<div>Table 1. Susceptibility profile of the <i>Pseudomona</i><i>aeroginosa</i> isolated from the corneal lesion.</div><div>To achieve a therapeutic level in the corneal stroma, piperacillin 1.5
mg/mL/tazobactam 12 mg/mL was administered every hour for three days,
then every awaken hour for three days, followed by 4 times a day for one
month. Regression of hypopyon and ciliary injection occurred, as well as
corneal ulcer re-epithelization, which were documented during the
following month (Figure 2).</div><div>The patient was finally discharged from the hospital after one month.
Her vision was light perception in the LE and slit-lamp examination
revealed diffuse, non-transparent corneal opacity, scarring, and
marginal ulcers.</div><div>Six months after (December 7, 2021) a triple procedure was performed,
i.e., combined cataract extraction and intraocular lens (IOL)
implantation with penetrating keratoplasty (Figure 3A). Before the
surgery, the IOL was calculated for the RE. Trepan 8.5 mm was used for
the donor cornea, and trepan 8.0 mm for the recipient cornea. After
dissection of the recipient cornea, a connective inflammatory membrane
was observed in the anterior chamber, in conjunction with the iris
(Figure 3B). After inspection, the fibrotic tissue and part of the iris
were removed (Figure 3C). The next step was an open-sky extracapsular
cataract extraction while maintaining the capsular bag and posterior
capsule intact. An IOL was implanted in the bag and, after successful
implantation, the donor cornea was sutured with 16 interrupted sutures
of 10-0 Nylon. Suturing was the most challenging part of the procedure,
owing to the change in thickness of the scared recipient cornea. After
the operation, topical dexamethasone/levofloxacin (1 mg/mL / 5 mg/mL)
was administered 6 times daily and gradually tapered until the end of
the first postoperative month, along with cyclopentolate twice a day.
Dexamethasone eye drops were administered twice daily until the sutures
were removed.</div><div>THE OUTCOME</div><div>More than 24 months after the penetrating keratoplasty and suture
removal, the BCVA with myopic shift was 20/150 and the intraocular
pressure was 8 mmHg. Slit-lamp examination revealed no signs of active
inflammation. A thin sclera was observed around the limbus, along with
transparent donor corneal tissue with clear margins, a deep anterior
chamber with an irregular mydriatic pupil, and an IOL located in the
capsular bag (Figure 4). Fundoscopy revealed no pathological changes in
the optic disc or macula. However, notable destruction of the vitreous
body was observed. The affected eye presented a considerable myopic
shift, with an axial length almost 5 mm longer (32.09 mm) than in the RE
(27.29 mm); the myopic shift and axial length extension occurred after
infectious keratitis.</div><div>DISCUSSION</div><div>This case report highlights that extended contact lens use allows the
adhesion of <i>P. aeruginosa</i>  to their surface and subsequently to
the cornea. <i>P. aeruginosa</i>  possesses specific virulence factors,
including pili, glycocalyx, and exotoxins, which allow for adherence and
invasion of the cornea (Dart &amp; Seal 1988). Additionally, <i>P.</i><i>aeruginosa</i> has developed resistance mechanisms, such as a
protective outer membrane of lipopolysaccharides, tendency to colonize
in biofilm form, and presence of antibiotic-resistant plasmids (Shrestha
et al. 2021). These attributes allow bacteria to be virulent, highly
destructive, and to develop multidrug resistance (Hilliam, Kaye &amp;
Winstanley 2020).</div><div>This clinical case reminds us that bacterial keratitis associated with
contact lenses is a sight-threatening condition, requiring immediate and
appropriate treatment to improve outcomes. (Austin, Lietman &amp;
Rose-Nussbaumer 2017). Pseudomonas is the leading gram-negative in
bacterial keratitis, and one of the most common agents of bacterial
keratitis overall. In a meta-analysis, the prevalence of <i>P.
aeruginosa</i>  isolates in bacterial keratitis ranged from 6.8–55%
(Teweldemedhin et al. 2017). Pseudomonas keratitis is strongly
associated with the use of contact lenses. In one study, the incidence
of Pseudomonas keratitis was 2.76 cases per 10000 individuals per year,
yet rose to 13.04 cases per 10000 individuals when only contact lens
wearers were considered; in the same study, 55% of Pseudomonas
keratitis cases were associated with contact lens use (Jeng 2010).</div><div>Recalcitrant keratitis caused by <i>P. aeruginosa</i>  is a serious and
potentially blinding condition. The aggressive nature of the organism
coupled with its evolving multidrug resistance is an important cause of
ocular morbidity (Chan et al. 2021). This case report illustrates the
importance of the initial treatment in bacterial keratitis. The reported
patient received dexamethasone and chloramphenicol as initial treatment,
which was one of the main factors leading to advanced stromal necrosis
and corneal scarring. <i>P. aeruginosa</i>  is usually intrinsically
resistant to chloramphenicol, and the addition of corticosteroids as an
initial treatment for infectious keratitis impairs the body’s ability to
fight the infection, which may prove catastrophic if an appropriate
antibiotic is not administered, as in this case (Morita et al.
