scholarly journals In vitro Activity of Cefiderocol Against Gram-Negative Clinical Isolates Collected from Urinary Track Source: SIDERO-WT-2014/SIDERO-WT-2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S375-S376 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Meredith Hackel ◽  
Roger Echols ◽  
Yoshinori Yamano ◽  
Dan Sahm

Abstract Background The global rise of carbapenem resistant Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant non-fermenting bacteria is alarming and become threats to patient as only a few drugs remain active (e.g. colistin). Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin with potent activity against a wide variety of Gram-negative pathogens including carbapenem-resistant strains. This study evaluated the in vitro activity of cefiderocol and comparator agents against clinical isolates collected from urinary track source from North America. Methods A total of 3,323 Enterobacteriaceae, 263 Acinetobacter spp, 509 Pseudomonas aeruginosa, and 38 Stenotrophomonas maltophilia collected from the USA and Canada in 2014–2016 were tested. MIC was determined for cefiderocol, cefepime (FEP), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to CLSI 2016 guidelines. All testing was done at IHMA, Inc. As recommended by CLSI, cefiderocol was tested in iron-depleted cation-adjusted Mueller Hinton broth. Based upon CLSI breakpoints, carbapenem-non-susceptible (CarbNS) strains were defined as follows: MEM: MIC ≥2 µg/mL for Enterobacteriaceae, ≥4 µg/mL for non-fermenters. Quality control testing was performed on each day of testing by using E. coli ATCC25922 and P. aeruginosa ATCC27853. Results Cefiderocol exhibited in vitro activity against 4,133 strains of Gram-negative bacteria with an overall MIC90 of 0.5 µg/mL. At 4 µg/mL cefiderocol inhibited the growth of 99.9% of the all isolates. MIC90 of cefiderocol against CarbNS Enterobacteriaceae was 4 µg/mL although MIC90 of other comparators were >64 or >8 (CST) µg/mL. The cefiderocol MIC90value was 1 µg/mL for CarbNS non-fermeneters. Conclusion Cefiderocol demonstrated potent in vitro activity against Enterobacteriaceae, A. baumannii, P. aeruginosa, and S. maltophilia isolates collected from a UTI source, with greater than 99.9% of isolates having MIC values ≤4 µg/mL. These findings indicate that this agent has high potential for treating cUTI infections caused by these problematic organisms, including isolates resistant to colistin. Disclosures M. Tsuji, Shionogi & Co.: Employee, Salary; M. Hackel, IHMA: Employee, Salary; R. Echols, Shionogi & CO., LTD: Consultant, Consulting fee; Y. Yamano, Shionogi & Co.: Employee, Salary

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S643-S644
Author(s):  
Miki Takemura ◽  
Krystyna Kazmierczak ◽  
Meredith Hackel ◽  
Daniel F Sahm ◽  
Roger Echols ◽  
...  

