The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria

References

• Spellberg B , Blaser M , Guidos RJ , et al. Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis. 2011;52(Suppl 5):S397–428.
   PubMedGoogle Scholar
• Van Duin D , Kaye KS , Neuner EA , et al. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75(2):115–120.
   PubMed Web of Science ®Google Scholar
• Nordmann P , Dortet L , Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med. 2012;18(5):263–272.
   PubMed Web of Science ®Google Scholar
• Queenan AM , Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20(3): 440–458. table of contents.
   PubMed Web of Science ®Google Scholar
• Van Duin D , Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8(4):460–469.
   PubMed Web of Science ®Google Scholar
• Yigit H , Queenan AM , Anderson GJ , et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45(4):1151–1161.
   PubMed Web of Science ®Google Scholar
• 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. 2005;56(1):128–132.
   PubMed Web of Science ®Google Scholar
• Woodford N , Tierno PM , Young K , et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center. Antimicrob Agents Chemother. 2004;48(12):4793–4799.
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention . Tracking CRE; 2018. [cited 2018 May 23]. Available from: https://www.cdc.gov/hai/organisms/cre/trackingcre.html.
   Google Scholar
• Mendes RE , Bell JM , Turnidge JD , et al. Carbapenem-resistant isolates of Klebsiella pneumoniae in China and detection of a conjugative plasmid (blaKPC-2 plus qnrB4) and a blaIMP-4 gene. Antimicrob Agents Chemother. 2008;52(2):798–799.
   PubMed Web of Science ®Google Scholar
• Villegas MV , Lolans K , Correa A , et al. First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob Agents Chemother. 2006;50(8):2880–2882.
   PubMed Web of Science ®Google Scholar
• Pournaras S , Protonotariou E , Voulgari E , et al. Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece. J Antimicrob Chemother. 2009;64(2):348–352.
   PubMed Web of Science ®Google Scholar
• Wolter DJ , Kurpiel PM , Woodford N , et al. Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4. Antimicrob Agents Chemother. 2009;53(2):557–562.
   PubMed Web of Science ®Google Scholar
• Endimiani A , Carias LL , Hujer AM , et al. Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae isolates possessing blaKPC in the United States. Antimicrob Agents Chemother. 2008;52(7):2680–2682.
   PubMed Web of Science ®Google Scholar
• Liu YY , Wang Y , Walsh TR , et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161–168.
   PubMed Web of Science ®Google Scholar
• Moland ES , Hong SG , Thomson KS , et al. Klebsiella pneumoniae isolate producing at least eight different beta-lactamases, including AmpC and KPC beta-lactamases. Antimicrob Agents Chemother. 2007;51(2):800–801.
   PubMed Web of Science ®Google Scholar
• Cai JC , Zhou HW , Zhang R , et al. Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli Isolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital. Antimicrob Agents Chemother. 2008;52(6):2014–2018.
   PubMed Web of Science ®Google Scholar
• Zhang R , Yang L , Cai JC , et al. High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression. J Med Microbiol. 2008;57(Pt 3):332–337.
   PubMed Web of Science ®Google Scholar
• Yigit H , Queenan AM , Rasheed JK , et al. Carbapenem-resistant strain of Klebsiella oxytoca harboring carbapenem-hydrolyzing beta-lactamase KPC-2. Antimicrob Agents Chemother. 2003;47(12):3881–3889.
   PubMed Web of Science ®Google Scholar
• Robledo IE , Aquino EE , Santé MI , et al. Detection of KPC in Acinetobacter spp. in Puerto Rico. Antimicrob Agents Chemother. 2010;54(3):1354–1357.
   PubMed Web of Science ®Google Scholar
• Villegas MV , Lolans K , Correa A , et al. First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing beta-lactamase. Antimicrob Agents Chemother. 2007;51(4):1553–1555.
   PubMed Web of Science ®Google Scholar
• Fair RJ , Tor Y . Antibiotics and bacterial resistance in the 21st century. Perspect Medicin Chem. 2014;6:25–64.
   PubMedGoogle Scholar
• Tamma PD , Goodman KE , Harris AD , et al. Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae bacteremia. Clin Infect Dis. 2017;64(3):257–264.
