Carbapenem resistance in Acinetobacter baumannii: Laboratory challenges, mechanistic insights and therapeutic strategies

Expert Review of Anti-Infective Therapy

Volumn 11, Issue 4, 2013, Pages 395-409

  Abbott, Iain ^a   Cerqueira, Gustavo M ^b   Bhuiyan, Saruar ^b   Peleg, Anton Y ^a,b  

^a ALFRED HOSPITAL   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

A. baumannii; Acinetobacter baumannii; antibiotic resistance; combination antibiotic therapy; host pathogen interaction; laboratory detection; minimum inhibitory concentration; pharmacodynamics; pharmacokinetics

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; AMOXICILLIN PLUS CLAVULANIC ACID; AMPICILLIN; CARBAPENEM DERIVATIVE; CEFAZOLIN; CEFOTAXIME; CEFTAZIDIME; CEFTRIAXONE; CIPROFLOXACIN; COLISTIMETHATE; COLISTIN; DORIPENEM; ERTAPENEM; FOSFOMYCIN; IMIPENEM; MEROPENEM; PIPERACILLIN; PIPERACILLIN PLUS TAZOBACTAM; POLYMYXIN B; POLYMYXIN DERIVATIVE; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIFAMPICIN; SULBACTAM; SULTAMICILLIN; TETRACYCLINE DERIVATIVE; TICARCILLIN; TIGECYCLINE; TIMENTIN; TRIMETHOPRIM;

ACINETOBACTER BAUMANNII; ACINETOBACTER INFECTION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; BACTEREMIA; BACTERIAL PNEUMONIA; BACTERIUM IDENTIFICATION; BLOODSTREAM INFECTION; COMBINATION CHEMOTHERAPY; DISTRIBUTION VOLUME; DRUG EFFICACY; DRUG MEGADOSE; EPIDEMIC; GRAM NEGATIVE INFECTION; GRAM NEGATIVE SEPSIS; HOSPITAL INFECTION; HOST PATHOGEN INTERACTION; HUMAN; LOADING DRUG DOSE; MINIMUM INHIBITORY CONCENTRATION; MONOTHERAPY; MULTIDRUG RESISTANCE; NEPHROTOXICITY; NONHUMAN; POLYMERASE CHAIN REACTION; REVIEW;

ACINETOBACTER BAUMANNII; ACINETOBACTER INFECTIONS; AMINOGLYCOSIDES; ANTI-BACTERIAL AGENTS; BETA-LACTAM RESISTANCE; BETA-LACTAMASES; CARBAPENEMS; CROSS INFECTION; DISEASE MANAGEMENT; EPIDEMIOLOGICAL MONITORING; HUMANS; POLYMYXINS; PORINS;

EID: 84879918924     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.13.21     Document Type: Review

References (162)

1. Kempf M, Rolain JM. Emergence of resistance to carbapenems in Acinetobacter baumannii in Europe: clinical impact and therapeutic options. Int. J. Antimicrob. Agents 39(2), 105-114 (2012).
2. Berlau J, Aucken HM, Houang E, Pitt TL. Isolation of Acinetobacter spp. including A. baumannii from vegetables: implications for hospital-acquired infections. J. Hosp. Infect. 42(3), 201-204 (1999).
3. Chu YW, Leung CM, Houang ET et al. Skin carriage of Acinetobacters in Hong Kong. J. Clin. Microbiol. 37(9), 2962-2967 (1999).
4. Seifert H, Dijkshoorn L, Gerner-Smidt P, Pelzer N, Tjernberg I, Vaneechoutte M. Distribution of Acinetobacter species on human skin: comparison of phenotypic and genotypic identification methods. J. Clin. Microbiol. 35(11), 2819-2825 (1997).
5. Di Popolo A, Giannouli M, Triassi M, Brisse S, Zarrilli R. Molecular epidemiological investigation of multidrug-resistant Acinetobacter baumannii strains in four Mediterranean countries with a multilocus sequence typing scheme. Clin. Microbiol. Infect. 17(2), 197-201 (2011).
6. Perez F, Ponce-Terashima R, Adams MD, Bonomo RA. Are we closing in on an'elusive enemy'? The current status of our battle with Acinetobacter baumannii. Virulence 2(2), 86-90 (2011).
7. Perez F, Endimiani A, Bonomo RA. Why are we afraid of Acinetobacter baumannii? Expert Rev. Anti. Infect. Ther. 6(3), 269-271 (2008).
8. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51(10), 3471-3484 (2007).
9. Young LS, Sabel AL, Price CS. Epidemiologic, clinical, and economic evaluation of an outbreak of clonal multidrug-resistant Acinetobacter baumannii infection in a surgical intensive care unit. Infect. Control Hosp. Epidemiol. 28(11), 1247-1254 (2007).
