Skip to main content
SpringerLink
Log in

Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Cefiderocol is an injectable siderophore cephalosporin discovered and being developed by Shionogi & Co., Ltd., Japan. As with other β-lactam antibiotics, the principal antibacterial/bactericidal activity of cefiderocol occurs by inhibition of Gram-negative bacterial cell wall synthesis by binding to penicillin binding proteins; however, it is unique in that it enters the bacterial periplasmic space as a result of its siderophore-like property and has enhanced stability to β-lactamases. The chemical structure of cefiderocol is similar to both ceftazidime and cefepime, which are third- and fourth-generation cephalosporins, respectively, but with high stability to a variety of β-lactamases, including AmpC and extended-spectrum β-lactamases (ESBLs). Cefiderocol has a pyrrolidinium group in the side chain at position 3 like cefepime and a carboxypropanoxyimino group in the side chain at position 7 of the cephem nucleus like ceftazidime. The major difference in the chemical structures of cefiderocol, ceftazidime and cefepime is the presence of a catechol group on the side chain at position 3. Together with the high stability to β-lactamases, including ESBLs, AmpC and carbapenemases, the microbiological activity of cefiderocol against aerobic Gram-negative bacilli is equal to or superior to that of ceftazidime-avibactam and meropenem, and it is active against a variety of Ambler class A, B, C and D β-lactamases. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem versus Acinetobacter baumannii, including meropenem non-susceptible and multidrug-resistant (MDR) isolates. Cefiderocol’s activity against meropenem–non-susceptible and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriales is comparable or superior to ceftazidime-avibactam. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem against all resistance phenotypes of Pseudomonas aeruginosa and against Stenotrophomonas maltophilia. The current dosing regimen being used in phase III studies is 2 g administered intravenously every 8 h (q8 h) using a 3-h infusion. The pharmacokinetics of cefiderocol are best described by a three-compartment linear model. The mean plasma half-life (t½) was ~ 2.3 h, protein binding is 58%, and total drug clearance ranged from 4.6–6.0 L/h for both single- and multi-dose infusions and was primarily renally excreted unchanged (61–71%). Cefiderocol is primarily renally excreted unchanged and clearance correlates with creatinine clearance. Dosage adjustment is thus required for both augmented renal clearance and in patients with moderate to severe renal impairment. In vitro and in vivo pharmacodynamic studies have reported that as with other cephalosporins the pharmacodynamic index that best predicts clinical outcome is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (%fT > MIC). In vivo efficacy of cefiderocol has been studied in a variety of humanized drug exposure murine and rat models of infection utilizing a variety of MDR and extremely drug resistant strains. Cefiderocol has performed similarly to or has been superior to comparator agents, including ceftazidime and cefepime. A phase II prospective, multicenter, double-blind, randomized clinical trial assessed the safety and efficacy of cefiderocol 2000 mg q8 h versus imipenem/cilastatin 1000 mg q8 h, both administered intravenously for 7–14 days over 1 h, in the treatment of complicated urinary tract infection (cUTI, including pyelonephritis) or acute uncomplicated pyelonephritis in hospitalized adults. A total of 452 patients were initially enrolled in the study, with 303 in the cefiderocol arm and 149 in the imipenem/cilastatin arm. The primary outcome measure was a composite of clinical cure and microbiological eradication at the test-of-cure (TOC) visit, that is, 7 days after the end of treatment in the microbiological intent-to-treat (MITT) population. Secondary outcome measures included microbiological response per pathogen and per patient at early assessment (EA), end of treatment (EOT), TOC, and follow-up (FUP); clinical response per pathogen and per patient at EA, EOT, TOC, and FUP; plasma, urine and concentrations of cefiderocol; and the number of participants with adverse events. The composite of clinical and microbiological response rates was 72.6% (183/252) for cefiderocol and 54.6% (65/119) for imipenem/cilastatin in the MITT population. Clinical response rates per patient at the TOC visit were 89.7% (226/252) for cefiderocol and 87.4% (104/119) for imipenem/cilastatin in the MITT population. Microbiological eradication rates were 73.0% (184/252) for cefiderocol and 56.3% (67/119) for imipenem/cilastatin in the MITT population. Additionally, two phase III clinical trials are currently being conducted by Shionogi & Co., Ltd., Japan. The two trials are evaluating the efficacy of cefiderocol in the treatment of serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens and evaluating the efficacy of cefiderocol in the treatment of adults with hospital-acquired bacterial pneumonia, ventilator-associated pneumonia or healthcare-associated pneumonia caused by Gram-negative pathogens. Cefiderocol appears to be well tolerated (minor reported adverse effects were gastrointestinal and phlebitis related), with a side effect profile that is comparable to other cephalosporin antimicrobials. Cefiderocol appears to be well positioned to help address the increasing number of infections caused by carbapenem-resistant and MDR Gram-negative bacilli, including ESBL- and carbapenemase-producing strains (including metallo-β-lactamase producers). A distinguishing feature of cefiderocol is its activity against resistant P. aeruginosa, A. baumannii, S. maltophilia and Burkholderia cepacia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55:4943–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis. 2011;53:60–7.