   PubMed Web of Science ®Google Scholar
• Ben-David D , Kordevani R , Keller N , et al. Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections. Clin Microbiol Infect. 2012;18(1):54–60.
   PubMed Web of Science ®Google Scholar
• Marchaim D , Chopra T , Perez F , et al. Outcomes and genetic relatedness of carbapenem-resistant Enterobacteriaceae at Detroit medical center. Infect Control Hosp Epidemiol. 2011;32(9):861–871.
   PubMed Web of Science ®Google Scholar
• Borer A , Saidel-Odes L , Riesenberg K , et al. Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia. Infect Control Hosp Epidemiol. 2009;30(10):972–976.
   PubMed Web of Science ®Google Scholar
• Neuner EA , Yeh JY , Hall GS , et al. Treatment and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Diagn Microbiol Infect Dis. 2011;69(4):357–362.
   PubMed Web of Science ®Google Scholar
• Swaminathan M , Sharma S , Poliansky Blash S , et al. Prevalence and risk factors for acquisition of carbapenem-resistant Enterobacteriaceae in the setting of endemicity. Infect Control Hosp Epidemiol. 2013;34(8):809–817.
   PubMed Web of Science ®Google Scholar
• Ling ML , Tee YM , Tan SG , et al. Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore. Antimicrob Resist Infect Control. 2015;4:26.
   PubMed Web of Science ®Google Scholar
• Pang F , Jia XQ , Zhao QG , et al. Factors associated to prevalence and treatment of carbapenem-resistant Enterobacteriaceae infections: a seven years retrospective study in three tertiary care hospitals. Ann Clin Microbiol Antimicrob. 2018;17(1):13.
   PubMedGoogle Scholar
• Hyle EP , Ferraro MJ , Silver M , et al. Ertapenem-resistant Enterobacteriaceae: risk factors for acquisition and outcomes. Infect Control Hosp Epidemiol. 2010;31(12):1242–1249.
   PubMed Web of Science ®Google Scholar
• Trecarichi EM , Tumbarello M . Therapeutic options for carbapenem-resistant Enterobacteriaceae infections. Virulence. 2017;8(4):470–484.
   PubMed Web of Science ®Google Scholar
• Papp-Wallace KM , Endimiani A , Taracila MA , et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943–4960.
   PubMed Web of Science ®Google Scholar
• Munita JM , Arias CA . Mechanisms of antibiotic resistance. Microbiol Spectr. 2016;4(2):1–24.
   PubMed Web of Science ®Google Scholar
• Bush K , Jacoby GA , Medeiros AA . A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39(6):1211–1233.
   PubMed Web of Science ®Google Scholar
• Morrill HJ , Pogue JM , Kaye KS , et al. Treatment Options for Carbapenem-Resistant Enterobacteriaceae Infections. Open Forum Infect Dis. 2015;2(2):ofv050.
   PubMed Web of Science ®Google Scholar
• Chow JW , Yu VL . Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999;11(1):7–12.
   PubMed Web of Science ®Google Scholar
• Di Carlo P , Gulotta G , Casuccio A , et al. KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiol. 2013;13(1):13.
   PubMed Web of Science ®Google Scholar
• Hindler JA , Humphries RM . Colistin MIC variability by method for contemporary clinical isolates of multidrug-resistant Gram-negative bacilli. J Clin Microbiol. 2013;51(6):1678–1684.
   PubMed Web of Science ®Google Scholar
• Phe K , Lee Y , McDaneld PM , et al. In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy. Antimicrob Agents Chemother. 2014;58(5):2740–2746.
   PubMed Web of Science ®Google Scholar
• 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. 2011;55(7):3284–3294.
   PubMed Web of Science ®Google Scholar
• De Pascale G , Montini L , Pennisi M , et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18(3):R90.
   PubMed Web of Science ®Google Scholar
• Satlin MJ , Kubin CJ , Blumenthal JS , et al. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Antimicrob Agents Chemother. 2011;55(12):5893–5899.
   PubMed Web of Science ®Google Scholar
• Alexander BT , Marschall J , Tibbetts RJ , et al. Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort. Clin Ther. 2012;34(6):1314–1323.
