Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2008
Student: SEDAT ARIKAN
Supervisor: ŞENGÜL ÖZDEK
Abstract:Fungal endophthalmitis is a rare clinical condition that can potentially cause severe visual loss, and it is easily misdiagnosed unless detailed ocular examination have been done by ophthalmologists. The successful treatment rate of fungal endophthalmitis is closely associated with early diagnose of the disorder and administration of the appropriate antifungal therapy. After the exploration of amphotericin B, fungal endophthalmitis has been treated successfully as good as the other fungal infections. Amphotericin B ise the most effective antifungal drug among all of them. However, since amphotericin B poses great risk of severe ocular and systemic toxicity, its usage is limited frequently. Fluoroquinolones are the broad spectrum antibiotics prefered for bacterial ocular enfections as well as prophylaxis for intraocular surgery. Its action of mechnanism mainly depends on their inhibitory effects on bacterial DNA gyrase (topoisomerase II) enzyme. Shen and Fostel suggested pathogenic fungus such as Candida albicans ve Aspergillus niger has a significant amount of DNA topoisomerase II, and therefore fluoroquinolones may be used as a new antifungal drug by inhibiting the DNA topoisomerase II. In the literature there are few investigation that reports the effectiveness of quinolone antibiotics in modulating the effects of antifungal drugs. However, direct antifungal effects and vitreous and aqueous penetration of this kind of antibiotics have not been evaluated adequetly. In this study 32 New Zealend rabbits weighing between 2 and 3 kg were randomized into four groups. The right eye of each animal was infected by inoculation of 105 CFU (colony-forming units) per 0.1 milliliters of C.albicans into the vitreous cavity. Approximately, 5th day after inoculation of microorganism into the vitreous cavity, the presence of clinical signs of endophthalmitis were determined and the infected eyes were then randomly assigned to one of the four groups equally, and the first group (intravitreal moxifloxacin group) were treated intravitreally with a single dose of 160 μg moxifloxacin per 0.1 milliliters, second group (combined intravitreal and oral moxifloxacin group) were treated both with a single dose of intravitreal 160 μg moxifloxacin per 0.1 milliliters and orally by using 7 mg/kg/day for four days, third group (oral moxifloxacin group) was treated with orally administered 7mg/kg/day moxifloxacin for four days, and the last group (control group) was not subjected to any treatment process because it was used as a control group. At the begining (first day of the treatment process) and at the end of the of the study (fourth day of the treatment process), aqueous and vitreous aspirates of 0.1 ml were collected from each of these infected (right eye) and non-infected (left eye) eye to measure the concentration of moxifloxacin after orally and intravitreally administration. Also, vitreous aspirates of 0.1 ml were collected from each of these eyes and plated on Saboraud Dextrose Agar (SDA) to assay the quantity of microorganism before begining to treatment with moxifloxacin. At the end of the of the study (fourth day of the treatment process), vitreous aspirates of 0.1 ml from each infected eyes were obtained and plated on Saboraud Dextrose Agar (SDA) to compere the quantity of microorganism with the others that were detected before the treatment. At the begining of the treatment, the mean colony counts obtained from infected vitreous aspirates of group 1,2,3, and 4 were 64.3 ± 8.2 (55-80), 63.1 ± 20.8 (40-95), 73.7 ± 19.2 (50- 100) and 76.2 ± 14.3 (50-90) respectively. When we compared these results between the groups, we did not find any statistically significant difference (Kruskal-Wallis test, p=0.2). At the end of the treatment, the mean colony counts obtained from infected vitreous aspirates of group 1,2,3, and 4 were 43.7 ± 8.7 (30-60), 35.6 ± 26.6 (10-80), 78.1 ± 16.4 (60-110) and 90 ± 16 (65-110) repectively. When we compared these results between the groups, the number of microorganism counted from group 1 and group 2 were statistically lower than group 3 and group 4 (Mann-Whitney U test, p=0.001 and p=0.04 respectively), however there was not any statistically significant difference between group 3 and group 4 (Mann-Whitney U test, p=0.100), and between group 1 and group 2 (Mann-Whitney U test, p=0.6). When we compared the differences of drug levels in the aqueus and vitreous humour of infected eyes between the fourth and first day of the treatments, we found that there were a significant differences between the three groups). In the intravitreal group (Group 1) mean moxifloxacin levels determined in the aqueous and vitreous humour were tend to decrease, however in the orally administered group (Group 3) these drug levels were tend to increase. There was also a decline in the drug levels that is avaliable in the aqueous and vitreous humour of Group 2, but this decrement was not as significant as Group 3. In an unpublished study from Clinical Microbiology Department of Gazi University Medical School, they reported that the MIC90 value of moxifloxacin for the same species of C.albicans as used in our study was 100μg/ml. In the current study after injecting 160 μg/0.1ml dose of moxifloxacin intravitreally, we could have a moxifloxacin level which is approximately 1.5 times of MIC90 value for C.albicans. This drug level achieved in the infected vitreous was in insuffecient to eradicate all fungal microorganisms since MIC90 value for C.albicans is too much as 100μg/ml, but it possibly contributed to reduce fungal burden as it caused to decline in the quantity of fungal microorganisms from the pretreatment state to the posttreatment state. At the end of the fourth day the moxifloxacin level of mean aqueous humour of group 2 and Group 3 were 0.58 μg/0.1ml and 0.34 μg/0.1ml respectively, and vitreous level of moxifloxacin of Group 2 and Group 3 were determined as 0.50 μg/0.1ml and 0.26 μg/0.1ml. These drug concentration values achieved in the intraocular fluids supports that by the oral administration of moxifloxacin, it is possible to achieve suffecient penetration into the aqueous and vitreous humour against most of the microorganism related with bacterial endophthalmitis. In conclusion, neither intravitreally, nor orally administered moxifloxacin can achieve suffecient drug penetration into the aqueous and vitreous humour of eyes suffered from endophthalmitis due to C.albicans because of its high MIC90 value. However, both of this drug administration route may allows to achieve effective moxifloxacin concentration in the aqueous and vitreous humour of the most of the microorganisms that is related to postoperatif, posttraumatic and bleb-associated endophthalmitis.