Penetration of moxifloxacin into the human aqueous humour after oral administration

Aims: To determine the pharmacokinetics of moxifloxacin, a new generation fluoroquinolone, in the anterior chamber of the human uninflamed eye. Methods: 35 patients undergoing cataract surgery received two doses of 400 mg of oral moxifloxacin with a 12 hour interval and were divided into six groups. Moxifloxacin levels in aqueous humour and serum were determined by a microbiological agar well diffusion technique at 2, 4, 6, 8, 10, and 12 hours after the second dose in each group respectively. Results: Mean moxifloxacin levels in the anterior chamber were 1.20 (SD 0.35) μg/ml at the 2 hours group, 1.22 (0.48) μg/ml at the 4 hours group, 1.20 (0.45) μg/ml at the 6 hours group, 1.58 (0.38) μg/ml at the 8 hours group, 1.37 (0.44) μg/ml at the 10 hours group, and 1.23 (0.55) μg/ml at the 12 hours group. The mean ratio of aqueous to serum moxifloxacin level was 38%. Conclusion: Moxifloxacin penetrates well into the anterior chamber of the human uninflamed eye after oral administration, reaching early significant levels, which are maintained for at least 12 hours and are much higher than the MIC(90) values of Gram positive and Gram negative pathogens commonly implicated in intraocular infections with the exceptions of fluoroquinolone resistant staphylococci, MRSA, and Pseudomonas aeruginosa

Penetration of moxifloxacin into the human aqueous humour after oral administration

Aims: To determine the pharmacokinetics of moxifloxacin, a new generation fluoroquinolone, in the anterior chamber of the human uninflamed eye. Methods: 35 patients undergoing cataract surgery received two doses of 400 mg of oral moxifloxacin with a 12 hour interval and were divided into six groups. Moxifloxacin levels in aqueous humour and serum were determined by a microbiological agar well diffusion technique at 2, 4, 6, 8, 10, and 12 hours after the second dose in each group respectively. Results: Mean moxifloxacin levels in the anterior chamber were 1.20 (SD 0.35) mg/ml at the 2 hours group, 1.22 (0.48) mg/ml at the 4 hours group, 1.20 (0.45) mg/ml at the 6 hours group, 1.58 (0.38) mg/ml at the 8 hours group, 1.37 (0.44) mg/ml at the 10 hours group, and 1.23 (0.55) mg/ml at the 12 hours group. The mean ratio of aqueous to serum moxifloxacin level was 38%. Conclusion: Moxifloxacin penetrates well into the anterior chamber of the human uninflamed eye after oral administration, reaching early significant levels, which are maintained for at least 12 hours and are much higher than the MIC90 values of Gram positive and Gram negative pathogens commonly implicated in intraocular infections with the exceptions of fluoroquinolone resistant staphylococci, MRSA, and Pseudomonas aeruginosa

Vancomycin levels in human aqueous humour after intravenous and subconjunctival administration

The purpose of the present study was to evaluate the level of vancomycin in human aqueous humour after intravenous (i.v.) and subconjunctival administration. One hundred patients scheduled to undergo cataract extraction participated in the study. Fifty-three of them received 20 mg vancomycin subconjunctivally and 47 received two doses of vancomycin i.v. (1 g b.i.d.). Specimens of aqueous humour From the first group were collected 1, 2, 2.5, 3, 3.5, 5, 6, 7, and 8 h after the subconjunctival injection. In the second group, specimens of blood and aqueous humour were collected 1, 2, 4, 6, 8, 10, and 12 h after the end of infusion of the second dose of the antibiotic. The levels of vancomycin were determined by fluorescent polarization immunoassay. In the first group peak levels of 24.82 +/- 3.55 mug/ml were achieved in aqueous humour at 5 h, whereas in the second group peak levels of 1.42 +/- 0.47 mug/ml were detected at 6 h. The latter levels, although higher than the MICs of most of the Gram-positive pathogens causing eye infections, are inadequate for the treatment of infections in vivo. These results support the need for subconjunctival instead of i.v. administration of vancomycin in order to achieve therapeutic levels of the drug in human aqueous humour or for prophylactic use whenever indicated. (C) 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved

COMPARATIVE PHARMACOKINETICS OF CIPROFLOXACIN, OFLOXACIN AND PEFLOXACIN IN HUMAN AQUEOUS-HUMOR

Eighty-five patients undergoing cataract surgery were given for prophylaxis of intraocular infection two intravenous doses each of 200 mg, 300 mg or 400 mg ciprofloxacin (35 patients), 400 mg or 800 mg pefloxacin (30 patients), or 400 mg ofloxacin (20 patients). Ciprofloxacin levels in aqueous humour ranged from 0.02 to 0.50 mug/ml, pefloxacin levels from 1.04 to 7.80 mug/ml, and ofloxacin levels from 0.44 to 2.27 mug/ml with ratios of aqueous humour to serum levels ranging from 3.8 % to 25 %, 21 % to 48.1 % and 44 % to 88.4 %, respectively. It is concluded that the quinolones studied might be suitable for surgical prophylaxis or treatment of anterior chamber infections due to Enterobacteriaceae, while ciprofloxacin at high doses is preferable for Pseudomonas aeruginosa infections

The effect of acetazolamide on the kinetics of four newer beta-lactams in the aqueous humor

