Treatment of carbapenem-resistant Klebsiella pneumoniae: The state of the art

Expert Review of Anti-Infective Therapy

Volumn 11, Issue 2, 2013, Pages 159-177

  Petrosillo, Nicola ^a   Giannella, Maddalena ^a   Lewis, Russell ^b   Viale, Pierluigi ^b  

^a NATIONAL INSTITUTE FOR INFECTIOUS DISEASES L SPALLANZANI   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

carbapenem resistant Klebsiella pneumoniae; carbapenemase producing strains; combination antimicrobial therapy

Indexed keywords

AMINOGLYCOSIDE; ANTIBIOTIC AGENT; CARBAPENEM DERIVATIVE; COLISTIMETHATE; COLISTIN; DORIPENEM; FOSFOMYCIN; GENTAMICIN; IMIPENEM; MEROPENEM; RIFAMPICIN; TIGECYCLINE;

ANTIBIOTIC RESISTANCE; AREA UNDER THE CURVE; BACTERIAL COLONIZATION; BACTERIUM IDENTIFICATION; BACTERIUM ISOLATE; CONTINUOUS INFUSION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; HEART FAILURE; HOSPITAL INFECTION; HUMAN; HYPOKALEMIA; INFECTION RISK; INJECTION SITE PAIN; KLEBSIELLA PNEUMONIAE; KLEBSIELLA PNEUMONIAE INFECTION; LOADING DRUG DOSE; LOW DRUG DOSE; MAINTENANCE DRUG DOSE; MINIMUM INHIBITORY CONCENTRATION; MORTALITY; NEPHROTOXICITY; NEUROTOXICITY; NONHUMAN; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PNEUMONIA; PREDICTION; REVIEW; RISK ASSESSMENT; RISK FACTOR; SURVIVAL RATE; URINARY TRACT INFECTION;

AMINOGLYCOSIDES; ANTI-BACTERIAL AGENTS; CARBAPENEMS; COLISTIN; DRUG THERAPY, COMBINATION; FOSFOMYCIN; HUMANS; KLEBSIELLA INFECTIONS; KLEBSIELLA PNEUMONIAE; MINOCYCLINE; RIFAMPIN; RISK FACTORS;

EID: 84873905889     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.12.162     Document Type: Review

References (125)

