those most at risk from illness with these pathogens, and to provide a platform to answer future questions about these pathogens.

Methods

Population

Laboratory and population-based surveillance was conducted through the EIP’s MuGSI program in selected counties in Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee from January 1 through December 31, 2019 (see Supplement) 17. The total population under surveillance in 2019 was 19,313,303 18.

Due to small numbers, and to maintain confidentially of individual cases, sites were grouped as follows: “South” (TN, GA); “Northeast” (CT, NY, MD); and “West” (OR, CO, MN, NM).

Case Definition

An incident case was the first isolation of carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (A. baumannii complex) from a normally sterile site (including blood, cerebrospinal fluid, bone, joint/synovial fluid, internal body site, peritoneal fluid, pleural fluid, muscle, deep tissue, etc.) or urine resistant to meropenem, imipenem, or doripenem, in a 30-day period, from a surveillance area resident who’s specimen was collected for a clinical purpose (see Supplement) 6,19. Each unique patient (case-patient) could contribute a new incident case to this surveillance every 30 days.

A patient’s isolate was considered healthcare-associated (HCA) if it met any of the following criteria: 1) the isolate was collected 3 or more days post hospital admission, 2) the patient had any of the following healthcare exposures in the prior year to case-defining culture–long-term care stay, prior hospitalization, prior outpatient or inpatient surgery, 3) the presence of an indwelling device at any time in the 2 days prior to case-defining culture (e.g., foley catheter, central line, etc.), and/or 4) current chronic dialysis treatment. All other patients were considered community-associated (CA).

Case Identification and Data Collection

Cases were identified by reviewing clinical laboratory-provided lists of A. baumannii complex isolated from a sterile site or urine. EIP site staff confirmed the organism met the defined phenotype and reviewed residential addresses to confirm that a case-patient was a surveillance area resident. Associated medical records were reviewed as described in the supplement, and the Charlson Co-morbidity Index (CCI) was calculated 6,20–22. Cases were matched with state vital records data to determine if death occurred within 30 days following the specimen collection date of the case-defining culture.

Analytic and Statistical Methods

A Chi-square test or Fisher’s exact test (where applicable) were used to generate a P-value which was used to compare cases with and without a detected aCP, using SAS 9.4 (SAS Institute Inc., Cary, NC, United States) using a ≤ 0.05 significance level. The crude incidence rate was calculated using denominator data from the 2019 U.S. Census Bridged-Race File 18. Data reported to CDC as of August 26, 2022, were included in the analysis.

Isolate Collection, Submission and Evaluation at CDC Laboratory

Isolate submission to CDC was initiated in 2019, and EIP site staff facilitated the collection by regularly communicating with local clinical laboratories.

All isolates submitted to CDC underwent full evaluation (fully characterized), including identification, antimicrobial susceptibly testing (AST), real-time PCR, and whole genome sequencing (see Supplemental Methods for more details). Identification was conducted using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) on the BioTyper 3.1 MALDI-TOF system (Bruker Daltonics, Billerica, MA, United States). Real-time PCR assays for the detection of an aCP, defined as, blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48-like, blaOXA-23-like, blaOXA-24/40-like, blaOXA-58-like, and blaOXA-235-like were developed in-house and performed on all submitted isolates 23–26.

Antimicrobial susceptibility testing was performed for 18 of the antibiotics represented in Table 3 at CDC (methods for cefiderocol are described separately) using frozen reference broth microdilution panels created in-house according to Clinical and Laboratory Standards Institute (CLSI) guidelines with cation-adjusted Mueller-Hinton broth (BD Difco, Sparks, MD, United States). Susceptibility was defined based on the 2022 CLSI breakpoints 27,28. Details on this testing can be found in the Supplement. Isolates were classified as difficult-to-treat (DTR) based on the criteria set by Kadri et al. (2018) 29.

Table 3.

Count of acquired carbapenemase gene by Multi-locus Sequence Type (MLST) for isolates of carbapenem-resistant Acinetobacter baumannii complex collected though the Emerging Infections Program, 2019 (n=66)

