Callegan M C, O'Callaghan R J, Hill J M
Department of Microbiology, Louisiana State University Medical Center School of Medicine, New Orleans.
Clin Pharmacokinet. 1994 Aug;27(2):129-49. doi: 10.2165/00003088-199427020-00005.
The eye is relatively impermeable to micro-organisms and other environmental elements. However, if corneal integrity is breached by trauma, a sight-threatening bacterial infection can result. Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae are the most common bacterial pathogens associated with infection of compromised corneas. Bacterial enzymes and toxins, as well as factors associated with the host immune response, can lead to tissue destruction during corneal infection. For successful therapy, an antibacterial agent must be active against the pathogen and must be able to overcome the permeability barrier of the cornea. Topical application of antibacterial agents adequately delivers drugs to the cornea and aqueous humour. However, drug concentrations at the site of infection are not always sufficient to rapidly kill infective organisms. Infections with antibiotic-resistant strains present an even greater therapeutic challenge. In addition, sterilisation of the cornea by antibacterial agents does not eliminate inflammation and corneal scarring that accompany infection. Steroidal and non-steroidal antiinflammatory agents limit corneal scarring during experimentally induced bacterial keratitis. However, although promising, concomitant use of these drugs with antibacterial agents remains controversial. Two ocular drug delivery systems that provide high and sustained concentrations of drug to ocular tissues are corneal collagen shields and transcorneal iontophoresis. The collagen shield, originally designed as a bandage lens, prolongs drug contact with the cornea. Chemotherapeutic studies of experimental bacterial keratitis demonstrate that shields hydrated with antibacterial agents reduce bacteria in the cornea as well as or better than frequent applications of fortified antibacterial drops. Transcorneal iontophoresis uses an electric current to drive charged drugs into the cornea. In experimentally induced bacterial keratitis, transcorneal iontophoresis of antibacterial agents is superior to topically administered ocular drops for reducing the numbers of bacteria in the cornea. Although both drug delivery systems appear to be well tolerated and nontoxic in animal models, clinical trials in patients are required to determine the usefulness of these drug delivery systems in clinical trials. Based on present experimental results, future therapy of bacterial keratitis will involve efficient drug delivery devices, the use of new antibacterial agents or combinations of presently available antibacterial agents, and careful use of adjuvant anti-inflammatory agents.
眼睛对微生物和其他环境因素相对具有屏障作用。然而，如果角膜完整性因外伤而遭到破坏，就可能导致威胁视力的细菌感染。金黄色葡萄球菌、铜绿假单胞菌和肺炎链球菌是与受损角膜感染相关的最常见细菌病原体。细菌酶和毒素，以及与宿主免疫反应相关的因素，可导致角膜感染期间的组织破坏。为了成功治疗，抗菌剂必须对病原体有活性，并且必须能够克服角膜的通透性屏障。局部应用抗菌剂可将药物充分递送至角膜和房水。然而，感染部位的药物浓度并不总是足以迅速杀死感染性生物体。对抗生素耐药菌株的感染带来了更大的治疗挑战。此外，抗菌剂对角膜的杀菌作用并不能消除伴随感染的炎症和角膜瘢痕形成。甾体和非甾体抗炎剂在实验性诱导的细菌性角膜炎期间可限制角膜瘢痕形成。然而，尽管前景看好，但这些药物与抗菌剂联合使用仍存在争议。两种能向眼组织提供高浓度且持续药物浓度的眼部给药系统是角膜胶原盾和经角膜离子电渗疗法。胶原盾最初设计为绷带镜片，可延长药物与角膜的接触时间。对实验性细菌性角膜炎的化疗研究表明，用抗菌剂水化的胶原盾在减少角膜细菌方面与频繁应用强化抗菌滴眼液的效果相同或更好。经角膜离子电渗疗法利用电流将带电药物驱入角膜。在实验性诱导的细菌性角膜炎中，抗菌剂的经角膜离子电渗疗法在减少角膜细菌数量方面优于局部应用眼药水。尽管这两种给药系统在动物模型中似乎耐受性良好且无毒，但仍需要在患者中进行临床试验，以确定这些给药系统在临床试验中的实用性。基于目前的实验结果，未来细菌性角膜炎的治疗将涉及高效的给药装置、使用新型抗菌剂或现有抗菌剂的联合使用，以及谨慎使用辅助性抗炎剂。