10. Yuji K, Oiso G, Matsumura T, Murashige N, Kami M. Police investigation into multidrug-resistant Acinetobacter baumannii outbreak in Japan. Clin. Infect. Dis. 52(3), 422 (2011).
11. Chang HC, Wei YF, Dijkshoorn L, Vaneechoutte M, Tang CT, Chang TC. Species-level identification of isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex by sequence analysis of the 16S-23S rRNA gene spacer region. J. Clin. Microbiol. 43(4), 1632-1639 (2005).
12. Nemec A, Krizova L, Maixnerova M et al. Genotypic and phenotypic characterization of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex with the proposal of Acinetobacter pittii sp. nov. (formerly Acinetobacter genomic species 3) and Acinetobacter nosocomialis sp. nov. (formerly Acinetobacter genomic species 13TU). Res. Microbiol. 162(4), 393-404 (2011).
13. Chuang YC, Sheng WH, Li SY et al. Influence of genospecies of Acinetobacter baumannii complex on clinical outcomes of patients with Acinetobacter bacteremia. Clin. Infect. Dis. 52(3), 352-360 (2011).
14. European Centre for Disease Prevention and Control. Annual Epidemiological Report 2011. Reporting on 2009 surveillance data and 2010 epidemic intelligence data.: ECDC, Stockholm, Sweden (2011).
15. Nordmann P, Picazo JJ, Mutters R et al.; COMPACT study group. Comparative activity of carbapenem testing: the COMPACT study. J. Antimicrob. Chemother. 66(5), 1070-1078 (2011).
16. Wisplinghoff H, Paulus T, Lugenheim M et al. Nosocomial bloodstream infections due to Acinetobacter baumannii, Acinetobacter pittii and Acinetobacter nosocomialis in the United States. J. Infect. 64(3), 282-290 (2012).
17. Brauers J, Frank U, Kresken M, Rodloff AC, Seifert H. Activities of various β-lactams and β-lactam/β-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains. Clin. Microbiol. Infect. 11(1), 24-30 (2005).
18. Lim YM, Shin KS, Kim J. Distinct antimicrobial resistance patterns and antimicrobial resistance-harboring genes according to genomic species of Acinetobacter isolates. J. Clin. Microbiol. 45(3), 902-905 (2007).
19. Lee JH, Choi CH, Kang HY et al. Differences in phenotypic and genotypic traits against antimicrobial agents between Acinetobacter baumannii and Acinetobacter genomic species 13TU. J. Antimicrob. Chemother. 59(4), 633-639 (2007).
20. Lin YC, Sheng WH, Chen YC, Chang SC, Hsia KC, Li SY. Differences in carbapenem resistance genes among Acinetobacter baumannii, Acinetobacter genospecies 3 and Acinetobacter genospecies 13TU in Taiwan. Int. J. Antimicrob. Agents 35(5), 439-443 (2010).
21. Adams-Haduch JM, Onuoha EO, Bogdanovich T et al. Molecular epidemiology of carbapenem-nonsusceptible Acinetobacter baumannii in the United States. J. Clin. Microbiol. 49(11), 3849-3854 (2011).
22. Mendes RE, Bell JM, Turnidge JD, Castanheira M, Jones RN. Emergence and widespread dissemination of OXA-23, -24/40 and -58 carbapenemases among Acinetobacter spp. in Asia-Pacific nations: report from the SENTRY Surveillance Program. J. Antimicrob. Chemother. 63(1), 55-59 (2009).
23. Mendes RE, Farrell DJ, Sader HS, Jones RN. Comprehensive assessment of tigecycline activity tested against a worldwide collection of Acinetobacter spp. (2005-2009). Diagn. Microbiol. Infect. Dis. 68(3), 307-311 (2010).
24. Wang YF, Dowzicky MJ. In vitro activity of tigecycline and comparators on Acinetobacter spp. isolates collected from patients with bacteremia and MIC change during the Tigecycline Evaluation and Surveillance Trial, 2004 to 2008. Diagn. Microbiol. Infect. Dis. 68(1), 73-79 (2010).
25. Endo S, Yano H, Hirakata Y et al. Molecular epidemiology of carbapenemnon-susceptible Acinetobacter baumannii in Japan. J. Antimicrob. Chemother. 67(7), 1623-1626 (2012).
26. Poirel L, Berçot B, Millemann Y, Bonnin RA, Pannaux G, Nordmann P. Carbapenemase-producing Acinetobacter spp. in cattle, France. Emerging Infect. Dis. 18(3), 523-525 (2012).
27. Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin. Infect. Dis. 43(Suppl. 2), S49-S56 (2006).
28. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin. Microbiol. Rev. 21(3), 538-582 (2008).
29. Fournier PE, Vallenet D, Barbe V et al. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet. 2(1), e7 (2006).
30. Iacono M, Villa L, Fortini D et al. Whole-genome pyrosequencing of an epidemic multidrug-resistant Acinetobacter baumannii strain belonging to the European clone II group. Antimicrob. Agents Chemother. 52(7), 2616-2625 (2008).
31. Imperi F, Antunes LC, Blom J et al. The genomics of Acinetobacter baumannii: insights into genome plasticity, antimicrobial resistance and pathogenicity. IUBMB Life 63(12), 1068-1074 (2011).
32. Falagas ME, Rafailidis PI, Matthaiou DK, Virtzili S, Nikita D, Michalopoulos A. Pandrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients. Int. J. Antimicrob. Agents 32(5), 450-454 (2008).
33. Queenan AM, Bush K. Carbapenemases: the versatile β-lactamases. Clin. Microbiol. Rev. 20(3), 440-458, table of contents (2007).
34. Piddock LJ. Multidrug-resistance efflux pumps - not just for resistance. Nat. Rev. Microbiol. 4(8), 629-636 (2006).
35. Coyne S, Courvalin P, Périchon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob. Agents Chemother. 55(3), 947-953 (2011).
36. Marchand I, Damier-Piolle L, Courvalin P, Lambert T. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob. Agents Chemother. 48(9), 3298-3304 (2004).
37. Piddock LJ. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev. 19(2), 382-402 (2006).
38. Huang L, Sun L, Xu G, Xia T. Differential susceptibility to carbapenems due to the AdeABC efflux pump among nosocomial outbreak isolates of Acinetobacter baumannii in a Chinese hospital. Diagn. Microbiol. Infect. Dis. 62(3), 326-332 (2008).
39. Hornsey M, Ellington MJ, Doumith M et al. AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii. J. Antimicrob. Chemother. 65(8), 1589-1593 (2010).
40. Peleg AY, Adams J, Paterson DL. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob. Agents Chemother. 51(6), 2065-2069 (2007).
41. Héritier C, Poirel L, Lambert T, Nordmann P. Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii. Antimicrob. Agents Chemother. 49(8), 3198-3202 (2005).
42. Rosenfeld N, Bouchier C, Courvalin P, Périchon B. Expression of the resistancenodulation-cell division pump AdeIJK in Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator. Antimicrob. Agents Chemother. 56(5), 2504-2510 (2012).
43. Damier-Piolle L, Magnet S, Brémont S, Lambert T, Courvalin P. AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrob. Agents Chemother. 52(2), 557-562 (2008).
44. Coyne S, Rosenfeld N, Lambert T, Courvalin P, Périchon B. Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii. Antimicrob. Agents Chemother. 54(10), 4389-4393 (2010).
45. Vila J, Martí S, Sánchez-Céspedes J. Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J. Antimicrob. Chemother. 59(6), 1210-1215 (2007).
46. Catel-Ferreira M, Nehmé R, Molle V et al. Deciphering the function of the outer membrane protein OprD homologue of Acinetobacter baumannii. Antimicrob. Agents Chemother. 56(7), 3826-3832 (2012).
47. Mussi MA, Limansky AS, Viale AM. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of β-barrel outer membrane proteins. Antimicrob. Agents Chemother. 49(4), 1432-1440 (2005).
48. Mussi MA, Relling VM, Limansky AS, Viale AM. CarO, an Acinetobacter baumannii outer membrane protein involved in carbapenem resistance, is essential for L-ornithine uptake. FEBS Lett. 581(29), 5573-5578 (2007).
49. Catel-Ferreira M, Coadou G, Molle V et al. Structure-function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. J. Antimicrob. Chemother. 66(9), 2053-2056 (2011).
50. del Mar Tomás M, Beceiro A, Pérez A et al. Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton outer membrane protein associated with carbapenem resistance in Acinetobacter baumannii. Antimicrob. Agents Chemother. 49(12), 5172-5175 (2005).
51. Bratu S, Landman D, Martin DA, Georgescu C, Quale J. Correlation of antimicrobial resistance with β-lactamases, the OmpA-like porin, and efflux pumps in clinical isolates of Acinetobacter baumannii endemic to New York City. Antimicrob. Agents Chemother. 52(9), 2999-3005 (2008).
52. Gaddy JA, Tomaras AP, Actis LA. The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells. Infect. Immun. 77(8), 3150-3160 (2009).
53. Smith MG, Gianoulis TA, Pukatzki S et al. New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev. 21(5), 601-614 (2007).