Acquired Carbapenemase Gene Multi-locus Sequence Type Scheme (count of isolates)
Oxford MLST Scheme Pasteur MLST Scheme
NDM-1 (n=1) ST2544 (1) ST279 (1)
OXA-225a (n=2) ST1788 (2) ST2 (2)
OXA-23 (n=31) ST208 (16) ST2 (26)
ST281 (5) ST499 (4)
ST345 (4) ST638 (1)
ST1962 (2)
ST368 (1)
ST369 (1)
ST1000 (1)
ST1788 (1)
OXA-23 and OXA-24/40 (n=2) ST124 (1) ST2 (1)
ST1962 (1) ST79 (1)
OXA-24/40 (n=11) ST1697 (5) ST2 (7)
ST208 (2) ST79 (1)
ST124 (1) ST250 (1)
ST345 (1) ST499 (1)
ST1739 (1) ST2102 (1)
ST2543 (1)
OXA-72b (n=1) ST348 (1) ST2 (1)
No acquired carbapenemase identified (n=18) ST281 (9) ST2 (17)
ST208 (7) ST108 (1)
ST105 (1)
ST1806 (1)
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Notes

a

blaOXA-223 is a variant of blaOXA-23

b

blaOXA-72 is a variant of blaOXA-24/40

Cefiderocol (Shionogi & Co. Ltd, Osaka, Japan) susceptibility testing was performed, separately from the above testing, on all isolates received at CDC using a frozen reference broth microdilution panel created in-house with iron-depleted cation-adjusted Mueller Hinton Broth (BD Difco, Sparks, MD, United States) and Chelex (Bio-Rad Laboratories, Hercules, CA). Both the 2019 CLSI and Food and Drug Administration (FDA) breakpoints were used to define susceptibility (Table 4) 30,31. Isolates were tested in triplicate for cefiderocol susceptibility following the same methods as described in the Supplement, and the mode for the MIC was reported for each isolate to account for trailing and skipped wells that can occur during testing. If a mode was not obtained after the third attempt of triplicate testing, the isolate was excluded from the analysis.

Table 4.

Antimicrobial susceptibility testing results, using the 2019 Clinical Laboratory Standards Institute (CLSI) breakpoints, for incident carbapenem-resistant Acinetobacter baumannii complex cases with and without an acquired carbapenemase gene, 2019, n=66

Number and Percent of Isolates that Tested Susceptible
Antimicrobial Agent Acquired Carbapenemase Gene Status for CRAB Isolate
Overall Yes No
N = 66 (%) N = 48 (%) N = 18 (%)
Carbapenem
   Doripenem 0 (0) 0 (0) 0 (0)
   Imipenem 4 (6.1) 0 (0) 4 (22.2)a
   Meropenem 0 (0) 0 (0) 0 (0)
β-Lactam/β-Lactamase Combinations
   Ampicillin-sulbactam 9 (13.6) 0 (0) 9 (50.0)a
   Piperacillin-tazobactam 0 (0) 0 (0) 0 (0)
Cephalosporin
   Ceftazidime 2 (3.0) 2 (4.2) 0 (0)
   Cefepime 1 (1.5) 1 (2.1) 0 (0)
   Cefotaxime 1 (1.5) 1 (2.1) 0 (0)
   Ceftriaxone 1 (1.5) 1 (2.1) 0 (0)
   Cefiderocolb 63 (96.9) 46 (97.9) 17 (94.4)
Lipopeptide
   Colistinc 0 (0) 0 (0) 0 (0)
Aminoglycoside
   Gentamicin 17 (25.8) 11 (22.9) 6 (33.3)
   Tobramycin 31 (47.0) 18 (37.5) 13 (72.2)
   Amikacin 45 (68.2) 33 (68.8) 12 (66.8)
Tetracycline
   Minocycline 38 (57.6) 27 (56.3) 11 (61.1)
   Tetracycline 4 (6.1) 4 (8.3) 0 (0)
Fluoroquinolone
   Ciprofloxacin 2 (3.0) 2 (4.2) 0 (0)
   Levofloxacin 3 (4.5) 3 (6.3) 0 (0)
Folate Pathway Antagonist
   Trimethoprim-sulfamethoxazole 11 (16.7) 10 (20.8) 1 (5.6)
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Notes: Abbreviations – CRAB: carbapenem-resistant Acinetobacter baumannii complex. Isolates were tested against tigecycline however were not included in this table because of lack of 2019 CLSI breakpoints.

a

P -value determined to be significant

b

Interpretations displayed in the table were using CLSI breakpoints. Cefiderocol results were missing for 1 isolate; Using FDA breakpoints, 52 (80.0%) of all CRAB isolates tested susceptible, 39 (83.0%) of CRAB isolates with an acquired carbapenemase tested susceptible, and 13 (72.2%) of CRAB isolates without an acquired carbapenemase tested susceptible

c

Colistin results were missing for 1 isolate; using 2019-CLSI breakpoints 56 (86.2%) of all CRAB isolates tested intermediate, 43 (91.5%) of CRAB isolates with an acquired carbapenemase tested intermediate, and 13 (72.2%) of CRAB isolates without an acquired carbapenemase tested intermediate.