2001)(Aberdein &amp; Singer 2006). Broad-spectrum topical antibiotics are
the first-line empirical treatment in such cases of unknown etiology.
Topical corticosteroids can be considered and cautiously introduced
24–48 hours after initiation of topical antibiotics if the causative
organism is identified or if a demonstrated response to topical
antibiotics is observed (Ray et al. 2014). The main goal of
corticosteroids is to reduce the morbidity associated with uncontrolled
inflammation and decrease permanent corneal scarring (Al-Shehri,
Jastaneiah &amp; Wagoner 2009). In contrast, the adjunctive therapeutic
results of corticosteroids for infectious keratitis reported in
different studies are controversial (Sy et al. 2012).</div><div>Pseudomonas keratitis is treated with intensive topical antibiotic
therapy with fluoroquinolones or fortified gram-negative targeted
antibiotics, including aminoglycosides (e.g., tobramycin),
cephalosporins (e.g., ceftazidime), and synthetic penicillins (e.g.,
carbenicillin). The microbiological response is usually rapid, with
stabilization of the growth of stromal infiltrates and halt of further
stromal necrosis and thinning within 24–48 hours (Al-Shehri, Jastaneiah
&amp; Wagoner 2009).</div><div>Few studies have reported recalcitrant multidrug-resistant Pseudomonas
keratitis that responded to alternative antibiotic choices, such as
piperacillin/tazobactam (Chew et al. 2010), colistin (Chatterjee &amp;
Agrawal 2016), meropenem (Chatterjee &amp; Agrawal 2016), and imipenem
(Fernandes et al. 2016).</div><div>Chew et al. (Chew et al. 2010) described three cases that did not
respond to various antimicrobials, except piperacillin/tazobactam, with
no adverse side effects noted; each case showed good resolution after a
month of instillation with a slow taper. These three cases also
presented pan-sensitivity on antibiotic sensitivity testing, yet showed
significant clinical drug resistance, which was similar to our
experience in the current case. Such disparity could be due to the
degree of corneal drug penetration, increasing use of fluoroquinolones
with an associated increase in resistance, and different minimum
inhibitory concentrations of antibiotics in the cornea (Chew et al.
2010). The treatment of Pseudomonas keratitis is becoming increasingly
challenging owing to the evolving drug resistance of this pathogen.</div><div>Although progression to endophthalmitis is rare, Pseudomonas is commonly
cited as the causative pathogen of microbial keratitis leading to
endophthalmitis, resulting in evisceration or enucleation (Stevenson et
al. 2020). Despite the destructive nature and rapid course of the
described keratitis with late but appropriate treatment, progression
ceased. The patient underwent a penetrating keratoplasty with IOL
implantation to prevent corneal blindness. Vazirani et al. described 23
cases of multidrug-resistant <i>P. aeruginosa</i> in a retrospective
case-control study, in which 12 eyes were complicated by corneal
perforation and 11 required keratoplasty. The incidence of corneal
perforation and keratoplasty need was significantly higher than that in
the control group of drug-sensitive <i>P. aeruginosa</i> keratitis
(Vazirani, Wurity &amp; Ali 2015). The evidence in the literature and the
case described in this report conclude that multidrug-resistant
Pseudomonas keratitis is extremely difficult to treat, and accompany a
high risk of requiring surgical intervention to restore vision and avoid
blindness.</div><div>The triple procedure was the only option for the patient to regain
eyesight; however, significant corneal opacity developed, including
scarring in the anterior chamber as well as changes in the lens due to
inflammation. The advantages of the triple procedure were the following:
the possibility of performing lens extraction at the time of surgery
would allow preservation of endothelial cells of the donor’s cornea from
phacoemulsification in the future; and significant visual improvement
was possible immediately after a single-step surgical intervention under
general anesthesia with fewer follow-ups. However, the potential risks
of the triple procedure should be considered like vitreous loss, IOL
decentration or dislocation intraoperatively, as well as secondary
glaucoma and graft rejection postoperatively. (Al-Mohaimeed 2013).</div><div>Unfortunately, lens extraction and IOL implantation as separate
procedures before penetrating keratoplasty were not possible in this
case because of significant corneal opacity. The only feasible approach
would be to perform penetrating keratoplasty followed by lens extraction
and IOL implantation in other surgical interventions, putting the
endothelial cells at risk. However, in this case, keratometry data would
be available for IOL calculation.</div><div>Predicting the value of the IOL in a triple procedure is challenging.
