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Received: 7 December 2018 

|  Revised: 5 April 2019 


|  Accepted: 18 June 2019

DOI: 10.1111/vop.12693

ORIGINAL ARTICLE

Feline bacterial keratitis: Clinical features, bacterial isolates, and


in vitro antimicrobial susceptibility patterns

Jennifer E. Goldreich  | Rebecca J. Franklin‐Guild  | Eric C. Ledbetter

Department of Clinical Sciences, College


of Veterinary Medicine, Cornell University,
Abstract
Ithaca, NY Objective: To describe clinical characteristics, bacterial isolates, and in vitro antimi-
crobial susceptibility patterns for cats with bacterial keratitis.
Correspondence
Eric C. Ledbetter, College of Veterinary Animals Studied: Eighty one cats with bacterial keratitis.
Medicine, Hospital for Animals, Cornell Procedures: Medical records of cats with a clinical diagnosis of bacterial keratitis,
University, VMC Box 34, Ithaca, NY
confirmed by corneal culture, were reviewed from June 2004 to July 2017. Animal
14853‐6401.
Email: ecl32@cornell.edu signalment, bacterial isolates, aerobic bacteria in vitro antimicrobial susceptibility
test results, and pertinent clinical features were recorded. Percentages of susceptible
aerobic bacterial isolates were statistically compared among selected antimicrobials.
Results: There were 102 aerobic bacterial isolates recovered from corneal samples
of the 81 cats presented with bacterial keratitis. The most frequent bacteria isolated
were Staphylococcus species, which constituted 55% (56/102) of total isolates. All
aerobic bacterial isolates grouped together had the highest percentage of susceptibility
to ofloxacin (100%), ciprofloxacin (94%), chloramphenicol (93%), doxycycline (92%),
ticarcillin (90%), gentamicin (89%), moxifloxacin (89%), tobramycin (86%), neomycin
(85%), amikacin (84%), and cefazolin (84%). The same isolates had the lowest percent-
age of susceptibility to polymyxin B (2%), bacitracin (15%), and clindamycin (31%).
When analyzed separately, the isolated Staphylococcus species had the highest per-
centage of susceptibility to ofloxacin (100%), tobramycin (93%), and neomycin (85%)
and the lowest percentage of susceptibility to polymyxin B (3%) and bacitracin (13%).
Conclusions: Members of the Staphylococcus genus were the most frequent bacteria
isolated from cases of feline bacterial keratitis. On the basis of in vitro susceptibility
testing and mechanism of action, ofloxacin, ciprofloxacin, ticarcillin, gentamicin, or
moxifloxacin are recommended for initial antimicrobial therapy of suspected bacte-
rial keratitis in cats.

KEYWORDS
bacteria, cornea, feline, keratitis, ulcer

1  |   IN T RO D U C T ION many other domestic animal species.1-11 Despite this, bacte-


rial keratitis is a clinically important ocular disease of cats that
Based upon the frequency of peer‐reviewed publications de- can be both vision and globe‐threatening if not treated appro-
scribing the condition, bacterial keratitis appears to be a rel- priately.12 Bacterial keratitis is often diagnosed presumptively
atively uncommon disease in domestic cats compared with and treated with empirical antimicrobial therapy, yet there are

Veterinary Ophthalmology. 2019;00:1–7. wileyonlinelibrary.com/journal/vop © 2019 American College of Veterinary     1 |


