meropenem and Keratitis

To compare the efficacy of topical meropenem and cefepime treatments with respect to moxifloxacin as new treatment options in an experimental Pseudomonas keratitis model.. Twenty-four rabbits in which keratitis are induced using Pseudomonas aeruginosa were divided into four groups according to treatment options. A solution of 50 mg/mL meropenem was prepared and topically applied to the first group, 50 mg/mL cefepime solution to the second group, topical 0.5% moxifloxacin drop to the third group, and topical isotonic (0.9% saline) solution to the fourth (control) group. The eyes were examined before and after treatment to score the clinical severity. After the subjects were sacrificed, their corneas were excised. To determine the efficacy of treatments, clinical score, bacterial load, and histopathological and immunohistochemical findings were evaluated.. When the three treatment groups were compared, there was a significant difference in the colony-forming unit (CFU) value, polymorph-nuclear leukocyte (PMNL) infiltration, and matrix metalloproteinase (MMP)-9 immunoreactivity (P=0.022, P=0.038, and P=0.037, respectively). The CFU values, PMNL infiltration scores and MMP-9 immunoreactivity were significantly lower in the meropenem and moxifloxacin groups compared with the cefepime group (P<0.05 for all). There was no significant difference between the meropenem and moxifloxacin groups in respect of the CFU values, PMNL infiltration, and MMP-9 immunoreactivity (P=0.842, P=0.784, and P=0.699, respectively).. The results of our study indicate that topical meropenem is at least as effective as topical moxifloxacin in the treatment of Pseudomonas keratitis. The meropenem and moxifloxacin are safer and suitable in the limited corneal invasion than cefepime. Thus, topical meropenem may be an alternative drug in the treatment of this condition. Clinical studies are needed to be conducted to assess this possibility more accurately.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Cefepime; Colony Count, Microbial; Disease Models, Animal; Eye Infections, Bacterial; Fluoroquinolones; Keratitis; Meropenem; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

To investigate the toxicity and corneal pharmacokinetics of meropenem as a potential antimicrobial for bacterial keratitis.. Corneal epithelial cell and keratocyte toxicity was investigated using methyl thiazolyl tetrazolium (MTT) and LIVE/DEAD assays. The penetration of meropenem through the human cornea was measured using an artificial anterior chamber. In one group of corneas, the epithelial and endothelial layers were removed and in a second group these layers were left intact. We applied 50 μL (10 mg/mL) meropenem to the corneal surface and collected samples in the anterior chamber from 45 minutes up to 24 hours. Meropenem concentrations were estimated with a bioassay and HPLC.. Meropenem had significantly higher cellular metabolic activity (MTT assay) at both 5 mg/mL and 2.5 mg/mL compared with moxifloxacin (P = 0.029 and P = 0.018, respectively), with 96% cell viability (LIVE/DEAD assay). The measured values for meropenem concentrations in corneal and aqueous samples were significantly higher using a bioassay than with HPLC (P = 0.004). For both intact and denuded corneas, the concentrations in the anterior chamber increased from 0.48 μg/mL (SD 0.89) and 0.89 μg/mL (SD 0.81) to 6.35 μg/mL (SD 0.81) and 13.48 μg/mL (SD 14.82) using HPLC, and from 0.68 μg/mL (SD 1.50) and 1.31 μg/mL (SD 1.55) to 47.03 μg/mL (SD 5.51) and 43.69 μg/mL (SD 27.22) measured with a bioassay.. Meropenem has very low toxicity in vitro. It has good corneal penetration, achieving anterior chamber concentrations above MIC90 for bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, streptococci, coagulase-negative staphylococci, and the Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Cells, Cultured; Epithelial Cells; Epithelium, Corneal; Eye Infections, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Keratinocytes; Keratitis; Meropenem; Microbial Sensitivity Tests; Staphylococcal Infections; Thienamycins