Healthcare-associated carbapenem-resistant Acinetobacter baumannii (CRAB) infections are a serious threat associated with global epidemic clones and a variety of carbapenemase gene classes. In this study, we describe the molecular epidemiology, including whole-genome sequencing analysis and antimicrobial susceptibility profiles of 92 selected, nonredundant CRAB collected through public health efforts in the United States from 2013 to 2017. Among the 92 isolates, the Oxford (OX) multilocus sequence typing scheme identified 30 sequence types (STs); the majority of isolates (n = 59, 64%) represented STs belonging to the international clonal complex 92 (CC92OX). Among these, ST208OX (n = 21) and ST281OX (n = 20) were the most common. All isolates carried an OXA-type carbapenemase gene, comprising 20 alleles. Ninety isolates (98%) encoded an intrinsic OXA-51-like enzyme; 67 (73%) harbored an additional acquired blaOXA gene, most commonly blaOXA-23 (n = 45; 49%).
Compared with isolates harboring only intrinsic oxacillinase genes, acquired blaOXA gene presence was associated with higher prevalence of resistance and a higher median minimum inhibitory concentration to the carbapenem imipenem (64 μg/mL vs. 8 μg/mL), and antibiotics from other drug classes, including penicillin, aminoglycosides, cephalosporins, and polymyxins. These data illustrate the wide distribution of CC92OX and high prevalence of acquired blaOXA carbapenemase genes among CRAB in the United States.
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References
1.
Bergogne-BerezinE., and TownerK.J.. 1996. Acinetobacter spp. as nosocomial pathogens: microbiological,, clinical, and epidemiological features. Clin. Microbiol. Rev. 9:148–165.
2.
KarageorgopoulosD.E., and FalagasM.E.. 2008. Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet. Infect. Dis. 8:751–762.
3.
TheakerC, AzadianB., and SoniN.. 2003. The impact of Acinetobacter baumannii in the intensive care unit. Anaesthesia, 58:271–274.
EvansB.A., and AmyesS.G.B. 2014. OXA β-lactamases. Clin. Microbiol. Rev. 27:241–263.
7.
QueenanA.M., and BushK.. 2007. Carbapenemases: the versatile beta-lactamases. Clin. Microbiol. Rev. 20:440–458.
8.
BulensS.N., YiS.H, WaltersM.S, et al.2018. Carbapenem-nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012–2015. Emerg. Infect. Dis. 24:727–734.
9.
BartualS.G., SeifertH., HipplerC., LuzonM.A.D, WisplinghoffH., and Rodríguez-ValeraF.. 2005. Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii. J. Clin. Microbiol. 43:4382–4390.
10.
DiancourtL., PassetV., NemecA., DijkshoornL., and BrisseS.. 2010. The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS One, 5:e10034.
11.
HigginsP.G., DammhaynC., HackelM., and SeifertH.. 2010. Global spread of carbapenem-resistant Acinetobacter baumannii. J. Antimicrob. Chemother. 65:233–238.
12.
ZarrilliR., PournarasS., GiannouliM., and TsakrisA.. 2013. Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. Int. J. Antimicrob. Agents, 41:11–19.
13.
Adams-HaduchJ.M., OnuohaE.O, BogdanovichT., et al.2011. Molecular epidemiology of carbapenem-nonsusceptible Acinetobacter baumannii in the United States. J. Clin. Microbiol. 49:3849–3854.
14.
HalpinA.L., McDonaldL.C, and ElkinsC.A.. 2021. Framing bacterial genomics for public health(care). J. Clin. Microbiol. 59:e0013521.
15.
StantonR.A., McAllisterG., DanielsJ.B, et al.2020. Development and application of a core genome multilocus sequence typing scheme for the health care-associated pathogen Pseudomonas aeruginosa. J. Clin. Microbiol. 58:e00214–20.
16.
JolleyK.A., and MaidenM.C.. 2010. BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics. 11:595.
17.
FranciscoA.P., BugalhoM., RamirezM., and CarricoJ.A.. 2009. Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics, 10:152.
ArgimónS., AbudahabK., GoaterR.J.E, et al.2016. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb. Genom. 2:e000093.
20.
Clinical and Laboratory Standards Institute. 2018. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. Wayne, PA.
21.
Clinical and Laboratory Standards Institute. 2019. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Ninth Informational Supplement. Wayne, PA.
22.
CodjoeF.S., and DonkorE.S.. 2018. Carbapenem resistance: a review. Med. Sci. 6:1.
23.
LimaW.G., Silva AlvesG.C, SanchesC., Antunes FernandesS.O, and de PaivaM.C.. 2019. Carbapenem-resistant Acinetobacter baumannii in patients with burn injury: a systematic review and meta-analysis. Burns, 45:1495–1508.
24.
MagiorakosA.P., SrinivasanA., CareyR.B, et al.2012. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18:268–281.
25.
NemecA., JandaL., MelterO., and DijkshoornL.. 1999. Genotypic and phenotypic similarity of multiresistant Acinetobacter baumannii isolates in the Czech Republic. J. Med. Microbiol. 48:287–296.
26.
GaiarsaS., Batisti BiffignandiG., EspositoE.P, et al.2019. Comparative analysis of the two Acinetobacter baumannii multilocus sequence typing (MLST) schemes. Front. Microbiol. 10:930.
27.
HamidianM., NigroS.J, and HallR.M.. 2017. Problems with the oxford multilocus sequence typing scheme for Acinetobacter baumannii: do sequence type 92 (ST92) and ST109 exist? J. Clin. Microbiol. 55:2287–2289.
28.