Unacceptable refractive errors can significantly affect the patient and
surgeon satisfaction. For the precise calculation of IOL biometric data,
the corneal curvature, anterior chamber depth, and axial length are
relevant. However, these parameters can change significantly
postoperatively. The BCVA of our patient after surgery was 20/150. The
patient presented a significant increase in axial length comparing to
the opposite eye. This could be explained by scleral degenerative
changes due to inflammation and surgically-induced changes in axial
length. Previous studies have reported a BCVA of &gt;20/40 in
at least 38% of all cases after the triple procedure (Javadi, Feizi &amp;
Moein 2013). Although the macula and optic disc were unaltered, the
current patient presented a significant myopic shift (-20.0 D),
surgery-induced astigmatism, destructive changes in the vitreous, and an
iris defect that could affect the visual potential. According to the
literature, 26–68% of eyes achieved ±2 D of target refraction after
the triple procedure (Javadi, Feizi &amp; Moein 2013). Our data reflected
worse refractive outcomes even though the triple procedure was performed
successfully. Refractive error correction with spectacles achieved a
BCVA of solely 20/150. The patient refused contact lenses, including
scleral contact lenses, which could have provided better BCVA.</div><div>In ophthalmic surgery, the main factors that reflects patient
satisfaction with treatment are visual outcomes and eyeball preservation
in complicated cases. However, aesthetic reasons, such as the appearance
of the eye, played a main role in the patient’s satisfaction in this
case report, in addition to the low visual acuity after surgery.</div><div>CONCLUSION</div><div>Pseudomonous keratitis remains one of the most important potential
complications of contact lens use. With this in mind, early diagnosis
and treatment are key to minimizing the visually threatening sequelae.
Moreover, close follow-up, attention to laboratory data, and changing
antibiotics in case of no evident clinical improvement are important
factors for a successful outcome. The evidence in the literature and the
case described in this report indicate that multidrug-resistant
Pseudomonas keratitis is exceptionally difficult to treat, and a high
risk exists of requiring surgical intervention to restore vision and
avoid blindness.</div><div>PATIENT CONSENT STATEMENT:</div><div>The authors certify that they have obtained all appropriate patient
consent forms. In the form the patient has/have given his/her consent
for his/her images and other clinical information to be reported in the
journal. The patients understand that their names and initials will not
be published and due efforts will be made to conceal their identity.</div><div>AUTHOR CONTRIBUTIONS:</div><div>Ēriks Elksnis: Literature review, data collection</div><div>Eva Elksne: Literature review, data collection</div><div>Olita Lūse: Literature review, data collection</div><div>Juris Vanags: Final manuscript revision</div><div>Guna Laganovska: Final manuscript approval</div><div>ACKNOWLEDGEMENTS:</div><div>No acknowledgments.</div><div>REFERENCES</div><div>Aberdein J &amp; Singer M (2006): Clinical review: a systematic review of
corticosteroid use in infections. Crit Care <b>10</b> : 203.</div><div>Al-Mohaimeed MM (2013): Graft survival and visual outcome after
simultaneous penetrating keratoplasty and cataract extraction. Int J
Ophthalmol <b>6</b> : 385–389.</div><div>Al-Shehri A, Jastaneiah S &amp; Wagoner MD (2009): Changing trends in the
clinical course and outcome of bacterial keratitis at King Khaled Eye
Specialist Hospital. Int Ophthalmol <b>29</b> : 143–152.</div><div>Austin A, Lietman T &amp; Rose-Nussbaumer J (2017): Update on the
management of infectious keratitis. Ophthalmology <b>124</b> :
1678–1689.</div><div>Chan A, Oo HH, Stanley P &amp; Chang B (2021): Recalcitrant Pseudomonas
aeruginosa keratitis with hyphaema. Case Rep Ophthalmol <b>12</b> :
214–218.</div><div>Chatterjee S &amp; Agrawal D (2016): Multi-drug resistant Pseudomonas