   PubMed Web of Science ®Google Scholar
• Meagher AK , Ambrose PG , Grasela TH , et al. The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin Infect Dis. 2005;41(Suppl 5):S333–40.
   PubMed Web of Science ®Google Scholar
• Nation RL , Velkov T , Li J . Colistin and polymyxin B: peas in a pod, or chalk and cheese? Clin Infect Dis. 2014;59(1):88–94.
   PubMed Web of Science ®Google Scholar
• Ahn C , Syed A , Hu F , et al. Microbiological features of KPC-producing Enterobacter isolates identified in a U.S. hospital system. Diagn Microbiol Infect Dis. 2014;80(2):154–158.
   PubMed Web of Science ®Google Scholar
• Dinh A , Salomon J , Bru JP , et al. Fosfomycin: efficacy against infections caused by multidrug-resistant bacteria. Scand J Infect Dis. 2012;44(3):182–189.
   PubMed Web of Science ®Google Scholar
• 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. 2011;17(12):1798–1803.
   PubMed Web of Science ®Google Scholar
• 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. 2012;56(4):2108–2113.
   PubMed Web of Science ®Google Scholar
• 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. 2012;55(7):943–950.
   PubMed Web of Science ®Google Scholar
• Bulik CC , Nicolau DP . Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2011;55(6):3002–3004.
   PubMed Web of Science ®Google Scholar
• Daikos GL , Tsaousi S , Tzouvelekis LS , et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58(4):2322–2328.
   PubMed Web of Science ®Google Scholar
• Roberts JA , Kirkpatrick CM , Roberts MS , et al. 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. 2009;64(1):142–150.
   PubMed Web of Science ®Google Scholar
• Gutiérrez-Gutiérrez B , Salamanca E , De Cueto M , et al. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017;17(7):726–734.
   PubMed Web of Science ®Google Scholar
• Paul M , Daikos GL , Durante-Mangoni E , et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018;18(4):391–400.
   PubMed Web of Science ®Google Scholar
• Zasowski EJ , Rybak JM , Rybak MJ . The β-Lactams Strike Back: ceftazidime-Avibactam. Pharmacotherapy. 2015;35(8):755–770.
   PubMed Web of Science ®Google Scholar
• Lagacé-Wiens P , Walkty A , Karlowsky JA . Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core Evid. 2014;9:13–25.
   PubMedGoogle Scholar
• Lucasti C , Popescu I , Ramesh MK , et al. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother. 2013;68(5):1183–1192.
   PubMed Web of Science ®Google Scholar
• Vazquez JA , González Patzán LD , Stricklin D , et al. Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin. 2012;28(12):1921–1931.
   PubMed Web of Science ®Google Scholar
• King M , Heil E , Kuriakose S , et al. Multicenter study of outcomes with ceftazidime-avibactam in patients with carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother. 2017;61(7).
   Web of Science ®Google Scholar
• Shields RK , Nguyen MH , Chen L , et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother. 2017; 61(8).
   Web of Science ®Google Scholar
• Van Duin D , Lok JJ , Earley M , et al. Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis. 2018;66(2):163–171.
   PubMed Web of Science ®Google Scholar
• Tumbarello M , Trecarichi EM , Corona A , et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by KPC-producing Klebsiella pneumoniae. Clin Infect Dis. 2018.
   PubMed Web of Science ®Google Scholar
• Shields RK , Potoski BA , Haidar G , et al. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis. 2016;63(12):1615–1618.
   PubMed Web of Science ®Google Scholar
• Gaibani P , Campoli C , Lewis RE , et al. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment. J Antimicrob Chemother. 2018;73(6):1525–1529.
   PubMed Web of Science ®Google Scholar
• Nelson K , Hemarajata P , Sun D , et al. Resistance to ceftazidime-avibactam is due to transposition of KPC in a porin-deficient strain of Klebsiella pneumoniae with increased efflux activity. Antimicrob Agents Chemother. 2017;61(10).
   Web of Science ®Google Scholar
• Humphries RM , Hemarajata P . Resistance to ceftazidime-avibactam in Klebsiella pneumoniae due to porin mutations and the increased expression of KPC-3. Antimicrob Agents Chemother. 2017;61(6).
