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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 1  |  Issue : 4  |  Page : 643-647

Role of topical high concentration levofloxacin 1.5% in bacterial keratitis


Dr. Shroff's Charity Eye Hospital, New Delhi, India

Date of Submission25-Dec-2020
Date of Acceptance10-May-2021
Date of Web Publication09-Oct-2021

Correspondence Address:
Dr. Gunjan Budhiraja
Dr. Shroff's Charity Eye Hospital, 5027, Kedarnath Ln, Daryaganj, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_3745_20

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  Abstract 


Bacterial keratitis is a common clinical condition that may lead to visual impairment if untreated. We report our clinical experience of treating bacterial keratitis with levofloxacin (LVFX) 1.5% ophthalmic solution in 10 patients. Eight patients with confirmed bacterial keratitis received monotherapy with LVFX 1.5% and two patients received an additional antibiotic. All patients demonstrated progressive improvement in keratitis and visual acuity over 1 to 2 weeks of treatment. There were no treatment-emergent adverse events. LVFX 1.5% solution is an effective and well-tolerated option for the treatment of bacterial keratitis.

Keywords: Bacterial keratitis, corneal ulcer, levofloxacin 1.5%, monotherapy


How to cite this article:
Budhiraja G, Acharya M, Kumar M. Role of topical high concentration levofloxacin 1.5% in bacterial keratitis. Indian J Ophthalmol Case Rep 2021;1:643-7

How to cite this URL:
Budhiraja G, Acharya M, Kumar M. Role of topical high concentration levofloxacin 1.5% in bacterial keratitis. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Oct 26];1:643-7. Available from: https://www.ijoreports.in/text.asp?2021/1/4/643/327635



Topical fluoroquinolones have been widely used for the treatment of ocular bacterial infections owing to their broad spectrum coverage, good ocular penetration, strong potency, and good safety.[1]

In India, higher concentration levofloxacin (LVFX) 1.5% is indicated for the treatment of bacterial ocular infections caused by susceptible organisms.[2] It exhibits potent activity against various common gram-positive, gram-negative, and anaerobic causative bacteria.[3] It has been demonstrated to have a higher maximum concentration (Cmax) and area under the curve compared with moxifloxacin 1.5% resulting in better bacterial eradication and clinical efficacy.[4] Furthermore, LVFX 1.5% attained the highest concentration in cornea and aqueous humor after topical instillation when compared with moxifloxacin 0.5%, gatifloxacin 0.3%, and besifloxacin 0.6%.[5] The concentration achieved was higher than the minimum inhibitory concentration of bacteria.[5] The list of organisms covered under the spectrum of LVFX and moxifloxacin is provided in [Table 1]. LVFX has been effective against Staphylococcus aureus Scientific Name Search  and Pseudomonas aeruginosa in rabbit keratitis irrespective of the antibacterial resistance.[6]
Table 1: Spectrum of coverage of topical moxifloxacin 0.5% and levofloxacin 1.5%

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In this case series, we report the clinical experience with LVFX 1.5% in 10 patients with bacterial keratitis at our center. There has been limited literature on the use of topical LVFX in India, and this is the first study reporting outcomes in bacterial keratitis in India.


  Case Report Top


[Table 2] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7] shows the demographic characteristics, symptoms, and microbiological profiles of the patients with bacterial keratitis. Eight patients [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7] received monotherapy with topical LVFX 1.5% (every 5 minutes for the first 30 minutes, followed by hourly instillation for 3 days, and then continued four times a day, and stopped after healing of keratitis). Two patients (Cases 9 and 10) received combination therapy for bacterial keratitis.
Table 2: Demographic characteristics, presenting features, and microbiological profiles

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Figure 1: Case 1 – (a) Day 1: Shows cornea of left eye with graft host junction well apposed, severe circumciliary congestion, and epithelial defect 4.0 × 4.0 mm and stromal edema with surface infiltrate 2.0 × 2.0 mm and hypopyon 2.0 mm. (b) Day 3: Shows cornea of left eye with decreased circumciliary congestion and healed surface infiltrate and no hypopyon. Macular scarring is appreciated 3.0 × 3.0 mm. (c) Day 10: Shows cornea of left eye with healed lesion and nebular scarring 2.0 × 2.0 mm with deep neovascularization