aeruginosa keratitis and its effective treatment with topical
colistimethate. Indian J Ophthalmol <b>64</b> : 153–157.</div><div>Chew FLM, Soong TK, Shin HC, Samsudin A &amp; Visvaraja S (2010): Topical
piperacillin/tazobactam for recalcitrant Pseudomonas aeruginosa
keratitis. J Ocul Pharmacol Ther <b>26</b> : 219–222.</div><div>Dart JK &amp; Seal DV (1988): Pathogenesis and therapy of Pseudomonas
aeruginosa keratitis. Eye (Lond) <b>2 Suppl</b> : S46–S55.</div><div>Fernandes M, Vira D, Medikonda R &amp; Kumar N (2016): Extensively and
pan-drug resistant Pseudomonas aeruginosa keratitis: clinical features,
risk factors, and outcome. Graefes Arch Clin Exp Ophthalmol<b>254</b> : 315–322.</div><div>Hilliam Y, Kaye S &amp; Winstanley C (2020): Pseudomonas aeruginosa and
microbial keratitis. J Med Microbiol <b>69</b> : 3–13.</div><div>Javadi MA, Feizi S &amp; Moein HR (2013): Simultaneous penetrating
keratoplasty and cataract surgery. J Ophthalmic Vis Res <b>8</b> :
39–46.</div><div>Jeng BH, Gritz DC, Kumar AB, et al. (2010): Epidemiology of ulcerative
keratitis in northern California. Arch Ophthalmol <b>128</b> :
1022–1028.</div><div>Morita Y, Kimura N, Mima T, Mizushima T &amp; Tsuchiya T (2001): Roles of
MexXY- and MexAB-multidrug efflux pumps in intrinsic multidrug
resistance of Pseudomonas aeruginosa PAO1. J Gen Appl Microbiol<b>47</b> : 27–32.</div><div>Ray KJ, Srinivasan M, Mascarenhas J, et al. (2014): Early addition of
topical corticosteroids in the treatment of bacterial keratitis. JAMA
Ophthalmol <b>132</b> : 737–741.</div><div>Reynolds D &amp; Kollef M (2021): The epidemiology and pathogenesis and
treatment of Pseudomonas aeruginosa infections: An update. Drugs<b>81</b> : 2117–2131.</div><div>Shrestha GS, Vijay AK, Stapleton F, Henriquez FL &amp; Carnt N (2021):
Understanding clinical and immunological features associated with
Pseudomonas and Staphylococcus keratitis. Contact Lens Anterior Eye<b>44</b> : 3–13.</div><div>Stevenson LJ, Dawkins RCH, Sheorey H, McGuinness MB, Hurley AH &amp; Allen
PJ (2020): Gram-negative endophthalmitis: A prospective study examining
the microbiology, clinical associations and visual outcomes following
infection. Clin Exp Ophthalmol <b>48</b> : 813–820.</div><div>Sy A, Srinivasan M, Mascarenhas J, et al. (2012): Pseudomonas aeruginosa
keratitis: Outcomes and response to corticosteroid treatment. Investig
Opthalmology Vis Sci <b>53</b> : 267–272.</div><div>Teweldemedhin M, Gebreyesus H, Atsbaha AH, Asgedom SW &amp; Saravanan M
(2017): Bacterial profile of ocular infections: a systematic review. BMC
Ophthalmol <b>17</b> : 212.</div><div>Ting DSJ, Ho CS, Deshmukh R, Said DG &amp; Dua HS (2021): Infectious
keratitis: an update on epidemiology, causative microorganisms, risk
factors, and antimicrobial resistance. Eye <b>35</b> : 1084–1101.</div><div>Vazirani J, Wurity S &amp; Ali MH (2015): Multidrug-resistant Pseudomonas
aeruginosa keratitis: Risk factors, clinical characteristics, and
outcomes. Ophthalmology <b>122</b> : 2110–2114.</div><div>FIGURE LEGENDS</div><div>Figure 1. (A) Ring-like stromal infiltrate, “soupy” in appearance due
to stromal necrosis, with hypopyon present in the anterior chamber. (B)
Spreading of stromal infiltration 360 ° around the limbus with corneal
edema and increase of hypopyon 12 hours after hospitalization. (C)
Stromal necrosis of the nasal limbus.</div><div>Figure 2. The dynamics of the corneal reepithelization during one month
of hospitalization after starting treatment with
piperacillin/tazobactam.</div><div>Figure 3. (A) Corneal scar with neovascularization and scleral thinning
6 months after acute keratitis. (B) Connective inflammatory membrane,
probably remnants of the anterior chamber abscess, in conjunction with
the iris. (C) Occluded pupil with iatrogenic damage after removal of the
connective tissue.</div><div>Figure 4. More than 24 months after keratitis onset, the patient
presented a transparent donor cornea, a thin, translucent sclera in the
upper hemisphere, an IOL in the bag, and a clear red fundus reflex.</div>