Case report

Intravitreal colistin for multidrug resistant acute endophthalmitis following Descemet-stripping endothelial keratoplasty due toKlebsiella pneumoniae

Taneja, Mukesh MD; Senthil, Sirisha MD; Paulose, Remya MD; Joseph, Joveeta PhD; Sharma, Savitri MD; Dave, Vivek Pravin MD, DNB, FRCS*

Author Information
Journal of Cataract and Refractive Surgery Online Case Reports: August 2016 - Volume 4 - Issue 3 - p 52-56
doi: 10.1016/j.jcro.2016.05.002
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Abstract

Over the past decade, Descemet-stripping endothelial keratoplasty (DSEK) has become a popular alternative to penetrating keratoplasty (PKP) in corneal endothelial dysfunction. A comprehensive review of the safety and outcomes of DSEK by the American Academy of Ophthalmology1 stated that DSEK outcomes appear similar to those of PKP in graft clarity, visual acuity, surgical risks, complication rates, and endothelial cell loss.

Although uncommon, endophthalmitis is a dreaded complication of DSEK surgery.

Isolated cases of endophthalmitis associated with the surgery have been reported.2–4 Gram-negative bacteria are less commonly isolated than gram-positive bacteria in patients with acute-onset postoperative endophthalmitis. The emergence of multidrug resistant strains poses a definite challenge in the management of these infections. Occasionally, an extremely drug-resistant strain may be encountered and require the use of uncommon antibiotics for treatment. We report a case of multidrug-resistant Klebsiella pneumoniae endophthalmitis after DSEK surgery, resistant to all standard and commonly tested antibiotics, which was successfully treated with intravitreal colistin.

CASE REPORT

A 67-year-old man presented to our institute with decreased vision in the left eye of 2 months duration. At presentation, the corrected distance visual acuity (CDVA) was 20/20, J7 in the right eye and light perception present with accurate projection of rays in the left eye. Pseudophakic bullous keratopathy was diagnosed in the left eye, and uneventful DSEK was performed. Donor corneal tissue was provided by the in-house eye bank. The endothelial cell count of the donor tissue was 3378 cells/mm2. The donor cornea had been harvested 3 hours postmortem from a patient with a brain stem hemorrhage following a traffic accident. Donor tissue was stored in McCarey-Kaufman (M-K) medium for 51 hours before transplantation.

On postoperative day 1, the corrected distance visual acuity (CDVA) was light perception with high digital intraocular pressure (IOP). The donor lenticule was confirmed in situ by anterior segment optical coherence tomography and showed edema with cellular infiltration. B-scan ultrasonography showed multiple hyperechoic areas with attached retina consistent with endophthalmitis. Donor lenticule extraction with therapeutic PKP, vitreous biopsy, core vitrectomy, and intravitreal antibiotic (vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 mL) injection was performed.

Microbiological processing of the vitreous sample included direct microscopy and culture. Smears were stained with calcofluor white 0.1%, Gram, and Giemsa stains and examined. The media included for culture were sheep blood agar 5.0%, chocolate agar, thioglycolate broth, brain-heart infusion broth, Robertson cooked meat broth, Sabouraud dextrose agar, and potato dextrose agar. All media were incubated aerobically at 37°C except Sabouraud dextrose agar and potato dextrose agar, which were incubated at 27°C for 2 weeks. Chocolate agar was incubated in carbon dioxide 5.0% at 37°C. The morphology of the organism in direct microscopy and culture characteristics are shown in Figure 1. A vitreous biopsy specimen showed thick capsulated gram-negative coccobacilli in Gram stain. Intravitreal imipenem (50 μg/0.1 mL) and dexamethasone were given the following day, and intravenous colistin (300 mg/day) was started empirically in view of the florid clinical picture. Colistin 1.0% eyedrops were given hourly in addition to atropine 1.0% and timolol 0.5% eyedrops.

Figure 1.
Figure 1.:
A: Direct microscopy of the vitreous sample showing numerous capsulated gram-negative coccobacilli along with inflammatory cells (Gram stain; original magnification ×1000). B: Direct microscopy of the vitreous sample showing numerous capsulated coccobacilli along with inflammatory cells (Giemsa stain; original magnification ×1000). C: Confluent moist yellow colonies on blood agar after 2 days of incubation at 37°C. D: Confluent creamy-white moist colonies around the donor lenticule in chocolate agar after 2 days of incubation at 37°C.

Over the next 24 hours, media containing the donor lenticule, vitreous sample, and all M-K media (donor cornea, mate cornea, and the donor rim) showed growth of cream-colored moist colonies, which were gram-negative coccobacilli with lactose fermenting mucoid colonies on MacConkey agar. Vitek-2 Compact system (Biomérieux SA) was used for species identification, and the isolate was identified as K pneumoniae.

Clinical improvement was noted after 2 doses of intravitreal colistin (0.1 mg/0.1 mL) and dexamethasone (0.4 mg/0.1 mL) 3 days apart, and the CDVA improved to 20/252 with a clear corneal graft, quiet anterior chamber, and hazy view of the fundus. B-scan at the same visit showed reduced echogenicity in the vitreous cavity (Figure 2, A).

Figure 2.
Figure 2.:
A: B-scan ultrasound showing minimal echogenicity in the vitreous cavity suggestive of decreasing vitritis. B: B-scan ultrasound showing increased echogenicity in the vitreous cavity suggestive of increased vitritis.

