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2024 OMIG Abstract

Cefiderocol is Effective against Numerous Gram-Negative
Keratitis Isolates In Vitro

Jonathan B. Mandell, Eric G. Romanowski, Robert M.Q. Shanks

Campbell Ophthalmic Microbiology Laboratory, Department of Ophthalmology,
University of Pittsburgh School of Medicine, Pittsburgh, PA

Purpose: We have previously shown that the siderophore-cephalosporin antibiotic cefiderocol, was effective against Pseudomonas aeruginosa (PA) keratitis isolates in vitro, demonstrating 100% susceptibility among 135 isolates using epsilometer tests. We further showed that a 50 mg/ml formulation of cefiderocol was non-toxic to the ocular surface and was effective in topical treatment of antibiotic susceptible and extensively drug resistant (XDR) PA keratitis in a rabbit model. Cefiderocol has also been shown to have excellent in vitro susceptibility against numerous Gram-negative bacterial species isolated from systemic infections. Here, our goal was to determine the susceptibility of keratitis isolates from several Gram-negative bacterial species to cefiderocol.

Methods: The MICs for cefiderocol for keratitis isolates were determined by three independent evaluators. The following Gram-negative bacteria were included: PA (n=17); Serratia marcescens (SM) (n=14); Proteus mirabilis (PM) (n=13) Acinetobacter baumannii (AB) (n=13); Escherichia coli (EC) (n=15); Klebsiella (Enterobacter) aerogenes (KA) (n=14); Stenotrophomonas maltophilia (ST) (n=12); *Moraxella spp. (MO) (n=15); *Achromobacter xylosoxidans (AX) (n=14); Klebsiella oxytoca (KO) (n=14); Klebsiella pneumoniae (KP) (n=13). MICs were determined using the broth microdilution method using cation-adjusted, iron-depleted Mueller-Hinton broth. Susceptibility was determined using current CLSI breakpoints for cefiderocol (≤4 µg/ml for all species except ST [<1 µg/ml]).

Results: 100% of the isolates for all Gram-negative species were susceptible to cefiderocol in vitro. The following table displays MIC90 values for all groups in µg/ml.

Pathogen	PA	SM	PM	AB	EC	KA	ST	MO	AX	KO	KP
MIC90	0.5	0.5	0.25	0.5	0.5	1.0	0.25	0.5	0.25	0.5	0.5

In each trial, ATCC control strains 25922 (EC) and 27853 (PA) displayed MICs within accepted range for cefiderocol MIC testing.

Conclusions: Cefiderocol demonstrated excellent in vitro activity against several Gram-negative keratitis isolates. The results of this study suggest the cefiderocol may be useful for the treatment of keratitis caused by numerous Gram-negative pathogens. Further investigation of cefiderocol for the topical treatment of Gram-negative keratitis is indicated.

*There are no CLSI standards for MO and AX, but ≤1 µg/ml was used for standard to determine susceptibility.

Disclosure:

S Shionogi, Inc.