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Review

Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy

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Pages 71-93 | Published online: 10 Jan 2014

References

  • Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin. Infect. Dis.43(Suppl. 2), 49–56 (2006).
  • Grossi P, Dalla GD. Treatment of Pseudomonas aeruginosa infection in critically ill patients. Expert Rev. Anti Infect. Ther.4(4), 639–662 (2006).
  • Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin. Infect. Dis.34(5), 634–640 (2002).
  • Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat. Rev. Microbiol.5(12), 939–951 (2007).
  • Paterson DL. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin. Infect. Dis.43(Suppl. 2), 43–48 (2006).
  • Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin. Microbiol. Rev.21(3), 538–582 (2008).
  • Falagas ME, Rafailidis PI. Attributable mortality of Acinetobacter baumannii: no longer a controversial issue. Crit. Care11(3), 134 (2007).
  • Zavascki AP, Barth AL, Gonçalves AL et al. The influence of metallo-β-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections. J. Antimicrob. Chemother.58(2), 387–392 (2006).
  • Boucher HW, Talbot GH, Bradley JS et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis.48(1), 1–12 (2009).
  • Talbot GH. What is in the pipeline for Gram-negative pathogens? Expert Rev. Anti Infect. Ther.6(1), 39–49 (2008).
  • Falagas ME, Koletsi PK, Bliziotis IA. The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J. Med. Microbiol.55(Pt 12), 1619–1629 (2006).
  • Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in Gram-negative bacilli. Clin. Infect. Dis.45(9), 1179–1181 (2007).
  • Falagas ME, Karageorgopoulos DE. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli: need for international harmonization in terminology. Clin. Infect. Dis.46(7), 1121–1122 (2008).
  • Livermore DM, Woodford N. The β-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol.14(9), 413–420 (2006).
  • Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother.39(6), 1211–1233 (1995).
  • Ambler RP. The structure of β-lactamases. Philos. Trans. R. Soc. Lond B. Biol. Sci.289(1036), 321–331 (1980).
  • Jacoby GA. AmpC β-lactamases. Clin. Microbiol. Rev.22(1), 161–182 (2009).
  • Rodriguez-Martinez JM, Poirel L, Nordmann P. Extended-spectrum cephalosporinases in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.53(5), 1766–1771 (2009).
  • Hujer KM, Hamza NS, Hujer AM et al. Identification of a new allelic variant of the Acinetobacter baumannii cephalosporinase, ADC-7 β-lactamase: defining a unique family of class C enzymes. Antimicrob. Agents Chemother.49(7), 2941–2948 (2005).
  • Jacobs C, Frere JM, Normark S. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible β-lactam resistance in Gram-negative bacteria. Cell88(6), 823–832 (1997).
  • Schmidtke AJ, Hanson ND. Model system to evaluate the effect of ampD mutations on AmpC-mediated β-lactam resistance. Antimicrob. Agents Chemother.50(6), 2030–2037 (2006).
  • Corvec S, Caroff N, Espaze E, Giraudeau C, Drugeon H, Reynaud A. AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains. J. Antimicrob. Chemother.52(4), 629–635 (2003).
  • Heritier C, Poirel L, Nordmann P. Cephalosporinase over-expression resulting from insertion of ISAba1 in Acinetobacter baumannii. Clin. Microbiol. Infect.12(2), 123–130 (2006).
  • Pai H, Jacoby GA. Sequences of the NPS-1 and TLE-1 β-lactamase genes. Antimicrob. Agents Chemother.45(10), 2947–2948 (2001).
  • Strateva T, Yordanov D. Pseudomonas aeruginosa – a phenomenon of bacterial resistance. J. Med. Microbiol.58(Pt 9), 1133–1148 (2009).
  • Sanschagrin F, Bejaoui N, Levesque RC. Structure of CARB-4 and AER-1 carbenicillin-hydrolyzing β-lactamases. Antimicrob. Agents Chemother.42(8), 1966–1972 (1998).
  • Poirel L, Corvec S, Rapoport M et al. Identification of the novel narrow-spectrum β-lactamase SCO-1 in Acinetobacter spp. from Argentina. Antimicrob. Agents Chemother.51(6), 2179–2184 (2007).
  • Potron A, Poirel L, Croize J, Chanteperdrix V, Nordmann P. Genetic and biochemical characterization of the first extended-spectrum CARB-type β-lactamase, RTG-4, from Acinetobacter baumannii. Antimicrob. Agents Chemother.53(7), 3010–3016 (2009).
  • Livermore DM. Defining an extended-spectrum β-lactamase. Clin. Microbiol. Infect.14(Suppl. 1), 3–10 (2008).
  • Weldhagen GF, Poirel L, Nordmann P. Ambler class A extended-spectrum β-lactamases in Pseudomonas aeruginosa: novel developments and clinical impact. Antimicrob. Agents Chemother.47(8), 2385–2392 (2003).
  • Picao RC, Poirel L, Gales AC, Nordmann P. Further identification of CTX-M-2 extended-spectrum β-lactamase in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.53(5), 2225–2226 (2009).
  • Moubareck C, Bremont S, Conroy MC, Courvalin P, Lambert T. GES-11, a novel integron-associated GES variant in Acinetobacter baumannii. Antimicrob. Agents Chemother.53(8), 3579–3581 (2009).
  • Rejiba S, Limam F, Belhadj C, Belhadj O, Ben Mahrez K. Biochemical characterization of a novel extended-spectrum β-lactamase from Pseudomonas aeruginosa. Microb. Drug Resist.8(1), 9–13 (2002).
  • da Fonseca EL, Vieira VV, Cipriano R, Vicente AC. Emergence of blaGES-5 in clinical colistin-only-sensitive (COS) Pseudomonas aeruginosa strain in Brazil. J. Antimicrob. Chemother.59(3), 576–577 (2007).
  • Wang C, Cai P, Chang D, Mi Z. A Pseudomonas aeruginosa isolate producing the GES-5 extended-spectrum β-lactamase. J. Antimicrob. Chemother.57(6), 1261–1262 (2006).
  • Weldhagen GF, Prinsloo A. Molecular detection of GES-2 extended spectrum β-lactamase producing Pseudomonas aeruginosa in Pretoria, South Africa. Int. J. Antimicrob. Agents24(1), 35–38 (2004).