1. Akova M, Daikos GL, Tzouvelekis L, Carmeli Y. Interventional strategies and current clinical experience with carbapenemase- producing Gram-negative bacteria. Clin. Microbiol. Infect. 18(5), 439-448 (2012).
2. Petrosillo N, Capone A, Di Bella S, Taglietti F. Management of antibiotic resistance in the intensive care unit setting. Expert Rev. Anti. Infect. Ther. 8(3), 289-302 (2010).
3. Rahal JJ. Antimicrobial resistance among and therapeutic options against Gramnegative pathogens. Clin. Infect. Dis. 49(Suppl. 1), S4-S10 (2009).
4. Kumar A, Safdar N, Kethireddy S, Chateau D. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta- regression study. Crit. Care Med. 38(8), 1651-1664 (2010).
5. Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with Gram-negative bacteria. Clin. Microbiol. Rev. 25(3), 450-470 (2012).
6. Mouton JW, van Ogtrop ML, Andes D, Craig WA. Use of pharmacodynamic indices to predict efficacy of combination therapy in vivo. Antimicrob. Agents Chemother. 43(10), 2473-2478 (1999).
7. Carmeli Y, Troillet N, Eliopoulos GM, Samore MH. Emergence of antibioticresistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob. Agents Chemother. 43(6), 1379-1382 (1999).
8. Lister PD, Wolter DJ. Levofloxacinimipenem combination prevents the emergence of resistance among clinical isolates of Pseudomonas aeruginosa. Clin. Infect. Dis. 40(Suppl. 2), S105-S114 (2005).
9. Lister PD, Wolter DJ, Wickman PA, Reisbig MD. Levofloxacin/imipenem prevents the emergence of high-level resistance among Pseudomonas aeruginosa strains already lacking susceptibility to one or both drugs. J. Antimicrob. Chemother. 57(5), 999-1003 (2006).
10. Elphick HE, Tan A. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database Syst. Rev. (2), CD002007 (2005).
11. Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? a meta-analysis. Lancet Infect. Dis. 4(8), 519-527 (2004).
12. Bliziotis IA, Petrosillo N, Michalopoulos A, Samonis G, Falagas ME. Impact of definitive therapy with ?-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia. PLoS ONE 6(10), e26470 (2011).
13. Bodey GP, Jadeja L, Elting L. Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch. Intern. Med. 145(9), 1621-1629 (1985).
14. Vidal F, Mensa J, Almela M et al. Epidemiology and outcome of Pseudomonas aeruginosa bacteremia, with special emphasis on the influence of antibiotic treatment. Analysis of 189 episodes. Arch. Intern. Med. 156(18), 2121-2126 (1996).
15. Siegman-Igra Y, Ravona R, Primerman H, Giladi M. Pseudomonas aeruginosa bacteremia: an analysis of 123 episodes, with particular emphasis on the effect of antibiotic therapy. Int. J. Infect. Dis. 2(4), 211-215 (1998).
16. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. ?-Lactam monotherapy versus ? lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and metaanalysis of randomised trials. BMJ 328(7441), 668 (2004).
17. Korvick JA, Bryan CS, Farber B et al. Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob. Agents Chemother. 36(12), 2639-2644 (1992).
18. Bradford PA, Urban C, Mariano N, Projan SJ, Rahal JJ, Bush K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmidmediated AmpC ?-lactamase, and the foss of an outer membrane protein. Antimicrob. Agents Chemother. 41(3), 563-569 (1997).
19. MacKenzie FM, Forbes KJ, Dorai-John T, Amyes SG, Gould IM. Emergence of a carbapenem-resistant Klebsiella pneumoniae. Lancet 350(9080), 783 (1997).
20. Walsh TR, Weeks J, Livermore DM, Toleman MA. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect. Dis. 11(5), 355-362 (2011).
21. Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging NDM carbapenemases. Trends Microbiol. 19(12), 588-595 (2011).
22. Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J. Antimicrob. Chemother. 65(6), 1119-1125 (2010).
23. Yigit H, Queenan AM, Anderson GJ et al. Novel carbapenem-hydrolyzing ?-lactamase, KPC-1, from a carbapenemresistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45(4), 1151-1161 (2001).
24. Naas T, Nordmann P, Vedel G, Poyart C. Plasmid-mediated carbapenem-hydrolyzing ?-lactamase KPC in a Klebsiella pneumoniae isolate from France. Antimicrob. Agents Chemother. 49(10), 4423-4424 (2005).
