Optimizing Therapy for Acinetobacter baumannii

Anton Y. Peleg

doi:10.1055/s-2007-996413

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000075.xml

Share / Bookmark

Facebook Linkedin Weibo

Download PDF

Semin Respir Crit Care Med 2007; 28(6): 662-671
DOI: 10.1055/s-2007-996413

Optimizing Therapy for Acinetobacter baumannii

Anton Y. Peleg¹ ^, ²

¹Division of Infectious Diseases, Beth Israel Deaconess Medical Center
²Harvard Medical School, Boston, Massachusetts

Further Information

Publication History

Publication Date:
20 December 2007 (online)

Abstract
Full Text
References

Buy Article Permissions and Reprints

ABSTRACT

Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that thrives within the unique and complex ecological setting of an intensive care unit. This evolving pathogen has now surpassed human capacity to create new antimicrobials, and has led physicians into a concerning era for hospital-acquired infections. This review presents the available evidence on the therapeutic strategies for A. baumannii infection, with a particular focus on clinical human data. The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline. Other important adjunctive strategies such as pharmacodynamic target attainment and infection control implementation are briefly discussed. It is now clear that new antimicrobials with unique mechanisms of action are urgently required to combat the rising trends seen globally with drug-resistant A. baumannii.

KEYWORDS

A. baumannii - sulbactam - colistin - polymyxins - tigecycline

REFERENCES

1 Donskey C J. Antibiotic regimens and intestinal colonization with antibiotic-resistant gram-negative bacilli. Clin Infect Dis. 2006; 43(Suppl 2) S62-S69

Crossref PubMed Search in Google Scholar
2 Wendt C, Dietze B, Dietz E, Ruden H. Survival of Acinetobacter baumannii on dry surfaces. J Clin Microbiol. 1997; 35 1394-1397

PubMed Search in Google Scholar
3 Wisplinghoff H, Schmitt R, Wohrmann A, Stefanik D, Seifert H. Resistance to disinfectants in epidemiologically defined clinical isolates of Acinetobacter baumannii . J Hosp Infect. 2007; 66 174-181

Crossref PubMed Search in Google Scholar
4 Villegas M V, Hartstein A I. Acinetobacter outbreaks, 1977-2000. Infect Control Hosp Epidemiol. 2003; 24 284-295

Crossref PubMed Search in Google Scholar
5 Abbo A, Navon-Venezia S, Hammer-Muntz O, Krichali T, Siegman-Igra Y, Carmeli Y. Multidrug-resistant Acinetobacter baumannii . Emerg Infect Dis. 2005; 11 22-29

PubMed Search in Google Scholar
6 Coelho J M, Turton J F, Kaufmann M E et al.. Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J Clin Microbiol. 2006; 44 3623-3627

Crossref PubMed Search in Google Scholar
7 Dalla-Costa L M, Coelho J M, Souza H A et al.. Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba, Brazil. J Clin Microbiol. 2003; 41 3403-3406

Crossref PubMed Search in Google Scholar
8 Hsueh P R, Teng L J, Chen C Y et al.. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis. 2002; 8 827-832

PubMed Search in Google Scholar
9 Landman D, Quale J M, Mayorga D et al.. Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned. Arch Intern Med. 2002; 162 1515-1520

Crossref PubMed Search in Google Scholar
10 Peleg A Y, Franklin C, Bell J M, Spelman D W. Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia. Infect Control Hosp Epidemiol. 2006; 27 759-761

Crossref PubMed Search in Google Scholar
11 Scott P, Deye G, Srinivasan A et al.. An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq. Clin Infect Dis. 2007; 44 1577-1584

Crossref PubMed Search in Google Scholar
12 Van Looveren M, Goossens H. Antimicrobial resistance of Acinetobacter spp. in Europe. Clin Microbiol Infect. 2004; 10 684-704

Crossref PubMed Search in Google Scholar
13 Abbott A. Medics braced for fresh superbug. Nature. 2005; 436 758