  • Naas T, Nordmann P. OXA-type β-lactamases. Curr. Pharm. Des.5(11), 865–879 (1999).
  • Poirel L, Naas T, Nordmann P. Class D β-lactamases: diversity, epidemiology and genetics. Antimicrob. Agents Chemother. DOI: 10.1128/AAC.01512–01508 (2009) (Epub ahead of print).
  • Paterson DL, Bonomo RA. Extended-spectrum β-lactamases: a clinical update. Clin. Microbiol. Rev.18(4), 657–686 (2005).
  • Juan C, Mulet X, Zamorano L, Albertí S, Pérez JL, Oliver A. Detection of the novel extended spectrum β-lactamase (ESBL) OXA-161 from a plasmid-located integron in Pseudomonas aeruginosa clinical isolates in Spain. Antimicrob. Agents Chemother.53(12), 5288–5290 (2009).
  • Poirel L, Pitout JD, Nordmann P. Carbapenemases: molecular diversity and clinical consequences. Future Microbiol.2(5), 501–512 (2007).
  • Girlich D, Naas T, Nordmann P. Biochemical characterization of the naturally occurring oxacillinase OXA-50 of Pseudomonas aeruginosa. Antimicrob. Agents Chemother.48(6), 2043–2048 (2004).
  • Brown S, Amyes S. OXA (β)-lactamases in Acinetobacter: the story so far. J. Antimicrob. Chemother.57(1), 1–3 (2006).
  • Evans BA, Brown S, Hamouda A, Findlay J, Amyes SG. Eleven novel OXA-51-like enzymes from clinical isolates of Acinetobacter baumannii. Clin. Microbiol. Infect.13(11), 1137–1138 (2007).
  • Tsakris A, Ikonomidis A, Spanakis N, Pournaras S, Bethimouti K. Identification of a novel bla(OXA-51) variant, bla(OXA-92), from a clinical isolate of Acinetobacter baumannii. Clin. Microbiol. Infect.13(3), 348–349 (2007).
  • Vahaboglu H, Budak F, Kasap M et al. High prevalence of OXA-51-type class D β-lactamases among ceftazidime-resistant clinical isolates of Acinetobacter spp.: co-existence with OXA-58 in multiple centres. J. Antimicrob. Chemother.58(3), 537–542 (2006).
  • Figueiredo S, Poirel L, Croize J, Recule C, Nordmann P. In vivo selection of reduced susceptibility to carbapenems in Acinetobacter baumannii related to ISAba1-mediated overexpression of the natural bla(OXA-66) oxacillinase gene. Antimicrob. Agents Chemother.53(6), 2657–2659 (2009).
  • Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin. Microbiol. Infect.8(6), 321–331 (2002).
  • Segal H, Jacobson RK, Garny S, Bamford CM, Elisha BG. Extended-10 promoter in ISAba-1 upstream of blaOXA-23 from Acinetobacter baumannii. Antimicrob. Agents Chemother.51(8), 3040–3041 (2007).
  • Turton JF, Ward ME, Woodford N et al. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol. Lett.258(1), 72–77 (2006).
  • Walsh TR. Clinically significant carbapenemases: an update. Curr. Opin. Infect. Dis.21(4), 367–371 (2008).
  • Poirel L, Figueiredo S, Cattoir V, Carattoli A, Nordmann P. Acinetobacter radioresistens as a silent source of carbapenem resistance for Acinetobacter spp. Antimicrob. Agents Chemother.52(4), 1252–1256 (2008).
  • Mendes RE, Bell JM, Turnidge JD, Castanheira M, Deshpande LM, Jones RN. Codetection of blaOXA-23-like gene (blaOXA-133) and blaOXA-58 in Acinetobacter radioresistens: report from the SENTRY Antimicrobial Surveillance Program. Antimicrob. Agents Chemother.53(2), 843–844 (2009).
  • Higgins PG, Poirel L, Lehmann M, Nordmann P, Seifert H. OXA-143, a novel carbapenem-hydrolyzing Class D ss-lactamase in Acinetobacter baumannii. Antimicrob. Agents Chemother.53(12), 5035–5038 (2009).
  • Sevillano E, Gallego L, Garcia-Lobo JM. First detection of the OXA-40 carbapenemase in P. aeruginosa isolates, located on a plasmid also found in A. baumannii. Pathol. Biol. (Paris)57(6), 493–495 (2009).
  • Villegas MV, Lolans K, Correa A, Kattan JN, Lopez JA, Quinn JP. First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing β-lactamase. Antimicrob. Agents Chemother.51(4), 1553–1555 (2007).
  • Wolter DJ, Khalaf N, Robledo IE et al. Surveillance of carbapenem-resistant Pseudomonas aeruginosa isolates from Puerto Rican Medical Center Hospitals: dissemination of KPC and IMP-18 β-lactamases. Antimicrob. Agents Chemother.53(4), 1660–1664 (2009).
  • Bennett JW, Herrera ML, Lewis JS, Wickes BW, Jorgensen JH. KPC-2-producing Enterobacter cloacae and Pseudomonas putida coinfection in a liver transplant recipient. Antimicrob. Agents Chemother.53(1), 292–294 (2009).
  • Yong D, Bell JM, Ritchie B, Pratt R, Toleman MA, Walsh TR. A novel sub-group metallo-β-lactamase (MBL), AIM-1, emerges in Pseudomonas aeruginosa (PSA) from Australia. Presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 17–20 September 2007 (Abstract C1–593).
  • Poirel L, Rodriguez-Martinez JM, al Naiemi N, Debets-Ossenkopp Y, Nordmann P. Characterization of blaDIM1, a novel integron-located metallo-β-lactamase gene from a Pseudomonas stutzeri clinical isolate in The Netherlands. Presented at: 19th European Congress of Clinical Microbiology and Infectious Diseases. Helsinki, Finland, 16–19 May 2009 (Abstract O309).
  • Castanheira M, Toleman MA, Jones RN, Schmidt FJ, Walsh TR. Molecular characterization of a β-lactamase gene, blaGIM-1, encoding a new subclass of metallo-β-lactamase. Antimicrob. Agents Chemother.48(12), 4654–4661 (2004).
