Ocular Microbiology and Immunology Group
Back to OMIG Main Page

< Previous | 2023 Agenda and Abstracts | Next >

2023 OMIG Abstract

Activity Of Cefiderocol against Pseudomonas Aeruginosa Keratitis Isolates in vitro

Jonathan B. Mandell, Sonya M. Mumper, Hazel Q. Shanks, Eric G. Romanowski, and Robert M.Q. Shanks

The Charles T. Campbell Ophthalmic Microbiology Laboratory, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA

Purpose: In the summer of 2022, an outbreak of extensively drug resistant (XDR) Pseudomonas aeruginosa (PA) infections occurred in patients from over 16 states. Epidemiological work determined these dangerous infections originated from over the counter eyedrops ordered online. Unfortunately, at least 68 patients have been infected with this XDR PA strain which has led to eight confirmed accounts of blindness, four cases of enucleation, and three deaths. Cefiderocol was the only antibiotic for which the XDR PA strain was susceptible; however, this drug has not been tested for topical ocular safety or efficacy. Cefiderocol is ß-lactam which contains a novel siderophore side group. This drug mimics substrates Gram - bacteria require and actively absorb using iron uptake machinery, and thus known as a trojan horse strategy antibiotic. The goal of this study was to evaluate cefiderocol susceptibility of a panel of PA keratitis isolates in order to determine suitability of cefiderocol for topical antibiotic treatment of ocular infections compared to standard of care antibiotics.

Methods: We tested MICs of cefiderocol, ceftazidime, ciprofloxacin, and tobramycin to de-identified PA keratitis isolates, PA strain (K900), and the XDR PA strain collected during the outbreak and obtained from the CDC (CDC1270). We determined the MIC of cefiderocol, ceftazidime, ciprofloxacin, and tobramycin using E-strips on isolate lawns grown on Mueller-Hinton agar. Susceptibility was determined using current CLSI breakpoints.

Results:

Antibiotic	N=	Median	Mode	MIC50	MIC90	Range	%S	K900	CDC
Cefiderocol	135	0.094	0.064	0.094	0.125	<0.016-0.94	100	0.023S	0.125R
Ceftazidime	137	2	1.5	2	8	0.75->256	94.9	ND	>256R
Ciprofloxacin	164	0.19	0.19	0.19	0.5	.047-1.5	93.3	0.19S	>32R
Tobramycin	164	1.5	1.5	1.5	3	.047-8	28	0.5S	>256R

Conclusions: Cefiderocol demonstrated good efficacy against keratitis isolates of P. aeruginosa including an XDR isolate from the artificial tears outbreak. Formulation of a fortified topical cefiderocol for the use in difficult and XDR PA ocular infections could prove invaluable and save future patient eyesight and lives.

Disclosure: N, S (The Campbell Lab)

< Previous | 2023 Agenda and Abstracts | Next >