Whole genome sequencing (WGS) was completed on all isolates, and the methods are described in the Supplement. Figure 1 was created using iTOL Interactive Tree of Life v6 (https://itol.embl.de/).

Data Availability

Whole-genome sequencing (WGS) raw reads for this collection were deposited in the Sequence Read Archive (SRR21065242 to SRR21065307) and are associated with NCBI Bio-Project PRJNA288601.

Ethical Review

The EIP’s MuGSI has been determined to be a non-research activity by the human subjects advisors at CDC’s National Center of Emerging and Zoonotic Infectious Diseases, and therefore CDC institutional review board (IRB) review was not required. This activity also underwent ethical review at each of the participating EIP sites and was either approved with a waiver of informed consent or was deemed a non-human research activity by respective EIP site’s IRBs.

Results

From January 1 through December 31, 2019, 136 incident CRAB cases, representing 125 unique case-patients, were identified (Table 1). The crude incidence rate was 0.70 cases per 100,000 population. Sixty-six isolates (48.5%), representing 58 unique case-patients, were submitted to CDC from all participating sites except OR and NY. Five unique case-patients contributed more than one isolate to this sample, with a range of 2-5 isolates per case-patient. We compared characteristics of cases with an isolate received at CDC to cases without an isolate submitted and determined the data were comparable (see Table 1, Supplement). All patient’s isolates were considered healthcare-associated based on characteristics collected from the medical record. Sites in the South contributed 68.2% of the isolates, sites in the Northeast contributed 22.7%, and sites in the West contributed 9.1% of isolates. All 66 isolates were determined to be part of the A. baumannii complex after sequencing, and 65 were confirmed to be A. baumannii; a single isolate was determined to be Acinetobacter nosocomialis.

Table 1.

Characteristics of incident cases with and without a carbapenem-resistant Acinetobacter baumannii isolate submitted to the Centers for Disease Control and Prevention for testing, 2019, n=136

Isolate Submitted to CDC
Characteristic Overall Yes No
N = 136 (%) N = 66 (%) N = 70 (%)
Patient demographic (case level)
   Sex
      Female 55 (40.4) 29 (43.9) 26 (37.1)
      Male 81 (59.6) 37 (56.1) 44 (62.0)
   Racea
      Black or African American, non-Hispanic 77 (56.6) 36 (54.6) 41 (58.6)
      White, non-Hispanic 47 (34.6) 25 (37.9) 22 (31.4)
      Asian, non-Hispanic 3 (2.2) 2 (3.0) 1 (1.4)
      Hispanic, any race 3 (2.2) 1 (1.5) 2 (2.9)
      Unknown race and ethnicity 5 (3.7) 2 (3.0) 3 (4.3)
      Unknown race, non-Hispanic 1 (0.7) 0 (0.0) 1 (1.4)
   Median age in years (IQR) 61.5 (49.0-77.0) 63.5 (51.0-78.0) 61.0 (46.0-76.0)
N = 136 (%) N = 66 (%) N = 70 (%)
Culture sourceb
   Urine 98 (72.1) 51 (77.3) 47 (67.1)
   Normally sterile site 38 (27.9) 15 (22.7) 23 (32.9)
N = 136 (%) N = 66 (%) N = 70 (%)
Location of culture collection
   Outpatient locationc 69 (50.7) 33 (50.0) 36 (51.4)
   Hospital inpatientd 48 (35.3) 21 (31.8) 27 (38.6)
   Long-term care or long-term acute care 19 (14.0) 12 (18.2) 7 (10.0)
N = 131 (%) N = 64 (%) N = 67 (%)
Common types of infectionse
   Urinary tract infection or 76 (58.0) 45 (40.3) 31 (46.3)n
   pyelonephritis 35 (26.7) 12 (18.8) 23 (34.3)n
   Bacteremia/sepsis 13 (9.9) 4 (6.3) 9 (13.4)
   Septic shock 6 (4.6) 4 (6.3) 2 (3.0)
   Skin infectionf 4 (2.9) 4 (6.3) 0 (0.0)
   Osteomyelitis 2 (1.5) 1 (1.6) 1 (1.5)
   Pneumonia
N = 133 N = 65 N = 68
M, MD (IQR) M, MD (IQR) M, MD (IQR)
Co-morbiditiesg
   Charlson Comorbidity Index 3.0, 2.0 (2.0-4.0) 2.7, 2.0 (2.0-3.0) 3.0, 3.0 (2.0-4.0)
N =133 (%) N =65 (%) N = 68 (%)
   Chronic skin conditionsh 78 (58.6) 41 (63.1) 37 (54.4)
   Urinary tract problems/abnormalities 61 (45.9) 32 (49.2) 29 (42.7)
   Hemiplegia/paraplegia/quadriplegia 52 (39.1) 27 (41.5) 25 (36.8)
   Diabetes 52 (39.1) 23 (35.4) 29 (42.7)
   Cardiovascular disease 56 (42.1) 27 (41.5) 29 (42.7)
   Chronic kidney disease 29 (21.8) 9 (13.9) 20 (29.4)
N = 136 (%) N = 66 (%) N = 70 (%)
Healthcare facility exposures in the year prior to culture datei
   Admission to an ACH 118 (86.8) 58 (87.9) 60 (85.7)
   Stay in a LTCF 93 (68.4) 45 (68.2) 48 (68.6)
   Prior outpatient or inpatient surgery 38 (27.9) 18 (27.3) 20 (28.6)
   Admission to a LTACH 6 (4.4) 4 (6.1) 2 (2.9)
N = 136 (%) N = 66 (%) N = 70 (%)
Placement of an indwelling device in the 2 days prior to culture datej
   Urinary catheter 83 (61.0) 43 (65.2) 40 (57.1)
   Other indwelling devicek 38 (27.9) 9 (13.6) 29 (41.4)n
   Central vascular catheter 32 (23.5) 14 (21.2) 18 (25.7)
N = 136 (%) N = 66 (%) N = 70 (%)
Other risk factors in the 7 days prior to the date of culture
   Admission to an ICU 25 (18.4) 14 (22.6) 11 (19.0)
   Nebulizer treatment 13 (9.6) 1 (15) 12 (17.1)n
   Mechanical ventilation 12 (8.8) 3 (4.6) 9 (12.9)
   Non-invasive positive pressure ventilation 5 (3.7) 1 (1.5) 4 (5.7)
N = 136 (%) N = (%) N = (%)
Current chronic dialysis treatment 4 (2.9) 1 (1.5) 3 (4.3)
N = 136 (%) N = 66 (%) N = 70 (%)
Hospitalized at the time of or within 30 days of culture collectionl
   Yes 110 (80.9) 51 (77.3) 59 (84.3)
   No 23 (16.9) 14 (21.1) 9 (12.9)
   Unknown 3 (2.2) 1 (1.5) 2 (2.9)
N = 136 (%) N = 66 (%) N = 70 (%)
Patient outcome at 30 daysm
   Survived 107 (78.7) 55 (83.3) 52 (74.3)
   Died 29 (21.3) 11 (16.7) 18 (25.7)
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Notes: Abbreviations – ACH: acute care hospital; CRAB: carbapenem-resistant Acinetobacter baumannii complex; ICU: intensive care unit; IQR: interquartile range; LTACH: long-term acute care hospital; LTCF: long-term care facility; MD: median. This table includes cases from all sites. OR did not identify CRAB cases in 2019 and NY identified only a single incident case.

