Int Ophthalmol DOI 10.1007/s10792-014-9951-7

ORIGINAL PAPER

Clinical and epidemiological characteristics of infectious keratitis in Paraguay Martin M. Nentwich • M. Bordo´n • D. Sa´nchez di Martino • A. Ruiz Campuzano W. Martı´nez Torres • F. Laspina • S. Lichi • M. Samudio • N. Farina • Rosa R. Sanabria • Herminia Mino de Kaspar



Received: 12 May 2013 / Accepted: 17 April 2014 Ó Springer Science+Business Media Dordrecht 2014

Abstract To describe the clinical and epidemiological characteristics of patients with severe infectious keratitis in Asuncio´n, Paraguay between April 2009 and September 2011. All patients with the clinical diagnosis of severe keratitis (ulcer C2 mm in size and/ or central location) were included. Empiric treatment consisted of topical antibiotics and antimycotics; in cases of advanced keratitis, fortified antibiotics were used. After microbiological analysis, treatment was changed if indicated. In total 48 patients (62.5 % males, 25 % farmers) were included in the analysis. A central ulcer was found in 81.3 % (n = 39). The median delay between onset of symptoms and time of first presentation at our institution was 7 days (range 1–30 days). Fungal keratitis was diagnosed in 64.5 % (n = 31) of patients, of which Fusarium sp. (n = 17) was the most common. Twenty-one patients (43.8 %)

Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), May 2012, Fort Lauderdale, USA. M. M. Nentwich (&)  H. M. de Kaspar Department of Ophthalmology, Ludwig-MaximiliansUniversity, Mathildenstr. 8, 80336 Munich, Germany e-mail: [email protected] M. Bordo´n  D. S. di Martino  A. R. Campuzano  W. M. Torres  F. Laspina  S. Lichi  M. Samudio  N. Farina  R. R. Sanabria Fundacio´n Banco de Ojos ‘‘Fernando Oca del Valle’’, Instituto de Investigaciones en Ciencias de la Salud, Asuncio´n, Paraguay

reported previous trauma to the eye. The globe could be preserved in all cases. While topical therapy only was sufficient in most patients, a conjunctival flap was necessary in six patients suffering from fungal keratitis. The high rate of fungal keratitis in this series is remarkable, and microbiological analysis provided valuable information for the appropriate treatment. In this setting, one has to be highly suspicious of fungal causes of infectious keratitis. Keywords Antibiotics  Epidemiology  Infectious keratitis  Fungal keratitis

Introduction Severe infectious keratitis is a serious, potentially sight-threatening condition, which requires prompt treatment. Corneal opacities still represent important causes of global visual impairment (1 % of all visually impaired people worldwide) and blindness (4 % of all blind people worldwide) [1]. Corneal ulceration may even be responsible for 1.5–2.0 million new cases of monocular blindness annually [2]. The distribution of microorganisms responsible for infectious keratitis varies depending on the geographic region. A recent review article found the highest proportion of bacterial corneal ulcers in studies from North America, Australia, the Netherlands, and Singapore, while the highest proportions of fungal infections were seen in studies from India and Nepal

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[3]. Risk factors for infectious keratitis include systemic factors such as diabetes mellitus, local factors like lid/skin abnormalities, blepharitis, and external factors such as trauma due to contact lens wear [3, 4]. Results of microbiological cultures are essential for the appropriate antibiotic treatment of infectious keratitis [5]. However, as these results are not available at the time of first presentation of patients, empirical treatment based on the clinical aspect of the lesion and on epidemiological data for the specific region is necessary until culture results are available. Especially in cases of severe infectious keratitis with progressed disease and a large, centrally located infiltrate, the use of potent topical antibiotics is important in order to control active infection as early as possible. In this work, we aim to describe the clinical and epidemiological characteristics of patients with severe infectious keratitis at Fundacio´n Banco de Ojos Eye Hospital, a non-profit ophthalmic center in Asuncio´n, Paraguay between April 2009 and September 2011.

Materials and methods After approval of the Institutional Review Board of our institution had been obtained, all patients with the clinical diagnosis of severe keratitis (inclusion criteria: ulcer C2 mm in size and/or central location) were included in this study. Demographic and clinical data, as well as treatment, clinical outcome, and risk factors were retrospectively analyzed. Empiric treatment consisted of topical antibiotics (moxifloxacin 5 mg/ml) and antimycotics (fluconazole 2 mg/ml); in cases of advanced keratitis, fortified antibiotics were used (cefazolin 50 mg/ml or vancomycin 50 mg/ml ? gentamicin). After topical anesthetics had been applied corneal scraping was performed in all patients to obtain material for microbiological culture. The specimens were inoculated onto blood-, chocolate-, and Sabouraud agar and in thioglycolate broth. Blood and chocolate agar culture media were incubated for 5 to 7 days at 37 °C, while Sabouraud agar was incubated at 28 °C for 10 days in a humidified incubator [6]. All media were controlled for bacterial and fungal growth on a daily basis and in case of growth, the microorganisms were identified by a microbiologist.

