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Early Presentation of Fluoroquinolone-Resistant Pseudomonas Keratitis
Kim-Anh N. Jow, OD
Pseudomonas aeruginosa is the most common and virulent pathogen associated with contact lens
wear. This case presents an early manifestation of fluoroquinolone-resistant Pseudomonas
keratitis that was promptly and aggressively treated with no visual sequelae.
1. Case History
A 20 year old black female presented with a red, painful left eye that had begun the prior
morning after sleeping in her soft contact lenses. The patient also reported photophobia, white
discharge, tearing, and swollen tender lids. She had been wearing FreshLook ColorBlends® and
denied sleeping in her contact lenses except for the night of the incident. She reported using
Opti-Free® solution and rubbed her lenses occasionally. After inserting her contact lenses in the
morning, the patient normally left the solution in the case all day, then rinsed it with warm water
immediately before putting her contact lenses and new solution into the case. Her current pair of
contact lenses was two weeks old, and she discontinued wear and disposed of her lenses and case
immediately after the onset of the red eye.
In addition, the patient reported that she had been caring for a child with a red eye at a
children’s camp the day before the onset of her red eye. Also, one week before her red eye, the
patient had accompanied her friend to the emergency room on three consecutive days for
assessment and management of severe flu-like symptoms. The friend was finally diagnosed with
mononucleosis.
The patient’s ocular history was unremarkable. She used a prednisone inhaler as needed for
asthma as well as Nuvaring® contraceptive. She denied any drug allergies, and her family
history was unremarkable.
2.
Pertinent Findings
The patient’s uncorrected visual acuities were 20/40 in the right eye and 20/200 in the left
eye. With pinhole, her acuities improved to 20/20- in the right eye and 20/30- in the left. The
left pupil showed decreased direct and consensual responses when compared to the right, but no
afferent pupillary defect was found. Confrontation fields and extra-ocular motilities were
normal. The lids of the left eye were mildly chemotic and were painful upon palpation. There
were no palpable preauricular nodes.
Anterior segment evaluation revealed normal findings in her right eye. However, her left
eye had 3+ diffuse conjunctival injection, 2+ stromal edema, and an inferior-temporal,
midperipheral cluster of three stromal infiltrates, ranging from 0.5mm to 1.0 mm in size. No
ulceration was present, but there was superficial punctuate staining overlying the infiltrative area.
The left anterior chamber had eight to ten plastic cells per high power field and 3+ flare. Using
non-contact tonometry, her intraocular pressures were measured to be 19 mmHg in the right eye
and 20 mmHg in the left. Internal ocular health was unremarkable in both eyes. Corneal
scrapings were obtained from the left eye to be sent for laboratory identification and
susceptibility analysis.
3. Differential Diagnosis
Due to the history of poor contact lens care and extended wear, Pseudomonas keratitis
was the leading differential diagnosis. However, Acanthamoeba and Fusarium or other fungi are
other pathogens associated with contact lens wear and must be ruled out. In light of the patient’s
recent history of hospital visits with her friend, methicillin-resistant Staphylococcus aureus
(MRSA) and Epstein-Barr viral stromal keratitis were also considered.
4. Diagnosis and discussion
Five days after the initial presentation, a preliminary microbial report of the corneal
scrapings indicated possible Pseudomonas aeruginosa, which was confirmed two days later.
Susceptibility testing indicated that the organism was sensitive to ceftazidime, amikacin,
gentamicin, tobramycin, imipenem, and piperacillin/tazobactam. However, the microbe was
resistant to ciprofloxacin, levofloxacin, cefepime, and ticarcillin/clavulanate.
Without the laboratory identification, this case would have been difficult to diagnose as
the presenting signs of stromal infiltrate, corneal edema, lid edema, conjunctival injection, and
anterior chamber reaction are nonspecific and may indicate any pathogen, including bacteria,
fungus, or Acanthamoeba. The patient’s symptoms of decreased vision, pain, redness, and
photophobia are also very general. However, the report of mucopurulent discharge would likely
indicate a bacterial infection. Also, the severe anterior chamber reaction was out of proportion to
the small, peripheral corneal lesion, leading us to believe that this was a very potent infection.
Pseudomonas aeruginosa is the most common and virulent pathogen associated with
contact lens wear. While it cannot penetrate an intact cornea, microtrauma from contact lens
wear allows microbes such as Pseudomonas to invade the damaged cornea.1 Pseudomonas
causes corneal damage by releasing multiple cytotoxins that destroy the epithelium, which
allows it to advance into the stroma. It also has a surface glycocalyx which protects it from the
host’s immune response.2 While it is difficult to identify in its early stages, eye care providers
can often recognize a Pseudomonas keratitis after it has progressed to a large suppurative stromal
infiltrate.3 However, one must not delay in treating a Pseudomonas keratitis as it can perforate
the cornea within three days.4
5. Treatment, management
The patient was initially treated with vancomycin and ceftazidime drops, which were
alternated every thirty minutes. Scopolamine was also instilled in office. After one day, the
patient reported a noticeable improvement in symptoms. However, the corneal lesion had
ulcerated, and the three sub-epithelial infiltrates had coalesced into one lesion. The anterior
chamber reaction was slightly improved. An ophthalmologist was then consulted, who
recommended adding levofloxacin (Iquix) drops every hour to the regimen. At the second and
third daily follow-ups, the stromal infiltrates were stable, although the ulceration, anterior
chamber reaction, and other clinical signs were gradually improving. However, the patient did
report the onset of general malaise. The patient was referred to a corneal specialist, who
discontinued the vancomycin and ceftazidime. He also reduced the levofloxacin dosing interval
from every hour to every six hours and added prednisolone acetate 1% (Pred Forte) to be used
four times a day as well. The keratitis was resolved within two weeks, and only a small,
peripheral corneal scar remains.
