细菌性角膜溃疡的医院流行病学，诱因和微生物诊断
-
首席医学网
2009年04月14日 18:30:21 Tuesday
-
作者：Ashok Kumar Narsani, Shafi Muhammad Jatoi, Mahesh Kumar Lohana, Syed Asher Dabir, Siddiqa Gul, Mahtab Alam Khanzada 作者单位：巴基斯坦海德拉巴, Liaquat大学眼科医院眼科
加入收藏夹
【摘要】 目的：确定细菌性角膜溃疡的发病诱因，临床和微生物特性。方法：本研究涉及300例(300眼)临床上疑似微生物感染的角膜溃疡患者。通过病史回顾和裂隙灯检查获得病例资料。采用标准技术完成角膜刮片检查。取部分刮片样本加入100g/L的氢氧化钾液后，以及采用革兰氏和吉姆萨染色，再直接在显微镜下观察是否存在真菌、细菌和棘阿米巴。另一部分刮片样本直接接种在血琼脂、麦康基琼脂、巧克力琼脂和萨布罗琼脂表面。通过角膜刮片检查，细菌性角膜溃疡被确诊为化脓性角膜溃疡浸润和表层上皮细胞缺失伴细菌感染。对患者应用抗菌治疗。结果：在随访期间，因丢失而被排除的有60个病例。在剩下的240人中，被确诊为细菌性角膜溃疡的156人(65%)，大多数为男性(102眼)，年龄分布14～74岁。角膜溃疡位于角膜中央的96人(61.5%)，位于外周的60人(38.5%)。溃疡深度<1/3角膜厚度的82人(52.6%)。前房炎症为：Tyndall现象和浮游细胞1+～2+64人。角膜涂片中分离出细菌的有125人(80%)，其中69%为革兰氏阳性，39%为革兰氏阴性。革兰氏阴性菌感染患者伴有重症前房炎症(P=0.003)并且深度>2/3角膜厚度(P=0.001)。分离得到的最常见致病微生物为金黄色葡萄球菌。治疗后40%的患者视力恢复到入院时的水平甚至更好，其余60%的患者预后差。结论：细菌性角膜溃疡是一种严重的眼部感染性疾病，对眼部存在视力威胁，在治疗上仍具挑战性。快速分离细菌和眼部抗生素的应用是治疗此类疾病的关键。
【关键词】 细菌性角膜炎；植物性外伤；微生物
Abstract
AIM: To determine the predisposing factors, clinical and microbial characteristics of bacterial corneal ulcer.
METHODS: Three hundred patients (300 eyes) of clinically suspected microbial corneal ulcer were included in the study. Data was collected through history and slit lamp examination. Using standard techniques, corneal scraping was performed. A portion of each scraping was examined by direct microscopy for the presence of bacteria, fungi and acanthamoeba by using 100g/L potassium hydroxideand also by Gramand staining. Another portion was inoculated directly on the surface of solid media such as blood agar, MacConkey agar, chocolate agar and Sabouraud's agar. A bacterial corneal ulcer was defined as a suppurative corneal infiltrate and overlying epithelial defect associated with presence of bacteria on corneal scraping examination and cured with antibacterial therapy.
RESULTS: Of the 300 patients, sixty were lost in follow up, they were excluded from study. Of the remaining 240, bacterial corneal ulcer was identified in 156 (65.0%) patients. The age of patients ranged from 14 to 74 (mean age of 48) years. Majority of them were male (102). Corneal localization of the ulcers was distributed as central in 96 (61.5%) patients and peripheral in 60 (38.5%) patients. Ulcer depth in 82 (52.6%) patients was less than 1/3 of corneal thickness. In 64 (41.0%) patients, anterior chamber inflammation was 1+ to 2+ Tyndall effect with 1+ to 2+ cells present. Bacteria were isolated in 125 (80.0%) patients from the corneal smears. Sixtynine percent of isolated bacteria were Grams positive, and 39% were Grams' negative. Gram negative bacteria were associated with severe anterior chamber inflammation (P=0.003) and depth more than 2/3 of cornea (P=0.001). The most frequent organism isolated was Staphylococcus aureus. Forty percent of patients had good visual outcome with visual acuity same or better than the level at admission. Among the others 60% patients, final outcome was poor.