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Figure 2: Case 2 – (a) Day 1: Shows cornea of right eye with circumciliary congestion, graft infiltrate was noted at 2 O'clock to 3 O'clock, stromal edema, and hypopyon 1.5 mm. (b) Day 3: Shows cornea of right eye with decreased circumciliary congestion and healing surface infiltrate and Streak hypopyon and stromal edema. (c) Day 10: Shows cornea of right eye with healing surface infiltrate 0.5 × 0.5 mm and no hypopyon. Macular scarring noted

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Figure 3: Case 3 – (a) Day 1: Shows cornea of left eye with surface infiltrate 2.0 × 3.0 mm and surrounding edema. (b) Day 3: Left eye shows healing infiltrate 1.0 × 1.0 mm and macular scarring noted. (c) Day 10: Healed infiltrate with nebular scarring 1.0 × 2.0 mm

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Figure 4: Case 4 – (a) Day 1: Right eye cornea shows 1.0 × 1.0 mm with surrounding corneal edema. (b) Day 3: Cornea of right eye shows healed infiltrate, and nebulomacular scarring noted. (c) Day 10: Right eye shows nebular scarring

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Figure 5: Case 5 – (a) Day 1: Shows cornea of right eye of 4.0 × 4.0 mm surface infiltrate with corneal edema. (b) Day 3: Right eye cornea shows healing surface infiltrate and rounding of margins. (c) Day 10: Shows right eye cornea with nebular scarring of 3.5 × 3.5 mm

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Figure 6: Case 6 – (a) Day 1: Shows left eye cornea with surface infiltrate 7.0 × 3.0 mm with stromal edema. (b) Day 3: Left eye with healing surface infiltrate with decreased stromal edema. (c) Day 10: Shows left eye cornea with diffuse macular corneal scarring

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Figure 7: Case 7 – (a) Day 1: Cornea of left eye shows 6.0 × 6.0 mm with stromal edema and circumciliary congestion. (b) Day 3: Left eye cornea shows decreased surface infiltrate with healing response. (c) Day 10: Shows left eye cornea 5.0 × 5.0 mm macular corneal scarring with healed infiltrate

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Monotherapy with higher concentration LVFX 1.5%

With treatment, there was progressive improvement in bacterial keratitis (in terms of symptoms, reduction in healing surface infiltrate, hypopyon, stromal edema) and best-corrected visual acuity (BCVA) in eight cases [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7] and [Table 2].

Combination therapy with higher concentration LVFX 1.5%

In combination with other pharmacologic agents, treatment with LVFX resulted in remarkable improvement in bacterial keratitis (in terms of symptoms and healing keratitis) and BCVA [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]. Both patients were of the pediatric age-group [Table 3]. As available scientific literature on LVFX 1.5% monotherapy in the pediatric age-group is quite limited, we decided to treat these patients with combination therapy.
Table 3: Demographic characteristics, presenting features, and microbiological profiles of patient on combination therapy

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  Discussion Top


Recently it has been shown that the efficacy of antibiotics is closely associated with their pharmacokinetics on the basis of pharmacokinetic–pharmacodynamic theory.[3] From this point of view, high-concentration LVFX 1.5% is expected to exert potent anti-infective effect and inhibit the growth of drug-resistant bacteria.[3]

This property, combined with the broader antibacterial coverage, excellent ocular penetration, and good safety, makes LVFX 1.5% a good candidate for the treatment of bacterial keratitis.

The worrying trends of rising multidrug resistance are currently being observed across the world.[7] Multiple studies from India have shown similar findings, especially moxifloxacin and gatifloxacin resistance in common ocular pathogens.[8] Recently, we have published data on clinical–microbiological profiles and antibiotic sensitivity patterns in about 2,950 bacterial isolates seen in our practice.[9],[10] Following the global trends, we also observed low sensitivity of Staphylococcus spp., Streptococcus spp., and Pseudomonas aeruginosa toward commonly used ciprofloxacin, gatifloxacin, and moxifloxacin.

In our study, microbiological profiles of nine cases were identified as purely bacterial keratitis and one case was of secondary bacterial infection on viral keratitis. Based on the microbiological profiles and antibiotic sensitivity pattern data from our center, we used LVFX 1.5% in all these cases. Most of the identified bacterial keratitis cases treated at our center (besides these 10 cases) have shown improvement with topical LVFX 1.5%. None of the patients required any additional procedures, such as tissue adhesive or therapeutic penetrating keratoplasty.