Crossref PubMed Search in Google Scholar
14 Hawley J S, Murray C K, Griffith M E et al.. Susceptibility of Acinetobacter strains isolated from deployed U.S. military personnel. Antimicrob Agents Chemother. 2007; 51 376-378

PubMed Search in Google Scholar
15 Spellberg B, Powers J H, Brass E P, Miller L G, Edwards Jr J E. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. 2004; 38 1279-1286

Crossref PubMed Search in Google Scholar
16 Wenzel R P. The antibiotic pipeline: challenges, costs, and values. N Engl J Med. 2004; 351 523-526

Crossref PubMed Search in Google Scholar
17 Talbot G H, Bradley J, Edwards Jr J E, Gilbert D, Scheld M, Bartlett J G. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006; 42 657-668

Crossref PubMed Search in Google Scholar
18 National Institutes of Health .Partnerships to Improve Diagnosis and Treatment of Selected Drug-Resistant Healthcare-Associated Infections (U01). RFA-AI-06-036
19 Gaynes R, Edwards J R. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005; 41 848-854

Crossref PubMed Search in Google Scholar
20 Halstead D C, Abid J, Dowzicky M J. Antimicrobial susceptibility among Acinetobacter calcoaceticus-baumannii complex and Enterobacteriaceae collected as part of the Tigecycline Evaluation and Surveillance Trial. J Infect. 2007; 55 49-57

Crossref PubMed Search in Google Scholar
21 Rhomberg P R, Fritsche T R, Sader H S, Jones R N. Clonal occurrences of multidrug-resistant gram-negative bacilli: report from the Meropenem Yearly Susceptibility Test Information Collection Surveillance Program in the United States (2004). Diagn Microbiol Infect Dis. 2006; 54 249-257

Crossref PubMed Search in Google Scholar
22 Jeon B C, Jeong S H, Bae I K et al.. Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in Korea. J Clin Microbiol. 2005; 43 2241-2245

Crossref PubMed Search in Google Scholar
23 Pascual A, Perea E, Alvarez M et al.. The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis. Diagn Microbiol Infect Dis. 2007; 57 195-200

Crossref PubMed Search in Google Scholar
24 Playford E G, Craig J C, Iredell J R. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences. J Hosp Infect. 2007; 65 204-211

Crossref PubMed Search in Google Scholar
25 Mulin B, Talon D, Viel J F et al.. Risk factors for nosocomial colonization with multiresistant Acinetobacter baumannii . Eur J Clin Microbiol Infect Dis. 1995; 14 569-576

Crossref PubMed Search in Google Scholar
26 Carbonne A, Naas T, Blanckaert K et al.. Investigation of a nosocomial outbreak of extended-spectrum beta-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a hospital setting. J Hosp Infect. 2005; 60 14-18

Crossref PubMed Search in Google Scholar
27 Husni R N, Goldstein L S, Arroliga A C et al.. Risk factors for an outbreak of multi-drug-resistant Acinetobacter nosocomial pneumonia among intubated patients. Chest. 1999; 115 1378-1382

Crossref PubMed Search in Google Scholar
28 Scerpella E G, Wanger A R, Armitige L, Anderlini P, Ericsson C D. Nosocomial outbreak caused by a multiresistant clone of Acinetobacter baumannii: results of the case-control and molecular epidemiologic investigations. Infect Control Hosp Epidemiol. 1995; 16 92-97

PubMed Search in Google Scholar
29 Villers D, Espaze E, Coste-Burel M et al.. Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology. Ann Intern Med. 1998; 129 182-189

PubMed Search in Google Scholar
30 Corbella X, Montero A, Pujol M et al.. Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii . J Clin Microbiol. 2000; 38 4086-4095

PubMed Search in Google Scholar
31 del Mar Tomas M, Cartelle M, Pertega S et al.. Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection. Clin Microbiol Infect. 2005; 11 540-546

Crossref PubMed Search in Google Scholar
32 Lee S O, Kim N J, Choi S H et al.. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study. Antimicrob Agents Chemother. 2004; 48 224-228