CONCLUSION: Bacterial corneal ulcer is aserious ocular infectious disease that remains a therapeutic challenge and vision threatening ocular condition. Rapid isolation of bacteria and treatment with intensive ocular antibiotics represent decisive steps in the management of such pathologies.
KEYWORDS: bacterial keratitis; agriculture trauma; organism
INTRODUCTION
Microbial keratitis is a serious ocular infectious disease that can lead to significant vision loss and ophthalmic morbidity[1]. Bacterias are the most common infective organisms responsible for this morbidity. The severity of corneal infection depends on the underlying condition of the cornea and pathogenecity of the infecting bacteria[2]. It is rare in the absence of predisposing factors, and hence most commonly associated with ocular trauma or ocular surface disease. However the increasing prevalent with the use of contact lenses in the general community has resulted well established association between keratitis and contact lens[3].
The spectrum of bacterial keratitis can also be influenced by geographic and climatic factors. Many differences in keratitis profile have been noted between populations living in rural or in urban areas in western, or in developing countries[4]. Gram positive bacterial species are more frequently recovered in temperate zones, and Gram negative species in tropic climates. Untreated, infective keratitis may lead to opacification and, ultimately, to perforation of the cornea. The associated morbidity is the result of several factors and is directly affected by difficulties in patients management because of a lack of diagnostic facilities and appropriate treatment. Specific treatment requires prompt and accurate identification of causative microorganisms[5]. This study is an effort to analyze the epidemiologic features, predisposing factors and the main causative organisms for bacterial corneal ulcer in this part of Asia to provide a useful guide for the practicing ophthalmologists. This two years Quasiexperimental study (from April 2006 to March 2008) of bacterial corneal ulcer was conducted at Liaquat University Eye Hospital, Hyderabad, a Tertiary Referral Center in Southern Pakistan.
MATERIALS AND METHODS
Subjects Patients above 15 years of age presenting with suspected corneal ulceration and having symptoms of pain, redness, watering, photophobia and decreased vision were registered for the study. Patients written consent was obtained and a standardized proforma was used to record the data. Detailed history and examination of the patients was taken regarding demographic features, time of onset of symptoms, predisposing factors including corneal injuries (agriculture, non agriculture, foreign bodies), contact lens wear, keratopathies (due to previous herpetic infection, corneal dystrophy or surgical procedure, as in bullous keratopathy), dry eye syndrome, eye lid abnormalities (blephritis, entropion, ectropion, lagophthalmos, and others). Visual acuity was measured with Snellen chart. All patients underwent through slit lamp examination to locate the site, size and depth of ulcer. Anterior chamber inflammation, when present, was scored, according to Hoagan and associates, a 0+ to 4+ for Tyndall effect and cells.
After the instillation of local anesthetic 5g/L proparacaine hydrochloride, corneal scrapping was obtained aseptically with a sterile No.15 surgical blade from the base and edges of each ulcer. A portion of each scrapping was examined microscopically for the presence of bacteria, fungi or acanthamoeba by using Gram staining, 100g/L potassium hydroxide (KOH) and Giemsa staining methods. Another portion was inoculated on to blood agar, chocolate agar, MacConkey agar, Sarborauds agar, brain heart infusion broth respectively, in Cshaped streaks and cultured for the potential growth of, bacteria, fungi or acanthamoeba. Sarborauds agar slants were incubated at 28℃ while others at 37℃. All media were cultured for a period of seven days and observed daily. Isolated bacteria were tested by chemical reaction for identification. Further the bacteria were tested for their resistance against the following ocular antibiotics: cefuraxime, cefazolin, moxifloxacin, gentamycin, tobramycin, ceftazidime, norfloxacin, ofloxacin, levofloxacin, gatifloxacin. The resistance to antibiotics was evaluated with the standard disc diffusion method according to the modified test recommended by the NCCLS.