54. McConnell MJ, Actis L, Pachón J. Acinetobacter baumannii: human infections, factors contributing to pathogenesis and animal models. FEMS Microbiol. Rev. 37(2), 130-155 (2013).
55. Dorsey CW, Tomaras AP, Connerly PL, Tolmasky ME, Crosa JH, Actis LA. The siderophore-mediated iron acquisition systems of Acinetobacter baumannii ATCC 19606 and Vibrio anguillarum 775 are structurally and functionally related. Microbiology 150(Pt 11), 3657-3667 (2004).
56. Mihara K, Tanabe T, Yamakawa Y et al. Identification and transcriptional organization of a gene cluster involved in biosynthesis and transport of acinetobactin, a siderophore produced by Acinetobacter baumannii ATCC 19606T. Microbiology 150(Pt 8), 2587-2597 (2004).
57. Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH. Development of a highthroughput cloning strategy for characterization of Acinetobacter baumannii drug transporter proteins. J. Mol. Microbiol. Biotechnol. 20(4), 211-219 (2011).
58. Penwell WF, Arivett BA, Actis LA. The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence. PLoS ONE 7(5), e36493 (2012).
59. Dorsey CW, Beglin MS, Actis LA. Detection and analysis of iron uptake components expressed by Acinetobacter baumannii clinical isolates. J. Clin. Microbiol. 41(9), 4188-4193 (2003).
60. Cerqueira GM, Peleg AY. Insights into Acinetobacter baumannii pathogenicity. IUBMB Life 63(12), 1055-1060 (2011).
61. Iwashkiw JA, Seper A, Weber BS et al. Identification of a general O-linked protein glycosylation system in Acinetobacter baumannii and its role in virulence and biofilm formation. PLoS Pathog. 8(6), e1002758 (2012).
62. Tomaras AP, Dorsey CW, Edelmann RE, Actis LA. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 149(Pt 12), 3473-3484 (2003).
63. de Breij A, Gaddy J, van der Meer J et al. CsuA/BABCDE-dependent pili are not involved in the adherence of Acinetobacter baumannii ATCC19606(T) to human airway epithelial cells and their inflammatory response. Res. Microbiol. 160(3), 213-218 (2009).
64. de Breij A, Dijkshoorn L, Lagendijk E et al. Do biofilm formation and interactions with human cells explain the clinical success of Acinetobacter baumannii? PLoS ONE 5(5), e10732 (2010).
65. Tomaras AP, Flagler MJ, Dorsey CW, Gaddy JA, Actis LA. Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology 154(Pt 11), 3398-3409 (2008).
66. Choi AH, Slamti L, Avci FY, Pier GB, Maira-Litrán T. The pgaABCD locus of Acinetobacter baumannii encodes the production of poly-β-1-6- Nacetylglucosamine, which is critical for biofilm formation. J. Bacteriol. 191(19), 5953-5963 (2009).
67. Loehfelm TW, Luke NR, Campagnari AA. Identification and characterization of an Acinetobacter baumannii biofilm-associated protein. J. Bacteriol. 190(3), 1036-1044 (2008).
68. Bentancor LV, Camacho-Peiro A, Bozkurt-Guzel C, Pier GB, Maira-Litrán T. Identification of Ata, a multifunctional trimeric autotransporter of Acinetobacter baumannii. J. Bacteriol. 194(15), 3950-3960 (2012).
69. Choi CH, Lee EY, Lee YC et al. Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells. Cell. Microbiol. 7(8), 1127-1138 (2005).
70. Kim SW, Choi CH, Moon DC et al. Serum resistance of Acinetobacter baumannii through the binding of factor H to outer membrane proteins. FEMS Microbiol. Lett. 301(2), 224-231 (2009).
71. Choi CH, Hyun SH, Lee JY et al. Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity. Cell. Microbiol. 10(2), 309-319 (2008).
72. Choi CH, Lee JS, Lee YC, Park TI, Lee JC. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol. 8, 216 (2008).
73. Russo TA, MacDonald U, Beanan JM et al. Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumannii in vitro and in vivo. J. Infect. Dis. 199(4), 513-521 (2009).
74. Jacobs AC, Hood I, Boyd KL et al. Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis. Infect. Immun. 78(5), 1952-1962 (2010).
75. Luke NR, Sauberan SL, Russo TA et al. Identification and characterization of a glycosyltransferase involved in Acinetobacter baumannii lipopolysaccharide core biosynthesis. Infect. Immun. 78(5), 2017-2023 (2010).
76. Russo TA, Luke NR, Beanan JM et al. The K1 capsular polysaccharide of Acinetobacter baumannii strain 307-0294 is a major virulence factor. Infect. Immun. 78(9), 3993-4000 (2010).