a

Persons whose race was reported to be American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander, were not identified in our population

b

To reduce re-identifiability of data when reporting, due to small numbers, culture sources were combined into two categories: normally sterile body sites (i.e., blood, cerebral spinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint/synovial fluid, bone, internal body site, muscle) and urine

c

Outpatient collection locations include emergency room, outpatient clinic, outpatient surgical center, or another outpatient location

d

Hospital inpatient collection locations include ICU, operation room, or another inpatient location

e

The top 6 types of infection are reported here. A case can have more than one type of infection reported, 5 of the 136 cases had unknown types of infections recorded on the medical abstraction form and have been removed for this analysis, 15 of the 131 cases had no types of infections reported. A urinary tract infection was defined as a medical record abstractor seeing the term in the medical record

f

Skin infections included skin abscess, chronic or decubitus ulcers

g

The top 6 co-morbid conditions are reported here. Case can have more than one type of co-morbid condition reported, 3 cases had unknown comorbid conditions documented in the medical record and were excluded from this analysis

h

Chronic skin conditions include decubitus/pressure ulcers, other chronic or surgical wounds, and burns

i

Cases could have more than one healthcare facility exposure in the year prior reported in the medical record

j

Cases could have more than one type of indwelling device placed in the 2 days prior to culture collection

k

Other indwelling devices include ET/NT tube, gastrostomy tube, NG tube, tracheostomy, nephrostomy tube, or other unspecified indwelling device

m

Patients’ outcomes were assessed using the state death registry data. A patient was considered to have survived if there was no matching record in the state death registry data in the 30 days after the date of the case-defining culture

