title: Treatment options for carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii infections.
abstract: Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Because of various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical Center, S319 Falk Medical Building, 3601 Fifth Avenue, Pittsburgh, PA, 15213, USA.
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Viehman
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
references.citation: Chron Respir Dis. 2005;2(1):35-41
references.pmid: 16279747
references.citation: Intensive Care Med. 2003 Nov;29(11):2072-6
references.pmid: 14556048
references.citation: Int J Antimicrob Agents. 2014 Apr;43(4):370-4
references.pmid: 24560919
references.citation: J Antimicrob Chemother. 2007 Aug;60(2):317-22
references.pmid: 17540672
references.citation: Antimicrob Agents Chemother. 2013 Nov;57(11):5247-57
references.pmid: 23939894
references.citation: Antimicrob Agents Chemother. 2014 Sep;58(9):5598-601
references.pmid: 24982065
references.citation: J Korean Med Sci. 2012 May;27(5):471-5
references.pmid: 22563209
references.citation: J Infect Chemother. 2012 Aug;18(4):522-8
references.pmid: 22327516
references.citation: Antimicrob Agents Chemother. 2005 Nov;49(11):4485-91
references.pmid: 16251286
references.citation: Antimicrob Agents Chemother. 2013 Apr;57(4):1756-62
references.pmid: 23357775
references.citation: Antimicrob Agents Chemother. 2011 Jul;55(7):3284-94
references.pmid: 21555763
references.citation: Antimicrob Agents Chemother. 2010 May;54(5):2235-8
references.pmid: 20211887
references.citation: BMC Infect Dis. 2011 Apr 27;11:109
references.pmid: 21521536
references.citation: Antimicrob Agents Chemother. 2007 Nov;51(11):4209-10
references.pmid: 17785513
references.citation: Antimicrob Agents Chemother. 2002 Jun;46(6):1946-52
references.pmid: 12019113
references.citation: Int J Antimicrob Agents. 2009 Dec;34(6):575-9
references.pmid: 19740628
references.citation: Clin Infect Dis. 2003 May 1;36(9):1111-8
references.pmid: 12715304
references.citation: Int J Antimicrob Agents. 2010 Feb;35(2):194-9
references.pmid: 20006471
references.citation: Int J Antimicrob Agents. 2007 Jan;29(1):51-5
references.pmid: 17189095
references.citation: Infect Control Hosp Epidemiol. 2013 Jan;34(1):1-14
references.pmid: 23221186
references.citation: Antimicrob Agents Chemother. 2011 Aug;55(8):3743-51
references.pmid: 21646482
references.citation: Antimicrob Agents Chemother. 2005 Jul;49(7):2941-8
references.pmid: 15980372
references.citation: FEMS Microbiol Lett. 2006 May;258(1):72-7
references.pmid: 16630258
references.citation: Antimicrob Agents Chemother. 2013 Dec;57(12):6270-5
references.pmid: 24100492
references.citation: Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6
references.pmid: 19433570
references.citation: J Microbiol Immunol Infect. 2014 Aug;47(4):324-32
references.pmid: 23726465
references.citation: Clin Microbiol Rev. 2008 Jul;21(3):538-82
references.pmid: 18625687
references.citation: Clin Infect Dis. 2012 Jul;55(2):209-15
references.pmid: 22495546
references.citation: Antimicrob Agents Chemother. 2013 May;57(5):2103-8
references.pmid: 23422916
references.citation: Diagn Microbiol Infect Dis. 2012 Jul;73(3):267-70
references.pmid: 22579652
references.citation: Antimicrob Agents Chemother. 2009 Sep;53(9):4045-7
references.pmid: 19564367
references.citation: J Infect Dis. 2013 Oct 1;208(7):1142-51