  • Gales AC, Menezes LC, Silbert S, Sader HS. Dissemination in distinct Brazilian regions of an epidemic carbapenem-resistant Pseudomonas aeruginosa producing SPM metallo-β-lactamase. J. Antimicrob. Chemother.52(4), 699–702 (2003).
  • Lee K, Yum JH, Yong D et al. Novel acquired metallo-β-lactamase gene, bla(SIM-1), in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Antimicrob. Agents Chemother.49(11), 4485–4491 (2005).
  • Shakil S, Khan R, Zarrilli R, Khan AU. Aminoglycosides versus bacteria – a description of the action, resistance mechanism, and nosocomial battleground. J. Biomed. Sci.15(1), 5–14 (2008).
  • Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.49(2), 479–487 (2005).
  • Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: activity and resistance. Antimicrob. Agents Chemother.43(4), 727–737 (1999).
  • Seward RJ, Lambert T, Towner KJ. Molecular epidemiology of aminoglycoside resistance in Acinetobacter spp. J. Med. Microbiol.47(5), 455–462 (1998).
  • Nemec A, Dolzani L, Brisse S, van den Broek P, Dijkshoorn L. Diversity of aminoglycoside-resistance genes and their association with class 1 integrons among strains of pan-European Acinetobacter baumannii clones. J. Med. Microbiol.53(Pt 12), 1233–1240 (2004).
  • Poole K. Efflux-mediated antimicrobial resistance. J. Antimicrob. Chemother.56(1), 20–51 (2005).
  • Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA. Efflux-mediated resistance to tigecycline in Pseudomonas aeruginosa PAO1. Antimicrob. Agents Chemother.47(3), 972–978 (2003).
  • Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann. Med.39(3), 162–176 (2007).
  • Piddock LJV. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev.19(2), 382–402 (2006).
  • Farra A, Islam S, Stralfors A, Sorberg M, Wretllind B. Role of outer membrane protein OprD and penicillin-binding proteins in resistance of Pseudomonas aeruginosa to imipenem and meropenem. Int. J. Antimicrob. Agents3(5), 427–433 (2008).
  • Okamoto K, Gotoh N, Nishino T. Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-OprM, MexCD-OprJ and MexXY/OprM to carbapenems: substrate specificities of the efflux systems. J. Infect. Chemother.8(4), 371–373 (2002).
  • Ruzin A, Keeney D, Bradford PA. AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus–Acinetobacter baumannii complex. J. Antimicrob. Chemother.59(5), 1001–1004 (2007).
  • Peleg AY, Adams J, Paterson DL. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob. Agents Chemother.51(6), 2065–2069 (2007).
  • 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).
  • Nemec A, Maixnerová M, van der Reijden TJK, van der Broek PJ, Dijkshoorn L. Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains. J. Antimicrob. Chemother.60(3), 483–489 (2007).
  • Damir-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).
  • Hancock RE, Brinkman ES. Function of pseudomonas porins in uptake and efflux Annu. Rev. Microbiol.56(1), 17–38 (2002).
  • Livermore DM. Of Pseudomonas, porins, pumps and carbapenems. J. Antimicrob. Chemother.47(3), 247–250 (2001).
  • Gotoh N, Nishino T. Decreases of the susceptibility to low molecular weight β-lactam antibiotics in imipenem-resistant Pseudomonas aeruginosa mutants: role of the outer membrane protein D2 in their diffusion. J. Antimicrob. Chemother.25(2), 191–198 (1990).
  • Sobel ML, McKay GA, Poole K. Contribution of the MexXY multidrug transporter to aminoglycosides resistance in Pseudomonas aeruginosa clinical isolates. Antimicrob. Agents Chemother.47(10), 3202–3207 (2003).
  • Pai H, Kim J, Kim K, Lee JH, Choe KW, Gotoh N. Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob. Agents Chemother.45(2), 480–484 (2001).
  • Piddock LJV, Hall MC, Bellido F, Brains M, Hancock REW. A pleitropic posttherapy, enoxacin-resistant mutant of Pseudomonas aeruginosa. Antimicrob. Agents Chemother.36(5), 1057–1061 (1992).
  • El Amin N, Giske CG, Jala S, Keijser B, Kronvall G, Wretlind B. Carbapenem resistance mechanisms in Pseudomonas aeruginosa alterations of porin OprD and efflux proteins do not fully explain resistance patterns observed in clinical isolates. APMIS113(3), 187–196 (2005).
  • Bratu S, Landman D, Gupta J, Quale J. Role of AmpD, OprF and penicillin-binding proteins in β-lactam resistance in clinical isolates of Pseudomonas aeruginosa. J. Med. Microbiol.56(6), 809–814 (2007).
  • Brinkman FSL, Brains M, Hancock REW. The amino terminus of Pseudomonas aeruginosa outer membrane protein OprF forms channes in lipid bilayer membranes: correlation with a threedimensional model. J. Bacteriol.182(18), 5251–5259 (2000).
  • Sato K, Nakae T. Outer membrane permeability of Acinetobacter calcoaceticus and its implication in antibiotic resistance. J. Antimicrob. Chemother.28(1), 35–45 (1991).
  • Gribun A, Nitzan Y, Pechatnikov I, Hershkovits G, Katcoff DJ. Molecular and structural characterization of the HMP-AB gene encoding a pore-forming protein from a clinical isolate of Acinetobacter baumannii. Curr. Microbiol.47(5), 434–443 (2003).
  • Nitzan Y, Pechatnikov I, Bar-El D, Wexler H. Isolation and characterization of heat-modifiable proteins from the outer membrane of Porphyromonas asaccharolytica and Acinetobacter baumannii. Anaerobe5(1), 43–50 (1999).
  • Clark RB. Imipenem resistance among Acinetobacter baumannii: association with reduced expression of a 33–36 kDa outer membrane protein. J. Antimicrob. Chemother.38(2), 245–251 (1996).
  • Limansky AS, Mussi MA, Viale AM. Loss of a 29-kilodalton outer membrane protein in Acinetobacter baumannii is associated with imipenem resistance. J. Clin. Microbiol.40(12), 4776–4778 (2002).
  • 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).
  • Vila J, Martí S, Sánchez-Céspedes J. Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J. Antimicrob. Chemother.59(6), 1210–1215 (2007).
