PG CORNER

Year : 2018  |  Volume : 30  |  Issue : 2  |  Page : 152-154

Preparation of fortified antimicrobial eye drops

Hilda K Nixon
Department of Ophthalmology, Little Flower Hospital and Research Centre, Ernakulam, Kerala, India

Correspondence Address:
Hilda K Nixon
M T Joseph Meleppuram, Meleppuram House, Potta P.O, Chalakudy, Thrissur - 680 722, Kerala
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/kjo.kjo_63_18

Fortification means to intensify or strengthen the medication, to achieve adequate drug concentration. Fortified antimicrobials are not commercially available, thus should be, prepared of optimal constitution in a sterile pharmaceutical dispensary. This article provides guidelines on topical fortified therapy dosage concentration and methodology of preparation of drugs for patients with infectious keratitis. Acquaintance on fortified antimicrobial medication, its appropriate usage and timely intervention will help us to treat most of the resistant microbial keratitis and prevent the need for surgical intervention.

Keywords: Fortified medication, microbial keratitis, topical therapy

Fortified Antimicrobial Eyedrops

The Need for Fortification of Antibiotics

• For resistant microbial keratitis, to attain appropriate drug concentration and to stop the fulminant rapid progression of keratitis
• For moderate-to-severe corneal ulcers
• For pediatric patients as ocular surface bacterial infections affect with a high frequency in newborns and children ^[3]
• For drugs that are available only in parenteral form. For example - vancomycin and amphotericin B.

• High cost
• Contamination risk
• Since it is a preservative-free preparation, they have short shelf-life
• Need for refrigeration.

[Table 1]">  List of Fortified Drugs [Table 1]

Table 1: Drugs and their coverage[1],[9] Click here to view

1. Fortified tobramycin: 14 mg/ml (1.4%)
2. Fortified gentamicin eyedrops: 14 mg/ml (1.4%)
3. Fortified amikacin eyedrops: 40 mg/ml

1. Fortified cefazolin eyedrops: 50 mg/ml (5%)
2. Fortified ceftazidime eyedrops: 50 mg/ml (5%)
3. Topical vancomycin eyedrops: 50 mg/ml (5%)
4. Topical linezolid 2 mg/ml (0.2%)
5. Topical colistin (0.19%)
6. Topical imipenem–cilastatin eyedrops (1%).

• Topical amphotericin B (0.15%)
• Topical voriconazole eyedrops (1%).

• Selection of fortified antimicrobials must be adapted to the type of bacteria suspected for safe and effective treatment
• Fortified drops should be prepared by a doctor or a pharmacist inside a laminar air hood/operation room under aseptic precautions
• Disposable syringe should be used
• Date of preparation and date of expiry should be mentioned in prepared drops
• Frequency of application with storage instructions should be explained to the patient
• Short shelf-life (preservative free)
• Since there is a risk for contamination and also it is preservative free, it should be refrigerated and can be kept up to 7 days at 4°C
• Shake well before instillation.

• Method: Take 2 ml from an injectable vial of intravenous (IV) tobramycin or gentamicin (40 mg/ml). Add the injected 2 ml to a 5-ml bottle of commercially available tobramycin or gentamycin eyedrops (0.3%)^[1],[5]
• Shelf-life: Refrigerate and shake well before instillation.

• Method: IV formulation can be used (80 mg/2 cc ampules)^[1],[5]
• Shelf-life: Refrigerate and shake well before instillation.

• Method: Add 9.2 ml of artificial tears to a vial of cefazolin 1 g (powder for injection) and dissolve. Take 5 ml of this solution and add it to 5 ml of artificial tears ^[1],[5]
• Shelf-life: Refrigerate and shake well before instillation.

• Method: To a 500 mg vial of vancomycin:^[1],[5]



1. Add 33 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears to produce a solution of 15 mg/ml.
2. Add 20 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears to produce a solution of 25 mg/ml.
3. Add 10 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears to produce a solution of 50 mg/ml.



• Storage: Refrigerate and shake well before instillation.