77. González RH, Nusblat A, Nudel BC. Detection and characterization of quorum sensing signal molecules in Acinetobacter strains. Microbiol. Res. 155(4), 271-277 (2001).
78. Niu C, Clemmer KM, Bonomo RA, Rather PN. Isolation and characterization of an autoinducer synthase from Acinetobacter baumannii. J. Bacteriol. 190(9), 3386-3392 (2008).
79. Zimbler DL, Park TM, Arivett BA et al. Stress response and virulence functions of the Acinetobacter baumannii NfuA Fe-S scaffold protein. J. Bacteriol. 194(11), 2884-2893 (2012).
80. Smani Y, McConnell MJ, Pachón J. Role of fibronectin in the adhesion of Acinetobacter baumannii to host cells. PLoS ONE 7(4), e33073 (2012).
81. Camarena L, Bruno V, Euskirchen G, Poggio S, Snyder M. Molecular mechanisms of ethanol-induced pathogenesis revealed by RNA-sequencing. PLoS Pathog. 6(4), e1000834 (2010).
82. Peleg AY, Tampakakis E, Fuchs BB, Eliopoulos GM, Moellering RC Jr, Mylonakis E. Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 105(38), 14585-14590 (2008).
83. Joly-Guillou ML. Clinical impact and pathogenicity of Acinetobacter. Clin. Microbiol. Infect. 11(11), 868-873 (2005).
84. Knapp S, Wieland CW, Florquin S et al. Differential roles of CD14 and toll-like receptors 4 and 2 in murine Acinetobacter pneumonia. Am. J. Respir. Crit. Care Med. 173(1), 122-129 (2006).
85. Erridge C, Moncayo-Nieto OL, Morgan R, Young M, Poxton IR. Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling. J. Med. Microbiol. 56(Pt 2), 165-171 (2007).
86. van Faassen H, KuoLee R, Harris G, Zhao X, Conlan JW, Chen W. Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice. Infect. Immun. 75(12), 5597-5608 (2007).
87. Mortensen BL, Skaar EP. Host-microbe interactions that shape the pathogenesis of Acinetobacter baumannii infection. Cell. Microbiol. 14(9), 1336-1344 (2012).
88. Breslow JM, Meissler JJ Jr, Hartzell RR et al. Innate immune responses to systemic Acinetobacter baumannii infection in mice: neutrophils, but not interleukin-17, mediate host resistance. Infect. Immun. 79(8), 3317-3327 (2011).
89. Goel VK, Kapil A. Monoclonal antibodies against the iron regulated outer membrane Proteins of Acinetobacter baumannii are bactericidal. BMC Microbiol. 1, 16 (2001).
90. Smith AW, Alpar KE. Immune response to Acinetobacter calcoaceticus infection in man. J. Med. Microbiol. 34(2), 83-88 (1991).
91. McConnell MJ, Pachón J. Active and passive immunization against Acinetobacter baumannii using an inactivated whole cell vaccine. Vaccine 29(1), 1-5 (2010).
92. McConnell MJ, Rumbo C, Bou G, Pachón J. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii. Vaccine 29(34), 5705-5710 (2011).
93. Bentancor LV, O'Malley JM, Bozkurt-Guzel C, Pier GB, Maira-Litran T. Poly-N-acetyl-β-(1-6)-glucosamine is a target for protective immunity against Acinetobacter baumannii infections. Infect Immun., 80(2), 651-656 (2012).
94. Bentancor LV, Routray A, Bozkurt-Guzel C, Camacho-Peiro A, Pier GB, Maira-Litrán T. Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections. Infect. Immun. 80(10), 3381-3388 (2012).
95. Fattahian Y, Rasooli I, Mousavi Gargari SL, Rahbar MR, Darvish Alipour Astaneh S, Amani J. Protection against Acinetobacter baumannii infection via its functional deprivation of biofilm associated protein (Bap). Microb. Pathog. 51(6), 402-406 (2011).
96. Luo G, Lin L, Ibrahim AS et al. Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumannii infection. PLoS ONE 7(1), e29446 (2012).
97. Sedo O, Vorác A, Zdráhal Z. Optimization of mass spectral features in MALDI-TOF MS profiling of Acinetobacter species. Syst. Appl. Microbiol. 34(1), 30-34 (2011).
98. Espinal P, Seifert H, Dijkshoorn L, Vila J, Roca I. Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS. Clin. Microbiol. Infect. 18(11), 1097-1103 (2012).
99. Alvarez-Buylla A, Culebras E, Picazo JJ. Identification of Acinetobacter species: is Bruker biotyper MALDI-TOF mass spectrometry a good alternative to molecular techniques? Infect. Genet. Evol. 12(2), 345-349 (2012).
