Fortified Antibiotics

-Dr.Prathibha.M.Chachadi

for·ti·fy  (fôrt-f) v. for·ti·fied, for·ti·fy·ing, for·ti·fies v.tr. To make strong, as: a. To strengthen and secure (a position) with fortifications. b. To reinforce by adding material

Most of the available ophthalmic antibiotics are in the concentration of 0.3% which is not sufficient to attain minimum inhibitory concentration for organisms, especially the resistant , non healing ulcers. For moderate to severe corneal ulcers intensive antibiotic treatment is needed, which reinforces the need for fortified antibiotics to halt the progression of ulcer and promote healing

Is started in the initial empirical treatment as conventional method ( vs monotherapy with quinolones) Once culture reports are available for specific organisms- pseudomonas; staphylococci; candida; pneumococcus-streptococcus Conventionally active corneal ulcer needs intensive treatment where the drops are applied topically- 1 hourly for 24-48 hrs( stabilised); 2hrly- during day & 4 hrly in night till healing ; 4-6 hrly.

BACTERIA TYPE (GRAM STAIN)

DRUG OF CHOICE (FORTIFIED)

ALTERNATIVE DRUGS (FORTIFIED/ NON -FORTIFIED)

GRAM POSITIVECOCCI

Cefazolin- 50mg/ml 0r 100mg/ml

Vancomycin -25mg/ml Bacitracin- 10000 u/ml Ciprofloxacin Ofloxacin Levofloxacin

GRAM POSITIVE BACILLI Penicillin G-100000 u/ml Tobramycin -14mg/ml

Vancomycin 25-50mg/ml Bacitracin -10000 u/ml Gentamicin -14mg/ml

GRAM NEGATIVE COCCI Ceftriaxone-50mg/ml or 100mg/ml

Ofloxacin Levofloxacin Ciprofloxacin

GRAM NEGATIVE BACILLI

Gentamicin -14mg/ml Polymyxin B-50000 u/ml Ciprofloxacin Ofloxacin Levofloxacin

Tobramycin -14mg/ml Amikacin -10mg/ml Ticarcillin -6mg/ml

NO ORGANISM SEEN BUT BACTERIA SUSPECTED

Cefazolin- 50mg/ml or 100mg/ml + Tobramycin -14mg/ml

Gentamicin14mg/ml(OR) Amikacin-10mg/ml + Vancomycin -25mg/ml (OR) Bacitracin 10000 u/ml

ORGANISM

TOPICAL

SUBCONJUNCTIVAL

PSEUDOMONAS

Tobramycin -14mg /ml(OR) Amikacin 10mg/ml / a quinolone

Tobramycin -40mg Amikacin -25mg Ticarcillin -100mg

STAPHYLOCOCCUS

Cefazolin -50mg/ml Vancomycin – 25-50 mg/ml Bacitracin 10000 u/ml

Cefazolin 100mg Oxacillin 100mg Vancomycin 25mg

PROTEUS ENTEROBACTER E.COLI KLEBSIELLA ACINETOBACTER

Tobramycin -14mg/ml Gentamicin -14mg/ml Amikacin -10mg/ml Ceftriaxone -50mg/ml

Tobramycin -40mg Amikacin – 25mg Carbenicillin -100mg

1.AMIKACIN- (atypical mycobacteria; post lasik infectious keratitis)( poor corneal penetration) topical

100 mg/ml +9ml tears 10mg/ml subconjunctival 100mg/ml +1ml tears 50mg/ml Shelf life 30 Days

2. BACITRACIN – TOPICAL

bacitracin

6ml(10ml) of tear drops 3ml 3ml 1 vial of bacitracin

1 vial of

(50000 u) (50000 u) 6ml(10ml) of tear drops (1ml- 10000u) SUBCONJUNCTIVAL 0.5ml (5000u) SHELF LIFE 7 Days(4 deg)

3.CEFAZOLIN -(non penicillinase gram+) ( topical

1g/10ml +2ml tears(100mg/ml+2ml) 33mg/ml Also 500mg +10ml; 50mg/ml Also 1g/7.5ml 133mg/ml Subconjunctival 100mg/ml Shelf life 10 Days ( yellow ; discard)

GENTAMICIN topical

80mg/2ml +3.6ml of tears 14mg/ml Subconjunctival 40mg/ml Shelf life 30 Days

Penicillin G topical u/ml Subconjunctival Shelf life

1 vial- 5 million u +5ml of tears5ml+2.5 ml333333u/ml 1 million u/ml 7 Days

1 million

TOBRAMYCIN – topical - 80mg/2ml + 0.3 % tobramycin e/d(5ml) - 13.6mg/ml Subconjunctival - 40mg Shelf life - 30 days