TomaschekF., HigginsP.G, StefanikD., WisplinghoffH., and SeifertH.. 2016. Head-to-head comparison of two multi-locus sequence typing (MLST) schemes for characterization of Acinetobacter baumannii outbreak and sporadic isolates. PLoS One, 11:e0153014.
29.
Alcántar-CurielM.D., Rosales-ReyesR., Jarillo-QuijadaM.D, et al. 2019. Carbapenem-resistant, Acinetobacter baumannii, in three tertiary care hospitals in Mexico: virulence profiles, innate immune response and clonal dissemination. Front. Microbiol. 10:, 2116.
30.
BoydD.A., MatasejeL.F, PeludeL., et al.2018. Results from the Canadian Nosocomial Infection Surveillance Program for detection of carbapenemase-producing Acinetobacter spp. in Canadian, hospitals, 2010–16. J. Antimicrob. Chemother. 74:315–320.
31.
BuserG.L., CassidyP.M, CunninghamM.C, et al.2017. Failure to communicate: transmission of extensively drug-resistant bla OXA-237-containing Acinetobacter baumannii-multiple facilities in Oregon, 2012–2014. Infect. Control Hosp. Epidemiol. 38:1335–1341.
32.
KimD.H., ChoiJ.-Y, KimH.W, et al.2013. Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands. Antimicrob. Agents Chemother. 57:5239–5246.
33.
QuJ., DuY., YuR., and LüX.. 2016. The first outbreak caused by Acinetobacter baumannii ST208 and ST195 in China. BioMed Res. Int. 2016:9254907.
34.
LeeY., BaeI.K, KimJ., JeongS.H, and LeeK.. 2012. Dissemination of ceftazidime-resistant Acinetobacter baumannii clonal complex 92 in Korea. J. Appl. Microbiol. 112:1207–1211.
35.
NemecA., KřížováL., MaixnerováM., et al.2008. Emergence of carbapenem resistance in Acinetobacter baumannii in the Czech Republic is associated with the spread of multidrug-resistant strains of European clone II. J. Antimicrob. Chemother. 62:484–489.
36.
WuW, HeY., LuJ., LuY., WuJ., and LiuY.. 2015. Transition of blaOXA-58-like to blaOXA-23-like in Acinetobacter baumannii Clinical Isolates in Southern China: an 8-year study. PLoS One, 10:e0137174.
37.
MugnierP.D., PoirelL., NaasT., and NordmannP.. 2010. Worldwide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg. Infect. Dis. 16:35–40.
38.
HigginsP.G., Pérez-LlarenaF.J, ZanderE., FernándezA., BouG., and SeifertH.. 2013. OXA-235, a novel class D β-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. Antimicrob. Agents Chemother. 57:2121–2126.
39.
HujerA.M., HigginsP.G, RudinS.D, et al.2017. Nosocomial outbreak of extensively drug-resistant Acinetobacter baumannii isolates containing bla(OXA-237) carried on a plasmid. Antimicrob. Agents Chemother. 61:e00797–17.
40.
de Sá CavalcantiF.L., AlmeidaA.C.S, VilelaM.A, de Morais JuniorM.A, de MoraisM.M.C, and Leal-BalbinoT.C.. 2013. Emergence of extensively drug-resistant OXA-72–producing Acinetobacter baumannii in Recife, Brazil: risk of clonal dissemination? Diagn. Microbiol. Infect. Dis. 77:250–251.
41.
DortetL., BonninR.A, BernabeuS., et al.2016. First occurrence of OXA-72-producing Acinetobacter baumannii in Serbia. Antimicrob. Agents Chemother. 60:5724–5730.
42.
Franolić-KukinaI., BedenićB., BudimirA., HerljevićZ., VranešJ., and HigginsP.G.. 2011. Clonal spread of carbapenem-resistant OXA-72-positive Acinetobacter baumannii in a Croatian university hospital. Int. J. Infect. Dis. 15:e706–e709.
43.
GeorgescuM., GheorgheI., DuduA., et al.2016. First report of OXA-72 producing Acinetobacter baumannii in Romania. N. Microb. N. Infect. 13:87–88.
44.
KuoS.C., YangS.-P, LeeY.-T, et al.2013. Dissemination of imipenem-resistant Acinetobacter baumannii with new plasmid-borne blaOXA-72 in Taiwan. BMC Infect. Dis. 13:319.
45.
MontealegreM.C., MayaJ.J, CorreaA., et al.2012. First identification of OXA-72 carbapenemase from Acinetobacter pittii in Colombia. Antimicrob. Agents Chemother. 56:3996–3998.
46.
SaavedraS.Y., R. Cayô, A.C. Gales, A.L. Leal, and C.H. Saavedra. Early dissemination of OXA-72-producing Acinetobacter baumannii strain in Colombia: a case report. Braz. J. Infect. Dis. 18:678–680.
47.
TianG.B., Adams-HaduchJ.M, BogdanovichT., et al.2011. Identification of diverse OXA-40 group carbapenemases, including a novel variant, OXA-160, from Acinetobacter baumannii in Pennsylvania. Antimicrob. Agents Chemother. 55:429–432.
48.
ZilberbergM.D., NathansonB.H, SulhamK., FanW., and ShorrA.F.. 2016. Multidrug resistance, inappropriate empiric therapy, and hospital mortality in Acinetobacter baumannii pneumonia and sepsis. Crit. Care. 20:221.
49.
OlivaA., CeccarelliG., De AngelisM., et al.2020. Cefiderocol for compassionate use in the treatment of complicated infections caused by extensively and pan-resistant Acinetobacter baumannii. J. Glob. Antimicrob. Resist. 23:292–296.
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