  • Quale J, Bratu S, Landman D, Heddurshetti R. Molecular epidemiology and mechanisms of carbapenem resistance in Acinetobacter baumannii endemic in New York City. Clin. Infect. Dis.37(2), 214–220 (2003).
  • Bou G, Cerveró G, Domínguez MA, Quereda C, Martínez-Beltrán J. Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme: high-level carbapenem resistance in A. baumannii is not due solely to the presence of β-lactamases. J. Clin. Microbiol.38(9), 3299–3305 (2000).
  • Fournier PE, Vallenet D, Barbe V et al. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet.2(1), e7 (2006).
  • 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).
  • Gales AC, Jones RN, Sader HS. Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY Antimicrobial Surveillance Programme (2001–2004). Clin. Microbiol. Infect.12(4), 315–321 (2006).
  • Park YK, Jung SI, Park KH et al. Independent emergence of colistin-resistant Acinetobacter spp. isolates from Korea. Diagn. Microbiol. Infect. Dis.64(1), 43–51 (2009).
  • Hogardt M, Schmoldt S, Gotzfried M, Adler K, Heesemann J. Pitfalls of polymyxin antimicrobial susceptibility testing of Pseudomonas aeruginosa isolated from cystic fibrosis patients. J. Antimicrob. Chemother.54(6), 1057–1061 (2004).
  • Landman D, Bratu S, Alam M, Quale J. Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B. J. Antimicrob. Chemother.55(6), 954–957 (2005).
  • Arroyo LA, García-Curiel A, Pachón-Ibañez ME et al. Reliability of the E-test method for detection of colistin resistance in clinical isolates of Acinetobacter baumannii. J. Clin. Microbiol.43(2), 903–905 (2005).
  • Gales AC, Reis AO, Jones RN. Contemporary assessment of antimicrobial susceptibility testing methods for polimyxin B and colistin: review of available interpretative criteria and quality control guidelines. J. Clin. Microbiol.39(1), 183–190 (2001).
  • Reis AO, Luz DA, Tognim MC, Sader HS, Gales AC. Polymyxin-resistant Acinetobacter spp. isolates: what is next? Emerg. Infect. Dis.9(8), 1025–1027 (2003).
  • Moore RA, Chan L, Hancock RE. Evidence for two distinct mechanisms of resistance to polymyxin B in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.26(4), 539–545 (1984).
  • Nicas TI, Hancock REW. Outer membrane protein H1 of Pseudomonas aeruginosa: involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin. J. Bacteriol.143(2), 872–878 (1980).
  • Bell A, Hancock RE. Outer membrane protein H1 of Pseudomonas aeruginosa: purification of the protein and cloning and nucleotide sequence of the gene. J. Bacteriol.171(6), 3211–3217 (1989).
  • Macfarlane EL, Kwasnicka A, Hancock REW. Role of Pseudomonas aeruginosa PhoP–PhoQ in resistance to antimicrobial cationic peptides and aminoglycosides. Microbiology146(10), 2543–2554 (2000).
  • McPhee JB, Bains M, Winsor G et al. Contribution of the PhoP–PhoQ and PmrA–PmrB two-component regulatory systems to Mg2+-induced gene regulation in Pseudomonas aeruginosa. J. Bacteriol.188(11), 3995–4006 (2006).
  • Schurek KN, Sampaio JL, Kiffer CR, Sinto S, Mendes CM, Hancock RE. Involvement of pmrAB and phoPQ in polymyxin B adaptation and inducible resistance in non-cystic fibrosis clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother.53(10), 4345–4351 (2009).
  • Clinical and Laboratory Standards Institute. Performance standards for β-antimicrobial susceptibility testing: nineteenth information supplement (M100-S19), CLSI, Wayne, PA, USA (2009).
  • 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).
  • Ko KS, Suh JY, Kwon KT et al. High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea. J. Antimicrob. Chemother.60(5), 1163–1167 (2007).
  • Megerle JA, Fritz G, Gerland U, Jung K, Radler JO. Timing and dynamics of single cell gene expression in the arabinose utilization system. Biophys. J.95(4), 2103–2115 (2008).
  • Booth IR. Stress and the single cell: intrapopulation diversity is a mechanism to ensure survival upon exposure to stress. Int. J. Food Microbiol.78(1–2), 19–30 (2002).
  • Adams MD, Nickel GC, Bajaksouzian S et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob. Agents Chemother.53(9), 3628–3634 (2009).
  • Avery SV. Microbial cell individuality and the underlying sources of heterogeneity. Nat. Rev. Microbiol.4(8), 577–587 (2006).
  • Li J, Nation RL, Owen RJ, Wong S, Spelman D, Franklin C. Antibiograms of multidrug-resistant clinical Acinetobacter baumannii: promising therapeutic options for treatment of infection with colistin-resistant strains. Clin. Infect. Dis.45(5), 594–598 (2007).
  • Mendes RE, Fritsche TR, Sader HS, Jones RN. Increased antimicrobial susceptibility profiles among polymyxin-resistant Acinetobacter baumannii clinical isolates. Clin. Infect. Dis.46(8), 1324–1326 (2008).
  • Noguchi H, Fukasawa M, Komatsu T, Mitsuhashi S, Matsuhashi M. Mutation in Pseudomonas aeruginosa causing simultaneous defects in penicillin-binding protein 5 and in enzyme activities of penicillin release and D-alanine carboxypeptidase. J. Bacteriol.162(2), 849–851 (1985).
  • Pucci MJ, Boice-Sowek J, Kessker RE, Dougherty TJ. Comparison of cefepime, cefpirome and cefaclidine binding affinities for penicillin-binding proteins in Escherichia coli K-12 and Pseudomonas aeruginosa SC8329. Antimicrob. Agents Chemother.35(11), 2312–2317 (1991).
  • Quinn JP, Dudek EJ, DiVincenzo CA, Lucks DA, Lerner SA. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J. Infect. Dis.154(2), 289–294 (1986).
  • Song J, Xie G, Elf PK, Young KD, Jensen RA. Comparative analysis of Pseudomonas aeruginosa penicillin-binding protein 7 in the context of its membership in the family of low-molecular-mass PBPs. Microbiology144(4), 975–983 (1998).
