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ARTICLES
Year : 1982  |  Volume : 30  |  Issue : 4  |  Page : 195-200

Bioestimation of carbenicillin and gentamycin after their intravitreal injection and evaluation of their toxic effect on ocular tissuses


Ravinder Nath Tagore Medical College, Udaipur, India

Correspondence Address:
M R Jain
Ravinder Nath Tagore Medical College, Udaipur
India
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Source of Support: None, Conflict of Interest: None


PMID: 7166389

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How to cite this article:
Jain M R, Hussain S. Bioestimation of carbenicillin and gentamycin after their intravitreal injection and evaluation of their toxic effect on ocular tissuses. Indian J Ophthalmol 1982;30:195-200

How to cite this URL:
Jain M R, Hussain S. Bioestimation of carbenicillin and gentamycin after their intravitreal injection and evaluation of their toxic effect on ocular tissuses. Indian J Ophthalmol [serial online] 1982 [cited 2020 Aug 11];30:195-200. Available from: http://www.ijo.in/text.asp?1982/30/4/195/29427

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The refractory nature of vitreous infection is a consequence to low and inconsistent levels of antimicrobial drugs attainable in the vitreous after systemic and topical therapy.

Several studies indicate that while many anti­biotics including carbenicillin, and gentamicin reach effective levels in the aqueous after sub­conjunctival injections[1],[2],[3],[4],[5] but the penetra­tion into the posterior segment is inadequate with oral, parenteral, subconjunctival and even retrobulbar routes for almost all the drugs[6],[7],[8]

Rich and Craw ford, Daily et a1[9], Peyman et a1[10], Richard et a1[11] and Schenk et al[12] were the few pioneer workers to use intravitreal in­jection of various antibiotics to demonstrate their clearance in the vitreous, effect on ocular pathogens and untoward effect on ocular structures.

Gentamicin sulphate and carbenicillin are water soluble drugs and have wide antibacterial specturm. Their effect on pseudomonas aerugenosa is of great significance since endo­phthalmitis due to this organism is refractory to treatment and frequently leads to complete blindness.

The study has been conducted with multi­ple following aims.

1. To estimate the concentration of genta­micin and carbenicillin in vitreous at various time intervals after single intravitreal injection.

2. To assess any pathological changes caused by these drugs given individually and combined in known therapeutic and double the therapeutic doses.

3. To evaluate the effect of both antibio­tics when injected separately and combined.


  MATERIAL & METHODS Top


The study was conducted in 51 albino rab­bits each weighing 2 to 3 Kg and having vitreouses ranging from 1.2 to 1.4 cc. The rabbits were divided into three groups.

Group I (Carbenicillin group) Consisted of 21 rabbits. Left eye of each rabbit served as control and was injected with 1 cc of normal saline solution intravitreally. In the right eye, 5 mg of carbenicillin dissolved in 0.1 ml of distilled water was injected intravitreally. These rabbits were divided into 10 subgroups depending upon the dose to sample interval which was ' 1, 2, 4, 8, 12, 24 hrs, 3 and 7 days. Each subgroup contained two rabbits except 10th subgroup which contained 4 rab­bits. In this subgroup, double dose of car­benicillin (10 mg) was injected in right eye & drug concentration estimated on 3rd & 7th day. Left eye served as control.

Group II (Gentamicin group) Consisted of 22 rabbits. As in group I, it was divided into ten subgroups and same procedure was follow­ed as in group I. Gentamicin sulphate dose used was 0.2 mg (200 ug) in nine subgroups & in 10th, 400 ug was injected. Group III (Combined group) consisted of 7 rabbits. In both eyes of each rabbit, a combination of gentamicin sulphate 0.2 mg & 5 mg of carbe­nicillin dissolved in 0.1 ml of sterile water and freshly mixed was injected intravitreally and the drug availability tested at time intervals of a, 1, 2, 4, 8, 12 and 24 hours.

