Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Feb 17;78(2):248-258.
doi: 10.1093/cid/ciad556.

Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions

Minggui Wang  1   2 , Lizhao Ge  3 , Liang Chen  4   5 , Lauren Komarow  3 , Blake Hanson  6 , Jinnethe Reyes  7 , Eric Cober  8 , Thamer Alenazi  9 , Zhiyong Zong  10 , Qing Xie  11 , Zhengyin Liu  12 , Lanjuan Li  13 , Yunsong Yu  14 , Hainv Gao  15 , Souha S Kanj  16 , Jairo Figueroa  17 , Erica Herc  18 , Ezequiel Cordova  19 , Gregory Weston  20 , Paul Ananth Tambyah  21 , Julia Garcia-Diaz  22 , Keith S Kaye  23   24 , Sorabh Dhar  25 , Jose M Munita  26 , Robert A Salata  27 , Samuel Vilchez  28 , Martin E Stryjewski  29 , Maria Virginia Villegas Botero  30 , Alina Iovleva  31 , Scott R Evans  2   32 , Keri Baum  33 , Carol Hill  33 , Barry N Kreiswirth  4 , Robin Patel  34   35 , David L Paterson  36 , Cesar A Arias  37   38 , Robert A Bonomo  27   39   40   41   42 , Henry F Chambers  43 , Vance G Fowler Jr  33 , Michael J Satlin  44 , David van Duin  45 , Yohei Doi  31   46 ; Multi-Drug Resistant Organism Network Investigators
Collaborators, Affiliations
Observational Study

Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions

Minggui Wang et al. Clin Infect Dis. .

Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb.

Methods: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis.

Results: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases.