While it may appear that the patient’s condition improved only after the addition of
levofloxacin, the sensitivity reports indicated that the organism was in fact resistant to this drug.
After one day of treatment, there was a vast improvement in symptoms and a decrease in the
anterior chamber response, which leads us to believe that the initial treatment was effective for
the Pseudomonas keratitis. It is not uncommon for severe corneal infections to progress for a
short while after initiating appropriate treatment, for while the medication may eliminate the
organism, it cannot prevent the outcome of cytotoxic cascades which have already been initiated.
Upon initial presentation, bacterial keratitis is often treated empirically with topical
broad-spectrum antibiotics. Cycloplegic drops can also be used for comfort. If the ulcer is small
and peripheral and has a mild anterior chamber reaction, it is often sufficient to treat without
obtaining a corneal scraping. However, if the ulcer is large, central, or accompanied by a marked
anterior chamber reaction, microbiological identification is recommended along with aggressive
treatment with fluoroquinolones or fortified antibiotics.5,6 The treatment can be modified after
results from laboratory identification and susceptibility reports are received.
As gram-negative bacteria, most Pseudomonas aeruginosa strains are susceptible to
aminoglycosides, cephalosporins, and fluoroquinolones.7-9 Levofloxacin, gatifloxacin, and
moxifloxacin have been found to be less effective for gram-negative bacteria than
ciprofloxacin.10 However, ciprofloxacin-resistant strains of Pseudomonas have been reported in
India, Taiwan, and the United States.11
6. Conclusion
Because of their minimal toxicity, broad-spectrum activity, and ready availability,
fluoroquinolones are often the initial choice in empirically treating suspected bacterial keratitis.12
In general, a small, peripheral, non-ulcerated, infiltrative keratitis would be expected to respond
well to such management. In this case however, a significant anterior chamber reaction and
diffuse stromal edema prompted the decision to obtain a scraping and initiate aggressive
treatment.
The importance of a thorough case history in guiding the decision to obtain a specimen
for culture cannot be overstated. This patient had multiple risk factors for virulent infection,
including: suboptimal contact lens hygiene, overnight contact lens wear, significant nosocomial
exposure, and close contact with an individual suffering from infectious mononucleosis. All of
these factors were taken into account in determining a list of differential diagnoses and
appropriate treatment.
Corneal scrapings allowed for identification and susceptibility testing. This case of
multi-drug resistant Pseudomonas aeruginosa exemplifies the public health problem widely
reported in the literature.13 We are, in our daily practice, obligated to consider the emerging
resistance to commonly prescribed broad-spectrum antibacterial drugs.
Bibliography
1. Li Y, Zeldovich A, Chua BJ, Rowe NJ, Martin FJ, McClellan KA. Hazardous contact: A
case of visual loss following Pseudomonas keratitis from novelty contact lens
wear. Med J Aust 2006 Aug 7;185(3):173-4.
2. McLeod SD. “Infectious Keratitis.” Yanoff M and Duker JS, eds. Ophthalmology. St.
Louis, MO: Mosby, Inc, 2004: 469.
3. Dahlgren MA, Lingappan A, Wilhelmus KR. The clinical diagnosis of microbial
keratitis. Am J Ophthalmol 2007 Jun; 143(6):940-944.
4. Cronin, B. The red eye in contact lens wearers: A high risk presentation. Aust Fam
Physicia 2007 Oct; 36(10):831-832.
5. “Bacterial Keratitis.” Kunimoto DY, Kanitkar KS, Makar MS, eds. The Wills Eye
Manual. Philadelphia, PA: Lippincott Williams & Wilkins, 2004: 55.
6. Holdeman, N. “Bacterial Keratitis.” Onofrey B, Skorin L, Holdeman N, eds. Ocular
Therapeutics Handbook. Philadelphia, PA: Lippincott Williams & Wilkins,
2005: 178-184.
7. Smitha S, Lalitha P, Prajna VN, Srinivasan M. Susceptibility trends of Pseudomonas
species from corneal ulcers. Indian J Med Microbiol 2005; 23(3):168-171.
8. Daniell M. Overview: Initial antimicrobial therapy for microbial keratitis. Br. J.
Ophthalmol 2003; 87:1172-1174.
9. Robinson A, Kremer I, Avisar R, Gaton D, Savir H, Yassur Y. The combination of
topical ceftazidime and aminoglycosides in the treatment of refractory
pseudomonal keratitis. Graefes Arch Clin Exp Ophthalmol 1999 Mar;237(3):17780
10. Duggirala A, Joseph J, Sharma S, Nutheti R, Garg P, Das T. Activity of newer
fluoroquinolones against gram-positive and gram-negative bacteria isolated from
ocular infections: An in vitro comparison. Indian J Ophthalmol 2007; 55:15-19.
11. Lomholt JA, Kilian M. Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates
from keratitis. Br J Ophthalmol 2003; 87:1238-1240.
12. McLeod SD. Integrating Iquix, Vigamox, and Zymar in the Management of Ocular
Infectious Disease. Int Ophthalmol Clin. 2006 Fall;46(4):41-5.
13. Garg P, Sharma S, Rao G. Ciprofloxacin-resistant Pseudomonas keratitis.
Ophthalmology 1999; 106:1319-23.