  • Legaree BA, Daniels K, Weadge JT, Cockburn D, Clarke AJ. Function of penicillin-binding protein 2 in viability and morphology of Pseudomonas aeruginosa. J. Antimicrob. Chemother.59(3), 411–424 (2007).
  • Godfrey AJ, Bryan LE, Rabin HR. β-lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment. Antimicrob. Agents Chemother.19(5), 705–711 (1981).
  • Gehrlein M, Leying H, Cullmann W, Wendt S, Opferkuch W. Imipenem resistance in Acinetobacter baumannii is due to altered penicillin-binding proteins. Chemotherapy37(6), 405–412 (1991).
  • Fernández-Cuenca F, Pascual A, Martínez Marínez L, Conejo MC, Perea EJ. Evaluation of SDS-polyacrylamide gel systems for the study of outer membrane protein profiles of clinical strains of Acinetobacter baumannii. J. Basic Microbiol.43(3), 194–201 (2003).
  • Russo TA, MacDonald U, Beanan JM et al. Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumanniiin vitro and in vivo. J. Infect. Dis.199(4), 513–521 (2009).
  • Higgins PG, Wisplinghoff H, Stefanik D, Seifert H. Selection of topoisomerase mutations and overexpression of adeB mRNA transcripts during an outbreak of Acinetobacter baumannii. J. Antimicrob. Chemother.54(4), 821–823 (2004).
  • Hamouda A, Amyes SG. Novel gyrA and parC point mutations in two strains of Acinetobacter baumannii resistant to ciprofloxacin. J. Antimicrob. Chemother.54(3), 695–696 (2004).
  • Nakano M, Deguchi T, Wamura T et al. Mutations in the gyrA and parC genes in fluoroquinolone-resistant clinical isolates of Pseudomonas aeruginosa. Antimicrobial. Agents Chemother.41(10), 2289–2291 (1997).
  • Seward RJ, Towner KJ. Molecular epidemiology of quinolone resistance in Acinetobacter spp. Clin. Microbiol. Infect.4(5), 248–254 (1998).
  • Su XZ, Chen J, Mizushima T, Kuroda T, Tsuchiya T. AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters. Antimicrob. Agents Chemother.49(10), 4362–4364 (2005).
  • Touati A, Brasme L, Benallaoua S, Gharout A, Madoux J, De Champs C. First report of qnrB-producing Enterobacter cloacae and qnrA-producing Acinetobacter baumannii recovered from Algerian hospitals. Diagn. Microbiol. Infect. Dis.60(3), 287–290 (2008).
  • Jana S, Deb JK. Molecular understanding of aminoglycoside action and resistance. Appl. Microbiol. Biotechnol.70(2), 140–150 (2006).
  • Doi Y, Arakawa Y. 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin. Infect. Dis.45(1), 88–94 (2007).
  • Zavascki AP, Li J. Intravenous colistimethate for multidrug-resistant Gram-negative bacteria. Lancet Infect. Dis.8(7), 403–405 (2008).
  • Zavascki AP, Goldani LZ, Li J, Nation RL. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J. Antimicrob. Chemother.60(6), 1206–1215 (2007).
  • Schafer JJ, Goff DA. Establishing the role of tigecycline in an era of antimicrobial resistance. Expert Rev. Anti Infect. Ther.6(5), 557–567 (2008).
  • Masterton RG. The new treatment paradigm and the role of carbapenems. Int. J. Antimicrob. Agents33(2), 105–110 (2009).
  • Queenan AM, Bush K. Carbapenemases: the versatile β-lactamases. Clin. Microbiol. Rev.20(3), 440–458 (2007).
  • Turnidge J, Paterson DL. Setting and revising antibacterial susceptibility breakpoints. Clin. Microbiol. Rev.20(3), 391–408 (2007).
  • Dalhoff A, Ambrose PG, Mouton JW. A long journey from minimum inhibitory concentration testing to clinically predictive breakpoints: deterministic and probabilistic approaches in deriving breakpoints. Infection37(4), 296–305 (2009).
  • Cornaglia G, Akova M, Amicosante G et al. Metallo-β-lactamases as emerging resistance determinants in Gram-negative pathogens: open issues. Int. J. Antimicrob. Agents29(4), 380–388 (2007).
  • Landman D, Georgescu C, Martin DA, Quale J. Polymyxins revisited. Clin. Microbiol. Rev.21(3), 449–465 (2008).
  • Li J, Coulthard K, Milne R et al. Steady-state pharmacokinetics of intravenous colistin methanesulphonate in patients with cystic fibrosis. J. Antimicrob. Chemother.52(6), 987–992 (2003).
  • Li J, Rayner CR, Nation RL et al. Pharmacokinetics of colistin methanesulfonate and colistin in a critically ill patient receiving continuous venovenous hemodiafiltration. Antimicrob. Agents Chemother.49(11), 4814–4815 (2005).
  • Kwa AL, Lim TP, Low JG et al. Pharmacokinetics of polymyxin B1 in patients with multidrug-resistant Gram-negative bacterial infections. Diagn. Microbiol. Infect. Dis.60(2), 163–167 (2008).
  • Zavascki AP, Goldani LZ, Cao G et al. Pharmacokinetics of intravenous polymyxin B in critically ill patients. Clin. Infect. Dis.47(10), 1298–1304 (2008).
  • Plachouras D, Karvanen M, Friberg LE et al. Population pharmacokinetic analysis of colistin methanesulphonate and colistin after intravenous administration in critically ill patients with Gram-negative bacterial infections. Antimicrob. Agents Chemother.53(8), 3430–3436 (2009).
  • Li J, Turnidge J, Milne R, Nation RL, Coulthard K. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob. Agents Chemother.45(3), 781–785 (2001).
  • Tam VH, Schilling AN, Vo G et al. Pharmacodynamics of polymyxin B against Pseudomonas aeruginosa. Antimicrob. Agents Chemother.49(9), 3624–3630 (2005).
  • Owen RJ, Li J, Nation RL, Spelman D. In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J. Antimicrob. Chemother.59(3), 473–477 (2007).
  • Li J, Rayner CR, Nation RL et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother.50(9), 2946–2950 (2006).
  • 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).