n

P-value determined to be significant at the 0.05 level

Of the 66 isolates collected for this analysis, 37 (56.1%) were from males, 36 (54.6%) were from Black or African American, non-Hispanic, persons, and the median age of cases was 63.5 years (Table 2). Most isolates (n=51, 77.2%) were from urine specimens, and half (n=33, 50.0%) were collected in the outpatient setting (e.g., emergency room, outpatient clinic, outpatient surgical center, or another outpatient location). Isolate characteristics, compared in Table 2, are not statistically different. Only 23% (n=15) cases had the case-defining culture collected >3 days after hospital admission (e.g. where hospital-onset). Exposure to more than one healthcare risk factor (e.g., exposure to more than one healthcare setting, or the presence of one or more indwelling device) did not result in a case being more likely to have an isolate harboring an aCP (aCP isolate: n=41, 85.4% vs. non-aCP isolate: n=15, 83.3% respectively, p<0.99). Of the 66 isolates, 26 (39.4%) were documented as being polymicrobial (the organism other than CRAB is unknown) based on the medical record review; 19/48 (39.6%) of the isolates with an aCP and 7/18 (38.9%) of the isolates without an aCP; this finding was not statistically significantly different.

Table 2.

Characteristics of incident carbapenem-resistant Acinetobacter baumannii complex cases with and without an acquired carbapenemase gene as identified by whole genome sequencing, 2019, n=66

Characteristic Acquired Carbapenemase Gene Status for CRAB Isolate
Overall Yes No
N = 66 (%) N = 48 (%) N = 18 (%)
Patient demographics ()
   Sex
      Female 29 (43.9) 20 (41.7) 9 (50.0)
      Male 37 (56.1) 28 (58.3) 9 (50.0)
   Racea
      Black or African American, non-Hispanic 36 (54.5) 29 (60.4) 7 (38.9)
      White, non-Hispanic 25 (37.9) 16 (33.3) 9 (50.0)
      Asian, non-Hispanic 2 (3.0) 0 (0.0) 2 (11.1)
      Hispanic, any race 1 (1.5) 1 (2.1) 0 (0.0)
      Unknown race and ethnicity 2 (3.0) 2 (4.2) 0 (0.0)
MD (IQR) MD (IQR) MD (IQR)
   Age in years 63.5 (51.0-78.0) 59.5 (50.5-74.5) 71 (61.0-82.0)
N = 66 (%) N = 48 (%) N = 18 (%)
Culture sourceb
   Urine 51 (77.3) 38 (79.2) 13 (72.2)
   Normally sterile site 15 (22.7) 10 (20.8) 5 (27.8)
N = 66 (%) N = 48 (%) N = 18 (%)
Location of culture collection
   Outpatient locationc 33 (50.0) 24 (50.0) 9 (50.0)
   Hospital inpatientd 21 (31.8) 17 (35.4) 4 (22.2)
   Long-term care facility or long-term Acute care hospital 12 (18.2) 7 (14.6) 5 (27.8)
N = 64 (%) N = 46 (%) N = 18 (%)
Common types of infectionse
   Urinary tract infection or 45 (70.3) 34 (73.9) 11 (61.1)
   pyelonephritis 10 (15.6) 6 (12.5) 4 (22.2)
   Bacteremia 4 (6.3) 3 (6.5) 1 (5.6)
   Septic shock 4 (6.3) 2 (4.4) 2 (11.1)
   Skin infectionf 4 (6.3) 4 (8.7) 0 (0.0)
   Osteomyelitis 1 (1.6) 1 (2.2) 0 (0.0)
   Pneumonia 4 (6.3) 2 (4.4) 2 (11.1)
   No infections reported
N = 65 N = 47 N = 18
MD (IQR) MD (IQR) MD (IQR)
Co-morbiditiesg
   Charlson Comorbidity Index 2 (2-3) 2 (2-4) 2 (2-3)
N = 65 (%) N = 47 (%) N = 18 (%)
   Chronic skin conditionsh 41 (63.1) 29 (61.7) 12 (66.7)
   Urinary tract problems/abnormalities 32 (49.2) 23 (48.9) 9 (50.0)
   Hemiplegia/paraplegia/quadriplegia 27 (41.5) 21 (44.68) 6 (33.3)
   Diabetes 23 (35.4) 18 (38.3) 5 (27.8)
   Cardiovascular disease 27 (41.5) 20 (42.6) 7 (38.9)
   Chronic kidney disease 9 (13.8) 6 (12.8) 3 (16.7)
N = 66 (%) N = 48 (%) N = 18 (%)
Healthcare facility exposures in the year prior to culture datei
   Admission to an ACH 58 (87.9) 41 (85.4) 17 (99.4)
   Stay in a LTCF 45 (68.2) 34 (70.8) 11 (61.1)
   Prior outpatient or inpatient surgery 18 (27.3) 15 (31.2) 3 (16.7)
   Admission to a LTACH 4 (6.1) 2 (4.2) 2 (11.1)
N = 66 (%) N = 48 (%) N = 18 (%)
Placement of an indwelling device in the 2 days prior to culture date
   Urinary catheter 43 (65.2) 33 (68.8) 10 (55.6)
   Central vascular catheter 14 (21.2) 9 (18.8) 5 (27.8)
   Other indwelling devicej 9 (13.6) 8 (16.7) 1 (5.6)
N = 66 (%) N = 48 (%) N = 18 (%)
Other risk factors in the 7 days prior to the date of culture
   Nebulizer treatment 1 (1.5) 1 (2.1) 0 (0.0)
   Mechanical ventilation 3 (4.5) 3 (6.3) 0 (0.0)
   Non-invasive positive pressure ventilation 1 (1.5) 0 (0.0) 1 (5.6)
   Admission to an ICU 14 (21.2) 13 (27.1) 1 (5.6)
N = 66 (%) N = 48 (%) N = 18 (%)
Current chronic dialysis treatment 1 (1.5) 1 (2.1) 0 (0.0)
N = 66 (%) N = 48 (%) N = 18 (%)
Hospitalized at the time of or within 30 days of culture collectionk
   Yes 51 (77.3) 39 (81.3) 12 (66.7)
   No 14 (21.2) 8 (16.7) 6 (33.3)
   Unknown 1 (1.5) 1 (2.1) 0 (0.0)
N = 66 (%) N = 48 (%) N = 18 (%)
Patient outcome at 30 daysl
   Survived 55 (83.3) 41 (85.4) 14 (77.8)
   Died 11 (16.7) 7 (14.6) 4 (22.2)
      Among cases with sterile sites 5/11 (45.5) 3/7 (42.9) 2/4 (50.0)
      Among cases with urine cultures 6/11 (54.5) 4/7 (57.1) 2/4 (50.0)
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Notes: Abbreviations – ACH: acute care hospital; CRAB: carbapenem-resistant Acinetobacter baumannii complex; ICU: intensive care unit; IQR: interquartile range; LTACH: long-term acute care hospital; LTCF: long-term care facility; MD: median. A test for significance was performed on each row in the table above; we found no significant difference between the two groups.