Ophthalmologists
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2       GOLDREICH et al

limited publications describing bacterial isolates and in vitro isolates grouped separately. The percentage of susceptible
antimicrobial susceptibility patterns for this condition in cats isolates was compared among the individual antimicrobi-
specifically in which to base these clinical decisions.1 als by use of Fisher's exact test. The P values were adjusted
The objectives of the retrospective study reported here for multiple comparisons by use of the Bonferroni correc-
were to determine the most common bacterial isolates and tion, and a P ≤ 0.005 was considered significant for all com-
their in vitro antimicrobial susceptibility patterns to assist in parisons. For the statistical analyses and reporting of results,
establishing appropriate empiric antimicrobial treatment for bacterial isolates scored as intermediate susceptibility were
cats with bacterial keratitis. In addition, clinical characteris- included in the resistant category.
tics and the frequency and types of concurrent ocular infec-
tions in cats with bacterial keratitis were evaluated.
3  |  RESULTS
2  |  M AT E R IA L S A N D ME T HODS
Eighty‐one cats with culture confirmed bacterial keratitis
2.1  |  Medical records review were identified during the study period with in vitro antimi-
crobial susceptibility test results. The mean age (± stand-
Medical records of cats with a clinical diagnosis of bacterial ard deviation) of the cats in the study population was 92
keratitis, confirmed by positive corneal bacterial culture re- (± 63) months. The study population included 43 castrated
sults, evaluated by the ophthalmology service at the Cornell males, five intact males, 29 spayed females, and four intact
University Hospital for Animals between June 1, 2004 and July females. Breed distribution was as follows: domestic short-
31, 2017, were reviewed. Animal signalment, past pertinent hair or domestic longhair (n = 58 cats), Persian (n = 14),
medical history, clinical findings, medical therapies admin- Himalayan (n  =  5), Burmese (n  =  2), Tonkinese (n  =  1),
istered, surgeries performed, duration of treatment, treatment and Bombay (n = 1). All cats had unilateral corneal lesions.
response, clinical outcome, bacterial isolates, aerobic bacte- Clients most often cited ocular discharge (n  =  22 cli-
rial in vitro antimicrobial susceptibility test results and other ents) and blepharospasm (n = 17) as their main complaints
microbiologic test results were recorded. Cats were included prompting medical evaluation. The clinical corneal lesions
in the study whether they had a clinical diagnosis of bacterial diagnosed in association with bacterial keratitis were anterior
keratitis, and antimicrobial susceptibility determinations were stromal corneal ulcer (n = 22 cats), corneal sequestrum with
completed with the results available in the record.13,14 surrounding abscessation (n = 16), deep stromal corneal ulcer
(n = 9), corneal laceration (n = 9), descemetocele (n = 7),
2.2  | Microbiology corneal perforation (n = 7), corneal abscess (n = 5), kerato-
malacia (n = 4), and corneal foreign body (n = 2) (Figure 1).
Corneal samples for aerobic bacterial microbiologic assess- In total, 102 aerobic bacteria were isolated from corneal
ment were obtained from cats through direct sampling of samples of the 81 cats with bacterial keratitis (Table 1).
the cornea using scrapings or swabs. Matrix‐Assisted Laser
Desorption/Ionization Time‐of‐Flight mass‐spectrometry
(A) (B)
(MALDI‐TOF) or an automated system (Sensititre, Trek
Diagnostic Systems Inc) were employed for bacteriological
identifications (New York State Animal Health Diagnostic
Center). Automated bacterial identifications were supple-
mented with bacterial phenotypic classification tests and RT‐
PCR speciation to confirm identifications when necessary.
Minimum inhibitory concentration (MIC) susceptibility test-
ing was performed using an automated broth microdilution (C) (D)
system (Sensititre, Trek Diagnostic Systems Inc). Bacterial
isolates were tested against a panel of antimicrobials with
MIC break points set for each drug using Clinical and
Laboratory Standard Institute guidelines when available.