25. Navon-Venezia S, Leavitt A, Schwaber MJ et al.; Israeli KPC Kpn Study Group. First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States. Antimicrob. Agents Chemother. 53(2), 818-820 (2009).
26. Samuelsen O, Naseer U, Tofteland S et al. Emergence of clonally related Klebsiella pneumoniae isolates of sequence type 258 producing plasmid-mediated KPC carbapenemase in Norway and Sweden. J. Antimicrob. Chemother. 63(4), 654-658 (2009).
27. Kitchel B, Rasheed JK, Patel JB et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob. Agents Chemother. 53(8), 3365-3370 (2009).
28. Leavitt A, Carmeli Y, Chmelnitsky I, Goren MG, Ofek I, Navon-Venezia S. Molecular epidemiology, sequence types, and plasmid analyses of KPC-producing Klebsiella pneumoniae strains in Israel. Antimicrob. Agents Chemother. 54(7), 3002-3006 (2010).
29. Osano E, Arakawa Y, Wacharotayankun R et al. Molecular characterization of an enterobacterial metallo ?-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob. Agents Chemother. 38(1), 71-78 (1994).
30. Miriagou V, Tzelepi E, Gianneli D, Tzouvelekis LS. Escherichia coli with a self-transferable, multiresistant plasmid coding for metallo-?-lactamase VIM-1. Antimicrob. Agents Chemother. 47(1), 395-397 (2003).
31. Canton R, Akova M, Carmeli Y et al.; European Network on Carbapenemases. Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clin. Microbiol. Infect. 18(5), 413-431 (2012).
32. Yong D, Toleman MA, Giske CG et al. Characterization of a new metallo-?- lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 53(12), 5046-5054 (2009).
33. Kumarasamy KK, Toleman MA, Walsh TR et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect. Dis. 10(9), 597-602 (2010).
34. Glupczynski Y, Huang TD, Bouchahrouf W et al. Rapid emergence and spread of OXA-48-producing carbapenem-resistant Enterobacteriaceae isolates in Belgian hospitals. Int. J. Antimicrob. Agents 39(2), 168-172 (2012).
35. Poirel L, H?ritier C, Nordmann P. Chromosome-encoded ambler class D ?-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob. Agents Chemother. 48(1), 348-351 (2004).
36. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin. Infect. Dis. 53(1), 60-67 (2011).
37. Srinivasan A, Patel JB. Klebsiella pneumoniae carbapenemase-producing organisms: an ounce of prevention really is worth a pound of cure. Infect. Control Hosp. Epidemiol. 29(12), 1107-1109 (2008).
38. Borer A, Saidel-Odes L, Riesenberg K et al. Attributable mortality rate for carbapenemresistant Klebsiella pneumoniae bacteremia. Infect. Control Hosp. Epidemiol. 30(10), 972-976 (2009).
39. Benenson S, Navon-Venezia S, Carmeli Y et al. Carbapenem-resistant Klebsiella pneumoniae endocarditis in a young adult. Successful treatment with gentamicin and colistin. Int. J. Infect. Dis. 13(5), e295-e298 (2009).
40. 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).
41. Michalopoulos A, Virtzili S, Rafailidis P, Chalevelakis G, Damala M, Falagas ME. Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem- resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin. Microbiol. Infect. 16(2), 184-186 (2010).
42. Humphries RM, Kelesidis T, Dien Bard J, Ward KW, Bhattacharya D, Lewinski MA. Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high-dose tigecycline and colistin. J. Med. Microbiol. 59(Pt 11), 1383-1386 (2010).
43. Orsi GB, Garcia-Fernandez A, Giordano A et al. Risk factors and clinical significance of ertapenem-resistant Klebsiella pneumoniae in hospitalised patients. J. Hosp. Infect. 78(1), 54-58 (2011).
44. Schwaber MJ, Klarfeld-Lidji S, Navon- Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob. Agents Chemother. 52(3), 1028-1033 (2008).
45. Souli M, Galani I, Antoniadou A et al. An outbreak of infection due to ?-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes. Clin. Infect. Dis. 50(3), 364-373 (2010).
46. Kwak YG, Choi SH, Choo EJ et al. Risk factors for the acquisition of carbapenemresistant Klebsiella pneumoniae among hospitalized patients. Microb. Drug Resist. 11(2), 165-169 (2005).
47. Gasink LB, Edelstein PH, Lautenbach E, Synnestvedt M, Fishman NO. Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Infect. Control Hosp. Epidemiol. 30(12), 1180-1185 (2009).