a

Persons whose race was reported to be American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander, were not identified in our population

b

To reduce re-identifiability of data when reporting, due to small numbers, culture sources were combined into two categories: normally sterile body sites (i.e., blood, cerebral spinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint/synovial fluid, bone, internal body site, muscle) and urine

c

Outpatient collection locations include emergency room, outpatient clinic, outpatient surgical center, or another outpatient location

d

Hospital inpatient collection locations include ICU, operation room, or another inpatient location

e

Cases could have more than one type of infection; 2 cases had unknown types of infections recorded on the medical abstraction form and have been removed for this analysis. A urinary tract infection was defined as a medical record abstractor seeing the term in the medical record

f

Skin infections included skin abscess, chronic or decubitus ulcers

g

The most frequent co-morbid conditions are presented here. Cases could have more than one co-morbid condition documented. A single CRAB case had unknown comorbid conditions documented in the medical record and was excluded from this analysis

h

Chronic skin conditions include decubitus/pressure ulcers, other chronic or surgical wounds, and burns

i

Cases could have more than one prior healthcare risk factor reported in the medical record

j

Other indwelling devices include endotracheal/nasotracheal tube, gastrostomy tube, nasogastric tube, tracheostomy, nephrostomy tube, or other unspecified indwelling devices

l

Patients’ outcomes were assessed using the state death registry data. A patient was considered to have survived if there was no matching record in the state death registry data in the 30 days after the date of the case-defining culture.

Among the 51 cases with isolates, that were hospitalized at the time of, or in the 30 days after, the date of the case-defining culture, the median total length of hospital stay was 10 days (IQR: 7-20 days). Cases with a CRAB isolate without an aCP had similar length of stay (median: 8, IQR: 6-19.5 days) compared to those with an aCP (median: 10, IQR: 7-20 days). Among cases that tested positive for CRAB after admission to an acute care hospital (n=15), the median time between admission and case-defining culture date was 7 days (IQR: 5-10 days), and the median length of stay was 19 days (IQR: 10-24 days). The median time from admission to case-defining culture date for CRAB cases with an aCP (n=13) was 7 days (IQR: 5-10 days). For the two cases without an aCP, times from admission to case-defining culture were 7 and 32 days.

