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Activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole against multidrug resistant Stenotrophomonas maltophilia.
Antimicrob Agents Chemother. 2020 Jun 22 [Online ahead of print]AA

Abstract

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.

Authors+Show Affiliations

College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.JMI Laboratories, North Liberty, IA, USA.College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA wenzler@uic.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32571820

Citation

Biagi, M, et al. "Activity of Cefiderocol Alone and in Combination With Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-sulfamethoxazole Against Multidrug Resistant Stenotrophomonas Maltophilia." Antimicrobial Agents and Chemotherapy, 2020.
Biagi M, Vialichka A, Jurkovic M, et al. Activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole against multidrug resistant Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2020.
Biagi, M., Vialichka, A., Jurkovic, M., Wu, T., Shajee, A., Lee, M., Patel, S., Mendes, R. E., & Wenzler, E. (2020). Activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole against multidrug resistant Stenotrophomonas maltophilia. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/AAC.00559-20
Biagi M, et al. Activity of Cefiderocol Alone and in Combination With Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-sulfamethoxazole Against Multidrug Resistant Stenotrophomonas Maltophilia. Antimicrob Agents Chemother. 2020 Jun 22; PubMed PMID: 32571820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole against multidrug resistant Stenotrophomonas maltophilia. AU - Biagi,M, AU - Vialichka,A, AU - Jurkovic,M, AU - Wu,T, AU - Shajee,A, AU - Lee,M, AU - Patel,S, AU - Mendes,R E, AU - Wenzler,E, Y1 - 2020/06/22/ PY - 2020/6/24/entrez JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/32571820/Activity_of_cefiderocol_alone_and_in_combination_with_levofloxacin,_minocycline,_polymyxin_B,_or_trimethoprim-sulfamethoxazole_against_multidrug_resistant_Stenotrophomonas_maltophilia L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=32571820 DB - PRIME DP - Unbound Medicine ER -
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