Crossref PubMed Search in Google Scholar
33 Kaye K S, Harris A D, Samore M, Carmeli Y. The case-case-control study design: addressing the limitations of risk factor studies for antimicrobial resistance. Infect Control Hosp Epidemiol. 2005; 26 346-351

Crossref PubMed Search in Google Scholar
34 Blot S, Vandewoude K, Colardyn F. Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study. Intensive Care Med. 2003; 29 471-475

PubMed Search in Google Scholar
35 Garcia-Garmendia J L, Ortiz-Leyba C, Garnacho-Montero J, Jimenez-Jimenez F J, Monterrubio-Villar J, Gili-Miner M. Mortality and the increase in length of stay attributable to the acquisition of Acinetobacter in critically ill patients. Crit Care Med. 1999; 27 1794-1799

PubMed Search in Google Scholar
36 Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J. Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: a matched cohort study. Crit Care Med. 2003; 31 2478-2482

Crossref PubMed Search in Google Scholar
37 Grupper M, Sprecher H, Mashiach T, Finkelstein R. Attributable mortality of nosocomial Acinetobacter bacteremia. Infect Control Hosp Epidemiol. 2007; 28 293-298

Crossref PubMed Search in Google Scholar
38 Falagas M E, Bliziotis I A, Siempos I I. Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies. Crit Care. 2006; 10 R48

Crossref PubMed Search in Google Scholar
39 Sunenshine R H, Wright M O, Maragakis L L et al.. Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization. Emerg Infect Dis. 2007; 13 97-103

PubMed Search in Google Scholar
40 Falagas M E, Kasiakou S K, Rafailidis P I, Zouglakis G, Morfou P. Comparison of mortality of patients with Acinetobacter baumannii bacteraemia receiving appropriate and inappropriate empirical therapy. J Antimicrob Chemother. 2006; 57 1251-1254

Crossref PubMed Search in Google Scholar
41 Falagas M E, Bliziotis I A. Pandrug-resistant gram-negative bacteria: the dawn of the post-antibiotic era?. Int J Antimicrob Agents. 2007; 29 630-636

Crossref PubMed Search in Google Scholar
42 Wood G C, Hanes S D, Boucher B A, Croce M A, Fabian T C. Tetracyclines for treating multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia. Intensive Care Med. 2003; 29 2072-2076

Crossref PubMed Search in Google Scholar
43 Levin A S. Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem. Clin Microbiol Infect. 2002; 8 144-153

Crossref PubMed Search in Google Scholar
44 Brauers J, Frank U, Kresken M, Rodloff A C, Seifert H. Activities of various beta-lactams and beta-lactam/beta-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains. Clin Microbiol Infect. 2005; 11 24-30

PubMed Search in Google Scholar
45 Higgins P G, Wisplinghoff H, Stefanik D, Seifert H. In vitro activities of the beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with beta-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains. Antimicrob Agents Chemother. 2004; 48 1586-1592

Crossref PubMed Search in Google Scholar
46 Urban C, Go E, Mariano N et al.. Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus . J Infect Dis. 1993; 167 448-451

PubMed Search in Google Scholar
47 Corbella X, Ariza J, Ardanuy C et al.. Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii . J Antimicrob Chemother. 1998; 42 793-802

PubMed Search in Google Scholar
48 Wood G C, Hanes S D, Croce M A, Fabian T C, Boucher B A. Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of Acinetobacter ventilator-associated pneumonia. Clin Infect Dis. 2002; 34 1425-1430

Crossref PubMed Search in Google Scholar
49 Valcke Y J, Rosseel M T, Pauwels R A, Bogaert M G, Van der Straeten M E. Penetration of ampicillin and sulbactam in the lower airways during respiratory infections. Antimicrob Agents Chemother. 1990; 34 958-962

PubMed Search in Google Scholar
50 Choi J Y, Kim C O, Park Y S et al.. Comparison of efficacy of cefoperazone/sulbactam and imipenem/cilastatin for treatment of Acinetobacter bacteremia. Yonsei Med J. 2006; 47 63-69