Abstract Background Metallo-β-lactamases (MBLs; eg, NDM, VIM, and IMP) can inactivate most commonly-used β-lactam antibiotics, including carbapenems. Infections caused by MBL producers are difficult to treat due to their resistance to many antibiotics. Cefiderocol (CFDC) is a siderophore cephalosporin antibiotic approved in the USA in 2019, with potent activity against carbapenem-resistant Gram-negative bacteria (GNB), including both serine- and metallo-carbapenemase positive strains. We evaluated the in vitro activity of CFDC and comparator agents against MBL-producing strains of GNB from North America and Europe in 3 years’ of consecutive surveillance studies (SIDERO-WT-2014–2016). Methods Susceptibility testing for CFDC, ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), meropenem (MEM), cefepime (FEP), ciprofloxacin (CIP), and colistin (CST) was performed by broth microdilution according to CLSI guidance. CFDC was tested in iron-depleted medium. A total of 275 MBL-producing strains, consisting of 120 Enterobacterales (45 NDM; 75 VIM), 5 NDM-producing Acinetobacter baumannii, and 150 Pseudomonas aeruginosa (134 VIM; 16 IMP), identified among 4985 (654 Enterobacterales and 4331 non-fermenters) MEM non-susceptible (based on CLSI breakpoints) strains were used for the current analysis. Results The minimum inhibitory concentration (MIC) range and MIC90 for CFDC and comparators for each MBL-producing organism group are shown in the Table. Against NDM-producing Enterobacterales, of which 42% and 33% were isolated in Turkey and Russia, respectively, CFDC inhibited the growth of 84% of isolates tested at ≤4 µg/mL. CFDC MIC90 was 4 μg/mL for VIM-producing Enterobacterales (41% and 31% isolated in Greece and Italy, respectively), 1 μg/mL for VIM-producing P. aeruginosa (50% isolated in Russia), and 4 μg/mL for IMP-producing P. aeruginosa (88% isolated in Czech Republic). Other comparators (except for CST) were not active against these MBL producers. Table. MIC range and MIC90 (μg/mL) for CFDC and comparators of MBL-producing organisms Conclusion CFDC inhibited the growth of 100% of MBL-positive GNB at ≤8 mg/mL and showed MIC90 of 4 μg/mL against all 275 MBL producers, indicating that CFDC has high potential for treating infections caused by these difficult-to-treat strains. Disclosures Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Krystyna Kazmierczak, PhD, Shionogi & Co., Ltd. (Independent Contractor) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor) Roger Echols, MD, Shionogi Inc. (Consultant) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee)


2004 ◽  
Vol 48 (1) ◽  
pp. 73-75 ◽  
Author(s):  
Nicolas C. Issa ◽  
Mark S. Rouse ◽  
Kerryl E. Piper ◽  
Walter R. Wilson ◽  
James M. Steckelberg ◽  
...  

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S326-S326
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John M Quale

Abstract Background Antibiotic-resistant Gram-negative bacteria, including KPC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, have been problematic hospital pathogens in NYC and other areas. Eravacycline (ERV), a fluorocycline antibiotic released in the USA in 2018, has demonstrated in vitro activity against many of these strains. We tested the activity of ERV against a recent collection of clinical isolates from NYC hospitals. Methods For a 3-month period in 2017, all unique patient isolates of E. coli, K. pneumoniae, Enterobacter spp., and A. baumannii were collected from 7 hospitals in Brooklyn, NY. MICs were performed by broth microdilution for ERV and Tigecycline (TGC) and agar dilution for other antibiotics according to CLSI methodology. Cephalosporin-resistant isolates were screened by PCR for common carbapenemases. Results The susceptibility results for tetracycline and ERV are listed in the Table. Overall, 95% of the Enterobacteriaceae were inhibited by ≤ 0.5 μg/mL of ERV, the FDA-suggested breakpoint. Of 1,876 isolates of E. coli, 4 possessed KPC. ERV MICs for these 4 isolates were 0.125–0.25 μg/mL. Of 518 isolates of K. pneumoniae, 20 possessed KPC. The ERV MIC50 and MIC90 for these isolates were 1 and 1 μg/mL, respectively. Of 172 isolates of Enterobacter spp., 3 possessed KPC. ERV MICs for these 3 isolates were 0.5–1 μg/mL. Of 45 isolates of A. baumannii, 11 isolates possessed a carbapenemase (OXA23 in 8, OXA24 in 2, and KPC in 1). The ERV MIC50 and MIC90 for these isolates were 1 and 2 μg/mL, respectively. Overall, ERV MICs were two-fold lower than TGC MICs for A. baumannii. Conclusion ERV possesses significant in vitro activity against contemporary clinical isolates of Enterobacteriaceae and A. baumannii from NYC, including many carbapenemase producing strains. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 75 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  

Abstract Background SPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented. Methods A collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016–17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined. Results SPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii. Conclusions SPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values.


1993 ◽  
Vol 37 (9) ◽  
pp. 2009-2016 ◽  
Author(s):  
G J Malanoski ◽  
L Collins ◽  
C Wennersten ◽  
R C Moellering ◽  
G M Eliopoulos

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