  • Zavascki AP, Li J, Nation RL et al. Stable polymyxin B susceptibility to Pseudomonas aeruginosa and Acinetobacter spp. despite persistent recovery of these organisms from respiratory secretions of patients with ventilator-associated pneumonia treated with this drug. J. Clin. Microbiol.47(9), 3064–3065 (2009).
  • 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).
  • Li J, Milne RW, Nation RL, Turnidge JD, Smeaton TC, Coulthard K. Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate. J. Antimicrob. Chemother.53(5), 837–840 (2004).
  • Cirioni O, Ghiselli R, Orlando F et al. Efficacy of colistin/rifampin combination in experimental rat models of sepsis due to a multiresistant Pseudomonas aeruginosa strain. Crit. Care Med.35(7), 1717–1723 (2007).
  • Giamarellou H. Treatment options for multidrug-resistant bacteria. Expert Rev. Anti Infect. Ther.4(4), 601–618 (2006).
  • Peterson LR. A review of tigecycline – the first glycylcycline. Int. J. Antimicrob. Agents32(Suppl. 4), 215–222 (2008).
  • 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).
  • Vasilev K, Reshedko G, Orasan R et al. A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae. J. Antimicrob. Chemother.62(Suppl. 1), 29–40 (2008).
  • 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).
  • Rahal JJ. Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species. Clin. Infect. Dis.43(Suppl. 2), S95–S99 (2006).
  • Casal M, Rodríguez F, Johnson B et al. Influence of testing methodology on the tigecycline activity profile against presumably tigecycline-non-susceptible Acinetobacter spp. J. Antimicrob. Chemother.64(1), 69–72 (2009).
  • Navon-Venezia S, Leavitt A, Carmeli Y. High tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J. Antimicrob. Chemother.59(4), 772–774 (2007).
  • Canigia LF, Bantar C. Susceptibility testing of tigecycline against Acinetobacter spp. by disc diffusion method: withdrawing a therapeutic option by varying the Mueller–Hinton agar? J. Antimicrob. Chemother.62(6), 1463–1464 (2008).
  • Petersen PJ, Bradford PA. Effect of medium age and Supplementation with the biocatalytic oxygen-reducing reagent oxyrase on in vitro activities of tigecycline against recent clinical isolates. Antimicrob. Agents Chemother.49(9), 3910–3918 (2005).
  • Hope R, Warner M, Mushtaq S, Ward ME, Parsons T, Livermore DM. Effect of medium type, age and aeration on the MICs of tigecycline and classical tetracyclines. J. Antimicrob. Chemother.56(6), 1042–1046 (2005).
  • Bradford PA, Petersen PJ, Young M, Jones CH, Tischler M, O’Connell J. Tigecycline MIC testing by broth dilution requires use of fresh medium or addition of the biocatalytic oxygen-reducing reagent oxyrase to standardize the test method. Antimicrob. Agents Chemother.49(9), 3903–3909 (2005).
  • Fernández-Mazarrasa C, Mazarrasa O, Calvo J et al. High concentrations of manganese in Mueller–Hinton agar increase MICs of tigecycline determined by Etest. J. Clin. Microbiol.47(3), 827–829 (2009).
  • MacGowan AP. Tigecycline pharmacokinetic/pharmacodynamic update. J. Antimicrob. Chemother.62(Suppl. 1), 11–16 (2008).
  • 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).
  • Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T. Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint. Int. J. Antimicrob. Agents34(1), 101–102 (2009).
  • Conte JE Jr, Golden JA, Kelly MG, Zurlinden E. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int. J. Antimicrob. Agents25(6), 523–529 (2005).
  • Tanaseanu C, Bergallo C, Teglia O et al. Integrated results of 2 Phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn. Microbiol. Infect. Dis.61(3), 329–338 (2008).
  • Bergallo C, Jasovich A, Teglia O et al. Safety and efficacy of intravenous tigecycline in treatment of community-acquired pneumonia: results from a double-blind randomized Phase 3 comparison study with levofloxacin. Diagn. Microbiol. Infect. Dis.63(1), 52–61 (2009).
  • Curcio D. Treatment of recurrent urosepsis with tigecycline: a pharmacological perspective. J. Clin. Microbiol.46(5), 1892–1893 (2008).
  • Cunha BA. Pharmacokinetic considerations regarding tigecycline for multidrug-resistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis. J. Clin. Microbiol.47(5), 1613 (2009).
  • Endimiani A, Perez F, Bonomo RA. Cefepime: a reappraisal in an era of increasing antimicrobial resistance. Expert Rev. Anti Infect. Ther.6(6), 805–824 (2008).
  • Bhat SV, Peleg AY, Lodise TP Jr et al. Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by Gram-negative organisms. Antimicrob. Agents Chemother.51(12), 4390–4395 (2007).
  • Gin A, Dilay L, Karlowsky JA, Walkty A, Rubinstein E, Zhanel GG. Piperacillin-tazobactam: a β-lactam/β-lactamase inhibitor combination. Expert Rev. Anti Infect. Ther.5(3), 365–383 (2007).
  • Tam VH, Gamez EA, Weston JS et al. Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin–tazobactam: implications on the appropriateness of the resistance breakpoint. Clin. Infect. Dis.46(6), 862–867 (2008).
  • Zavascki AP, Barth AL, Goldani LZ. Nosocomial bloodstream infections due to metallo-β-lactamase-producing Pseudomonas aeruginosa. J. Antimicrob. Chemother.61(5), 1183–1185 (2008).
  • Sader HS, Jones RN. Comprehensive in vitro evaluation of cefepime combined with aztreonam or ampicillin/sulbactam against multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. Int. J. Antimicrob. Agents25(5), 380–384 (2005).
  • Vinks AA, van Rossem RN, Mathôt RA, Heijerman HG, Mouton JW. Pharmacokinetics of aztreonam in healthy subjects and patients with cystic fibrosis and evaluation of dose–exposure relationships using Monte Carlo simulation. Antimicrob. Agents Chemother.51(9), 3049–3055 (2007).
  • Vidal L, Gafter-Gvili A, Borok S, Fraser A, Leibovici L, Paul M. Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials. J. Antimicrob. Chemother.60(2), 247–257 (2007).
  • Leibovici L, Paul M, Poznanski O et al. Monotherapy versus β-lactam-aminoglycoside combination treatment for Gram-negative bacteremia: a prospective, observational study. Antimicrob. Agents Chemother.41(5), 1127–1133 (1997).