PubMed Search in Google Scholar
51 Cisneros J M, Reyes M J, Pachon J et al.. Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis. 1996; 22 1026-1032

Crossref PubMed Search in Google Scholar
52 Jellison T K, McKinnon P S, Rybak M J. Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam. Pharmacotherapy. 2001; 21 142-148

PubMed Search in Google Scholar
53 Smolyakov R, Borer A, Riesenberg K et al.. Nosocomial multi-drug resistant Acinetobacter baumannii bloodstream infection: risk factors and outcome with ampicillin-sulbactam treatment. J Hosp Infect. 2003; 54 32-38

Crossref PubMed Search in Google Scholar
54 Jimenez-Mejias M E, Pachon J, Becerril B, Palomino-Nicas J, Rodriguez-Cobacho A, Revuelta M. Treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin/sulbactam. Clin Infect Dis. 1997; 24 932-935

PubMed Search in Google Scholar
55 Levin A S, Levy C E, Manrique A E, Medeiros E A, Costa S F. Severe nosocomial infections with imipenem-resistant Acinetobacter baumannii treated with ampicillin/sulbactam. Int J Antimicrob Agents. 2003; 21 58-62

Crossref PubMed Search in Google Scholar
56 Foulds G. Pharmacokinetics of sulbactam/ampicillin in humans: a review. Rev Infect Dis. 1986; 8(Suppl 5) S503-S511

PubMed Search in Google Scholar
57 Meyers B R, Wilkinson P, Mendelson M H, Walsh S, Bournazos C, Hirschman S Z. Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers. Antimicrob Agents Chemother. 1991; 35 2098-2101

PubMed Search in Google Scholar
58 Betrosian A P, Frantzeskaki F, Xanthaki A, Georgiadis G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii . Scand J Infect Dis. 2007; 39 38-43

PubMed Search in Google Scholar
59 Rodriguez-Hernandez M J, Cuberos L, Pichardo C et al.. Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains. J Antimicrob Chemother. 2001; 47 479-482

Crossref PubMed Search in Google Scholar
60 Tong W, Wang R, Chai D, Li Z, Pei F. In vitro activity of cefepime combined with sulbactam against clinical isolates of carbapenem-resistant Acinetobacter spp. Int J Antimicrob Agents. 2006; 28 454-456

PubMed Search in Google Scholar
61 Song J Y, Kee S Y, Hwang I S et al.. In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii . J Antimicrob Chemother. 2007; 60 317-322

Crossref PubMed Search in Google Scholar
62 Ko W C, Lee H C, Chiang S R et al.. In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain. J Antimicrob Chemother. 2004; 53 393-395

Crossref PubMed Search in Google Scholar
63 Savov E, Chankova D, Vatcheva R, Dinev N. In vitro investigation of the susceptibility of Acinetobacter baumannii strains isolated from clinical specimens to ampicillin/sulbactam alone and in combination with amikacin. Int J Antimicrob Agents. 2002; 20 390-392

PubMed Search in Google Scholar
64 Appleman M D, Belzberg H, Citron D M et al.. In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak. Antimicrob Agents Chemother. 2000; 44 1035-1040

Crossref PubMed Search in Google Scholar
65 Wolff M, Joly-Guillou M L, Farinotti R, Carbon C. In vivo efficacies of combinations of beta-lactams, beta-lactamase inhibitors, and rifampin against Acinetobacter baumannii in a mouse pneumonia model. Antimicrob Agents Chemother. 1999; 43 1406-1411

PubMed Search in Google Scholar
66 Markou N, Apostolakos H, Koumoudiou C et al.. Intravenous colistin in the treatment of sepsis from multiresistant gram-negative bacilli in critically ill patients. Crit Care. 2003; 7 R78-R83

Crossref PubMed Search in Google Scholar
67 Michalopoulos A S, Tsiodras S, Rellos K, Mentzelopoulos S, Falagas M E. Colistin treatment in patients with ICU-acquired infections caused by multiresistant gram-negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect. 2005; 11 115-121