In the following month, 2 episodes of recurrent vitritis occurred and were managed with repeated vitreous lavage, intravitreal colistin, and topical steroids. After the second recurrence, persistently high IOPs (>40 mm Hg) were noted despite the maximum tolerated medical therapy (possible steroid response) and trabeculectomy with mitomycin-C was performed. The elevated IOP persisted over the following month, and the trabeculectomy was deemed a failure. Implantation of an Ahmed glaucoma valve was planned. On the day of surgery, recurrence of the infection with hypopyon, anterior chamber reaction, and vitritis was noticed with an increase in echogenicity on the B-scan (Figure 2, B). Anterior chamber tap, posterior chamber intraocular lens (PC IOL) explantation, and intraocular colistin with dexamethasone injection were performed. Both anterior chamber fluid and the PC IOL in chocolate agar showed similar colonies of K pneumoniae, indicating chronic persistence of infection.

One month after the trabeculectomy, IOL implantation with a total capsulectomy was performed. Following the procedure, the vitritis resolved and the media cleared; the CDVA improved to 20/632. The retina was attached, with visualization beyond the second-order vessels; the IOP was 30 mm Hg on maximum glaucoma medications (Figure 3). Two weeks after the procedure, recurrent vitritis was noted. Eendoscopic pars plana vitrectomy was performed with silicone oil injection with intravitreal colistin and dexamethasone injection. Endoscopy-guided removal of thick exudative membranes from the vitreous cavity and those on the ciliary body and posterior aspect of iris was completed. After 2 weeks, transscleral cyclophotocoagulation was performed for IOP control.

Figure 3.
Figure 3.:
Fundus photograph showing hazy media with attached retina, pale optic disc, and attenuated vasculature visible.

Two weeks after cyclophotocoagulation, the final CDVA was 20/200 and the IOP was 14 mm Hg with no antiglaucoma medications. The fundus appeared as a pale glaucomatous disc with attached retina with silicone oil reflex (Figure 4).

Figure 4.
Figure 4.:
Fundus photograph at the final follow-up visit showing attached retina, pale optic disc, and silicone oil–filled globe.

DISCUSSION

We report a multidrug-resistant postsurgical acute endophthalmitis caused by K pneumoniae. The organism was resistant to all commonly used antibiotics (amikacin, ceftazidime, cefuroxime, chloramphenicol, ciprofloxacin, ofloxacin, gatifloxacin, gentamicin, imipenem, moxifloxacin) and was sensitive to only colistin. The antibiotic susceptibility testing (Table 1) was determined by the Kirby-Bauer disk diffusion method per the Clinical and Laboratory Standards Institute guidelines.5 The vitreous sample was also positive for bacterial DNA on 16S rDNA-based eubacterial polymerase chain reaction.6

Table 1
Table 1:
Antibiotic sensitivity of Klebsiella pneumonia isolated from vitreous sample, host corneal button, and donor lenticule.

Klebsiella pneumoniae is a highly virulent gram-negative bacterium that causes devastating endophthalmitis7 Although most cases of endophthalmitis due to K pneumoniae are endogenous, the organism is also a rare cause of postoperative endophthalmitis.7–9 Gram-negative organisms are less common causative organisms in acute-onset post-cataract surgery endophthalmitis, but reports suggest that gram-negative organisms have been isolated in 26% to 42% of patients with cataract surgery–related endophthalmitis in developing countries,10,11 which is higher than the percentages in developed countries.12

Although the use of antibiotics in storage media has substantially reduced the donor contamination rate, donor contamination poses a risk for endophthalmitis and graft infection in the recipient. Positive donor rim culture substantially increases the risk for endophthalmitis.13 The risk for endophthalmitis also increases with an increase in preservation time of the corneal buttons14 and harvesting the graft from donors with systemic illness.15

Multidrug resistance is defined as acquired nonsusceptibility to at least 1 agent across 3 or more antimicrobial categories.16,17Klebsiella pneumoniae is known to develop multidrug resistance due to the presence of capsular K1/K2 serotypes, hypermucoviscosity, and the presence of the magA gene and the blaNDM-1 gene, which is a carbapenemase β-lactamase.18,19

Colistin is a polymyxin antibiotic that was used extensively in the mid-20th century but was later phased out because of reports of nephrotoxicity following parenteral administration.20,21 In the past few years, there has been renewed interest in its use due to activity against a variety of gram-negative organisms, including those resistant to other common antimicrobials in vitro.22 The use of colistin in ocular infections has been reported rarely.23–27 Three of the reports are about topical use in multidrug resistant Pseudomonas.24–26 Only 1 report describes the use intravitreal colistin to treat multidrug resistant Pseudomonas endophthalmitis.27 Since colistin belongs to the polymyxin group of a drug, the recommended molar equivalent dose of these intravitreal drugs was used. To date, there is no reference in animal models and no known minimal inhibitory concentration for intravitreal use of colistin. The normal adult dose of colistin 2 million units was dissolved in 10 to 50 mL of sterile water for injections to form a clear solution. The solution is for single use only; any remaining solution should be discarded. The intravitreal dose was 0.1 mg/0.1 mL (1000 IU/0.1 mL).

In conclusion, our case represents a rare scenario of a multidrug-resistant K pneumoniae endophthalmitis that was treated with a drug of historic usage. Because no available pharmacodynamic and pharmacokinetic literature on colistin in an intravitreal setting is available, the dosing at present is empirical. Our case and similar cases point toward a need for animal studies to determine a suitable nontoxic and effective dosage for intravitreal colistin.

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