    Article  PubMed  Google Scholar 

  3. Buehrle DJ, Shields RK, Clarke LG, Potoski BA, Clancy CJ, Hong Nguyen M. Carbapenem-resistant Pseudomonas aeruginosa bacteremia: risk factors for mortality and microbiologic treatment failure. Antimicrob Agents Chemother. 2017;61:e01243-16.

    Article  PubMed  Google Scholar 

  4. Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2009;65:233–8.

    Article  CAS  PubMed  Google Scholar 

  5. World Health Organization. Antimicrobial resistance global report on surveillance [Internet]. 2014. Available from: http://www.who.int/drugresistance/documents/surveillancereport/en/.

  6. Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, et al. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Gram-negative bacilli. Drugs. 2014;74:31–51.

    Article  CAS  PubMed  Google Scholar 

  7. Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. 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:e00093-17.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. In vitro 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:e01968-17.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagacé-Wiens PRS, et al. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs. 2013;73:159–77.

    Article  CAS  PubMed  Google Scholar 

  10. Carlet J, Jarlier V, Harbarth S, Voss A, Goossens H, Pittet D. Ready for a world without antibiotics? The Pensières antibiotic resistance call to action. Antimicrob Resist Infect Control. 2012;1:11.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kohira N, West J, Ito A, Ito-Horiyama T, Nakamura R, Sato T, et al. In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriales clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother. 2016;60:729–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Arjona Ferreira JC, Ariyasu M, et al. Randomized controlled trial of a novel siderophore antibiotic cefiderocol versus imipenem/cilastatin for complicated urinary tract infections caused by Gram-negative uropathogens. Lancet Infect Dis. 2018;18(12):1319–28.

    Article  CAS  PubMed  Google Scholar 

  13. Dunn G. Ceftizoxime and other third-generation cephalosporins: structure-activity relationships. J Antimicrob Chemother Chemother. 1982;10(Suppl C):1–10.

    Article  CAS  Google Scholar 

  14. Neu HC. β-lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties. Rev Infect Dis. 1986;8:237–59.

    Article  Google Scholar 

  15. Ito A, Nishikawa T, Matsumoto S, Yoshizawa H, Sato T, Nakamura R, et al. Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2016;60:7396–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, et al. In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against Gram-negative bacteria. Antimicrob Agents Chemother. 2018;62:e01454-17.

    Article  PubMed  Google Scholar 

  17. Ito A, Toba S, Nishikawa T, Oota M, Kanazawa S, Fukuhara N, et al. S-649266, a novel siderophore cephalosporin: binding affinity to PBP and in vitro bactericidal activity. In: 25th Eur. Congr. Clin. Microbiol. Infect. Dis.; Copenhagen. 2015.

  18. Ito-Horiyama T, Ishii Y, Ito A, Sato T, Nakamura R, Fukuhara N, et al. Stability of novel siderophore cephalosporin S-649266 against clinically relevant carbapenemases. Antimicrob Agents Chemother. 2016;60:4384–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Domalaon R, Idowu T, Zhanel GG, Schweizer F. Antibiotic hybrids: the next generation of agents and adjuvants against Gram-negative pathogens? Clin Microbiol Rev. 2018;31:e00077-17.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Leemans E, Fisher JF, Mobashery S. The β-lactam antibiotics: their future in the face of resistance. In: Marinelli F, Genilloud O, editors. Antimicrob. new old mol. Fight against multi-resistant Bact. Switzerland AG: Springer; 2014. p. 59–84.

    Google Scholar 

  21. Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev. 2009;22:161–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bush K, Jacoby GA. Updated functional classification of β-lactamases. Antimicrob Agents Chemother. 2010;54:969–76.

    Article  CAS  PubMed  Google Scholar 

  23. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, De Jonge BLM, Bouchillon SK, et al. Global dissemination of bla KPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother. 2016;60:4490–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8:460–9.