48. Debby BD, Ganor O, Yasmin M et al. Epidemiology of carbapenem resistant Klebsiella pneumoniae colonization in an intensive care unit. Eur. J. Clin. Microbiol. Infect. Dis. 31(8), 1811-1817 (2012).
49. Falagas ME, Rafailidis PI, Kofteridis D et al. Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study. J. Antimicrob. Chemother. 60(5), 1124-1130 (2007).
50. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenemresistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect. Control Hosp. Epidemiol. 29(12), 1099-1106 (2008).
51. Hussein K, Sprecher H, Mashiach T, Oren I, Kassis I, Finkelstein R. Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns. Infect. Control Hosp. Epidemiol. 30(7), 666-671 (2009).
52. Mouloudi E, Protonotariou E, Zagorianou A et al. Bloodstream infections caused by metallo-b-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect. Control Hosp. Epidemiol. 31(12), 1250-1256 (2010).
53. Ben-David D, Kordevani R, Keller N et al. Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections. Clin. Microbiol. Infect. 18(1), 54-60 (2012).
54. Borer A, Saidel-Odes L, Eskira S et al. Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K. pneumoniae. Am. J. Infect. Control 40(5), 421-425 (2012).
55. Endimiani A, Depasquale JM, Forero S et al. Emergence of blaKPC-containing Klebsiella pneumoniae in a long-term acute care hospital: a new challenge to our healthcare system. J. Antimicrob. Chemother. 64(5), 1102-1110 (2009).
56. Perez F, Endimiani A, Ray AJ et al. Carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae across a hospital system: impact of post-acute care facilities on dissemination. J. Antimicrob. Chemother. 65(8), 1807-1818 (2010).
57. Ben-David D, Masarwa S, Navon-Venezia S et al.; Israel PACF CRKP (Post-Acute-Care Facility Carbapenem-Resistant Klebsiella pneumoniae) Working Group. Carbapenemresistant Klebsiella pneumoniae in post-acutecare facilities in Israel. Infect. Control Hosp. Epidemiol. 32(9), 845-853 (2011).
58. 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).
59. Paterson DL, Rogers BA. How soon is now? The urgent need for randomized, controlled trials evaluating treatment of multidrug-resistant bacterial infection. Clin. Infect. Dis. 51(11), 1245-1247 (2010).
60. Drusano GL. Antimicrobial pharmacodynamics: critical interactions of 'bug and drug'. Nat. Rev. Microbiol. 2(4), 289-300 (2004).
61. Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob. Agents Chemother. 56(6), 2795-2805 (2012).
62. McKenzie C. Antibiotic dosing in critical illness. J Antimicrob. Chemother. 66 (Suppl. 2), ii25-ii31 (2011).
63. Pea F, Brollo L, Viale P, Pavan F, Furlanut M. Teicoplanin therapeutic drug monitoring in critically ill patients: a retrospective study emphasizing the importance of a loading dose. J. Antimicrob. Chemother. 51(4), 971-975 (2003).
64. Taccone FS, Laterre P-F, Spapen H et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit. Care 14(2), R53 (2010).
65. Jones GR. Estimating renal function for drug dosing decisions. Clin. Biochem. Rev. 32(2), 81-88 (2011).
66. Gon?alves-Pereira J, P?voa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of ?-lactams. Crit. Care 15(5), R206 (2011).
67. Seyler L, Cotton F, Taccone FS et al. Recommended b-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Crit. Care 15(3), R137 (2011).
68. Sime FB, Roberts MS, Peake SL, Lipman J, Roberts JA. Does ?-lactam pharmacokinetic variability in critically ill patients justify therapeutic drug monitoring? A systematic review. Ann. Intensive Care 2(1), 35 (2012).
69. 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).
70. Lorente L, Lorenzo L, Martin MM, Jimenez 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).
71. Qureshi ZA, Paterson DL, Potoski BA et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob. Agents Chemother. 56(4), 2108-2113 (2012).
72. Daikos GL, Markogiannakis A. Carbapenemase- producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? Clin. Microbiol. Infect. 17(8), 1135-1141 (2011).
73. Tumbarello M, Viale P, Viscoli C et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin. Infect. Dis. 55(7), 943-950 (2012).
74. Couet W, Gregoire N, Marchand S, Mimoz O. Colistin pharmacokinetics: the fog is lifting. Clin. Microbiol. Infect. 18(1), 30-39 (2012).