• Indication: Multiple drug-resistant Pseudomonas aeruginosa bacterial keratitis
• Method: It is prepared from parenteral colistimethate sodium powder (Xylistin) 1 million IU/75 mg and added to 10 ml of distilled water to obtain 7.5 mg/ml (0.75%). 1 ml of the above solution is then added to 3 ml of distilled water to obtain 0.19% colistin drops.^[7]

• Method: To parenteral imipenem (500 mg)–cilastatin (500 mg), add 10 ml sterile water to create a solution of strength 50 mg/ml. Take 1 ml of this solution and add 4 ml of sterile water to make topical imipenem 1% to obtain 1 mg/ml ^[7]
• Storage: In amber-colored bottles.

• Method: Add 10 ml of distilled or sterile water to parenteral 50 mg of amphotericin B powder for injection. Draw 3 ml of this and add to 7 ml of artificial tear eyedrops ^[1],[5]
• Shelf-life: Refrigerate and shake well before instillation
• Storage: should not be exposed to light. The drops should be inspected at each visit for any turbidity, which may indicate contamination or drug precipitation.

• Method: Voriconazole powder (200 mg) was reconstituted with 19 ml of water for injections in order to obtain 20ml of a 10-mg/ml voriconazole solution: Voriconazole eyedrops (1%)^[8]
• Storage: Refrigerate at 4°C and shake well before instillation
• Others: Trimethoprim/sulfamethoxazole
• 16 mg/ml / 80 mg/ml commercial preparation can be used.^[1],[6]

Drawbacks of Fortified Preparations

Conclusion

References

1.	Gokhale NS. Medical management approach to infectious keratitis. Indian J Ophthalmol 2008;56:215-20.   [PUBMED]  [Full text]
2.	Chiquet C, Romanet JP. Prescribing fortified eye drops. J Fr Ophtalmol. 2007;30:423-30.
3.	Bremond-Gignac D, Chiambaretta F, Milazzo S. A European perspective on topical ophthalmic antibiotics: Current and evolving options. Ophthalmol Eye Dis 2011;3:29-43.
4.	Tas T, Kucukbayrak A, Hakyemez IN, Mengeloglu FZ, Simavli H, Ozyalvacli G, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus keratitis in rabbits. Cornea 2013;32:1052-7.
5.	Available from: https://www.aao.org/preferred-practice-pattern/bacterial-keratitis-ppp--2013. [Last accessed on 2018 Jul 20].
6.	Tas T, Kucukbayrak A, Hakyemez IN, Mengeloglu FZ, Simavli H, Ozyalvacli G, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus keratitis in rabbits. Cornea 2013;32:1052-7.
7.	Jain R, Murthy SI, Motukupally S. Clinical outcomes of corneal graft infections caused by Multi-drug resistant Pseudomonas aeruginosa keratitis. Cornea 2014;33: 22-26.
8.	Dupuis A, Tournier N, Le Moal G, and Venisse N. Preparation and Stability of Voriconazole Eye Drop Solution. Antimicrobial Agents and Chemotherapy, 2008;53: pp.798-9.
9.	Jay H. Krachmer, Mark J Mannis, Edward J Holland. Cornea. Vol 1. 3rd ed. St Louis, United States: Elsevier - Health Sciences Division; 2010. Chapter 77: Bacterial keratitis. [Table 77].4; p.934.

This article has been cited by 1 Development of antibiotic resistance in the ocular Pseudomonas aeruginosa clone ST308 over twenty years Mahjabeen Khan,Mark D.P. Willcox,Scott A. Rice,Savitri Sharma,Fiona Stapleton Experimental Eye Research. 2021; : 108504 [Pubmed] | [DOI] 2 Antimicrobial Nitric Oxide Releasing Contact Lens Gels for the Treatment of Microbial Keratitis Jenny Aveyard,Robert C. Deller,Rebecca Lace,Rachel L. Williams,Stephen B. Kaye,Keli N. Kolegraff,Judith M. Curran,Raechelle A. D’Sa ACS Applied Materials & Interfaces. 2019; [Pubmed] | [DOI]