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Depending on the results of the microbiological analysis, empirical treatment was changed if indicated. In case of fungal keratitis, patients received topical treatment every hour either natamycin 5 % or fluconazole 0.2 % and moxifloxacin six times a day. In case of bacterial keratitis, topical moxifloxacin was used. Cefazolin or vancomycin was chosen in cases with very large infiltrates for gram-positive bacteria, while gentamicin was used for gram-negative bacteria and ceftazidime in case of Pseudomonas aeruginosa. In every case, treatment was applied every hour until ten o’clock in the evening or even throughout the night during the first day of treatment.

Results In total 48 patients were included in the analysis. There were 30 male (62.5 %) and 18 female (37.5 %) patients. The age- distribution of patients is shown in Fig. 1. Twenty-five percent of patients (12/48) were farmers which represent a population at the increased risk for fungal keratitis. Previous trauma was reported by 21 patients (43.8 %) (16 males; 5 females). Organic material was involved in 14 of these patients. The median delay between the onset of symptoms and the time of first presentation at our institution was 7 days (range 1–30 days). Some kind of topical treatment had already been started in 18 patients before they presented at our institution (antibiotics n = 8; antibiotics ? antifungal treatment n = 1; antibiotics/steroid combination n = 7; cortisone n = 1; and traditional medication n = 1). In 89.6 % (n = 43) of cases, patients complained of a painful eye, while pain was absent in 5 patients (10.4 %). A central location of the ulcer was found in 81.3 % (n = 39). Mean visual acuity at presentation was 0.025 (no difference between fungal and bacterial keratitis). Hypopyon was present in 41.7 % (20/48) of patients (18/31 fungal keratitis cases and 2/12 bacterial keratitis cases; p = 0.019). Fungal keratitis was diagnosed in 64.5 % (n = 31) of patients (22 males; 9 females), of which Fusarium sp. (n = 17) Aspergillus sp., Acremonium sp., and Curvularia sp. were the most common (Figs. 2, 3, 4). Bacteria were identified in 22.9 % (11/48) of patients, while there was no growth in five patients (rate of positive cultures 89.6 %) (Table 1). With regard to the microbiological results of the 12 farmers, we noted

Int Ophthalmol Fig. 1 Age distribution of patients

Fig. 2 Direct microscopy of scraping specimen: fungi filaments of Aspergillus sp.

Fig. 3 Culture from Acremonium sp. onto Sabouraud and Blood agar

fungal growth in 66.7 % (8/12), growth of enterococci in 16.7 % (2/12) and no growth in two cases. In the cultures of the 14 patients who reported trauma by organic material, fungal growth was seen in 78.5 % (11/14) and enterococci were identified in 14.3 % (2/ 14) while one culture remained sterile.

After the results of the microbiological cultures had been obtained, empirical antibiotic therapy as described in the methods section was changed in 50 % (24/48) of patients. The globe could be preserved in all cases. Topical therapy only was sufficient in most patients. However,

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Fig. 4 Acremonium sp. keratitis: a Day 1 b Day 2 c Day 4 d Culture result

Table 1 Identified Microorganisms

Discussion

Fungi

31

Fusarium sp. Aspergillus sp.

17 5

Acremonium sp.

3

Curvularia sp.

3

Others

3

Bacteria

11

Streptococcus pneumoniae

1

Staphylococcus aureus

1

Pseudomonas aeruginosa

2

Propionicbacterium acnes

1

Moraxella sp.

1

Klebsiella pneumoniae

1

Enterococcus sp.

4

No growth

5

a conjunctival flap was necessary in 6 patients suffering from fungal keratitis to promote healing and one of these patients underwent penetrating keratoplasty after the infection had been controlled. Mean visual acuity after treatment of infectious keratitis was 0.063 at last follow-up with similar results for fungal and bacterial keratitis.

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Severe infectious keratitis is an important cause of monocular blindness, especially in developing countries [2]. In the present study, about two-thirds of patients were male and one out of four patients was a farmer, which is in accordance to previously published data from the same region acquired in the 1990s [6]. Male patients were especially affected in the workingage group 20–59 years-of-age, with regard to fungal infection (male: female ratio = 22:9) and trauma (male: female ratio = 16:5). As topical eye medication is readily available overthe-counter in Paraguay, 37.5 % (18/48) of patients reported self-medication before seeking professional help by an ophthalmologist. The most commonly used topical medications were antibiotics or a combination of antibiotic/steroid eye drops. These results are similar to the findings of the previously cited study from the 1990s in Paraguay [6]. In the present study, the rate of positive cultures was 89.6 % even though almost 40 % of patients had been using topical antibiotics at the time when the specimen was acquired. This may be due to the standardized microbiological work-up of the specimens and the use of different culture media. This rate

