PC-16- In Vitro Activity of the Siderophore Cephalosporin, - PowerPoint PPT Presentation

PC-16- In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Multidrug-Resistant Isolates of Gram-Negative Bacilli from France. S. Oueslati, L. Dortet , T. Naas (UPSay, AP-HP, CNR) Introduction Objective • CPOs are a public health issue with very limited therapeutic Here, we have evaluated the in vitro activity of cefiderocol options (S-649266), a novel siderophore cephalosporin against • CPEs continue their spread (300 in 2012; 2600 in 2018) Multidrug resistant Gram-Negative Bacilli from France. ceftazidime cefepime cathecol • The epidemiology is changing, MBLs and especially NDM are on the Rock linker • Novel molecules urgently needed Materials and Methods CPEs, France 2012-2018 348 MDR or carbapenem-resistant clinical isolates of - 220 Enterobacterales, - 52 Acinetobacter baumannii , - 51 Pseudomonas aeruginosa , - 15 Stenotrophomonas maltophilia , - 10 Burkholderia cepacian - Broth microdilution method with iron-Depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), for cefiderocol and CAMHB for all the other antimicrobial agents (ceftolozane-tazobactam, cefepime, ceftazidime, ceftazidime-avibactam, aztreonam, meropenem, amikacin ciprofloxacin, colistin, and tigecycline) - MIC breakpoints were those of EUCAST or CLSI in case they were not available at EUCAST.

Results Table 1: MIC50 and MIC90 of the 348 tested isolates Enterobacterales (n=220) P. aeruginosa (n=51) A. baumannii (n=52) B. cepacia (n=10) S. maltophilia (n=15) MIC (ug/ml) MIC (ug/ml) MIC (ug/ml) MIC (ug/ml) MIC (ug/ml) Antimicrobial agent Range MIC50 MIC90 Range MIC50 MIC90 Range MIC50 MIC90 Range MIC50 MIC90 Range MIC50 MIC90 Cefiderocol 0.03-64 1 4 0.06-4 0,5 2 0.06-64 1 64 0.03-8 0.03 1 0.03-0,12 0.03 0.06 Ceftolozane- tazobactam 0,25->64 >64 >64 0,5->64 >64 >64 1->64 <64 >64 1-32 3 10 0.03->64 32 >64 Cefepime 0,5->16 >16 >16 4->16 >16 >16 2->16 >16 >16 8->16 >16 >16 Ceftazidime 0,25->64 >64 >64 4->64 >64 >64 8->64 >64 >64 4-16 8 16 0,5->64 >64 >64 Ceftazidime-avibactam 0,12->64 4 >64 2->64 64 >64 8->64 64 >64 4-16 4 9 0,12->64 >64 >64 < Aztreonam 0,5->32 >32 >32 2->32 >32 >32 16->32 >32 >32 >32 >32 >32 Meropenem 2->64 64 >64 2->64 64 >64 2->64 64 >64 32-64 32 >64 2->64 >64 >64 Amikacin <4->64 4 >64 <4->64 >64 >64 <4->64 >64 >64 <4->64 >64 >64 <4->64 >64 >64 Ciprofloxacin <0.25->4 >4 >4 <0.25->4 >4 >4 <0.25->4 >4 >4 0,5->4 1 >4 Colistin <0.5->8 0,5 8 <0.5->8 1 2 <0.5->8 1 >4 >8 >8 >8 0,5->8 4 >8 Tigecycline <0.25->4 0,25 >4 <0.25->4 >4 >4 <0.25->4 1 2 <0.25->4 1 2 <0.25-2 <0.25 1,6 Minocycline <2 <2 <2 Levofloxacin <1-8 <1 8 Bactrim <0.25->16 4 >16 - CR-Enterobacterales: MIC90= 4 μ g/ml; MICs ranged from 0.03-64 μ g/ml, and 93.0% (205/220) with cefiderocol MICs of ≤ 4 μ g/ml. - MDR P. aeruginosa: MIC90= 2 μ g/ml; and 100% (52/52) with cefiderocol MICs of ≤ 4 μ g/ml. - MDR A. baumannii: MIC90= 64 μ g/ml; and 81% (42/52) with cefiderocol MICs of ≤ 4 μ g/ml. - B. cepacia: MIC90= 1 μ g/ml; and 90% (9/10) with cefiderocol MICs of ≤ 4 μ g/ml. - S. maltophilia: MIC90= 0.06 μ g/ml, and 100% (15/15) with cefiderocol MICs of ≤ 4 μ g/ml.

Results Conclusions Table 2: Antibiotic susceptibility of the 348 tested isolates % S/I/R - Cefiderocol is well adapted to CPEs, Cefiderocol C/T MEM CAZ CZA CST ATM AMK CIP FEP TGC and CPOs in general. 0 90 92 92 76 4 98 55 84 94 98 P. aeruginosa R Cefiderocol demonstrated potent in / / 6 8 / / 2 6 2 6 / I vitro activity against a collection of 100 10 2 0 24 96 0 39 14 0 2 S highly drug resistant Gram-negative 7 87 45 84 38 16 83 21 66 76 28 Enterobacterales R bacteria (Enterobacterales, MDR A. / / 20 8 / / 4 9 5 10 / I baumannii , MDR P. aeruginosa , S. 93 13 35 8 62 84 14 70 29 14 72 S maltophilia , and B. cepacia isolates) as 19 96 87 100 92 13 100 69 88 96 52 A. baumannii R >93 % of all (320/348) isolates tested / / 10 0 / / 0 2 0 4 / I had cefiderocol MICs of ≤4 μ g/ml. 81 4 4 0 8 87 0 29 12 0 48 S 10 80 100 70 10 100 100 100 90 100 100 B. cepacia R - Interestingly 100% of the tested P. / / 0 30 / / 0 0 10 0 / I aeruginosa isolates being mostly 90 20 0 30 90 0 0 0 10 0 0 S susceptible only to colistin had SXT LVX MIN cefiderocol MICs of ≤4 μ g/ml. 0 87 87 87 87 60 20 67 87 0 20 S. maltophilia R / / 0 0 / / / 13 0 0 / I 100 13 13 13 13 40 80 20 13 100 80 S