Conclusions: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Keywords: carbapenem-resistant Acinetobacter baumannii; clinical impact; international epidemiology.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. All authors report funding support from the ARLG of the NIH and the NIAID (UM1AI104681) during the conduct of this study. In addition, and outside of the submitted work the following authors declare: B. H. reports an NIH/NIAID grant K01AI148593–01 paid to his institution. S. S. K, reports speaker and advisory board payments from MSD, Pfizer, and Menarini. S. S. K. is the President-Elect of the International Society of Antimicrobial Chemotherapy. G. W. reports payment to his institution from Allergan for contracted activities. P. T. reports grants to his institution from Sanofi-Pasteur, Arcturus, and Roche, and honoraria payments to his institution from Aj Biologics and bioMérieux. J. G. D. reports grants and contracts paid to her institution from the NIH, Biomedical Advanced Research and Development Authority (BARDA), Janssen Research & Development LLC, Pfizer, BioNTech SE, Global Coalition for Adaptive Research (GCAR), Hoffman La-Roche, I-Mab Bioppharma Co. Ltd, Rebiotix, Inc., Target Health LLC, OBO Lilly USA, GlaxoSmithKline, Summit Limited, UK, Cidara Therapeutics, Merck Sharp & Dohme (MSD) Corp., Seres Therapeutics, Inc.; and Infectious Diseases Society of America (IDSA) Research Committee participation paid to her directly. K. S. K. reports consulting fees paid directly to him by Merck, Shionogi, Qpex, and Micrux. J. M. M. reports grants from Pfizer, MSD, and bioMérieux, the National Fund for Scientific and Technological Development (regular award number 1211947); and the Agencia Nacional de Investigation y Desarrollo Millennium Science Initiative/Millennium Initiative for Collaborative Research on Bacterial Resistance, Government of Chile (award number NCN17_081). M. S. reports speaker fees from Pfizer (Argentina); advisory board participation for Wockhardt; consultancy for Basilea; and DSMB participation with Fulcrum Therapeutics. M. V. V/ reports contracts, consulting fees, and honoraria payments from Pfizer; consulting fees and honoraria from MSD; consulting fee from West Quimica Colombia; and honoraria payments from bioMérieux. A. I. reports an NIH grant KL2TR001856 paid to her institution. S. E. reports grants from the NIAID and the NIH and Degruter (Editor in Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, SVB Leerink; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the US Food and Drug Administration, the Deming Conference on Applied Statistics, the Clinical Trial Transformation Initiative, the Council for International Organizations of Medical Sciences, the International Chinese Statistical Association Applied Statistics Symposium, and the Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, the Breast International Group, the University of Pennsylvania, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, Abbvie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, the American Statistical Association, the Society for Clinical Trials, and the Frontier Science Foundation. R. P. reports grants from ContraFect, TenNor Therapeutics Limited, and BioFire. R. P. is a consultant to PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, and HealthTrackRx; monies are paid to Mayo Clinic. Mayo Clinic and R. P. have a relationship with Pathogenomix. R. P. has research supported by Adaptive Phage Therapeutics. Mayo Clinic has a royalty-bearing know-how and equity in Adaptive Phage Therapeutics. R. P. is also a consultant to Netflix, Abbott Laboratories, and CARB-X. R. P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. R. P. receives honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. D. L. P. reports grants and contracts paid to his institution from Merck, Pfizer, and Shionogi; consulting and honoraria payments to him by Merck, Shionogi, QPex, Spero Therapeutics, Sumitomo, Pfizer, and bioMérieux; meeting support from Shionogi; board and committee participation with Symvivo, and Antimicrobial Resistance (AMR) action fund. C. A. A. reports the following grants and contracts paid to his institution NIH/NIAID 1 P01 AI152999, NIH/NIAID R01 AI148342, NIH/NIAID R01 AI134637, NIH/NIAID T32 AI141349, NIH/NIAID K24 AI121296, NIH/NIAID U19 AI144297, NIH/NIAID R01 AI150685, NIH/NIAID R21 AI151536, MeMed Diagnostics Ltd, Entasis Therapeutics, Merck Pharmaceuticals, Harris County Public Health; Payments to him for UpToDate royalties, reimbursement of meeting attendance and speaking from Infectious Diseases Society of America, American Society for Microbiology, Society of Hospital Epidemiology of America European Society for Clinical Microbiology and Infectious Diseases, Mérieux Foundation, Sociedad Argentina de Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, Brazilian Society for Infectious Diseases, reviewer participation as part of the NIH grant Review Study Sections, travel expenses from the IDSA Board of Directors, and for Editor in Chief for Antimicrobial Agents and Chemotherapy; non-paid participation includes World Health Organization Antibacterial Pipeline Advisory Group, and participation on the IDSA Board of Directors. R. A. B. reports grants and contracts, paid to his institution, by VenatoRx, Wockhardt, and Merck; payments made to him by Pfizer to moderate meeting sessions; a provisional patent with Case Western Reserve University on the development of boronic acid transition state inhibitors for beta-lactamases; served on a data and safety monitoring board (DSMB) as a logistics associate for DMID-CROMS, Safety Oversight Committee Support, and Technical Resources International, Inc. H. F. C. reports royalties from the Sanford Guide to Antimicrobial Therapy; payment for expert testimony from Nexus Pharmaceuticals; participation on a Merck DSMB for molnupiravir, and stock ownership in Moderna and Merck. V. G. F. reports grants to his institution from the NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; editorial stipend from the IDSA; a pending patent for a host gene expression signature diagnostic for sepsis; and stock options with Valanbio and ArcBio. M. J. S. reports contracts payments to his institution from Merck, bioMéreiux, and SNIPRBiome; personal consulting fees from Shionogi; and data and safety monitoring board participation for Spero Therapeutics and AbbVie. D. v. D. reports grants and contracts paid to his institution from the NIH and Merck; consulting fees paid directly to him from Merck, Qpex, Roche, Shionogi, Union, and Utility; honoraria from Clinical Care Options, Entasis, and Pfizer; participation on the Universidade Federal do Rio Grande do Sul Advisory Board; and an editor's stipend from the British Society for Antimicrobial Chemotherapy (BSAC). Y. D. reports grants paid to his institution from Entasis and Shionogi; consulting fees paid directly to him from GSK, Meiji Seika Pharma, Shionogi, Gilead, FujiFilm and bioMérieux; and speaker payments from MSD, Shionogi, and Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Acquired carbapenemases among CRAb isolates by region. CRAb isolates carried genes for the following acquired carbapenemases: USA: OXA-23 (n = 228), OXA-24 (n = 68), OXA-237 (n = 4), OXA-23 + OXA-24 (n = 3), OXA-23 + OXA-237 (n = 1), and OXA-58 (n = 1); China: OXA-23 (n = 288); South-Central America: OXA-23 (n = 57), OXA-58 (n = 5), NDM (n = 4), OXA-58 + NDM (n = 1), and OXA-24 (n = 1), ; Middle East: OXA-23 (n = 72), OXA-24 (n = 3), and NDM (n = 2); and Australia-Singapore: OXA-23 (n = 26), OXA-23 + NDM (n = 4), and OXA-23 + OXA-58 (n = 1). Abbreviation: CRAb, carbapenem-resistant Acinetobacter baumannii.
Figure 2.
Figure 2.
Population structure of CRAb isolates based on WGS. Phylogenetics are linked with country, clonal group (CG), acquired carbapenemase, capsular polysaccharide locus (KL), lipooligosaccharide outer core locus (OCL), DOOR outcome, and meropenem (MEM) MIC value. Abbreviations: CRAb, carbapenem-resistant Acinetobacter baumannii; DOOR, desirability of outcome ranking; MIC, minimum inhibitory concentration; NA, not applicable; WGS, whole-genome sequencing.
See this image and copyright information in PMC

References

    1. Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318–27. - PubMed
    1. Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis 2018; 18:391–400. - PubMed
    1. Hamidian M, Nigro SJ. Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii. Microb Genom 2019; 5:e000306. - PMC - PubMed
    1. Kostyanev T, Xavier BB, García-Castillo M, et al. Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study. Int J Antimicrob Agents 2021; 57:106345. - PubMed
    1. Rodríguez CH, Balderrama Yarhui N, Nastro M, et al. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in South America. J Med Microbiol 2016; 65:1088–91. - PubMed

Publication types

MeSH terms

Associated data