Treatment Protocol Ninetyfive (61%) patients were treated as an out patients department basis and 61 (39%) patients were hospitalized for treatment. The decision to admit patients and use of fortified antibiotics were influenced by the severity of the corneal ulcer and patients compliance. The standard fortified therapy consisted of topical cefuraxime 50g/L and fortified tobramycin 9g/L, where as commercially available antibiotics used were topical fluoroquinolones (Moxifloxacin). The antibiotic eye drops, administered alternately every fifteen minutes during the first 4 hours then every hour for the next 48 hours. Later, drops were progressively tapered according to the clinical response. Bottles of fortified antibiotics drops were freshly prepared and cefuraxime, was changed every 72 hours. This standard treatment protocol was started for every patient and modified on patients response and the bacterial susceptibility.
Statistical Analysis Univariate analysis was used to evaluate the possible association between bacterial type, clinical characteristics, risk factors and clinical outcomes. Data was analyzed on SPSS version 10.0.
RESULTS
General Situation Three hundred patients (300 eyes) were enrolled with a corneal infiltration that was clinically compatible with the diagnosis of bacterial corneal ulcer during the two years study period. Of these 60 patients were lost in followup, excluded from study. Of the remaining 240 cases, bacterial corneal ulcer was identified in 156 (65.0%) patients. Among these, 60 (38.5%) patients were examined first time in the out patients department, where as 96 (61.5%) were previously treated by general practitioners and ophthalmologists and were already being treated with topical antibiotics, corticosteroids and antifungal eye drops. The age of patients ranged from 14 to 74 (mean age of 48) years. Majority of them were male 102 (65.4%) with male to female ratio of 1.9∶1(Table 1). One hundred and two (69.2%) patients belonged to rural and 48 (30.0%) were from urban population. Trauma with vegetative material was by far the most common risk factor; this was encountered in 46 (29.5%) patients. History of nonvegetative trauma in 16(10.3%) patients(Table 2). In 18 (11.5%) patients, ocular surface disorder was observed, the keratitis was induced by foreign body in 24 (15.4%) patients. Eleven (7.1%) patients were affected by contact lenses. Keratopathies (including herpetic, bullous and post operative keratopathies) were presented in 17 (11.0%) patients. Blephritis was noted in 8 (5.1%) patients. While 16 (10.3%) patients had no significant prior history.
Corneal localization of the ulcers was distributed as in 96(61.5%) patients central and in 60 (38.5%) peripheral. The diameter of the corneal ulceration was of 12mm in 24(15.4%), 3 4mm in 78(50.0%), 5 6mm in 24(15.4%), 7 8mm in 26(16.7%) patients, 4 (2.6%) patients had entire corneal involvement. Ulceration depth was less than 1/3 conreal thickness in 82(52.6%), between 1/3 to 2/3 in 60(38.5%) patients and over 2/3 in 14(9.0%) patients (Table 3).
Anterior chamber inflammation was absent in 42 (26.9%) patients. A 1+ to 2+ Tyndall effect with 1+ to 2+ cells was present in 64 (41%) patients, and severe anterior chamber inflammation (3+ to 4+ Tyndall effect and cells, with or without hypopyon) was present in 50 (32.1%) patients (Table 3). In 125 (80%) patients, bacteria were isolated from the corneal smears (Table 4). Sixtynine percent of isolated bacteria were Gram positive, most of them 75(60%) were staphylococcus aureus. Gram negative bacteria were isolated in 39(31%) patients. Most of them were pseudomonas and yersina. Infection with Gram negative organisms associated with severe anterior chamber inflammation (P=0.003) and depth more than 2/3 of cornea (P=0.001). All isolated bacteria were tested on currently used 10 antibiotics.
One hundred and fourteen (73.1%) patients were treated according to the standard protocol by using fortified antibiotic drops for Gram positive and Gram negative organisms. The remaining 42 (26.9%) patients who did not stay at hospital and had small infiltration were, treated by commercially available antibiotic fluoroquinolone (Moxifloxacin).