Crossref PubMed Search in Google Scholar
68 Levin A S, Barone A A, Penco J et al.. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii . Clin Infect Dis. 1999; 28 1008-1011

PubMed Search in Google Scholar
69 Ouderkirk J P, Nord J A, Turett G S, Kislak J W. Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria. Antimicrob Agents Chemother. 2003; 47 2659-2662

Crossref PubMed Search in Google Scholar
70 Sobieszczyk M E, Furuya E Y, Hay C M et al.. Combination therapy with polymyxin B for the treatment of multidrug-resistant gram-negative respiratory tract infections. J Antimicrob Chemother. 2004; 54 566-569

Crossref PubMed Search in Google Scholar
71 Reina R, Estenssoro E, Saenz G et al.. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study. Intensive Care Med. 2005; 31 1058-1065

Crossref PubMed Search in Google Scholar
72 Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez F J et al.. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis. 2003; 36 1111-1118

Crossref PubMed Search in Google Scholar
73 Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis. 2007; 11 402-406

Crossref PubMed Search in Google Scholar
74 Kwa A L, Loh C, Low J G, Kurup A, Tam V H. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa . Clin Infect Dis. 2005; 41 754-757

Crossref PubMed Search in Google Scholar
75 Michalopoulos A, Kasiakou S K, Mastora Z, Rellos K, Kapaskelis A M, Falagas M E. Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis. Crit Care. 2005; 9 R53-R59

Crossref PubMed Search in Google Scholar
76 Feeley T W, Du Moulin G C, Hedley-Whyte J, Bushnell L S, Gilbert J P, Feingold D S. Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med. 1975; 293 471-475

PubMed Search in Google Scholar
77 Falagas M E, Bliziotis I A, Tam V H. Intraventricular or intrathecal use of polymyxins in patients with gram-negative meningitis: a systematic review of the available evidence. Int J Antimicrob Agents. 2007; 29 9-25

PubMed Search in Google Scholar
78 Ng J, Gosbell I B, Kelly J A, Boyle M J, Ferguson J K. Cure of multiresistant Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review. J Antimicrob Chemother. 2006; 58 1078-1081

Crossref PubMed Search in Google Scholar
79 Tunkel A R, Hartman B J, Kaplan S L et al.. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39 1267-1284

Crossref PubMed Search in Google Scholar
80 Bukhary Z, Mahmood W, Al-Khani A, Al-Abdely H M. Treatment of nosocomial meningitis due to a multidrug resistant Acinetobacter baumannii with intraventricular colistin. Saudi Med J. 2005; 26 656-658

PubMed Search in Google Scholar
81 Kasiakou S K, Rafailidis P I, Liaropoulos K, Falagas M E. Cure of post-traumatic recurrent multiresistant gram-negative rod meningitis with intraventricular colistin. J Infect. 2005; 50 348-352

Crossref PubMed Search in Google Scholar
82 Giamarellos-Bourboulis E J, Xirouchaki E, Giamarellou H. Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii . Diagn Microbiol Infect Dis. 2001; 40 117-120

Crossref PubMed Search in Google Scholar
83 Manikal V M, Landman D, Saurina G, Oydna E, Lal H, Quale J. Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage. Clin Infect Dis. 2000; 31 101-106

Crossref PubMed Search in Google Scholar
84 Timurkaynak F, Can F, Azap O K, Demirbilek M, Arslan H, Karaman S O. In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units. Int J Antimicrob Agents. 2006; 27 224-228

PubMed Search in Google Scholar
85 Yoon J, Urban C, Terzian C, Mariano N, Rahal J J. In vitro double and triple synergistic activities of polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii . Antimicrob Agents Chemother. 2004; 48 753-757

Crossref PubMed Search in Google Scholar
86 Tan T Y, Ng L S, Tan E, Huang G. In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates. J Antimicrob Chemother. 2007; 60 421-423