2.3  |  Statistical analysis


Percentages of susceptible aerobic bacterial isolates were F I G U R E 1   Clinical photographs of study cats with bacterial
statistically compared among selected antimicrobials for all keratitis, including anterior stromal corneal ulcers (A, C), deep corneal
bacterial isolates grouped together and for Staphylococcus ulcer (B), and descemetocele (D)
GOLDREICH et al   
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T A B L E 1   Distribution of aerobic bacteria isolates from 81 cats gram‐positive and 20 were gram‐negative (Table 1). The
with bacterial keratitis most frequent bacterial genera isolated were Staphylococcus
Bacteria Number of isolates
spp. (n  =  56 isolates), Pasteurella spp. (n  =  10), Bacillus
spp. (n = 9), Streptococcus spp. (n = 8), Enterococcus spp.
Staphylococcus spp. (56)
(n  =  6), and Pseudomonas spp. (n  =  4). Aerobic bacterial
Staphylococcus spp. (nonspeciated) 23 isolates grouped as a whole had the highest percentage of
Staphylococcus epidermidis 9 susceptibility to ofloxacin (100%), ciprofloxacin (94%),
Staphylococcus aureus 4 chloramphenicol (93%), doxycycline (92%), ticarcillin
Staphylococcus felis 4 (90%), tobramycin (86%), neomycin (85%), amikacin (84%),
Staphylococcus pseudintermedius 4 and cefazolin (84%) (Tables 2-4). Grouped aerobic bacterial
Staphylococcus warneri 4 isolates had the lowest percentage of susceptibility to poly-
Staphylococcus pseudintermedius 3 myxin B (2%), bacitracin (15%), and clindamycin (31%)
(Table 2). The percentage of isolates susceptible to ofloxacin,
Staphylococcus capitis 1
ciprofloxacin, chloramphenicol, doxycycline, and ticarcillin
Staphylococcus hominis 1
was significantly (P < 0.005) greater than polymyxin B, baci-
Staphylococcus hyicus 1
tracin, and clindamycin. One Pseudomonas sp isolate was too
Staphylococcus pettenkoferi 1 fastidious for antimicrobial susceptibility testing.
Staphylococcus sciuri 1 When evaluated separately as a group, the Staphylococcus
Pasteurella spp. (10) spp. isolated had the highest percentage of susceptibility
Pasteurella spp. (nonspeciated) 1 to ofloxacin (100%), tobramycin (93%), neomycin (93%),
Pasteurella multocida 8 ciprofloxacin (91%), and gentamicin (91%) (Table 3).
Pasteurella stomatis 1 Staphylococcus spp. had the lowest percentage of susceptibil-
Bacillus spp. (9)
ity to polymyxin B (3%), and bacitracin (13%) (Table 2). The
percentage of isolates susceptible to ofloxacin, tobramycin,
Bacillus spp. (nonspeciated) 4
neomycin, ciprofloxacin, and gentamicin was significantly
Bacillus cereus 3
(P < 0.005) greater than polymyxin B. The percentage of iso-
Bacillus licheniformis 1 lates susceptible to ofloxacin, tobramycin, neomycin, cipro-
Bacillus pumilus 1 floxacin, and gentamicin was also significantly (P < 0.005)
Streptococcus spp. (8) greater than bacitracin.
Streptococcus spp. (nonspeciated) 7 In addition to aerobic bacteria, 15 cats had one or more
Streptococcus thermophilus 1 concurrent infectious agents detected in ocular samples
Enterococcus spp. (6) from the eye with bacterial keratitis, including viruses, an-
Enterococcus spp. (nonspeciated) 1
aerobic bacteria, Mycoplasma spp., and Chlamydia spp..
Virus isolation was performed in 17 cases, yielding five
Enterococcus faecalis 5
positive results (29% positive where this assay was per-
Pseudomonas spp. (4)
formed): feline herpesvirus‐1 was isolated from two cats,
Pseudomonas spp. (nonspeciated) 2
feline syncytial virus from two cats, and feline calicivirus
Pseudomonas aeruginosa 2 from one cat. Anaerobic bacteria were cultured from 6 out of
Corynebacterium spp. (2) 48 cats (13%) where this assay was performed and included
Corynebacterium spp. (nonspeciated) 1 Bacteroides vulgatus (n = 4 isolates), Fusobacterium spp.
Corynebacterium felinum 1 (n = 2), Actinomyces spp.(n = 1), Clostridium perfringens
Achromobacter spp. (nonspeciated) 1 (n = 1), Peptostreptococcus sp (n = 1), Porphyromonas levii
Escherichia coli 1 (n = 1), and Propionibacterium acnes (n = 1). Additionally,
Macrococcus spp. (nonspeciated) 1
4 out of 13 cats (30%) cultured positive for Mycoplasma
spp. when tested. In total, 16 PCR assays for various in-
Pantoea spp. (nonspeciated) 1
fectious agents were performed on ocular samples. Feline
Proteus spp. (nonspeciated) 1
herpesvirus‐1 RT‐PCR was positive in 0 out of 4 tested cats
Psychrobacter spp. (nonspeciated) 1 and Chlamydia felis PCR was positive in 1 of 12 tested cats.
Sphingobacterium spp. (nonspeciated) 1 Of the 81 cats with bacterial keratitis evaluated in this study,
successful treatment with both vision and globe retention oc-
Single bacterial isolates were obtained from the corneal sam- curred in 71 (88%) of the cats. Seven cats were enucleated
ples of 62 cats, two isolates from 17 cats, and three isolates due to complications associated with the corneal lesion (most
from two cats. Of the 102 aerobic bacteria isolated, 82 were frequently corneal perforation), and three cats lost vision, but
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4       GOLDREICH et al