Table 1Demographic data of 156 patients with bacterial corneal ulcern（略）
Table 2Frequency of risk factors in bacterial corneal ulcern（略）
Table 3Clinical features of corneal ulcer（略）
Table 4Organisms isolated in bacterial corneal ulcers（略）
Figure 1Pre and post treatment visual status of patients（略）
Clinical Outcome Visual acuity on presentation ranged from 6/6 to no light perception. Mean visual acuity was 2.67 (SD 1.01). Forty percent of patients had good visual outcome with visual acuity same or better than the level at admission (Figure 1). Among the others 60% patients final outcome was poor. Complications of bacterial corneal ulcer were noted in 45 (28.8%) patients. Among them, glaucoma in 11 patients, endophthalmitis in 3 patients, anterior staphyloma in 3 patients and corneal perforation, descmetocele, cataract each develops in 3 (4.5%) patients. Where as one hundred and eleven (71.2%) patients had no severe complications, except scaring at the site of lesion. In our study statistical analysis revealed that poor visual outcome was correlated with history of ocular surface disease (P<0.01), large size and central localizations of the ulcer (P<0.01), and depth of infiltrate more than 1/3 corneal thickness (P<0.01).
DISCUSSION
Corneal infection is the leading cause of ocular morbidity and blindness worldwide. In the published reports, bacterial corneal ulcer has been found to be 13.0% to 29.3% of all cases of ulcerative corneal ulcer[6].
Of the remaining 240 patients with infective keratitis from April 2006 to March 2008 presenting at our department, bacterial corneal ulcer was diagnosed in 156 (65.0%) eyes. Although it is rare in the absence of a predisposing factor. Most of the cases of microbial keratitis were associated with ocular trauma. In this study 86 (55.0%) were associated with various types of ocular injuries. Vegetative trauma accounts 46 (29.5%) patients. Vajpayee et al reported 77.5% of cases of bacterial corneal ulcer occurred by trauma in low income countries, where a large number of population were concerned to agriculture. Moreover, the climate is mild and humid, and malnutrition is common[7] . Foreign body induced corneal ulcer was the second most common (24 cases,15.38%) predisposing factor in our study. Most of these patients had also history of foreign body removal by own or by other family members and followed by selfmedications.
Ocular surface disorders such as dry eye syndrome and eye lid pathologies and keratopathies accounted 17.3% of cases. Bourcier et al[2] reported 21% of cases of bacterial corneal ulcer were with ocular surface disorder. Contact lenses remained the least common cause of bacterial corneal ulcer in our study. In contrast Radford et al reported contact lenses had greatly increased the risk of bacterial keratitis which was estimated to be 1015 times higher with the use of extended wear disposable contact lenses. Many physiopathological effects of contact lenses wear have been reported. The most important of which is an induced hypoxia and hypercapinia of the cornea. In line with other studies[8,9] males (65.4%) were predominant in our study. The increased risk in males in our population was probably due to their more active involvement in out door activities, which subsequently increased their vulnerability to this blinding disease. The duration from the onset of symptoms to the presentation at our department ranged from 7 to 105 (mean 41） days. This delay presentation to tertiary center might be due to the fact that the patient already received the therapy from their nearest ophthalmologists or doctor and were referred when the ulcers did not respond. Xie et al[7] reported the first visit of 41.0% between 16 and 30 days.
In this study, the most common signs on slit lamp examination were epithelial defect, stromal infiltrate and suppuration presents in every case, while anterior chamber reaction and hypopyon was observed in 73% of patients. This is in accordance with another European study[2]. Older individuals were more frequently affected in this study, majority (61%) of patients were fifth or more decades. Age profile in our patients is comparable to Schaefer et al and Cohen et al study. In general older age, delay in referral, topical steroid treatment, past ocular surgery, poor vision at presentation, large size of ulcer[10], and central and deep ulcer are all major risk factors for evisceration and enucleation in patients with bacterial corneal ulcer. The situation in this study was not too different.
The success rate of bacterial isolation was high in the present study, with 80% of smear positive on blood, chocolate and MacConkey agar. While Waxman et al[11] reported 70% of isolation of organism on same medium. As with most published studies there was a high prevalence of Gram positive bacteria with staphylococcus aureus accounting for 75 (60%) of all 125 bacterial isolates. Our study match to the Hyderabad study. Stephen et al reported higher incidence of streptococcus pneumonia (20%) in his study. Jayahar et al[12] study also reported the same. While Maske et al reported high (27%) incidence of Staphylococcus epidermidis in their study. Thus etiology of the corneal ulcers varies significantly from region to region.