Most isolates (n=48, 72.7%) had an aCP identified through WGS (Figure 1). The real-time PCR results and WGS result for the detection of an aCP were 100% concordant. The frequency of the aCPs were as follows: 34 (51.5%) isolates had blaOXA-23, 13 (19.7%) isolates had blaOXA-24, 2 (3.0%) isolates had blaOXA-225, 1 (1.5%) isolate had blaOXA-72, and 1 (1.5%) isolate had blaNDM. Two isolates harbored both a blaOXA-23 and a blaOXA-24 carbapenemase gene. The blaNDM isolate was identified from the urine of a patient who was a nursing home resident with no prior travel history the year before culture, or indwelling device use (including the use of a tracheostomy); however, this patient was discharged from an acute care hospital about a month before the case-defining culture date. Forty-six isolates had both an acquired and intrinsic blaOXA gene; the most common combination was blaOXA-23 and blaOXA-66 (n=16). A depiction of key molecular characteristics overlayed by region where the isolate was collected, culture source, and if the patient had multiple isolates, can be found in Figure 1. A cross walk of the aCP and identified MLST types can be found in Table 3. Acinetobacter-derived cephalosporinase (ADC) genes were present in all 66 isolates (Figure 1).

Figure 1.

Figure 1.

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Key molecular characteristics for 65 isolates of carbapenem-resistant Acinetobacter baumannii collected through the Emerging Infections Program, 2019.

Notes: The sequencing information for these isolates can be found on NCBI (https://www.ncbi.nlm.nih.gov/bioproject/288601). Isolate characteristics are indicated in the key to the right of the figure. For the Patient Cluster column; 0 = a patient contributing one isolate, 1 = a unique patient contributing 5 isolates, 2 = a unique patient contributing 2 isolates, 3 = a unique patient contributing 2isolates, 4 = a unique patient contributing 2 isolates, 5 = a unique patient contributing 5 isolates).

Abbreviations: Multi-locus Sequencing Type (MLST); Acinetobacter-derived cephalosporinase (ADC) genes; Sequence Type (ST)

Sixteen unique sequence types (STs) were identified using the Oxford (OX) MLST scheme; the most common were ST208OX (n=25, 37.9%), and ST281OX (n=14, 21.1%). A total of 8 unique STs were identified using the Pasteur MLST scheme, ST2 IP predominated (n=54, 81.8%) (Figure 1). The count of isolates by MLST type and aCP is found in Table 3.

The number and percent susceptible of the isolates tested at CDC are presented in Table 4. All submitted isolates were confirmed to be carbapenem-resistant. None of the CRAB isolates with an aCP demonstrated susceptibility to ampicillin-sulbactam, although 50.0% of the isolates without an aCP were susceptible (p < 0.0001). Most CRAB isolates displayed susceptibility to cefiderocol according to 2019 CLSI breakpoints (96.9%), but fewer displayed susceptibility according to FDA breakpoints (80.0%) 30,31. Cefiderocol testing resulted in the frequent occurrence of trailing and skipped wells, which often made the MIC difficult to determine. There are no CLSI or FDA breakpoints for A. baumannii complex and tigecycline, but the MIC50 and MIC90 were 1 and 2 μg/mL, respectively, and demonstrated the identical distribution for isolates that were aCP and non-aCP. Most isolates (n = 50, 75.8%) met the DTR definition 29. Among the 11 case-patients that died, 9 had isolates that met the DTR definition. Four of the isolates were ST208OX (all 4 were DTR), 3 were ST281OX (1 was DTR), and 9 isolates were ST2IP, 7 of which were DTR. For comparison, among the 41 case-patients that survived, 41 isolates met the DTR definition. The most frequent STOX type among this group, that was also DTR, was ST208OX (n=17).

Discussion

During 2019, we identified a low incidence rate of CRAB, with 0.70 cases per 100,000 population, across geographically diverse U.S. metropolitan areas. Most CRAB cases occurred in older persons, and those of Black or African American (non-Hispanic) race. Seventy-three percent of isolates tested harbored an aCP, including a single isolate with blaNDM. Cefiderocol, which was approved by the FDA in November 2019, had the most in vitro activity among the 19 antimicrobial agents tested 32.

Our findings were similar to those from the Study Network of Acinetobacter as Carbapenem-Resistant Pathogen (SNAP), including similar characteristics of age, sex, and calculated CCI. SNAP included 23 hospitals in 4 health systems (Cleveland, Pittsburgh, Houston, Chapel Hill) in 2017-2018; they enrolled 120 patients with 1-5 isolates per patient identified through sentinel reporting 33. Our population differed from SNAP in the percentage of persons of Black or African American, non-Hispanic, race (54.0% vs. 28.0%), the percentage of cases who died by day 30 (16.7% vs. 24.0%), and difference in culture sources included (e.g., SNAP included respiratory and wound samples) 33. These differences may be attributable to the difference in the underlying populations, the diversity of the healthcare facilities and our methods of using population-based surveillance, which include only surveillance area residents, compared to SNAP’s sentinel approach.