100. Kempf M, Bakour S, Flaudrops C et al. Rapid detection of carbapenem resistance in Acinetobacter baumannii using matrixassisted laser desorption ionization-time of flight mass spectrometry. PLoS One, 7(2), e31676 (2012).
101. Silbert S, Boyken L, Hollis RJ, Pfaller MA. Improving typeability of multiple bacterial species using pulsed-field gel electrophoresis and thiourea. Diagn. Microbiol. Infect. Dis. 47(4), 619-621 (2003).
102. Schuetz AN, Huard RC, Eshoo MW et al. Identification of a novel Acinetobacter baumannii clone in a US hospital outbreak by multilocus polymerase chain reaction/ electrospray-ionization mass spectrometry. Diagn. Microbiol. Infect. Dis. 72(1), 14-19 (2012).
103. Winstanley T, Courvalin P. Expert systems in clinical microbiology. Clin. Microbiol. Rev. 24(3), 515-556 (2011).
104. Hsieh WS, Sung LL, Tsai KC, Ho HT. Evaluation of the VITEK 2 cards for identification and antimicrobial susceptibility testing of non-glucose- fermenting Gram-negative bacilli. APMIS 117(4), 241-247 (2009).
105. Kulah C, Aktas E, Comert F, Ozlu N, Akyar I, Ankarali H. Detecting imipenem resistance in Acinetobacter baumannii by automated systems (BD Phoenix, Microscan WalkAway, Vitek 2); high error rates with Microscan WalkAway. BMC Infect. Dis. 9, 30 (2009).
106. Akers KS, Chaney C, Barsoumian A et al. Aminoglycoside resistance and susceptibility testing errors in Acinetobacter baumannii-calcoaceticus complex. J. Clin. Microbiol. 48(4), 1132-1138 (2010).
107. Markelz AE, Mende K, Murray CK et al. Carbapenem susceptibility testing errors using three automated systems, disk diffusion, Etest, and broth microdilution and carbapenem resistance genes in isolates of Acinetobacter baumannii-calcoaceticus complex. Antimicrob. Agents Chemother. 55(10), 4707-4711 (2011).
108. Aybey AD, Aksit F, Oz Y, Kiremitci A, Durmaz G. Evaluation of an automated system for the detection of carbapenem resistant Acinetobacter baumannii and assessment of metallo-β-lactamase production using two different phenotyping methods. J. Microbiol. Methods 86(1), 121-123 (2011).
109. Clinical and Laboratory Standards Institute. Performance Standards For Antimicrobial Susceptibility Testing: Twenty-Third Informational Supplement M100-S23. CLSI, Wayne, PA, USA (2013).
110. Clinical and Laboratory Standards Institute. Performance Standards For Antimicrobial Susceptibility Testing: Nineteenth Informational Supplement M100-S19. CLSI, Wayne, PA, USA (2009).
111. Woodford N, Eastaway AT, Ford M et al. Comparison of BD Phoenix, Vitek 2, and MicroScan automated systems for detection and inference of mechanisms responsible for carbapenem resistance in Enterobacteriaceae. J. Clin. Microbiol. 48(8), 2999-3002 (2010).
112. Gordon NC, Wareham DW. Evaluation of CHROMagar Acinetobacter for detection of enteric carriage of multidrug-resistant Acinetobacter baumannii in samples from critically ill patients. J. Clin. Microbiol. 47(7), 2249-2251 (2009).
113. Ajao AO, Robinson G, Lee MS et al. Comparison of culture media for detection of Acinetobacter baumannii in surveillance cultures of critically-ill patients. Eur. J. Clin. Microbiol. Infect. Dis. 30(11), 1425-1430 (2011).
114. Akers KS, Barsoumian A, Beckius ML, Murray CK, Mende K. CHROMagar Acinetobacter is not selective for carbapenem-resistant Acinetobacter baumanniicalcoaceticus complex. Diagn. Microbiol. Infect. Dis. 67(2), 209-211 (2010).
115. Wareham DW, Gordon NC. Modifications to CHROMagar Acinetobacter for improved selective growth of multi-drug resistant Acinetobacter baumannii. J. Clin. Pathol. 64(2), 164-167 (2011).
116. Lee K, Lim YS, Yong D, Yum JH, Chong Y. Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-β-lactamaseproducing isolates of Pseudomonas spp. and Acinetobacter spp. J. Clin. Microbiol. 41(10), 4623-4629 (2003).
117. Amjad A, Mirza IA, Abbasi S, Farwa U, Malik N, Zia F. Modified Hodge test: a simple and effective test for detection of carbapenemase production. Iran. J. Microbiol. 3(4), 189-193 (2011).