  • Lacy MK, Nicolau DP, Nightingale CH, Quintiliani R. The pharmacodynamics of aminoglycosides. Clin. Infect. Dis.27(1), 23–27 (1998).
  • Lode HM. Rational antibiotic therapy and the position of ampicillin/sulbactam. Int. J. Antimicrob. Agents32(1), 10–28 (2008).
  • Akova M. Sulbactam-containing β-lactamase inhibitor combinations. Clin. Microbiol. Infect.14(Suppl. 1), 185–188 (2008).
  • Rafailidis PI, Ioannidou EN, Falagas ME. Ampicillin/sulbactam: current status in severe bacterial infections. Drugs67(13), 1829–1849 (2007).
  • Swenson JM, Killgore GE, Tenover FC. Antimicrobial susceptibility testing of Acinetobacter spp. by NCCLS broth microdilution and disk diffusion methods. J. Clin. Microbiol.42(11), 5102–5108 (2004).
  • Paul M, Leibovici L. Combination antimicrobial treatment versus monotherapy: the contribution of meta-analyses. Infect. Dis. Clin. North Am.23(2), 277–293 (2009).
  • 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. Agents32(5), 450–454 (2008).
  • Kalai BS, Achour W, Bejaoui M, Abdeladhim A, Ben Hassen A. Detection of SHV-1 β-lactamase in Pseudomonas aeruginosa strains by genetic methods. Pathol. Biol. (Paris)57(3), e73–e75 (2009).
  • Celenza G, Pellegrini C, Caccamo M, Segatore B, Amicosante G, Perilli M. Spread of bla(CTX-M-type) and bla(PER-2) β-lactamase genes in clinical isolates from Bolivian hospitals. J. Antimicrob. Chemother.57(5), 975–978 (2006).
  • Jiang X, Zhang Z, Li M, Zhou D, Ruan F, Lu Y. Detection of extended-spectrum β-lactamases in clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother.50(9), 2990–2995 (2006).
  • al Naiemi N, Duim B, Bart A. A CTX-M extended-spectrum β-lactamase in Pseudomonas aeruginosa and Stenotrophomonas maltophilia. J. Med. Microbiol.55(11), 1607–1608 (2006).
  • Giuliani F, Docquier JD, Riccio ML, Pagani L, Rossolini GM. OXA-46, a new class D β-lactamase of narrow substrate specificity encoded by a blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate. Antimicrob. Agents Chemother.49(5), 1973–1980 (2005).
  • Bert F, Vanjak D, Leflon-Guibout V et al. IMP-4-producing Pseudomonas aeruginosa in a French patient repatriated from Malaysia: impact of early detection and control measures. Clin. Infect. Dis.44(5), 764–765 (2007).
  • Ryoo NH, Lee K, Lim JB, Lee YH, Bae IK, Jeong SH. Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-β-lactamase in a Korean hospital. Diagn. Microbiol. Infect. Dis.63(1), 115–117 (2009).
  • Iyobe S, Kusadokoro H, Takahashi A et al. Detection of a variant metallo-β-lactamase, IMP-10, from two unrelated strains of Pseudomonas aeruginosa and an Alcaligenes xylosoxidans strain. Antimicrob. Agents Chemother.46(6), 2014–2016 (2002).
  • Docquier JD, Riccio ML, Mugnaioli C et al. IMP-12, a new plasmid-encoded metallo-β-lactamase from a Pseudomonas putida clinical isolate. Antimicrob. Agents Chemother.47(5), 1522–1528 (2003).
  • Garza-Ramos U, Morfin-Otero R, Sader HS et al. Metallo-β-lactamase gene bla(IMP-15) in a class 1 integron, In95, from Pseudomonas aeruginosa clinical isolates from a hospital in Mexico. Antimicrob. Agents Chemother.52(8), 2943–2946 (2008).
  • Mendes RE, Toleman MA, Ribeiro J, Sader HS, Jones RN, Walsh TR. Integron carrying a novel metallo-β-lactamase gene, blaIMP-16, and a fused form of aminoglycoside-resistant gene aac(6’)-30/aac(6’)-Ib’: report from the SENTRY Antimicrobial Surveillance Program. Antimicrob. Agents Chemother.48(12), 4693–4702 (2004).
  • Duljasz W, Gniadkowski M, Sitter S, Wojna A, Jebelean C. First organisms with acquired metallo-β-lactamases (IMP-13, IMP-22, and VIM-2) reported in Austria. Antimicrob. Agents Chemother.53(5), 2221–2222 (2009).
  • Koh TH, Wang GC, Sng LH. IMP-1 and a novel metallo-β-lactamase, VIM-6, in fluorescent Pseudomonads isolated in Singapore. Antimicrob. Agents Chemother.48(6), 2334–2336 (2004).
  • Siarkou VI, Vitti D, Protonotariou E, Ikonomidis A, Sofianou D. Molecular epidemiology of outbreak-related Pseudomonas aeruginosa strains carrying the novel variant blaVIM-17 metallo-β-lactamase gene. Antimicrob. Agents Chemother.53(4), 1325–1330 (2009).
  • Castanheira M, Bell JM, Turnidge JD, Mathai D, Jones RN. Carbapenem resistance among Pseudomonas aeruginosa strains from India: evidence for nationwide endemicity of multiple metallo-β-lactamase clones (VIM-2, -5, -6, and -11 and the newly characterized VIM-18). Antimicrob. Agents Chemother.53(3), 1225–1227 (2009).
  • Toleman MA, Simm AM, Murphy TA et al. Molecular characterization of SPM-1, a novel metallo-β-lactamase isolated in Latin America: report from the SENTRY antimicrobial surveillance programme. J. Antimicrob. Chemother.50(5), 673–679 (2002).
  • Hujer KM, Hamza NS, Hujer AM et al. Identification of a new allelic variant of the Acinetobacter baumannii cephalosporinase, ADC-7 β-lactamase: defining a unique family of class C enzymes. Antimicrob. Agents Chemother.49(7), 2941–2848 (2005).
  • Pasteran F, Rapoport M, Petroni A et al. Emergence of PER-2 and VEB-1a in Acinetobacter baumannii strains in the Americas. Antimicrob. Agents Chemother.50(9), 3222–3224 (2006).