Our isolates were resistant to many first-line drugs used to treat CRAB infections, and 75.8% were found to have difficult-to-treat resistance 11,29. In the Infectious Diseases Society of America (IDSA) guidance on treating CRAB, ampicillin-sulbactam, polymyxins, minocycline, tigecycline, and cefiderocol are suggested as possible treatments 11. A smaller percentage of isolates with an aCP were susceptible to ampicillin-sulbactam, colistin, and minocycline. Only 13.6% of our isolates demonstrated susceptibility to ampicillin-sulbactam, IDSA’s preferred treatment for CRAB, which is lower than in other studies of isolates from North America 11,12,34. Using the pre-2019 CLSI breakpoints (MIC ≤2 μg/mL) 86.2% of isolates tested susceptible to colistin, which is similar to other studies 12. Susceptibility to minocycline was low. All but two isolates had a tigecycline MIC ≤2 μg/mL in our collection; however, this agent has been associated with increased mortality when used for treating severe infections, so monotherapy is not recommended for severe infections 11,35.

Most of our CRAB isolates were susceptible to cefiderocol using either CLSI (96.9%) or FDA interpretive criteria (80.0%) suggesting that it remains a potentially useful therapeutic option as recommended in the current IDSA treatment guidance 11,36–38. Our data affirm the results of other studies and provide evidence suggesting that cefiderocol could be a valuable treatment option for these infections as more data on clinical effectiveness become available 11,36–38.

WGS demonstrated that blaOXA-23 was the most common aCP in this study (51.5%), followed by blaOXA-24 (19.7%), which is similar to other published studies 33,39. One isolate was found to harbor blaNDM, which is rare in CRAB in the U.S. 40–42. The CDC’s Antimicrobial Resistance Laboratory Network reported 2.03% of all CRAB isolates tested in 2022 have this gene 42. The patient with blaNDM identified in this assessment had no prior travel history, was a resident of a nursing home and had a prior acute care hospitalization which is similar to characteristics of patients reported in a multifacility outbreak of CRAB NDM in California 41. Many of our isolates were ST2IP by Pasteur MLST scheme (81.8%) and ST208OX or ST281OX by the Oxford MLST scheme (59.0%), which is similar to other U.S. studies of CRAB isolates 33,39. There were 54 isolates identified as ST2IP, but these 54 isolates were classified as 16 different STs using the Oxford MLST scheme 33,39. This suggests that the Oxford MLST scheme offers a higher resolution for distinguishing between isolates than the Pasteur MLST scheme 39.

Limitations to this surveillance program include the following: small populations under surveillance, small number of geographic areas represented, restriction of the case definition to residents of the surveillance area and sterile site or urine culture sources, patient treatment data is not collected, and the lack of participation of some private specialty laboratories (e.g., laboratories serving dialysis facilities) 6,22. Therefore, our results are not nationally representative. In 2021, this surveillance activity expanded the case definition to include wound and lower respiratory tract isolates, therefore allowing this program to better characterize patients with CRAB moving forward. Combination drugs, such as sulbactam-durlobactam, were not available for testing. However, in one year of data, this assessment demonstrates a unique population-level perspective of CRAB in the U.S., including detailed clinical and microbiological data, allowing for a deeper understanding of the epidemiology of CRAB across the spectrum of healthcare. Additionally, all isolates sent for testing by CDC were confirmed to be CRAB, indicating that a phenotypic case definition based on local clinical laboratory antimicrobial susceptibility testing results is well-suited for surveillance.

In summary, most CRAB isolates across geographically diverse U.S. metropolitan areas harbored an aCP and demonstrated characteristics suggesting limited potential treatment options, supporting that this group of pathogens remains an urgent threat in the U.S. Certain strains of CRAB (ST208OX and ST281OX) were prevalent, and the detection of an isolate harboring blaNDM was identified. We found that cefiderocol had the most in vitro activity of the drugs tested, suggesting the potential treatment utility of this drug. This surveillance activity has demonstrated its value in helping to definine the landscape of CRAB by providing a unique view of the molecular epidemiology of CRAB in the U.S., reinforcing the importance of tracking emerging and potentially transmissible resistance in A. baumannii complex to help inform and evaluate infection prevention and control strategies.

Supplementary Material

Supplemental

Disclaimer

The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental
NIHMS2061634-supplement-Supplemental.docx (44.1KB, docx)

Data Availability Statement

Whole-genome sequencing (WGS) raw reads for this collection were deposited in the Sequence Read Archive (SRR21065242 to SRR21065307) and are associated with NCBI Bio-Project PRJNA288601.

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