118. Girlich D, Poirel L, Nordmann P. Value of the modified Hodge test for detection of emerging carbapenemases in Enterobacteriaceae. J. Clin. Microbiol. 50(2), 477-479 (2012).
119. Bonnin RA, Naas T, Poirel L, Nordmann P. Phenotypic, biochemical, and molecular techniques for detection of metallo-β-lactamase NDM in Acinetobacter baumannii. J. Clin. Microbiol. 50(4), 1419-1421 (2012).
120. Takahashi A, Yomoda S, Kobayashi I, Okubo T, Tsunoda M, Iyobe S. Detection of carbapenemase-producing Acinetobacter baumannii in a hospital. J. Clin. Microbiol. 38(2), 526-529 (2000).
121. Swayne RL, Ludlam HA, Shet VG, Woodford N, Curran MD. Real-time TaqMan PCR for rapid detection of genes encoding five types of non-metallo-(class A and D) carbapenemases in Enterobacteriaceae. Int. J. Antimicrob. Agents 38(1), 35-38 (2011).
122. Woodford N, Warner M, Pike R, Zhang J. Evaluation of a commercial microarray to detect carbapenemase-producing Enterobacteriaceae. J. Antimicrob. Chemother. 66(12), 2887-2888 (2011).
123. Leclercq R, Cantón R, Brown DF et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin. Microbiol. Infect. 19(2), 141-160 (2013).
124. Daikos GL, Petrikkos P, Psichogiou M et al. Prospective observational study of the impact of VIM-1 metallo-β-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob. Agents Chemother. 53(5), 1868-1873 (2009).
125. Weisenberg SA, Morgan DJ, Espinal-Witter R, Larone DH. Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem. Diagn. Microbiol. Infect. Dis. 64(2), 233-235 (2009).
126. Cai Y, Chai D, Wang R, Liang B, Bai N. Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J. Antimicrob. Chemother. 67(7), 1607-1615 (2012).
127. Roberts JA, Lipman J. Editorial commentary: Closing the loop - a colistin clinical study to confirm dosing recommendations from PK/PD modeling. Clin. Infect. Dis. 54(12), 1727-1729 (2012).
128. Bergen PJ, Li J, Nation RL, Turnidge JD, Coulthard K, Milne RW. Comparison of once-, twice- and thrice-daily dosing of colistin on antibacterial effect and emergence of resistance: studies with Pseudomonas aeruginosa in an in vitro pharmacodynamic model. J. Antimicrob. Chemother. 61(3), 636-642 (2008).
129. Plachouras D, Karvanen M, Friberg LE et al. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by Gram-negative bacteria. Antimicrob. Agents Chemother. 53(8), 3430-3436 (2009).
130. Garonzik SM, Li J, Thamlikitkul V et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob. Agents Chemother. 55(7), 3284-3294 (2011).
131. Dalfino L, Puntillo F, Mosca A et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin. Infect. Dis. 54(12), 1720-1726 (2012).
132. Li J, Nation RL, Turnidge JD et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect. Dis. 6(9), 589-601 (2006).
133. Tan CH, Li J, Nation RL. Activity of colistin against heteroresistant Acinetobacter baumannii and emergence of resistance in an in vitro pharmacokinetic/pharmacodynamic model. Antimicrob. Agents Chemother. 51(9), 3413-3415 (2007).
134. Li J, Rayner CR, Nation RL et al. Heteroresistance to colistin in multidrugresistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 50(9), 2946-2950 (2006).
135. Hawley JS, Murray CK, Jorgensen JH. Colistin heteroresistance in Acinetobacter and its association with previous colistin therapy. Antimicrob. Agents Chemother. 52(1), 351-352 (2008).
136. Yoon J, Urban C, Terzian C, Mariano N, Rahal JJ. In vitro double and triple synergistic activities of polymyxin B, imipenem, and rifampin against multidrugresistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 48(3), 753-757 (2004).
137. Koomanachai P, Kim A, Nicolau DP. Pharmacodynamic evaluation of tigecycline against Acinetobacter baumannii in a murine pneumonia model. J. Antimicrob. Chemother. 63(5), 982-987 (2009).
138. Peleg AY, Potoski BA, Rea R et al. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J. Antimicrob. Chemother. 59(1), 128-131 (2007).
139. Navon-Venezia S, Leavitt A, Carmeli Y. High tigecycline resistance in multidrugresistant Acinetobacter baumannii. J. Antimicrob. Chemother. 59(4), 772-774 (2007).
140. Ku K, Pogue JM, Moshos J et al. Retrospective evaluation of colistin versus tigecycline for the treatment of Acinetobacter baumannii and/or carbapenem-resistant Enterobacteriaceae infections. Am. J. Infect. Control 40(10), 983-987 (2012).