   Web of Science ®Google Scholar
• Shields RK , Chen L , Cheng S , et al. Emergence of ceftazidime-avibactam resistance due to plasmid-borne mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother. 2017;61(3):e02097–16.
   Web of Science ®Google Scholar
• Wong D , Van Duin D . Novel beta-lactamase inhibitors: unlocking their potential in therapy. Drugs. 2017;77(6):615–628.
   PubMed Web of Science ®Google Scholar
• Lapuebla A , Abdallah M , Olafisoye O , et al. Activity of meropenem combined with RPX7009, a novel β-lactamase inhibitor, against gram-negative clinical isolates in New York City. Antimicrob Agents Chemother. 2015;59(8):4856–4860.
   PubMed Web of Science ®Google Scholar
• Castanheira M , Rhomberg PR , Flamm RK , et al. Effect of the β-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016;60(9):5454–5458.
   PubMed Web of Science ®Google Scholar
• Kaye KS , Bhowmick T , Metallidis S , et al. Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA. 2018;319(8):788–799.
   PubMed Web of Science ®Google Scholar
• Kaye KS , Mathers A , Daikos G , et al. Clinical outcomes of serious infections due to carbapenem-resistant Enterobacteriaceae (CRE) in TANGO II, a phase 3, randomized, multinational, open-label trial of meropenem-vaborbactam vs. best available therapy (BAT). IDWeek 2017. “Conference Proceedings”, San Diego, CA.
   Google Scholar
• Lomovskaya O , Castanheira M , Vazquez J , et al. Assessment of MIC increases with meropenem-vaborbactam (VABOMERE) and ceftazidime-avibactam in TANGO II (a phase 3 study of the treatment of CRE infections. IDWeek 2017. “Conference Proceedings”, San Diego, CA.
   Google Scholar
• Thaden JT , Pogue JM , Kaye KS . Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. Virulence. 2017;8(4):403–416.
   PubMed Web of Science ®Google Scholar
• Haidar G , Clancy CJ , Chen L , et al. Identifying spectra of activity and therapeutic niches for ceftazidime-avibactam and imipenem-relebactam against carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(9).
   Web of Science ®Google Scholar
• Sims M , Mariyanovski V , Mcleroth P , et al. Prospective, randomized, double-blind, phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections. J Antimicrob Chemother. 2017;72(9):2616–2626.
   PubMed Web of Science ®Google Scholar
• Merck Sharp and Dohme Corporation . Efficacy and safety of imipenem+ cilastatin/relebactam (MK-7655A) versus colistemethate sodium + imipenem + cilastatin in imipenem-resistant bacterial infection (MK-7655A-013) (RESTORE-IMI 1). ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2000 [ cited 2018 May 21 ]. Available from: https://clinicaltrials.gov/ct2/show/NCT02452047
   Google Scholar
• Yong D , Toleman MA , Giske CG , et al. Characterization of a new metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53:5046–5054.
   PubMed Web of Science ®Google Scholar
• Biedenbach DJ , Kazmierczak K , Bouchillon SK , et al. In vitro activity of aztreonam-avibactam against a global collection of Gram-negative pathogens from 2012 and 2013. Antimicrob Agents Chemother. 2015;59(7):4239–4248.
   PubMed Web of Science ®Google Scholar
• Karlowsky JA , Kazmierczak KM , De Jonge BLM , et al. Activity of aztreonam-avibactam against Enterobacteriaceae and pseudomonas aeruginosa isolated by clinical laboratories in 40 countries from 2012 to 2015. Antimicrob Agents Chemother. 2017;61(9).
   Web of Science ®Google Scholar
• Pfizer . A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2000 [ cited 2018 May 29 ]. Available from: https://clinicaltrials.gov/ct2/show/NCT02655419.