75. Bergen PJ, Li J, Nation RL. Dosing of colistin-back to basic PK/PD. Curr. Opin. Pharmacol. 11(5), 464-469 (2011).
76. 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).
77. Dudhani RV, Turnidge JD, Coulthard K et al. Elucidation of the pharmacokinetic/ pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob. Agents Chemother. 54(3), 1117-1124 (2010).
78. Bulitta JB, Yang JC, Yohonn L et al. Attenuation of colistin bactericidal activity by high inoculum of Pseudomonas aeruginosa characterized by a new mechanism-based population pharmacodynamic model. Antimicrob. Agents Chemother. 54(5), 2051-2062 (2010).
79. 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).
80. 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).
81. Imberti R. Intravenous colistimethate administration and colistin lung tissue concentrations. Intensive Care Med. 36(10), 1795; author reply 1796-1795; author reply 1797 (2010).
82. Imberti R, Cusato M, Villani P et al. Steady-state pharmacokinetics and BAL concentration of colistin in critically ill patients after IV colistin methanesulfonate administration. Chest 138(6), 1333-1339 (2010).
83. Kofteridis DP, Alexopoulou C, Valachis A et al. Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case-control study. Clin. Infect. Dis. 51(11), 1238-1244 (2010).
84. Florescu DF, Qiu F, McCartan MA, Mindru C, Fey PD, Kalil AC. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin. Infect. Dis. 54(5), 670-680 (2012).
85. Kelesidis T, Karageorgopoulos DE, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. J. Antimicrob. Chemother. 62(5), 895-904 (2008).
86. Nguyen M, Eschenauer GA, Bryan M et al. Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes. Diagn. Microbiol. Infect. Dis. 67(2), 180-184 (2010).
87. Barbour A, Schmidt S, Ma B et al. Clinical pharmacokinetics and pharmacodynamics of tigecycline. Clin. Pharmacokinet. 48(9), 575-584 (2009).
88. MacGowan AP. Tigecycline pharmacokinetic/ pharmacodynamic update. J. Antimicrob. Chemother. 62(Suppl. 1), i11-i16 (2008).
89. Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect. Dis. 11(11), 834-844 (2011).
90. Cunha BA. Pharmacokinetic considerations regarding tigecycline for multidrugresistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis. J. Clin. Microbiol. 47(5), 1613 (2009).
91. Falagas ME, Karageorgopoulos DE, Dimopoulos G. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of tigecycline. Curr. Drug Metab. 10(1), 13-21 (2009).
92. Drusano GL, Ambrose PG, Bhavnani SM, Bertino JS, Nafziger AN, Louie A. Back to the future: using aminoglycosides again and how to dose them optimally. Clin. Infect. Dis. 45(6), 753-760 (2007).
93. Rea RS, Capitano B. Optimizing use of aminoglycosides in the critically ill. Semin. Respir. Crit. Care Med. 28(6), 596-603 (2007).
94. 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).
95. Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum ?-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect. Dis. 10(1), 43-50 (2010).
96. Florent A, Chichmanian RM, Cua E, Pulcini C. Adverse events associated with intravenous fosfomycin. Int. J. Antimicrob. Agents 37(1), 82-83 (2011).
97. Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin. Infect. Dis. 46(7), 1069-1077 (2008).
98. Roussos N, Karageorgopoulos DE, Samonis G, Falagas ME. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. Int. J. Antimicrob. Agents 34(6), 506-515 (2009).
99. Chen LF, Kaye D. Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides. Med. Clin. North Am. 95(4), 819-42, viii (2011).
100. Forrest GN, Tamura K. Rifampin combination therapy for nonmycobacterial infections. Clin. Microbiol. Rev. 23(1), 14-34 (2010).
101. Mathers AJ, Cox HL, Bonatti H et al. Fatal cross infection by carbapenem-resistant Klebsiella in two liver transplant recipients. Transpl. Infect. Dis. 11(3), 257-265 (2009).
102. Daikos GL, Petrikkos P, Psichogiou M et al. Prospective observational study of the impact of VIM-1 metallo-?-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob. Agents Chemother. 53(5), 1868-1873 (2009).
103. Neuner EA, Yeh JY, Hall GS et al. Treatment and outcomes in carbapenemresistant Klebsiella pneumoniae bloodstream infections. Diagn. Microbiol. Infect. Dis. 69(4), 357-362 (2011).