    Article  CAS  PubMed  Google Scholar 

  25. Köhler T, Michea-Hamzehpour M, Epp SF, Pechere JC. Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother. 1999;43:424–7.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ito A, Nishikawa T, Matsumoto S, Fukuhara N, Nakamura R, Tsuji M, et al. S-649266, a novel siderophore cephalosporin: II. Impact of active transport via iron regulated outer membrane proteins on resistance selection. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  27. Ito A, Toba S, Nishikawa T, Kohira N, Sato T, Tsuji M, et al. Contribution of active iron transporters and binding ability to penicillin binding proteins of cefiderocol (S-649266) to its antibacterial/bactericidal activity against Klebsiella pneumoniae and Escherichia coli. In: ASM Microbe 2017; New Orleans. 2017.

  28. Olofsson SK, Cars O. Optimizing drug exposure to minimize selection of antibiotic resistance. Clin Infect Dis. 2007;45:S129–36.

    Article  CAS  PubMed  Google Scholar 

  29. Andersson DI. Improving predictions of the risk of resistance development against new and old antibiotics. Clin Microbiol Infect. 2015;21:894–8.

    Article  CAS  PubMed  Google Scholar 

  30. Kohira N, Nakamura R, Ito A, Nishikawa T, Ota M, Sato T, et al. Resistance acquisition studies of cefiderocol by serial passage and in vitro pharmacodynamic model under human simulated exposure. In: ASM Microbe 2018; Atlanta. 2018.

  31. Tsuji M, Kazmierczak K, Hackel M, Echols R, Yamano Y, Sahm D. Cefiderocol (S-649266) susceptibility against globally isolated meropenem non-susceptible Gram-negative bacteria containing serine and metallo-carbapenemase genes. In: ASM Microbe 2018; Atlanta. 2018.

  32. Yamano Y, Tsuji M, Hackel MA, Echols R, Sahm DF. In vitro activity of cefiderocol against globally collected carbapenem resistant Gram-negative bacteria including isolates resistant to ceftazidime/avibactam, ceftolozane/tazobactam and colistin: SIDERO-CR-2014/2016 study. In: 27th Eur. Congr. Clin. Microbiol. Infect. Dis.; Vienna. 2017.

  33. Tsuji M, Hackel M, Yamano Y, Echols R, Sahm DF. Surveillance of cefiderocol in vitro activity against Gram-negative clinical isolates collected in Europe: SIDERO-WT-2014. In: 27th Eur. Congr. Clin. Microbiol. Infect. Dis.; Vienna. 2017.

  34. Tsuji M, Hackel MA, Echols R, Yamano Y, Sahm DF. Global surveillance of cefiderocol (S-649266) against Gram-negative clinical strains collected in North America: SIDERO-WT-2014. In: ASM Microbe 2017; New Orleans. 2017.

  35. Hackel M, Tsuji M, Echols R, Sahm D. In vitro antibacterial activity of cefiderocol (S-649266) against Gram-negative clinical strains collected in North America and Europe (SIDERO-WT-2014 study). In: IDWeek; New Orleans. 2016.

  36. Tsuji M, Yamaguchi T, Nakamura R, Kanazawa S, Ito-Horiyama T, Sato T, et al. S-649266, a novel siderophore cephalosporin: In vitro activity against Gram-negative bacteria isolated in Japan including carbapenem resistant strains. In: IDWeek; San Diego. 2015.

  37. Tsuji M, Hackel M, Echols R, Yamano Y, Sahm DF. In vitro activity of cefiderocol against globally collected carbapenem-resistant Gram-negative bacteria isolated from urinary tract source: SIDERO-CR-2014/2016. In: IDWeek; San Diego. 2017.

  38. Ito A, Kohira N, Yoshizawa H, Nakamura R, Tsuji M, Yamano Y, et al. S-649266, a novel siderophore cephalosporin: I. In vitro activity against Gram-negative bacteria including multidrug-resistant strains. In: 54th Intersci. Conf. Antimicrob. Agents Chemother; Washington, DC. 2014.

  39. Tsuji M, Kohira N, Nakamura R, Sato T, Yamano Y. S-649266, a novel siderophore cephalosporin: in vitro combination effect of S-649266 and other antibiotics against Gram-negative bacteria. In: 26th Eur. Congr. Clin. Microbiol. Infect. Dis.; Amsterdam. 2016.

  40. Jacobs MR, Abdelhamed AM, Good CE, Rhoads DD, Hujer KM, Hujer AM, et al. In vitro activity of cefiderocol (S-649266), a siderophore cephalosporin, against Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases. In: IDWeek; San Francisco. 2018.