references.pmid: 23812239
references.citation: Antimicrob Agents Chemother. 2014;58(2):851-8
references.pmid: 24277037
references.citation: Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1311-22
references.pmid: 24532009
references.citation: Ann Clin Microbiol Antimicrob. 2013 Sep 05;12:24
references.pmid: 24006892
references.citation: Int J Antimicrob Agents. 2012 Jan;39(1):58-63
references.pmid: 22055530
references.citation: J Clin Microbiol. 2011 Nov;49(11):3849-54
references.pmid: 21918019
references.citation: Clin Infect Dis. 2008 Feb 15;46(4):567-70
references.pmid: 18199038
references.citation: Antimicrob Agents Chemother. 2011 Jul;55(7):3534-7
references.pmid: 21502628
references.citation: J Appl Microbiol. 2012 Jun;112(6):1207-11
references.pmid: 22404202
references.citation: Yonsei Med J. 2006 Feb 28;47(1):63-9
references.pmid: 16502486
references.citation: Antimicrob Agents Chemother. 2003 Apr;47(4):1382-90
references.pmid: 12654674
references.citation: Clin Microbiol Infect. 2005 Nov;11(11):874-9
references.pmid: 16216101
references.citation: Infect Control Hosp Epidemiol. 2010 Jan;31(1):92-4
references.pmid: 19929690
references.citation: Clin Infect Dis. 2007 Sep 1;45(5):594-8
references.pmid: 17682994
references.citation: J Antimicrob Chemother. 1992 Mar;29(3):245-77
references.pmid: 1592696
references.citation: Antimicrob Agents Chemother. 2012 Aug;56(8):4416-21
references.pmid: 22687507
references.citation: Antimicrob Agents Chemother. 1991 Oct;35(10):2098-101
references.pmid: 1759832
references.citation: Microb Drug Resist. 2012 Dec;18(6):574-7
references.pmid: 22928863
references.citation: Eur J Clin Microbiol Infect Dis. 2008 Jun;27(6):439-43
references.pmid: 18214558
references.citation: Infect Control Hosp Epidemiol. 2010 Oct;31(10):1057-62
references.pmid: 20715975
references.citation: J Antimicrob Chemother. 2008 Feb;61(2):417-20
references.pmid: 18174197
references.citation: Antimicrob Agents Chemother. 1993 Nov;37(11):2270-7
references.pmid: 8285606
references.citation: Clin Infect Dis. 2013 Aug;57(3):349-58
references.pmid: 23616495
references.citation: Clin Infect Dis. 2014 Jan;58(1):139-41
references.pmid: 24107410
references.citation: PLoS One. 2012;7(12):e52349
references.pmid: 23285002
references.citation: Genome Res. 2013 Jul;23(7):1155-62
references.pmid: 23564252
references.citation: Microbiol Rev. 1993 Mar;57(1):138-63
references.pmid: 8385262
references.citation: J Mol Biol. 2006 Jun 2;359(2):358-64
references.pmid: 16626740
references.citation: J Intensive Care Med. 2010 Nov-Dec;25(6):343-8
references.pmid: 20837632
references.citation: Clin Microbiol Infect. 2012 Mar;18(3):268-81
references.pmid: 21793988
references.citation: Emerg Infect Dis. 2006 Jun;12(6):981-3
references.pmid: 16707056
references.citation: J Clin Microbiol. 2004 Nov;42(11):5102-8
references.pmid: 15528702
references.citation: J Antimicrob Chemother. 2006 Aug;58(2):256-65
references.pmid: 16816396
references.citation: Antimicrob Agents Chemother. 2009 Aug;53(8):3579-81
references.pmid: 19451292
references.citation: Expert Rev Anti Infect Ther. 2013 Apr;11(4):383-93
references.pmid: 23566148
references.citation: Clin Infect Dis. 2011 Feb 1;52(3):352-60
references.pmid: 21193494
references.citation: Clin Microbiol Infect. 2014 May;20(5):416-23
references.pmid: 24131374
references.citation: Clinics (Sao Paulo). 2013 Apr;68(4):569-73