   Google Scholar
• Pfizer . A phase 3 prospective, randomized, multicenter, open-label, central assessor-blinded, parallel group, comparative study to determine the efficacy, safety and tolerability of aztreonam-avibactam (Atm-avi) ±metronidazole (Mtz) versus meropenem±colistin (Mer±Col) for the treatment of serious infections due to gram negative bacteria, including metallo-β-lactamase (Mbl) - producing multidrug resistant pathogens, for which there are limited or no treatment options. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2000 [ cited 2018 May 29 ]. Available from: https://clinicaltrials.gov/ct2/show/NCT03329092
   Google Scholar
• Haidar G , Alkroud A , Cheng S , et al. Association between the presence of aminoglycoside-modifying enzymes and in vitro activity of gentamicin, tobramycin, amikacin, and plazomicin against Klebsiella pneumoniae carbapenemase- and extended-spectrum-β-lactamase-producing Enterobacter species. Antimicrob Agents Chemother. 2016;60(9):5208–5214.
   PubMed Web of Science ®Google Scholar
• Galani I , Souli M , Daikos GL , et al. Activity of plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. from Athens, Greece. J Chemother. 2012;24(4):191–194.
   PubMed Web of Science ®Google Scholar
• Livermore DM , Mushtaq S , Warner M , et al. Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother. 2011;66(1):48–53.
   PubMed Web of Science ®Google Scholar
• McKinnell JA , Connolly LE , Pushkin R , et al. Improved outcomes with plazomicin compared with colistin in patients with bloodstream infections caused by carbapenem-resistant Enterobacteriaceae (CRE): results from the CARE study. IDWeek 2017. “Conference Proceedings”
   Google Scholar
• Zhanel GG , Cheung D , Adam H , et al. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs. 2016;76(5):567–588.
   PubMed Web of Science ®Google Scholar
• Zhang Y , Lin X , Bush K . In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J Antibiot. 2016;69(8):600–604.
   PubMed Web of Science ®Google Scholar
• Solomkin J , Evans D , Slepavicius A , et al. Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the investigating gram-negative infections treated with Eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg. 2017;152(3):224–232.
   PubMed Web of Science ®Google Scholar
• Ito A , Nishikawa T , Matsumoto S , et al. Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against pseudomonas aeruginosa. Antimicrob Agents Chemother. 2016;60(12):7396–7401.
   PubMed Web of Science ®Google Scholar
• Hackel MA , Tsuji M , Yamano Y , et al. In vitro activity of the siderophore cephalosporin, cefiderocol, against a recent collection of clinically relevant gram-negative bacilli from North America and Europe, including carbapenem-nonsusceptible isolates (SIDERO-WT-2014 Study). Antimicrob Agents Chemother. 2017;61(9).
   Web of Science ®Google Scholar
• Dobias J , Dénervaud-Tendon V , Poirel L , et al. Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant gram-negative pathogens. Eur J Clin Microbiol Infect Dis. 2017;36(12):2319–2327.
   PubMed Web of Science ®Google Scholar
• Hackel MA , Tsuji M , Yamano Y , et al. Activity of the siderophore cephalosporin, cefiderocol, against carbapenem-nonsusceptible and multidrug-resistant isolates of gram-negative bacilli collected worldwide in 2014 to 2016. Antimicrob Agents Chemother. 2018;62(2): e01968–17.
   Web of Science ®Google Scholar
• Falagas ME , Skalidis T , Vardakas KZ , et al. Activity of cefiderocol (S-649266) against carbapenem-resistant gram-negative bacteria collected from inpatients in Greek hospitals. J Antimicrob Chemother. 2017;72(6):1704–1708.
   PubMed Web of Science ®Google Scholar
• Shionogi . A multicenter, randomized, open-label clinical study of S-649266 or best available therapy for the treatment of severe infections caused by carbapenem-resistant gram-negative pathogens. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2000 [ cited 2018 May 21 ]. Available from: https://clinicaltrials.gov/ct2/show/NCT02714595
   Google Scholar
• Walkty A , Decorby M , Lagacé-Wiens PR , et al. In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study). Antimicrob Agents Chemother. 2011;55(6):2992–2994.
   PubMed Web of Science ®Google Scholar
• Shaw E , Rombauts A , Tubau F , et al. Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection. J Antimicrob Chemother. 2018;73(4):1104–1106.
   PubMed Web of Science ®Google Scholar
• Davido B , Fellous L , Lawrence C , et al. Ceftazidime-avibactam and aztreonam, an interesting strategy to overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61(9).
   PubMed Web of Science ®Google Scholar