For the purposes of sampling of vitreous and histopathological study, all eyes were enu­cleated and following procedure carried out. The vitreous was dissected out from the eye and was emulsified to estimate drug concentra­tion on the same day. Both antibiotics were assayed by Modified disc diffusion method[13] utilizing difco antibiotic media No. 5 and sus­pension of spores of B. subtilis N C I M 2063 .

For histopathological study, the tissue was fixed in Bouin's fixative, and then paraffin blocks prepared. The slides were stained with hematoxylin & eosin.


  Observations and discussions Top


In rabbit eyes single intravitreal injection of Carbenicillin 5 mg or gentamicin sulphate 0.2 mg provide maximum mean concentra­tion of 990± 10 ug/ml & 59 ± 1.0 ug/ml res­pectively in the first sample removed 15 minu­tes after the injection. Upto 24 hours. carbenicillin - & gentamicin concentration recorded are 90± 10 ug/ ml & 1 1.5±0.5ug/ml respectively. Even with double the doses, samples collected at 72 hours interval were free of drug, suggesting that adequate anti­biotic concentration is available for more than 24 hours but less than 72 hours. Bactericidal concentration of both antibiotics is available against all common ocular pathogens for at least 12 hours and against most of them for 24 hours or more. In rabbit eyes, 5 mg of carbenicillin or 0.2 mg 'of gentamicin or its combination in these doses is not toxic to ocular tissues. When doses are doubled, the toxicity noted were posterior lenticular opacity, vitreous haze, disorganisation of nuclear layer & finally disorganisation of all the layers of retina.

Rabbit vitreous is 1.2 to 1.4 cc whereas human vitreous is about 3.9 cc ie about 3 times

and hence 1.0 mg of carbenicillin & 400 ug of gentamicin may be considered perfectly safe in human eyes.

Where gentamycin is the primary drug of choice carbenicillin can be used simultaneously to enhance marginally the activity of gentamicin. But when carbenicillin is the primary drug of choice, gentamicin should not be used simultaneously as it adversly affect the activity of carbenicillin.


  Summary Top


Experimental study in 51 albino rabbits was conducted by injecting intravitreal injections of carbenicillin add gentamicin sulphate. Drug concentration in the vitreous of the rabbits were estimated at various time intervals. Also double the therapeutic doses were injected and macroscopic and microscopic untoward effect on ocular tissues noted.

 
  References Top

1.
Boyle G.L. and Arlone. E, 1972, Amer. J. Oph­thalmol. 73:754.  Back to cited text no. 1
    
2.
Rich A.M. and Crawford J.R., 1972, Invest, Ophthalmol. 26: 350.  Back to cited text no. 2
    
3.
Jain M.R. and Bansal V.D., 1979, All India Ophthalmological Conference at Amritsar.  Back to cited text no. 3
    
4.
Jain M.R. and Modi R., 1980, All India Ophthal­mological conference at Manipal.  Back to cited text no. 4
    
5.
Jain M.R. and Singhal, M., 1980, All India Ophthalmological conference at Manipal.  Back to cited text no. 5
    
6.
Furgiuele, F.D., 1970, Amer. J. Ophthalmol. 69:481.  Back to cited text no. 6
    
7.
Golden, B, and Coppel, P., 1970, Arch, Ophthalmol. 84:792.  Back to cited text no. 7
    
8.
Barza, M., Baum, J., 1973, Amer. J. Ophthal­mol. 75:307  Back to cited text no. 8
    
9.
Daily M.J., Peyman G.A. and Fishman G 1973 Amer. J. Ophthalmol. 76:343  Back to cited text no. 9
    
10.
Peyman G.A; May D.R. et al 1975. Arch Oph­thalmol. 92:42  Back to cited text no. 10
    
11.
Richard, K.F, 1976, Amer. J. Ophthalmol. 81:52.  Back to cited text no. 11
    
12.
Schenk. A.G. Peyman G.A. and Pague. J.J. 1974, Acta Ophthalmol, 57:707.  Back to cited text no. 12
    
13.
Grove, I.C. and Randall, W.A., 1955, Assay methods of antibiotics : laboratory manual Medical Encyclopaedia Inc. U.S.A. P. 34.  Back to cited text no. 13
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4]



 

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