T A B L E 2   Antimicrobials with the


Polymyxin B Bacitracin Clindamycin
lowest percentage of susceptibly for feline
Staphylococcus spp. 3% (1/29) 13% (7/55) 35% (7/20) bacterial keratitis isolates
Bacillus spp. 0% (0/4) 0% (0/8) 0% (0/1)
Pasteurella spp. n/a 0% (0/7) 0% (0/3)
Streptococcus spp. 0% (0/4) 57% (4/7) n/a
Enterococcus spp. 0% (0/3) 17% (1/6) n/a
Pseudomonas spp. 0% (0/1) 0% (0/2) n/a
Corynebacterium spp. n/a 50% (1/2) 0% (0/1)
Achromobacter spp. 0% (0/1) 0% (0/1) n/a
Escherichia coli n/a 0% (0/1) n/a
Macrococcus spp. n/a 100% (1/1) 100% (1/1)
Pantoea spp. n/a 0% (0/1) n/a
Proteus spp. n/a 0% (0/1) n/a
Psychrobacter spp. n/a 0% (0/1) n/a
Sphingobacterium spp. 0% (0/1) 0% (0/1) n/a
Total Susceptibility 2% (1/43) 15% (14/94) 31% (8/26)
Note: Data presented as percentage susceptible (number of bacterial isolates susceptible/number of bacterial
isolates tested). Not all isolates were tested against every antimicrobial.

T A B L E 3   Antimicrobials with the highest percentage of susceptibility for gram‐positive feline bacterial keratitis isolates

Staphylococcus Bacillus Streptococcus Enterococcus Corynebacterium Macrococcus Total


Ofloxacin 100% (8/8) 100% (3/3) 100% (1/1) n/a n/a 100% (1/1) 100% (13/13)
Ciprofloxacin 91% (50/55) 100% (8/8) 100% (7/7) 100% (6/6) 100% (2/2) n/a 94% (73/78)
Chloramphenicol 85% (23/27) 100% (8/8) 100% (3/3) 100% (4/4) 100% (2/2) 100% (1/1) 91% (41/45)
Doxycycline 86% (18/21) 100% (4/4) 100% (2/2) n/a 100% (2/2) 100% (1/1) 90% (27/30)
Moxifloxacin 88% (7/8) n/a n/a n/a n/a 100% (1/1) 89% (8/9)
Ticarcillin 86% (48/56) 89% (8/9) 100% (8/8) 83% (5/6) 100% (2/2) 100% (1/1) 88% (72/82)
Gentamicin 91% (51/56) 89% (8/9) 100% (8/8) 33% (2/6) 100% (2/2) 100% (1/1) 88% (72/82)
Tobramycin 93% (51/55) 100% (7/7) 83% (5/6) 29% (2/7) 100% (2/2) 100% (1/1) 87% (68/78)
Amikacin 89.0% (49/55) 100% (9/9) 78% (7/9) 17% (1/6) 100% (2/2) 100% (1/1) 84% (69/82)
Cefazolin 76% (16/21) 100% (4/4) 100% (2/2) n/a 100% (2/2) 100% (1/1) 83% (25/30)
Neomycin 93% (51/55) 88% (7/8) 71% (5/7) 0% (0/6) 100% (2/2) 100% (1/1) 66% (56/79)
Note: Data presented as percentage susceptible (number of bacterial isolates susceptible/number of bacterial isolates tested). Not all isolates were tested against every
antimicrobial.