  41. Tsuji M, Hackel M, Echols R, Yamano Y, Sahm D. In vitro activity of cefiderocol against Gram-negative clinical isolates collected in North America from urinary tract source: SIDERO-WT-2014/SIDERO-WT-2015. In: IDWeek; San Diego. 2017.

  42. Falagas M, Skalidis T, Vardakas K, Legakis N, Tsiplakou S, Papaioannou V, et al. Activity of cefiderocol (S-649266) against carbapenem-resistant Gram-negative bacteria collected from inpatients in Greek hospitals. J Antimicrob Chemother. 2017;72:1704–8.

    Article  CAS  PubMed  Google Scholar 

  43. Dobias J, Dénervaud-Tendon V, Poirel L, Nordmann P. Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens. Eur J Clin Microbiol Infect Dis. 2017;36:2319–27.

    Article  CAS  PubMed  Google Scholar 

  44. Tsuji M, Hackel M, Yamano Y, Echols R, Sahm DF. The in vitro activity of cefiderocol, a novel siderophore cephalosporin, against a global collection of Stenotrophomonas maltophilia. In: 27th Eur. Congr. Clin. Microbiol. Infect. Dis.; Vienna. 2017.

  45. Shields RK, Kline EG, Jones CE, Mettus RT, Clancy CJ, Hong Nguyen M, et al. Cefiderocol minimum inhibitory concentrations against ceftazidime-avibactam susceptible and resistant carbapenem-resistant Enterobacteriaceae. In: ASM Microbe 2018; Atlanta. 2018.

  46. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. M100, 28th ed; Wayne. 2018.

  47. International Organization for Standardization. ISO 20776-1:2006. Clinical laboratory testing and in vitro diagnostic test systems—susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices—part 1: reference method for testing the in vitro. 2006.

  48. Ito A, Ishibashi N, Kitanishi K, Osaki H, Sato T, Tsuji M, et al. Contribution of chelating ability with iron(III) and the utilization of iron transporters through the outer membrane to the in vitro activity of cefiderocol (S-649266) against Pseudomonas aeruginosa. In: ASM Microbe 2017; New Orleans. 2017.

  49. Saisho Y, Katsube T, White S, Fukase H, Shimada J. Pharmacokinetics, safety, and tolerability of cefiderocol, a novel siderophore cephalosporin for Gram-negative bacteria, in healthy subjects. Antimicrob Agents Chemother. 2018;62:e02163-17.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Katsube T, Echols R, Arjona Ferreira JC, Krenz HK, Berg JK, Galloway C. Cefiderocol, a siderophore cephalosporin for Gram-negative bacterial infections: pharmacokinetics and safety in subjects with renal impairment. J Clin Pharmacol. 2017;57:584–91.

    Article  CAS  PubMed  Google Scholar 

  51. Katsube T, Wajima T, Ishibashi T, Arjona Ferreira JC, Echols R. Pharmacokinetic/pharmacodynamic modeling and simulation of cefiderocol, a parenteral siderophore cephalosporin, for dose adjustment based on renal function. Antimicrob Agents Chemother. 2017;61:e01381-16.

    Article  PubMed  Google Scholar 

  52. Kawaguchi N, Katsube T, Echols R, Wajima T. Population pharmacokinetic analysis of cefiderocol, a parenteral siderophore cephalosporin, in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection or acute uncomplicated pyelonephritis. Antimicrob Agents Chemother. 2018;62:e01391-17.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Nakamura R, Toba S, Ito A, Tsuji M, Yamano Y, Shimada J. S-649266, a novel siderophore cephalosporin: V. Pharmacodynamic assessment in murine thigh infection models. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  54. Horiyama T, Toba S, Nakamura R, Tsuji M, Yamano Y, Shimada J. S-649266, a novel siderophore cephalosporin: VI. Magnitude of PK/PD parameter required for efficacy in murine lung infection model. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  55. Horiyama T, Toba S, Nakamura R, Tsuji M, Yamano Y, Shimada J. S-649266, a novel siderophore cephalosporin: VII. Magnitude of PK/PD parameter required for efficacy in murine thigh infection model. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  56. Ghazi IM, Monogue ML, Tsuji M, Nicolau DP. Pharmacodynamics of cefiderocol, a novel siderophore cephalosporin, in a Pseudomonas aeruginosa neutropenic murine thigh model. Int J Antimicrob Agents. 2018;51:206–12.