references.pmid: 23778333
references.citation: Antimicrob Agents Chemother. 2011 Oct;55(10):4922-5
references.pmid: 21788456
references.citation: Antimicrob Agents Chemother. 2010 Dec;54(12):4971-7
references.pmid: 20855724
references.citation: Antimicrob Agents Chemother. 2014 May;58(5):2570-9
references.pmid: 24550334
references.citation: Chemotherapy. 2013;59(3):225-31
references.pmid: 24356297
references.citation: Crit Care Med. 2014 May;42(5):1081-8
references.pmid: 24394630
references.citation: Infect Control Hosp Epidemiol. 2014 Jan;35(1):49-55
references.pmid: 24334798
references.citation: Antimicrob Agents Chemother. 2004 Jan;48(1):224-8
references.pmid: 14693543
references.citation: Emerg Infect Dis. 2006 Aug;12(8):1214-22
references.pmid: 16965700
references.citation: Antimicrob Agents Chemother. 2006 Sep;50(9):2946-50
references.pmid: 16940086
references.citation: Diagn Microbiol Infect Dis. 2001 Jul;40(3):117-20
references.pmid: 11502379
references.citation: J Infect. 2012 Mar;64(3):282-90
references.pmid: 22209744
references.citation: Scand J Infect Dis. 2013 Apr;45(4):315-9
references.pmid: 23113680
references.citation: J Antimicrob Chemother. 2001 Apr;47(4):479-82
references.pmid: 11266426
references.citation: Epidemiol Infect. 2013 Jun;141(6):1214-22
references.pmid: 22954403
references.citation: J Med Microbiol. 2012 Aug;61(Pt 8):1103-1108
references.pmid: 22499776
references.citation: J Infect. 2008 Jun;56(6):432-6
references.pmid: 18501431
references.citation: J Antimicrob Chemother. 2007 Mar;59(3):473-7
references.pmid: 17289768
references.citation: J Antimicrob Chemother. 2007 Jan;59(1):128-31
references.pmid: 17082201
references.citation: J Antimicrob Chemother. 2012 Jul;67(7):1607-15
references.pmid: 22441575
references.citation: Euro Surveill. 2013 Aug 01;18(31):
references.pmid: 23929226
references.citation: Antimicrob Agents Chemother. 2005 Jan;49(1):220-9
references.pmid: 15616299
references.citation: Infect Control Hosp Epidemiol. 2010 May;31(5):528-31
references.pmid: 20334552
references.citation: Antimicrob Agents Chemother. 2010 Mar;54(3):1165-72
references.pmid: 20047914
references.citation: Diagn Microbiol Infect Dis. 2010 Oct;68(2):140-51
references.pmid: 20846586
references.citation: Antimicrob Agents Chemother. 2011 Jul;55(7):3370-9
references.pmid: 21576434
references.citation: J Antimicrob Chemother. 2011 Feb;66(2):332-4
references.pmid: 21131322
references.citation: J Antimicrob Chemother. 2010 Dec;65(12):2645-9
references.pmid: 20876621
references.citation: Antimicrob Agents Chemother. 2013 Oct;57(10):4831-40
references.pmid: 23877686
references.citation: Antimicrob Agents Chemother. 2008 Nov;52(11):3837-43
references.pmid: 18725452
references.citation: Antimicrob Agents Chemother. 2010 Oct;54(10):4389-93
references.pmid: 20696879
references.citation: Drugs. 2007;67(13):1829-49
references.pmid: 17722953
references.citation: Microb Drug Resist. 2010 Sep;16(3):209-15
references.pmid: 20707714
references.citation: FEMS Microbiol Rev. 2011 Sep;35(5):736-55
references.pmid: 21303394
references.citation: Clin Infect Dis. 2002 Jun 1;34(11):1425-30
references.pmid: 12015687
references.citation: Clin Pharm. 1988 Jan;7(1):37-51
references.pmid: 3278833
references.citation: Antimicrob Agents Chemother. 2011 Oct;55(10):4844-9
references.pmid: 21825287
references.citation: Crit Care Med. 2006 Jun;34(6):1589-96