retained their globe. Of the 74 cats that retained their globe, laboratory standards are based on the anticipated serum drug
medical therapy alone was performed in 58 cats. The mean (± concentrations that are reached after administration of a spe-
standard deviation) treatment duration for cats receiving medi- cific antimicrobial.15 Currently, no separate standards are avail-
cal therapy alone was 37 (± 24) days. Surgical procedures were able to guide topical ophthalmic antimicrobial treatment. The
performed in 16 cats to aid in the resolution of bacterial keratitis serum standards are frequently used to interpret susceptibility
including conjunctival pedicle graft (n = 9 cats), anterior lamel- of bacteria to topical ophthalmic antimicrobials; however, it is
lar keratectomy (n = 6), and penetrating keratoplasty (n = 1). commonly assumed that corneal tissue concentrations of anti-
microbials will be equal to or greater than serum concentrations
with topical application.15 Consequently, in vitro resistance of
4  |   D IS C U SS ION bacteria to an antimicrobial may overcome in some situations
by the high corneal drug concentrations achieved with topical
In vitro susceptibility testing of microorganisms attempts to therapy. As a result of this, in vitro susceptibility testing for
predict the in vivo efficacy of antimicrobials ideally using corneal isolates may underestimate the percentage of bacteria
Clinical and Laboratory Standard Institute guidelines. These susceptible to a given drug in vivo when treated topically.16
GOLDREICH et al   
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These concepts are clinically relevant when applying results

100% (11/11)

100% (18/18)
of the present study to both systemic and topical ophthalmic

94% (15/16)
94% (15/16)
93% (14/15)

81% (13/16)
80% (12/15)
100% (4/4)

100% (8/8)

88% (7/8)
antimicrobial therapy of cats with bacterial keratitis.

Total
In this study, members of the Staphylococcus genus
were the most frequent corneal isolates in cats with bacte-
rial keratitis. On the basis of in vitro susceptibility testing
of aerobic bacterial isolates and bactericidal mechanism of
Sphingobacterium

action, ofloxacin, ciprofloxacin, ticarcillin, gentamicin, or


100% (1/1) moxifloxacin are recommended for initial topical antimicro-
100% (1/1)
100% (1/1)
100% (1/1)

0% (0/1)
0% (0/1)
bial therapy of suspected bacterial keratitis in cats.17,18 While
chloramphenicol and doxycycline were effective in vitro,
n/a
n/a
n/a

n/a
they are not recommended as a first line of therapy due to
their bacteriostatic activity.17 These recommendations do not
Psychrobacter

Data presented as percentage susceptible (number of bacterial isolates susceptible/number of bacterial isolates tested). Not all isolates were tested against every antimicrobial.
replace culture and antimicrobial susceptibility determina-
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
tions when bacterial keratitis is suspected, but can help guide
therapeutic decisions while awaiting diagnostic test results or
n/a

in select cases where culture cannot be performed.