    Article  CAS  PubMed  Google Scholar 

  57. Monogue ML, Tsuji M, Yamano Y, Echols R, Nicolaua DP. Efficacy of humanized exposures of cefiderocol (S-649266) against a diverse population of Gram-negative bacteria in a murine thigh infection model. Antimicrob Agents Chemother. 2017;61:e01022-17.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Matsumoto S, Singley CM, Hoover J, Nakamura R, Echols R, Rittenhouse S, et al. Efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli in immunocompetent-rat respiratory tract infection models recreating human plasma pharmacokinetics. Antimicrob Agents Chemother. 2017;61:e00700–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ito A, Kohira N, Bouchillon SK, West J, Rittenhouse S, Sader HS, et al. In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria. J Antimicrob Chemother. 2016;71:670–7.

    Article  CAS  PubMed  Google Scholar 

  60. Horiyama T, Singley CM, Nakamura R, Tsuji M, Echols R, Rittenhouse S, et al. S-649266, a novel siderophore cephalosporin: VIII. Efficacy against Pseudomonas aeruginosa and Acinetobacter baumannii in rat lung infection model with humanized exposure profile of 2 g dose with 1 h infusion. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  61. Nakamura R, Toba S, Tsuji M, Yamano Y, Shimada J. S-649266, a novel siderophore cephalosporin: IV. In vivo efficacy in various murine infection models. In: 54th Intersci. Conf. Antimicrob. Agents Chemother.; Washington, DC. 2014.

  62. Ghazi IM, Monogue ML, Tsuji M, Nicolau DP. Humanized exposures of cefiderocol, a siderophore cephalosporin, display sustained in vivo activity against siderophore-resistant Pseudomonas aeruginosa. Pharmacology. 2018;101:278–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Arjona Ferreira JC, Ariyasu M, et al. Clinical response of cefiderocol compared with imipenem/cilastatin in the treatment of adults with complicated urinary tract infections with or without pyelonephritis or acute uncomplicated pyelonephritis: results from a multicenter, double-blind, randomized study (APEKS-cUTI). In: IDWeek; San Diego. 2017.

Download references

Acknowledgements

The authors would like to thank Dr. Roger Echols, Alice Haynes and Dr. Yoshinori Yamano from Shionogi Inc. for their efforts obtaining published literature on cefiderocol.

Author information

Authors and Affiliations

  1. Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    George G. Zhanel, Alyssa R. Golden, Heather J. Adam, Frank Schweizer, Michael A. Zhanel, Philippe R. S. Lagacé-Wiens, Andrew J. Walkty & James A. Karlowsky

  2. College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Sheryl Zelenitsky, Karyn Wiebe & Courtney K. Lawrence

  3. Diagnostic Services, Shared Health, Winnipeg, MB, Canada

    Heather J. Adam, Philippe R. S. Lagacé-Wiens, Andrew J. Walkty & James A. Karlowsky

  4. Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada

    Temilolu Idowu, Ronald Domalaon & Frank Schweizer

  5. College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates

    Ayman Noreddin

  6. Division of Pulmonary, Critical Care, Allergy and Clinical Immunology, The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Joseph P. Lynch III

  7. Clinical Microbiology, Health Sciences Centre, MS673-820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada

    George G. Zhanel

Authors
  1. George G. Zhanel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alyssa R. Golden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sheryl Zelenitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karyn Wiebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Courtney K. Lawrence
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Heather J. Adam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Temilolu Idowu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ronald Domalaon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Frank Schweizer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael A. Zhanel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Philippe R. S. Lagacé-Wiens
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Andrew J. Walkty
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ayman Noreddin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Joseph P. Lynch III
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. James A. Karlowsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George G. Zhanel.

Ethics declarations

Funding

Summer research student Karyn Wiebe received a stipend from Shionogi Inc. for data collation and preparation of tables and figures.

Conflict of interest

George Zhanel has received research grant funding from Shionogi Inc. Alyssa Golden, Sheryl Zelenitsky, Karyn Wiebe, Courtney Lawrence, Heather Adam, Temilolu Idowu, Ronald Domalaon, Frank Schweizer, Michael Zhanel, Philippe Lagacé-Wiens, Andrew Walkty, Joseph Lynch and James Karlowsky have no conflicts to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhanel, G.G., Golden, A.R., Zelenitsky, S. et al. Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli. Drugs 79, 271–289 (2019). https://doi.org/10.1007/s40265-019-1055-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-019-1055-2

Search

Navigation