references.pmid: 16625125
references.citation: Eur J Clin Microbiol Infect Dis. 2010 May;29(5):527-31
references.pmid: 20182760
references.citation: Pharmacotherapy. 2007 Aug;27(8):1198-201
references.pmid: 17655518
references.citation: Clin Microbiol Infect. 2012 Sep;18(9):870-6
references.pmid: 21999321
references.citation: Antimicrob Agents Chemother. 2011 Mar;55(3):947-53
references.pmid: 21173183
references.citation: J Korean Med Sci. 2012 Aug;27(8):939-47
references.pmid: 22876063
references.citation: Diagn Microbiol Infect Dis. 2012 Nov;74(3):213-23
references.pmid: 22959816
references.citation: Eur J Clin Microbiol Infect Dis. 2013 Sep;32(9):1211-20
references.pmid: 23553594
references.citation: J Antimicrob Chemother. 2005 Oct;56(4):611-4
references.pmid: 16120626
references.citation: J Antimicrob Chemother. 2010 Jun;65(6):1311-2
references.pmid: 20378673
references.citation: Antimicrob Agents Chemother. 1997 Oct;41(10):2265-9
references.pmid: 9333059
references.citation: Clin Infect Dis. 2013 Nov;57(9):1300-3
references.pmid: 23840000
references.citation: Southeast Asian J Trop Med Public Health. 2011 Jul;42(4):890-900
references.pmid: 22299471
references.citation: Int J Antimicrob Agents. 2013 Jun;41(6):499-508
references.pmid: 23507414
references.citation: J Antimicrob Chemother. 2003 Mar;51(3):565-74
references.pmid: 12615856
references.citation: Antimicrob Agents Chemother. 2012 Aug;56(8):4241-9
references.pmid: 22615285
references.citation: J Antimicrob Chemother. 2011 Jun;66(6):1255-9
references.pmid: 21398294
references.citation: J Antimicrob Chemother. 2013 Dec;68(12):2786-91
references.pmid: 23838947
references.citation: Clin Microbiol Infect. 2006 Feb;12(2):123-30
references.pmid: 16441449
references.citation: Int J Infect Dis. 2010 Sep;14(9):e764-9
references.pmid: 20646946
references.citation: BMC Infect Dis. 2012 Dec 13;12:351
references.pmid: 23237530
references.citation: J Antimicrob Chemother. 2008 Jun;61(6):1369-75
references.pmid: 18367459
references.citation: Expert Rev Anti Infect Ther. 2013 Apr;11(4):395-409
references.pmid: 23566149
references.citation: Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011
references.pmid: 18947320
references.citation: Antimicrob Agents Chemother. 2013 May;57(5):2121-6
references.pmid: 23439638
references.citation: Antimicrob Agents Chemother. 2010 Mar;54(3):1354-7
references.pmid: 20038618
references.citation: Emerg Infect Dis. 2010 Jan;16(1):35-40
references.pmid: 20031040
references.citation: Int J Antimicrob Agents. 2013 Mar;41(3):285-7
references.pmid: 23312607
references.citation: J Antimicrob Chemother. 2007 May;59(5):1001-4
references.pmid: 17363424
references.citation: J Clin Microbiol. 2010 Apr;48(4):1132-8
references.pmid: 20107089
references.citation: Clin Microbiol Infect. 2013 Aug;19(8):737-42
references.pmid: 23034071
references.citation: Antimicrob Agents Chemother. 2005 Aug;49(8):3198-202
references.pmid: 16048925
references.citation: J Antimicrob Chemother. 2007 Aug;60(2):454-5
references.pmid: 17561497
references.citation: Antimicrob Agents Chemother. 2000 Feb;44(2):428-32
references.pmid: 10639377
references.citation: Antimicrob Agents Chemother. 2009 Nov;53(11):4907-10
references.pmid: 19704130
references.citation: Chest. 2013 Dec;144(6):1768-1775
references.pmid: 23989805
references.citation: Antimicrob Agents Chemother. 2010 May;54(5):1742-8
references.pmid: 20160050