The standard treatment of bacterial corneal ulcer in majority 114 (73.1%) of our patients consists of topical instillation of fortified antibiotics (cefuraxime 50g/L and fortified tobramycin 9g/L). Which has been the "gold standard" for the therapy of bacterial corneal ulcer[6]. However the use of fortified antibiotics were associated with complain of ocular irritation or intense conjunctival reactions during drop instillation. This was due to the local corneal and conjunctival toxicity to the fortified drops. The same issue was raised by Cutarelli et al in 1991. We also treated 42 (26.9%) patients by fluoroquinolones (Moxifloxacin) antibiotics. The antibacterial action results from inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV. This is a new fourth generation fluoroquinolone with a broad spectrum of activity against Gram positive(including methicillin resistant Staphylococcus aureus and ciprofloxacin resistant Staphylococus aureus) and Gram negative microorganisms. In addition, it penetrates well in the anterior chamber and remains fairly stable for at least 12 hours[13]. This treatment was advised to those patients who did not stay at hospital and had small infiltration.
Visual prognosis after bacterial corneal ulcer depends on the size, locality, and depth of the ulcers as well as on the risk factors, bacteria isolated, age and general health of patient. In our study poor out come seen in patients having chronic surface ocular disorder, large size of ulcers, involving more than 2/3 of depth of the cornea and poor visual acuity at presentation. Patient presented very late or previously treated by topical steroids has also poor end result in our study.
Only forty percent of patients had good visual out come with visual acuity better than the level at admission. Among the others 60% patient, final outcome was same or poor than time of presentation.
CONCLUSION
Bacterial corneal ulcer is a serious ocular infectious disease that remains a therapeutic challenge and vision threatening ocular condition. Rapid isolation of bacteria and treatment with intensive ocular antibiotics represent decisive steps in the management of such pathologies.
【参考文献】
1 Stapleton F, Keay LJ, Sanfilippo PG, Katiyar S, Edwards KP, Naduvilath T. Relationship between climate, disease severity, and causative organism for contact lensassociated microbial keratitis in Australia. Am J Ophthalmol 2007;144(5):690698
2 Bourcier T, Thomas F, Borderie V, Chaumeil C, Laroche L. Bacterial keratitis: predisposing factors, clinical and microbial review of 300 cases. Br J Ophthalmol 2003;87(7):834838
3 Keay L, Edwards K, Naduvilath T, Taylor HR, Snibson GR, Forde K, Stapleton F. Microbial keratitis predisposing factors and morbidity. Ophthalmology 2006;113(1):109116
4 Schaefer F, Bruttin O, Zografos L, GuexCrosier Y. Bacterial keratitis: a prospective clinical and microbiological study. Br J Ophthalmol 2001;85(7):842847
5 Khanal B, Kaini KR, Deb M, Badhu B, Thakur SK. Microbial keratitis in eastern Nepal. Tropical Doctor 2001;31(3):168169
6 Chaudhuri PR, Godfrey B. Treatment of bacterial corneal ulcers with concentrated antibiotics eye drops. Trans Ophthalmol Soc UK 1982;102(1): 1114
7 Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology 2006;113(11):19431948
8 Chowdhary A, Singh K. Spectrum of fungal keratitis in north India. Cornea 2005;24(1):815
9 Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN. The epidemiological features and laboratory results of fungal keratitis: a 10year review at a referral eye care centre in south India. Cornea 2002;21(6):555559
10 Poole TR, Hunter DL, Maliwa EM, Ramsay AR. Aetiology of microbial keratitis in northern Tanzania. Br J Ophthalmol 2002;86(8):941942
11 Waxman E, Chechelnitsky M, Mannis MJ, Schwab IR. Single culture media in infectious dermatitis. Cornea1999;18(3):257261
12 Jayahar BM, Ramkirshan R, Vasu S, Meenakashi R, Palaniappan R. In vitro efficacy of antibacterials against bacterial isolates from corneal ulcers. Ind J Ophthalmol 2002;50(2):109114
13 Kampougeris G, Antoniadou A, Kavouklis E, Chryssouli Z, Giamarellou H. Penetration of moxifloxacin into the human aqueous humor after oral administration. Br J Ophthalmol2005;89(5):628631
订阅登记：
请您在下面输入常用的Email地址、职业以便我们定期通过邮箱发送给您最新的相关医学信息，感谢您浏览首席医学网！