LVFX is shown to be safe for ocular instillation with no known treatment-related adverse events.[3] As seen in the Phase III trial, LVFX 1.5% in bacterial conjunctivitis or bacterial keratitis, treatment-related adverse events were reported in 2.9% patients.[3] No corneal epithelial damage or inflammation were reported with LVFX 1.5%.[3] None of our patients complained of any such symptoms or signs or experienced any adverse events during the treatment.

The common protocol for the treatment of moderate to severe bacterial keratitis remains to be a combination therapy of fortified antibiotics against gram-negative and gram-positive bacteria. However, fortified formulations have major limitations such as contamination risk, difficulty in achieving the right concentration, surface toxicity, shorter shelf-life, and so on.[6]

In our opinion, topical LVFX 1.5% in loading and hourly dosing can be effective monotherapy for the treatment of bacterial keratitis. It has got certain advantages such as broader antibacterial coverage, excellent ocular penetration, strong potency, and good safety. The commercially available preformulated topical LVFX 1.5% preparation can be a good alternative to fortified antibiotics as well.

The limitations of our study include a small sample size and nonrandomization of the selected cases. Future long-term randomized trials with large sample sizes should be conducted to confirm the efficacy of LVFX 1.5% in all types of bacterial keratitis.


  Conclusion Top


Topical LVFX 1.5% can be an effective monotherapy for the treatment of bacterial keratitis. Future long-term randomised trials with larger samples should be conducted to confirm the efficacy of LVFX 1.5% in all types of bacterial keratitis.

Acknowledgement

We would like to give a special acknowledgement to Dr. Arpan Gandhi (Head of Microbiology and Laboratory services , Dr. Shroff's Charity eye hospital, Delhi for providing us with all the support for microbiological analysis and reporting of the samples sent for all the study patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
American Academy of Ophthalmology. Focal points- excerpts: Commonly Used OphthalmicAntibiotics2021. Available from: https://www.aao.org/focalpointssnippetdetail.aspx?id=f71ff617-5c78-4b28-8177-a7549fc766bc. [Last accessed on 2021 Mar].  Back to cited text no. 1
    
2.
Suzuki T, Tanaka H, Toriyama K, Okamoto S, Urabe K, Hashida M, et al. Prospective Clinical Evaluation of 1.5% Levofloxacin Ophthalmic Solution in Ophthalmic Perioperative Disinfection. Journal of Ocular Pharmacology and Therapeutics. 2013;29:887-92.  Back to cited text no. 2
    
3.
Ohashi Y, Inoue Y, Hatano H, Sotozono C. Phase III clinical trial of 1.5% levofloxacin ophthalmic solution (DE-108) in bacterial conjunctivitis and bacterial keratitis. Atarashii Ganka 2012;29:669-78.  Back to cited text no. 3
    
4.
Bucci FA Jr, Nguimfack IT, Fluet AT. Pharmacokinetics and aqueous humor penetration of levofloxacin 1.5% and moxifloxacin 0.5% in patients undergoing cataract surgery. Clin Ophthalmol 2016;10:783-9.  Back to cited text no. 4
    
5.
Chung JL, Lim EH, Song SW, Kim BY, Lee JH, Mah FS, et al. Comparative intraocular penetration of 4 fluoroquinolones after topical instillation. Cornea 2013;32:1046-51.  Back to cited text no. 5
    
6.
Kowalski RP, Romanowski EG, Mah FS, Shanks RM, Gordon YJ. Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models. Acta Ophthalmol 2010;88:e120-5.  Back to cited text no. 6
    
7.
Egrilmez S, Yildirim-Theveny Ş. Treatment-resistant bacterial keratitis: Challenges and solutions. Clin Ophthalmol 2020;14:287-97.  Back to cited text no. 7
    
8.
Oldenburg CE, Lalitha P, Srinivasan M, Rajaraman R, Ravindran M, Mascarenhas J, et al. Emerging moxifloxacin resistance in Pseudomonas aeruginosa keratitis isolates in South India. Ophthalmic Epidemiol 2013;20:155-8.  Back to cited text no. 8
    
9.
Acharya M, Farooqui JH, Singh A, Gandhi A, Mathur U. Bacterial isolates in microbial keratitis: Three-year trend analysis from North India. Indian J Ophthalmol 2019;67:1508-9.  Back to cited text no. 9
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10.
Acharya M, Farooqui JH, Gaba T, Gandhi A, Mathur U. Delhi infectious keratitis Study: Update on clinico-microbiological profile and outcomes of infectious keratitis. J Curr Ophthalmol 2020;32:249-55.  Back to cited text no. 10
  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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