104. Zarkotou O, Pournaras S, Tselioti P et al. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin. Microbiol. Infect. 17(12), 1798-1803 (2011).
105. Rihani DS, Wallace MR, Sieger BE et al. Over-treatment of carbapenemase-producing Enterobacteriaceae. Scand. J. Infect. Dis. 44(5), 325-329 (2012).
106. Kollef MH, Golan Y, Micek ST, Shorr AF, Restrepo MI. Appraising contemporary strategies to combat multidrug resistant Gram-negative bacterial infections - proceedings and data from the Gram-Negative Resistance Summit. Clin. Infect. Dis. 53(Suppl. 2), S33-S55; quiz S56 (2011).
107. Bush K. Improving known classes of antibiotics: an optimistic approach for the future. Curr. Opin. Pharmacol. 12(5), 527-534 (2012).
108. Chandorkar G, Huntington JA, Gotfried MH, Rodvold KA, Umeh O. Intrapulmonary penetration of ceftolozane/ tazobactam and piperacillin/ tazobactam in healthy adult subjects. J. Antimicrob. Chemother. 67(10), 2463-2469 (2012).
109. Ehmann DE, Jahic H, Ross PL et al. Avibactam is a covalent, reversible, non-b-lactam b-lactamase inhibitor. Proc. Natl Acad. Sci. USA 109(29), 11663-11668 (2012).
110. Ciobotaro P, Oved M, Nadir E, Bardenstein R, Zimhony O. An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice. Am. J. Infect. Control 39(8), 671-677 (2011).
111. Bulik CC, Nicolau DP. In vivo efficacy of simulated human dosing regimens of prolonged-infusion doripenem against carbapenemase- producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 54(10), 4112-4115 (2010).
112. Bhavnani SM, Hammel JP, Cirincione BB, Wikler MA, Ambrose PG. Use of pharmacokinetic-pharmacodynamic target attainment analyses to support Phase 2 and 3 dosing strategies for doripenem. Antimicrob. Agents Chemother. 49(9), 3944-3947 (2005).
113. Le J. In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae. J. Clin. Med. Res. (2011).
114. Souli M, Rekatsina PD, Chryssouli Z, Galani I, Giamarellou H, Kanellakopoulou K. Does the activity of the combination of imipenem and colistin in vitro exceed the problem of resistance in metallo-?- lactamase-producing Klebsiella pneumoniae isolates? Antimicrob. Agents Chemother. 53(5), 2133-2135 (2009).
115. Pankey GA, Ashcraft DS. Detection of synergy using the combination of polymyxin B with either meropenem or rifampin against carbapenemase-producing Klebsiella pneumoniae. Diagn. Microbiol. Infect. Dis. 70(4), 561-564 (2011).
116. Jernigan MG, Press EG, Nguyen MH, Clancy CJ, Shields RK. The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 56(6), 3395-3398 (2012).
117. Wiskirchen DE, Koomanachai P, Nicasio AM, Nicolau DP, Kuti JL. In vitro pharmacodynamics of simulated pulmonary exposures of tigecycline alone and in combination against Klebsiella pneumoniae isolates producing a KPC carbapenemase. Antimicrob. Agents Chemother. 55(4), 1420-1427 (2011).
118. Pournaras S, Vrioni G, Neou E et al. Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay. Int. J. Antimicrob. Agents 37(3), 244-247 (2011).
119. Petersen PJ, Labthavikul P, Jones CH, Bradford PA. In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis. J. Antimicrob. Chemother. 57(3), 573-576 (2006).
120. Souli M, Galani I, Boukovalas S et al. In vitro interactions of antimicrobial combinations with fosfomycin against KPC-2-producing Klebsiella pneumoniae and protection of resistance development. Antimicrob. Agents Chemother. 55(5), 2395-2397 (2011).
121. Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME. Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur. J. Clin. Microbiol. Infect. Dis. 31(5), 695-701 (2012).
122. Bulik CC, Nicolau DP. Double-carbapenem therapy for carbapenemase- producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 55(6), 3002-3004 (2011).
123. Elemam A, Rahimian J, Doymaz M. In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemaseproducing Klebsiella pneumoniae. J. Clin. Microbiol. 48(10), 3558-3562 (2010).
124. Bratu S, Tolaney P, Karumudi U et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J. Antimicrob. Chemother. 56(1), 128-132 (2005).
125. Falagas ME, Rafailidis PI, Ioannidou E et al. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int. J. Antimicrob. Agents 35(2), 194-199 (2010).