Objective To evaluate whether the effect of acetazolamide on piperacillin’s aqueous humor concentrations observed in animals exists also in humans for ceftazidime, cefotaxime, ceftriaxone and aztreonam. Methods One hundred and eighty-eight patients undergoing eye cataract surgery were randomly allocated to receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with (subgroup A) or without (subgroup B) concomitant oral administration of acetazolamide. Antibiotic concentrations in serum and the aqueous humor, simultaneously sampled during the operation, were measured using an agar well diffusion technique, and the ratios of the concentrations of aqueous humor to serum were calculated and compared. Statistical analysis was performed by using the paired t-test. Results Mean aqueous humor ceftazidime concentrations at 2, 4, and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L (subgroup B). Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77 mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam 6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B). Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41 mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B). The differences in aqueous humor concentrations when acetazolamide was administered were statistically significant (P < 0.05), with the exception of ceftazidime 6 h, cefotaxime 6 h and ceftriaxone 2 h. Conclusions Although acetazolamide resulted in statistically significant increases in the aqueous humor concentrations of all the antibiotics tested, this effect was most marked for ceftazidime

LACK OF RESPONSE TO CORTICOSTEROIDS AND PULSE CYCLOPHOSPHAMIDE THERAPY IN COGANS-SYNDROME

A 17-year-old girl with Cogan’s syndrome is described. Total and irreversible hearing loss occurred which was unresponsive to corticosteroids and immunosuppressive therapy. The girl died a year later from subarachnoid haemorrhage. The lethal prognosis in Cogan’s syndrome despite the available treatment is emphasized

ANGIOID STREAKS IN SICKLE-THALASSEMIA

Angioid streaks have been described in a diverse group of diseases including hemoglobinopathies such as sickle cell anemia and beta-thalassemia. We investigated the prevalence of angioid streaks and pseudoxanthoma elasticum in the rare situation of patients who had compound heterozygous traits for hemoglobin S and beta-thalassemia. We examined 58 consecutive patients with sickle-thalassemia. Of these, 25 were men and 33 were women, and they ranged in age from 19 to 58 years (mean, 32.6 years). Angioid streaks were identified in six of 58 patients (10%), and of these three also displayed the cutaneous lesions of pseudoxanthoma elasticum, which were confirmed by skin biopsy. An expanded study on several relatives of the patients with angioid streaks failed to identify any similar cases. Statistical evaluation of the main hematologic and biochemical parameters in the patients with and without angioid streaks did not demonstrate any significant differences, except that the thalassemic component in all six patients with angioid streaks was beta degrees (that is, did not allow the synthesis of hemoglobin A). We conclude that angioid streaks and pseudoxanthoma elasticum skin lesions occur with an increased frequency in patients with sickle-thalassemia

Neutrophil elastase in patients with homozygous beta-thalassemia and pseudoxanthoma elasticum-like syndrome

In this study we investigated the possible role of neutrophil (PMN) elastase and its natural inhibitor, alpha 1-proteinase inhibitor (alpha 1-PI) in the pathogenesis of the pseudoxanthoma elasticum (PXE)-like syndrome which is found in patients with homozygous beta-thalassemia, We studied 30 beta-thalassemia homozygotes with the PXE-like syndrome [PXE(+) group], 20 beta-thalassemia homozygotes without this syndrome [PXE(-) group] and 15 healthy controls. Plasma PMN elastase concentration in the PXE(+) and in the PXE(-) group was 136.4 +/- 89 and 163.8 +/-126 mu g/L, respectively (P > 0.05), In the control group, the concentration was 42.9 +/- 16.8 mu g/L (P < 0.01 for the comparison with both patients’ groups). The plasma alpha 1-PI concentration in the PXE(+) and in the PXE(-) group was 2.28 +/- 0.75 and 2.6 +/- 0.96 g/L, respectively (P > 0.05). Using logistic regression, we studied the prognostic value for PXE of the following independent variables: number of transfusions, chelation therapy, mean hemoglobin concentration, PMN elastase concentration, alpha 1-PI concentration, chronic transaminase elevation, and positivity for anti-HCV. None of the above variables was found to have significant prognostic value for the PXE, Plasma PMN elastase concentration is elevated in all beta-thalassemia homozygotes; its role in the pathogenesis of the PXE-like syndrome in beta-thalassemia can not be established, but our findings suggest that neutrophils of beta-thalassemia patients are activated, since PMN elastase is a marker of neutrophil activation. Am, J. Hematol. 63:63-67, 2000. (C) 2000 Wiley-Liss, Inc

Arterial calcifications in beta-thalassemia

The purpose of this study was to define the incidence of arterial calcifications in patients with beta-Thalassemia. beta-thalassemia patients have been shown to present a high prevalence of angioid streaks and skin lesions characteristic of pseudoxanthoma elasticum (PXE). Given the fact that vascular involvement in the form of arterial calcifications is also a common manifestation of PXE, the authors investigated radiographically the presence of arterial calcifications in beta-thalassemia patients. They studied 40 patients with beta-thalassemia over 30 years of age. Forty healthy, age- and sex-matched subjects were chosen as a control group. Radiographs of the tibias were performed in order to disclose arterial calcifications. The occurrence of PXE skin lesions and of angioid streaks (AS) was also investigated. Arterial calcifications were detected in the posterior tibial artery in 22 (55%) beta-thalassemia patients and in six (15%) controls (P<0.01 for the comparison). PXE skin lesions and AS were found in eight (20%) and 21 (52%) patients respectively. A total of 34 patients (85%) had at least one of the three lesions, namely, arterial calcifications, angioid streaks, and/or PXE-like skin lesions. Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid. It was concluded that arterial calcifications are common in older beta-thalassemia patients. This finding could be a manifestation of an acquired PXE syndrome associated with beta-thalassemia, and consequently, vascular events complicating PXE should be expected in these patients