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

Objective Here, we have evaluated the in vitro activity of cefiderocol (S-649266), a novel siderophore cephalosporin against Multidrug resistant Gram-Negative Bacilli from France. Materials and Methods 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.

PC-16- In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Multidrug-Resistant Isolates of Gram-Negative Bacilli from France.

Introduction

• CPOs are a public health issue with very limited therapeutic
• ptions
• CPEs continue their spread (300 in 2012; 2600 in 2018)
• The epidemiology is changing, MBLs and especially NDM are
• n the Rock
• Novel molecules urgently needed

CPEs, France 2012-2018

• S. Oueslati, L. Dortet , T. Naas (UPSay, AP-HP, CNR)

ceftazidime cefepime linker cathecol

Results

Antimicrobial agent 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) 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 μg/ml; MICs ranged from 0.03-64 μg/ml, and 93.0% (205/220) with cefiderocol MICs of ≤4 μg/ml.
• MDR P. aeruginosa: MIC90= 2 μg/ml; and 100% (52/52) with cefiderocol MICs of ≤4 μg/ml.
• MDR A. baumannii: MIC90= 64 μg/ml; and 81% (42/52) with cefiderocol MICs of ≤4 μg/ml.
• B. cepacia: MIC90= 1 μg/ml; and 90% (9/10) with cefiderocol MICs of ≤4 μg/ml.
• S. maltophilia: MIC90= 0.06 μg/ml, and 100% (15/15) with cefiderocol MICs of ≤4 μg/ml.

Table 1: MIC50 and MIC90 of the 348 tested isolates <

Results Conclusions

% S/I/R Cefiderocol C/T MEM CAZ CZA CST ATM AMK CIP FEP TGC

• P. aeruginosa

R

90 92 92 76 4 98 55 84 94 98

I

/ / 6 8 / / 2 6 2 6 /

S

100 10 2 24 96 39 14 2

Enterobacterales R

7 87 45 84 38 16 83 21 66 76 28

I

/ / 20 8 / / 4 9 5 10 /

S

93 13 35 8 62 84 14 70 29 14 72

• A. baumannii

R

19 96 87 100 92 13 100 69 88 96 52

I

/ / 10 / / 2 4 /

S

81 4 4 8 87 29 12 48

• B. cepacia

R

10 80 100 70 10 100 100 100 90 100 100

I

/ / 30 / / 10 /

S

90 20 30 90 10 SXT LVX MIN

• S. maltophilia

R

87 87 87 87 60 20 67 87 20

I

/ / / / / 13 /

S

100 13 13 13 13 40 80 20 13 100 80 Table 2: Antibiotic susceptibility of the 348 tested isolates

• Cefiderocol is well adapted to CPEs,

and CPOs in general. Cefiderocol demonstrated potent in vitro activity against a collection of highly drug resistant Gram-negative bacteria (Enterobacterales, MDR A. baumannii, MDR P. aeruginosa, S. maltophilia, and B. cepacia isolates) as >93 % of all (320/348) isolates tested had cefiderocol MICs of ≤4 μg/ml.

• Interestingly 100% of the tested P.

aeruginosa isolates being mostly susceptible only to colistin had cefiderocol MICs of ≤4 μg/ml.