Crossref PubMed Search in Google Scholar
87 Falagas M E, Rafailidis P I, Kasiakou S K, Hatzopoulou P, Michalopoulos A. Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant gram-negative bacterial infections. Clin Microbiol Infect. 2006; 12 1227-1230

Crossref PubMed Search in Google Scholar
88 Motaouakkil S, Charra B, Hachimi A et al.. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii . J Infect. 2006; 53 274-278

Crossref PubMed Search in Google Scholar
89 Petrosillo N, Chinello P, Proietti M F et al.. Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: clinical outcome and adverse events. Clin Microbiol Infect. 2005; 11 682-683

Crossref PubMed Search in Google Scholar
90 Gales A C, Jones R N, Sader H S. 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. 2006; 12 315-321

Crossref PubMed Search in Google Scholar
91 Li J, Rayner C R, Nation R L et al.. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii . Antimicrob Agents Chemother. 2006; 50 2946-2950

Crossref PubMed Search in Google Scholar
92 Rahal J J. Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis. 2006; 43(Suppl 2) S95-S99

Crossref PubMed Search in Google Scholar
93 Chait R, Craney A, Kishony R. Antibiotic interactions that select against resistance. Nature. 2007; 446 668-671

Crossref PubMed Search in Google Scholar
94 Bonapace C R, White R L, Friedrich L V, Bosso J A. Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill, and checkerboard methods. Diagn Microbiol Infect Dis. 2000; 38 43-50

Crossref PubMed Search in Google Scholar
95 Chang S C, Chen Y C, Luh K T, Hsieh W C. In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood. Diagn Microbiol Infect Dis. 1995; 23 105-110

Crossref PubMed Search in Google Scholar
96 Drago L, De Vecchi E, Nicola L, Colombo A, Guerra A, Gismondo M R. Activity of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin-tazobactam and amikacin against different Pseudomonas aeruginosa phenotypes and Acinetobacter spp. Chemotherapy. 2004; 50 202-210

Crossref PubMed Search in Google Scholar
97 Ermertcan S, Hosgor M, Tunger O, Cosar G. Investigation of synergism of meropenem and ciprofloxacin against Pseudomonas aeruginosa and Acinetobacter strains isolated from intensive care unit infections. Scand J Infect Dis. 2001; 33 818-821

PubMed Search in Google Scholar
98 Joly-Guillou M L, Wolff M, Farinotti R, Bryskier A, Carbon C. In vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia. J Antimicrob Chemother. 2000; 46 827-830

Crossref PubMed Search in Google Scholar
99 Jung R, Husain M, Choi M K, Fish D N. Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates. Antimicrob Agents Chemother. 2004; 48 1055-1057

Crossref PubMed Search in Google Scholar
100 Roussel-Delvallez M, Wallet F, Delpierre F, Courcol R J. In vitro bactericidal effect of a beta-lactam + aminoglycoside combination against multiresistant Pseudomonas aeruginosa and Acinetobacter baumannii . J Chemother. 1996; 8 365-368

PubMed Search in Google Scholar
101 Sader H S, Rhomberg P R, Jones R N. In vitro activity of beta-lactam antimicrobial agents in combination with aztreonam tested against metallo-beta-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii . J Chemother. 2005; 17 622-627

PubMed Search in Google Scholar
102 Montero A, Ariza J, Corbella X et al.. Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model. J Antimicrob Chemother. 2004; 54 1085-1091

Crossref PubMed Search in Google Scholar
103 Saballs M, Pujol M, Tubau F et al.. Rifampicin/imipenem combination in the treatment of carbapenem-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2006; 58 697-700

Crossref PubMed Search in Google Scholar
104 Owen J, Darling I, Troy S, Cirincione B. Noncompartmental pharmacokinetics of tigecycline in patients with complicated skin and skin structure infections [abstract A-11]. In: Program and Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (Washington DC). Washington, DC; American Society for Microbiology 2004: 2