Any pathological process that disrupts normal corneal
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)

100% (1/1)

physiology, anatomy, or immunity can potentially lead to in-


Proteus

fection, resulting in clinical bacterial keratitis. The anatomical


T A B L E 4   Antimicrobials with the highest percentage of susceptibility for gram‐negative feline bacterial keratitis isolates

integrity of the cornea provides a physical barrier to bacte-


n/a
n/a
n/a

n/a
n/a

rial infection. The cornea is further susceptible to infections


when physiological protective mechanisms are lost, such as
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)

the physical and immunological properties of preocular tear


0% (0/1)
0% (0/1)
Pantoea

film and actions of the palpebrae.19 Additionally, resident


ocular floras interfere with the establishment of potentially
pathogenic organisms. The destruction of commensal flora
Escherichia

due to chronic antimicrobial or corticosteroid administration


100% (1/1)

100% (1/1)
100% (1/1)

100% (1/1)

100% (1/1)

may allow the overgrowth of pathogenic bacteria or fungi.20


The most common inciting cause of bacterial keratitis
n/a

n/a

n/a

n/a
n/a

in many animal species is speculated to be micro‐trauma of


the cornea resulting in defensive barrier breakdown or over-
Achromobacter

whelming of the ocular defense mechanisms.20 Other frequent


100% (1/1)
100% (1/1)
100% (1/1)
100% (1/1)

causes are tear film disturbances, disorders of the immune


0% (0/1)
0% (0/1)
0% (0/1)
0% (0/1)
0% (0/1)

system, and corneal surgical interventions.20 Some of the


potential predisposing conditions identified among the feline
n/a

study population in the present report that may have initiated


the bacterial keratitis include presumed feline herpesvirus‐1
Pseudomonas

corneal infection, corneal sequestrum, traumatic corneal lac-


100% (2/2)

100% (1/1)
100% (2/2)

100% (2/2)
100% (2/2)
50% (1/2)

erations, and corneal foreign bodies.21-24 These risk factors


may disrupt corneal anatomy, potentially leading to corneal
n/a
n/a
n/a

n/a

adhesion and invasion by opportunistic bacterial pathogens.


Following the breakdown of one or more defense mech-
100% (10/10)

100% (10/10)

100% (10/10)

anisms due to trauma, immunodeficiency, or other causes,


Pasteurella
100% (3/3)
100% (7/7)
100% (5/5)

100% (8/8)

100% (7/7)
100% (5/5)

100% (7/7)

the ocular surface is left susceptible to infection by, most


commonly, resident bacterial flora from the conjunctival or
skin surface.20 Previously, Staphylococcus epidermidis and
Staphylococcus aureus were demonstrated as the most com-
Chloramphenicol

mon isolated microorganisms in both healthy feline eyes and


Ciprofloxacin

eyes with conjunctivitis.25 In other studies, the most common


Doxycycline

Tobramycin
Gentamicin
Ticarcillin

Neomycin
Ofloxacin

Amikacin
Cefazolin

bacterial isolates from the ocular microflora of healthy eyes of


dogs and cats were Staphylococcus spp.8,19 In the current study,
Staphylococcus spp.was the most common species isolated
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6       GOLDREICH et al

from corneas of cats with bacterial keratitis. Previous research 2. Martin de Bustamante MG, Good KL, Leonard BC, et al. Medical
has demonstrated similar culture findings not only in cats, but management of deep ulcerative keratitis in cats: 13 cases. J Feline
across other domestic animal species. In multiple investiga- Med Surg. 2018. https​://doi.org/10.1177/10986​12X18​770514.
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tibility and minimal inhibitory concentration of Pseudomonas
lated organisms from bacterial ulcerative keratitis, followed by aeruginosa isolated from septic ocular surface disease in different
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in both cats and dogs with bacterial keratitis.26-28 in antibiotic resistance in equine bacterial ulcerative keratitis
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feline ulcerative keratitis in Taiwan, the most common gram‐ 5. Hindley KE, Groth AD, King M, Graham K, Billson FM. Bacterial
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gram‐negative microorganism. Ciprofloxacin, tobramy- factors for isolation of methicillin‐resistant Staphylococcus in dogs
cin, and gentamicin were reported to be the most effective with keratitis. Vet Ophthalmol. 2015;18(4):297‐303.
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