VANCOMYCIN – Topical Subconjunctival Shelf life

- 500mg/10ml + 5ml of tears – 25mg/ml – 25mg – 14 days

Amphotericin Btopical – 50mg+10ml- 5mg/ml(STOCK SOLUTION) 1.5 ml of stock solution+ 3.5 ml of tears- 0.15% Refrigerate; not exposed to light ; look for turbidity, precipitation, contamination

Original Article British Journal of Ophthalmology. 84(4):378-384, April 1, 2000. Gangopadhyay, Nibaran; Daniell, Mark; Weih, LeAnn; Taylor, Hugh R Abstract: AIM: To compare the clinical efficacy of commercially available fluoroquinolone drops with the use of combined fortified antibiotics (tobramycin 1.3%-cefazolin 5%) in treatment of bacterial corneal ulcer CONCLUSIONS: Monotherapy with fluoroquinolone eye drops for the treatment of bacterial corneal ulcers led to shorter duration of intensive therapy and shorter hospital stay compared with combined fortified therapy (tobramycin-cefazolin). This finding may have resulted from quicker clinical response of healing as a result of less toxicity found in the patients treated with fluoroquinolone. However, as some serious complications were encountered more commonly in the fluoroquinolone group, caution should be exercised in using fluoroquinolones in large, deep ulcers in the elderly.

Effect of Fortified Antibiotic Solutions on Corneal Epithelial Wound Healing. Basic Investigation Cornea. 19(2):204-206, March 2000. Lin, Chang-Ping M.D.; Boehnke, Matthias M.D. Abstract: Purpose. To evaluate the influence of fortified antibiotic eyedrops on corneal epithelial wound healing Methods. We developed an in vitro epithelial wound-healing model to evaluate the toxicity of antibiotics. An excimer laser was used to create an epithelial defect 1.5 mm in diameter, 70 [mu]m in depth on the central area of porcine cornea. The intact animal globes were maintained in the incubator by a perfusion system. Fortified antibiotics: 10% piperacillin, 5% cefazolin, 0.5% chloramphenicol, 5% vancomycin, 1% amikacin, 2% gentamicin, and 0.1% amphotericin B were applied to the wound in three applications. The wounds were evaluated 24 h after setup with fluorescein stain and a scoring system. Results. The 0.1% amphotericin B and 2% gentamicin disturbed the corneal epithelial healing rate significantly. The remaining antibiotics did not interfere with the epithelial healing rate in our study design. Conclusion. Fortified antibiotic eyedrops demonstrated ealvaried degrees of influence on corn epithelial wound healing. When antibiotic eyedrops are used, both the efficacy and toxicity of the antibiotics should be the major concern. If efficacy is equivalent, lesstoxic agents should be given preference.

IJO ORIGINAL ARTICLE Year : 2007  |  Volume : 55  |  Issue : 1  |  Page : 15-19 Activity of newer fluoroquinolones against gram-positive and gram-negative bacteria isolated from ocular infections: An in vitro comparison Background: To determine the antibacterial activity of newer fluoroquinolones and compare their activity between ciprofloxacin-susceptible and resistant bacterial isolates from patients with keratitis and endophthalmitis Conclusions: Levofloxacin, gatifloxacin and moxifloxacin are statistically more effective against gram-positive bacteria, the latter two being equally effective. Ciprofloxacin remains the most effective fluoroquinolone against gram-negative bacteria.

PARSON’S TEXT BOOK OF OPHTHALMOLOGY INDIAN JOURNAL OF OPHTHALMOLOGY CURRENT OPHTHALMOLOGY Year : 1994  |  Volume : 42  |  Issue : 4  |  Page : 171192   Current perspectives in infectious keratitis Agrawal Vinay1, Biswas Jyotirmay2, Madhavan HN2, Mangat Gurmeet3, Reddy Madhukar K4, Saini Jagjit S3, Sharma Savitri4, Srinivasan M5

  SYMPOSIUM Year : 2008  |  Volume : 56  |  Issue : 3  |  Page : 215-220   Medical management approach to infectious keratitis Gokhale Nikhil S  Gokhale Eye Hospital and Eyebank, Anant Building, Gokhale Road (S), Dadar West, Mumbai-400 028, India