  • Poirel L, Menuteau O, Agoli N, Cattoen C, Nordmann P. Outbreak of extended-spectrum β-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a French hospital. J. Clin. Microbiol.41(8), 3542–3547 (2003).
  • Huang LY, Chen TL, Lu PL et al. Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan. Clin. Microbiol. Infect.14(11), 1010–1019 (2008).
  • Naiemi NA, Duim B, Savelkoul PH et al. Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology. J. Clin. Microbiol.43(9), 4862–4864 (2005).
  • Nagano N, Nagano Y, Cordevant C, Shibata N, Arakawa Y. Nosocomial transmission of CTX-M-2 β-lactamase-producing Acinetobacter baumannii in a neurosurgery ward. J. Clin. Microbiol.42(9), 3978–3984 (2004).
  • Choury D, Szajnert MF, Joly-Guillou ML, Azibi K, Delpech M, Paul G. Nucleotide sequence of the bla(RTG-2) (CARB-5) gene and phylogeny of a new group of carbenicillinases. Antimicrob. Agents Chemother.44(4), 1070–1074 (2000).
  • Mammeri H, Poirel L, Mangeney N, Nordmann P. Chromosomal integration of a cephalosporinase gene from Acinetobacter baumannii into Oligella urethralis as a source of acquired resistance to β-lactams. Antimicrob. Agents Chemother.47(5), 1536–1542 (2003).
  • Sung JY, Kwon KC, Park JW et al. Dissemination of IMP-1 and OXA type β-lactamase in carbapenem-resistant Acinetobacter baumannii. Korean J. Lab. Med.28(1), 16–23 (2008).
  • Giordano A, Varesi P, Bertini A et al. Outbreak of Acinetobacter baumannii producing the carbapenem-hydrolyzing oxacillinase OXA-58 in Rome, Italy. Microb. Drug Resist.13(1), 37–43 (2007).
  • Wang H, Guo P, Sun H et al. Molecular epidemiology of clinical isolates of carbapenem-resistant Acinetobacter spp. from Chinese hospitals. Antimicrob. Agents Chemother.51(11), 4022–4028 (2007).
  • Tsakris A, Ikonomidis A, Pournaras S et al. VIM-1 metallo-β-lactamase in Acinetobacter baumannii. Emerg. Infect. Dis.12(6), 981–983 (2006).
  • Yum JH, Yi K, Lee H et al. Molecular characterization of metallo-β-lactamase-producing Acinetobacter baumannii and Acinetobacter genomospecies 3 from Korea: identification of two new integrons carrying the bla(VIM-2) gene cassettes. J. Antimicrob. Chemother.49(5), 837–840 (2002).
  • Lee MF, Peng CF, Hsu HJ, Chen YH. Molecular characterisation of the metallo-β-lactamase genes in imipenem-resistant Gram-negative bacteria from a university hospital in southern Taiwan. Int. J. Antimicrob. Agents32(6), 475–480 (2008).
  • Figueiredo S, Poirel L, Papa A, Koulourida V, Nordmann P. First identification of VIM-4 metallo-β-lactamase in Acinetobacter spp. Clin. Microbiol. Infect.14(3), 289–290 (2008).
  • Kohler T, Van Delden C, Curty LK et al. Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J. Bacteriol.183(18), 5213–5222 (2001).
  • Westbrock-Wadman S, Sherman DR, Hickey MJ et al. Characterization of a Pseudomonas aeruginosa efflux pump contributing to aminoglycoside impermeability. Antimicrob. Agents Chemother.43(12), 2975–2983 (2004).
  • Pozzi G, Iannelli F, Oggioni MR et al. Genetic elements carrying macrolide-efflux genes in streptococci. Curr. Drug Targets Infect. Disord.4(3), 203–206 (2004).
  • Li XZ, Poole K, Nikaido H. Contributions of MexAB-OprM and an ErmE homolog to intrinsic resistance of Pseudomonas aeruginosa to aminoglycosides and dyes. Antimicrob. Agents Chemother.47(1), 27–33 (2003).
  • Magnet S, Courvalin P, Lambert T. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob. Agents Chemother.45(12), 3375–3380 (2001).
  • Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.44(12), 3322–3327 (2000).
  • Masuda N, Sakagawa E, Ohya S. Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.39(3), 645–649 (1995).
  • Gotoh N, Tsujimoto H, Nomura A, Okamoto K, Tsuda M, Nishino T. Functional replacement of OprJ by OprM in the MexCD–OprJ multidrug efflux system of Pseudomonas aeruginosa. FEMS Microbiol. Lett.165(1), 21–27 (1998).
  • Zhao Q, Li XZ, Mistry A et al. Influence of the TonB energy-coupling protein on efflux-mediated multidrug resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother.42(9), 2225–2231 (1998).
  • Poole K, Zhao Q, Neshat S, Heinrichs DE, Dean CR. The Pseudomonas aeruginosatonB gene encodes a novel TonB protein. Microbiology142(Pt 6), 1449–1458 (1996).
  • Dupont M, Pagès JM, Lafitte D, Siroy A, Bollet C. Identification of an OprD homologue in Acinetobacter baumannii. J. Proteome Res.4(6), 2386–2390 (2005).
  • Jaruratanasirikul S, Sudsai T. Comparison of the pharmacodynamics of imipenem in patients with ventilator-associated pneumonia following administration by 2 or 0.5 h infusion. J. Antimicrob. Chemother.63(3), 560–563 (2009).
  • Roberts JA, Kirkpatrick CM, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J. Antimicrob. Chemother.64(1), 142–150 (2009).
  • Nicasio AM, Ariano RE, Zelenitsky AS et al. Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia. Antimicrob. Agents Chemother.53(4), 1476–1481 (2009).
  • Roos JF, Bulitta J, Lipman J, Kirkpatrick CM. Pharmacokinetic–pharmacodynamic rationale for cefepime dosing regimens in intensive care units. J. Antimicrob. Chemother.58(5), 987–993 (2006).
  • Kim A, Sutherland CA, Kuti JL, Nicolau DP. Optimal dosing of piperacillin–tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Pharmacotherapy27(11), 1490–1497 (2007).

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