In vitroactivities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistantPseudomonas aeruginosaandAcinetobacter baumannii, andStenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan

Hsueh, Shun Chung; Lee, Yuarn Jang; Huang, Yu-Tsung; Liao, Chun-Hsing; Tsuji, Masakatsu; Hsueh, Po Ren

doi:10.1093/jac/dky425

Cited by 92 publications

(73 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A total of 262 strains of MDR P. aeruginosa were exposed to various antibiotics; the MIC 90 values of colistin and cefiderocol were 1 mg/liter, versus Ͼ8 mg/liter for ciprofloxacin and Ͼ64 mg/liter for meropenem, cefepime, ceftazidime-avibactam, and ceftolozanetazobactam. The same finding was also observed when the activities of several antibiotics against 100 strains of imipenem-resistant P. aeruginosa were studied (320). The MIC 90 of cefiderocol was 1 mg/liter, and this drug was the most active of all the antipseudomonal antibiotics studied.…”

Section: Cefiderocolsupporting

confidence: 72%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

View full text Add to dashboard Cite

SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR)Pseudomonas aeruginosahas become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options.In vitroandin vivotreatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDRP. aeruginosainfections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other “old” antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDRP. aeruginosastrains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDRP. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

show abstract

Section: Cefiderocolsupporting

confidence: 72%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Despite widespread resistance to other agents included in this study, the maximum cefiderocol MIC observed was 1 mg/liter, 2 log 2 dilutions below the CLSI provisional susceptibility breakpoint of 4 mg/liter (24). Notwithstanding the fact that our sample was intentionally enriched with isolates resistant to levofloxacin and/or TMP-SMZ, these results are consistent with those of previous studies evaluating the in vitro susceptibility of S. maltophilia to cefiderocol (25)(26)(27)(28).…”

Section: Discussionsupporting

confidence: 90%

Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia

Biagi

Vialichka

Jurkovic

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Objectives: The production of a metallo-(L1) and serine-(L2) β-lactamase precludes the use of β-lactams for the treatment of Stenotrophomonas maltophilia infections. Pre-clinical data suggest cefiderocol is the first approved β-lactam with reliable activity against S. maltophilia, but data against strains resistant to current first -line agents are limited and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, and trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. Methods: The minimum inhibitory concentrations (MICs) of 37 S. maltophilia isolates not susceptible to levofloxacin and/or TMP-SMZ were determined for cefiderocol, ceftazidime, levofloxacin, minocycline, polymyxin B, and TMP-SMZ. Nine strains with varying MICs to cefiderocol were then tested in time-kill experiments alone and in combination with comparators. Results: The only agents with susceptibility rates exceeding 40% were cefiderocol (100%) and minocycline (97.3%). Cefiderocol displayed the lowest MIC50 and MIC90 values (0.125 and 0.5 mg/L, respectively). In time-kill experiments, synergy was observed when cefiderocol was combined with levofloxacin, minocycline, polymyxin B, and TMP-SMZ against 4/9 (44.4%), 6/9 (66.7%), 5/9 (55.5%), and 6/9 (66.7%) isolates, respectively. Conclusions: These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia, including strains resistant to currently preferred agents. Future dynamic and in vivo studies of cefiderocol alone and in combination are warranted to further define cefiderocol's synergistic capabilities and place in therapy for S. maltophilia infections.

show abstract

“… 4–8 The spectrum of activity of cefiderocol includes isolates harboring a wide range of carbapenemases, including serine (KPC, OXA-type) and metallo (VIM, IMP, NDM) β-lactamases. 7–13 Finally, in one clinical trial cefiderocol was comparable with imipenem–cilastatin for treatment of complicated urinary tract infections owing to carbapenem-susceptible pathogens. 14 …”

Section: Introductionmentioning

confidence: 99%

Activity of Cefiderocol AgainstEnterobacterales,Pseudomonas aeruginosa, andAcinetobacter baumanniiEndemic to Medical Centers in New York City

Iregui

Khan

Landman

et al. 2020

Microbial Drug Resistance

View full text Add to dashboard Cite

Therapeutic options for the treatment of infections owing to multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol is a novel siderophore cephalosporin with activity against Gram-negative pathogens, including many multidrug-resistant strains. The activity of cefiderocol was examined against Enterobacterales , Pseudomonas aeruginosa , and Acinetobacter baumannii that included (1) a recent surveillance collection of clinical isolates, (2) a collection of carbapenem-resistant isolates from a previous surveillance study, and (3) a collection of well-characterized isolates. Susceptibility testing for cefiderocol was performed with iron-depleted cation-adjusted Mueller–Hinton broth. Cefiderocol minimum inhibitory concentrations (MICs) were correlated with resistance mechanisms in the well-characterized isolates. For the Enterobacterales , including a collection of KPC-possessing Klebsiella pneumoniae , cefiderocol MICs were all ≤4 mg/L. Cefiderocol MICs were two- to fourfold higher in cephalosporin-resistant isolates. For K. pneumoniae , MICs did not correlate with expression of genes encoding porins or efflux systems. For P. aeruginosa , >99% of isolates were inhibited by ≤4 mg/L, including the collection of carbapenem-resistant isolates. For P. aeruginosa , cefiderocol activity was not affected by expression of ampC , oprD , or several efflux systems. All the surveillance isolates of A. baumannii , and 88% of the collection of carbapenem-resistant isolates, had cefiderocol MICs ≤4 mg/L. MICs were twofold higher in A. baummannii isolates with proven extended-spectrum beta-lactamases, and cefiderocol activity did not correlate with expression of efflux systems. Cefiderocol demonstrated potent activity against important nosocomial pathogens. Continued development of this agent as a therapeutic option against multidrug-resistant bacteria should be encouraged.

show abstract

In vitroactivities of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam and other comparative drugs against imipenem-resistantPseudomonas aeruginosaandAcinetobacter baumannii, andStenotrophomonas maltophilia, all associated with bloodstream infections in Taiwan

Cited by 92 publications

References 16 publications

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia

Activity of Cefiderocol AgainstEnterobacterales,Pseudomonas aeruginosa, andAcinetobacter baumanniiEndemic to Medical Centers in New York City

Contact Info

Product

Resources

About