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Incremental effect of topical and oral moxifloxacin administration with surgical intracameral prophylaxis

Published:January 27, 2021DOI:https://doi.org/10.1016/j.jcjo.2020.12.020

      Abstract

      Objective

      To determine how supplemental perioperative topical or oral moxifloxacin administration impacts anterior chamber (AC) antibiotic concentrations beyond those achieved by intracameral (IC) administration alone for postoperative endophthalmitis (POE) prophylaxis.

      Design

      Mathematical modeling.

      Methods

      The mathematical model developed by Arshinoff, Modabber, and Felfeli was adapted to calculate all reported data. A literature review of pharmacokinetic data for topical and oral moxifloxacin was used to inform the expansion of the model.

      Results

      Our previously constructed IC model yields a dose of moxifloxacin in the AC sufficient to confer bactericidal coverage against the most common POE pathogen, methicillin-sensitive Staphylococcus aureus (MSSA), for ∼40 hours postoperatively. Topical 0.5% moxifloxacin eye drops alone, administered every 4 or 6 hours, achieve an AC concentration just above or at the mutant prevention concentration (MPC) for MSSA, respectively, whereas 8-hour dosing produces levels generally below the MPC. Combining topical moxifloxacin with IC increases the AC concentration above IC alone only after 20 or more hours and maintains the AC concentration at, or just below, the MPC for MSSA for as long as the drops are continued. Combined perioperative oral moxifloxacin with IC increases AC levels over IC alone only after 16 hours and maintains the AC concentration above the MPC for MSSA for an additional 5 hours, owing to the systemic reservoir.

      Conclusions

      The addition of topical or oral moxifloxacin supplemental to IC can extend the duration of bactericidal coverage for the most common, but not the most resistant POE-causing pathogens.

      Objectif

      Déterminer les effets de l'administration peropératoire supplémentaire de moxifloxacine par voie topique ou orale sur les concentrations d'antibiotique dans la chambre antérieure (CA) comparativement à ce que permet l'administration intracamérulaire (IC) seule dans la prévention de l'endophtalmie postopératoire (EP).

      Nature

      Modélisation mathématique.

      Méthodes

      Le modèle mathématique mis au point par Arshinoff, Modabber et Felfeli a été adapté pour tenir compte de toutes les données transmises. Les données pharmacocinétiques de l'administration topique et orale de moxifloxacine issues d'une revue de la littérature médicale ont servi à l'expansion du modèle.

      Résultats

      Selon notre modèle antérieur sur l'administration IC, on obtient dans la CA une dose de moxifloxacine suffisante pour procurer un effet bactéricide contre l'agent pathogène le plus souvent responsable d'une EP – Staphylococcus aureus sensible à la méthicilline (SASM) – pendant environ 40 heures après l'intervention. Avec la seule instillation d'un collyre de moxifloxacine à 0,5 % toutes les 4 heures, toutes les 6 heures et toutes les 8 heures, les concentrations atteintes dans la CA sont, respectivement, légèrement supérieure, équivalente et généralement inférieure à la concentration prévenant les mutations (CPM) pour le SASM. Or, l'administration concomitante de moxifloxacine par voie topique et IC produit, dans la CA, après au moins 20 heures, une concentration plus élevée que l'administration IC seule, laquelle se maintient à un niveau équivalent ou juste en-deçà de la CPM pour le SASM tant que se poursuit l'instillation du collyre. De même, l'administration concomitante de moxifloxacine par voie orale et IC donne, au bout de 16 heures, une concentration plus élevée dans la CA que l'administration IC seule, et permet de maintenir celle-ci au-dessus de la CPM pour le SASM pendant 5 heures supplémentaires grâce à la présence d'un réservoir systémique.

      Conclusions

      L'ajout de moxifloxacine topique ou orale à son administration par voie IC peut prolonger l'effet bactéricide envers les agents pathogènes le plus fréquemment responsables d'une EP, mais pas contre les agents pathogènes les plus résistants.
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