141. Gordon NC, Wareham DW. A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacter baumannii with tigecycline. J. Antimicrob. Chemother. 63(4), 775-780 (2009).
142. Karageorgopoulos DE, Kelesidis T, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant (including carbapenem-resistant) Acinetobacter infections: a review of the scientific evidence. J. Antimicrob. Chemother. 62(1), 45-55 (2008).
143. Li C, Kuti JL, Nightingale CH, Nicolau DP. Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients. J. Clin. Pharmacol. 46(10), 1171-1178 (2006).
144. Samtani MN, Flamm R, Kaniga K, Nandy P. Pharmacokinetic- pharmacodynamicmodel-guided doripenem dosing in critically ill patients. Antimicrob. Agents Chemother. 54(6), 2360-2364 (2010).
145. Lorente L, Lorenzo L, Martín MM, Jiménez A, Mora ML. Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to Gram-negative bacilli. Ann. Pharmacother. 40(2), 219-223 (2006).
146. Smolyakov R, Borer A, Riesenberg K et al. Nosocomial multi-drug resistant Acinetobacter baumannii bloodstream infection: risk factors and outcome with ampicillinsulbactam treatment. J. Hosp. Infect. 54(1), 32-38 (2003).
147. Wang FD, Lin ML, Lee WS, Liu CY. In vitro activities of β-lactam antibiotics alone and in combination with sulbactam against Gram-negative bacteria. Int. J. Antimicrob. Agents 23(6), 590-595 (2004).
148. Oliveira MS, Prado GV, Costa SF, Grinbaum RS, Levin AS. Ampicillin/ sulbactam compared with polymyxins for the treatment of infections caused by carbapenem-resistant Acinetobacter spp. J. Antimicrob. Chemother. 61(6), 1369-1375 (2008).
149. Punpanich W, Munsrichoom A, Srisarang S, Treeratweeraphong V. In vitro activities of colistin and ampicillin/sulbactam against Acinetobacter baumannii. J. Med. Assoc. Thai. 94(Suppl. 3), S95-S100 (2011).
150. Cooper TW, Pass SE, Brouse SD, Hall Ii RG. Can pharmacokinetic and pharmacodynamic principles be applied to the treatment of multidrug-resistant Acinetobacter? (February). Ann. Pharmacother. doi:10.1016/j.bmcl.2010.12.121 (2011) (Epub ahead of print).
151. Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther. Drug Monit. 30(6), 674-681 (2008).
152. Ambrose PG, Bhavnani SM, Owens RC Jr. Clinical pharmacodynamics of quinolones. Infect. Dis. Clin. North Am. 17(3), 529-543 (2003).
153. DeRyke CA, Kuti JL, Nicolau DP. Pharmacodynamic target attainment of six beta-lactams and two fluoroquinolones against Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella species collected from
154. Yamamoto M, Nagao M, Matsumura Y et al. Interspecies dissemination of a novel class 1 integron carrying blaIMP-19 among Acinetobacter species in Japan. J. Antimicrob. Chemother. 66(11), 2480-2483 (2011).
155. Cornaglia G, Giamarellou H, Rossolini GM. Metallo-β-lactamases: a last frontier for β-lactams? Lancet Infect. Dis. 11(5), 381-393 (2011).
156. Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin. Microbiol. Infect. 12(9), 826-836 (2006).
157. Poirel L, Bonnin RA, Boulanger A, Schrenzel J, Kaase M, Nordmann P. Tn125-related acquisition of blaNDM-like genes in Acinetobacter baumannii. Antimicrob. Agents Chemother. 56(2), 1087-1089 (2012).
158. Pfeifer Y, Wilharm G, Zander E et al. Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007. J. Antimicrob. Chemother. 66(9), 1998-2001 (2011).
159. Kaase M, Nordmann P, Wichelhaus TA, Gatermann SG, Bonnin RA, Poirel L. NDM-2 carbapenemase in Acinetobacter baumannii from Egypt. J. Antimicrob. Chemother. 66(6), 1260-1262 (2011).
160. Espinal P, Fugazza G, López Y et al. Dissemination of an NDM-2-producing Acinetobacter baumannii clone in an Israeli rehabilitation center. Antimicrob. Agents Chemother. 55(11), 5396-5398 (2011).
161. The Center for Disease Dynamics, Economics and Policy website. www.cddep.org/ResistanceMap/bug-drug/ AB-CP (Accessed 15 April 2012)
162. European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables For Interpretation Of MICs And Zone Diameters, Version 2.0. www.eucast.org/fileadmin/src/media/ PDFs/EUCAST-files/Breakpoint-tables/ Breakpoint-table-v-2.0-120221.pdf (Accessed 1 January 2012)