Search in Google Scholar
105 Betriu C, Rodriguez-Avial I, Sanchez B A, Gomez M, Alvarez J, Picazo J J. In vitro activities of tigecycline (GAR-936) against recently isolated clinical bacteria in Spain. Antimicrob Agents Chemother. 2002; 46 892-895

Crossref PubMed Search in Google Scholar
106 Henwood C J, Gatward T, Warner M et al.. Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936). J Antimicrob Chemother. 2002; 49 479-487

Crossref PubMed Search in Google Scholar
107 Peleg A Y, Potoski B A, Rea R et al.. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J Antimicrob Chemother. 2007; 59 128-131

PubMed Search in Google Scholar
108 Conte Jr J E, Golden J A, Kelly M G, Zurlinden E. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int J Antimicrob Agents. 2005; 25 523-529

PubMed Search in Google Scholar
109 Jones M E. In-vitro profile of a new beta-lactam, ceftobiprole, with activity against methicillin-resistant Staphylococcus aureus . Clin Microbiol Infect. 2007; 13(Suppl 2) 17-24

PubMed Search in Google Scholar
110 Mushtaq S, Ge Y, Livermore D M. Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases. Antimicrob Agents Chemother. 2004; 48 1313-1319

Crossref PubMed Search in Google Scholar
111 Mushtaq S, Warner M, Ge Y, Kaniga K, Livermore D M. In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes. J Antimicrob Chemother. 2007; 60 300-311

Crossref PubMed Search in Google Scholar
112 Jaruratanasirikul S, Sriwiriyajan S, Punyo J. Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection. Antimicrob Agents Chemother. 2005; 49 1337-1339

Crossref PubMed Search in Google Scholar
113 Kuti J L, Dandekar P K, Nightingale C H, Nicolau D P. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol. 2003; 43 1116-1123

PubMed Search in Google Scholar
114 Li C, Kuti J L, Nightingale C H, Nicolau D P. Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients. J Clin Pharmacol. 2006; 46 1171-1178

PubMed Search in Google Scholar
115 Santos Filho L, Eagye K J, Kuti J L, Nicolau D P. Addressing resistance evolution in Pseudomonas aeruginosa using pharmacodynamic modelling: application to meropenem dosage and combination therapy. Clin Microbiol Infect. 2007; 13 579-585

Crossref PubMed Search in Google Scholar
116 Tam V H, Schilling A N, Neshat S, Poole K, Melnick D A, Coyle E A. Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa . Antimicrob Agents Chemother. 2005; 49 4920-4927

Crossref PubMed Search in Google Scholar
117 Harris A D, McGregor J C, Furuno J P. What infection control interventions should be undertaken to control multidrug-resistant gram-negative bacteria?. Clin Infect Dis. 2006; 43(Suppl 2) S57-S61

Crossref PubMed Search in Google Scholar
118 Chan P C, Huang L M, Lin H C et al.. Control of an outbreak of pandrug-resistant Acinetobacter baumannii colonization and infection in a neonatal intensive care unit. Infect Control Hosp Epidemiol. 2007; 28 423-429

Crossref PubMed Search in Google Scholar
119 Peleg A Y, Paterson D L. Multi-drug-resistant Acinetobacter: a threat to the antibiotic era. Intern Med J. 2006; 36 479-482

Crossref PubMed Search in Google Scholar
120 Pimentel J D, Low J, Styles K, Harris O C, Hughes A, Athan E. Control of an outbreak of multi-drug-resistant Acinetobacter baumannii in an intensive care unit and a surgical ward. J Hosp Infect. 2005; 59 249-253

Crossref PubMed Search in Google Scholar
121 Dellit T H, Owens R C, McGowan Jr J E et al.. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 44 159-177

Crossref PubMed Search in Google Scholar
122 American Thoracic Society; Infectious Diseases Society of America . Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171 388-416

Crossref PubMed Search in Google Scholar
123 Chastre J, Wolff M, Fagon J Y et al.. Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003; 290 2588-2598

Crossref PubMed Search in Google Scholar

Anton Y PelegM.D.

Division of Infectious Diseases

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

Email: apeleg@bidmc.harvard.edu