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of positive cultures is on the high end compared to similar studies, where microbiological cultures were positive in 35–86 % of cases [3, 4, 7, 8]. The high rate of 64.5 % of patients suffering from fungal keratitis which was found in microbiological culture is remarkable but comparable to a study in Paraguay from the late 1980s. Here 26/45 (58 %) of cases of infectious keratitis were caused by filamentous fungi [9]. This high number is comparable to studies from India, while northern countries report a lower incidence-rate [3, 8, 10, 11]. The great proportion of fungal keratitis in the present series may well be influenced by the high percentage of farmers in this study and the climate in the region. Microbiological analysis of the specimen provided valuable information for the appropriate antifungal treatment in these patients and resulted in a change of antibiotic/antifungal therapy in 50 % of patients. There are clinical signs which help to distinguish between bacterial and fungal keratitis such as the presence of an irregular/feathery border, which was associated with fungal keratitis, or an epithelial plaque, which was associated with bacterial keratitis in a recently published study [12]. Additionally, patients’ history, such as previous trauma or contact lens wear, gives important information on the type of microorganism and helps to choose empirical antibiotic/antifungal therapy. In the present series, hypopyon was more often present in fungal keratitis compared to bacterial keratitis cases. However, in a recent study, corneal specialists were able to distinguish between fungal and bacterial etiology of infective keratitis in 66 % of patients only, based on these clinical signs, which supports the importance of an appropriate microbiological work-up of specimens obtained from affected patients [12]. In the present study, 54.2 % (26/48) of patients presented within 7 days after onset of symptoms, while presentation of 13 patients was delayed by 15 days or more. So, the rate of patients who presented within one week after onset of symptoms is more than twice the one seen in Paraguay in the 1990s and higher than in a study from India, in which 44 % of patients presented within seven days after onset of symptoms [6, 13]. Therefore, one might postulate that awareness to seek appropriate ophthalmologic treatment in cases of eye-pain or ocular trauma has increased during the last 10 years in Paraguay. Self-medication, on the other hand, and even the use of topical corticosteroid

eye drops is still performed by a high percentage of patients. With intensive treatment and regular controls active infection could be controlled and an increase of visual acuity could be achieved in most patients. However, central scars may persist and keratoplasty may be necessary to improve the visual outcome in these patients. There are several limitations to this study. Due to its retrospective design, only patients who actually came to Fundacio´n Banco de Ojo for treatment were included in the study. Therefore, no data on actual incidence of infectious keratitis could be gathered, as patients with less-severe infection might not have sought medical help. As the number of patients with severe infectious keratitis, who met the inclusion criteria, was limited, the optimal antibiotic/antifungal treatment for each causative organism cannot be judged on the basis of this data. However, the results of this study show that at Fundacio´n Banco de Ojos Eye Hospital, Asuncio´n, Paraguay, one has to be highly suspicious of fungal keratitis in patients presenting with infectious keratitis. Therefore, we recommend in our setting, the empirical use of antifungal medication in cases of trauma with organic material and farmers in all cases until microbiological results are available. Acknowledgments Conflict of interest None of the authors has any conflict of interest with the submission.

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Int Ophthalmol 7. Passos RM, Cariello AJ, Yu MC, Hofling-Lima AL (2010) Microbial keratitis in the elderly: a 32-year review. Arquivos Brasileiros de Oftalmologia 73(4):315–319 8. Kumar A, Pandya S, Kavathia G, Antala S, Madan M, Javdekar T (2011) Microbial keratitis in Gujarat, Western India: findings from 200 cases. Pan Afr Med J 10:48 9. Mino de Kaspar H, Zoulek G, Paredes ME, Alborno R, Medina D, Centurion de Morinigo M, Ortiz de Fresco M, Aguero F (1991) Mycotic keratitis in Paraguay. Mycoses 34(5–6):251–254 10. Basak SK, Basak S, Mohanta A, Bhowmick A (2005) Epidemiological and microbiological diagnosis of suppurative keratitis in Gangetic West Bengal, eastern India. Indian J Ophthalmol 53(1):17–22

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11. Sirikul T, Prabriputaloong T, Smathivat A, Chuck RS, Vongthongsri A (2008) Predisposing factors and etiologic diagnosis of ulcerative keratitis. Cornea 27(3):283–287 12. Dalmon C, Porco TC, Lietman TM, Prajna NV, Prajna L, Das MR, Kumar JA, Mascarenhas J, Margolis TP, Whitcher JP, Jeng BH, Keenan JD, Chan MF, McLeod SD, Acharya NR (2012) The clinical differentiation of bacterial and fungal keratitis: a photographic survey. Invest Ophthalmol Vis Sci 53(4):1787–1791 13. Gonzales CA, Srinivasan M, Whitcher JP, Smolin G (1996) Incidence of corneal ulceration in Madurai district, South India. Ophthalmic Epidemiol 3(3):159–166

Clinical and epidemiological characteristics of infectious keratitis in Paraguay.

To describe the clinical and epidemiological characteristics of patients with severe infectious keratitis in Asunción, Paraguay between April 2009 and...
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