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INTERNATIONAL REPORT

Corneal Ulcer Caused by Pseudomonas pseudomallei: Report of Three Cases S. Siripantbong, s. Teerapantuwat, w. Prugsanusak, Y. Suputtamongkol, P. Viriyasitbavat, w. Cbaowagul, D. A. B. Dance, and N. J. White

From the Department of Ophthalmology and Medicine, Sappasitprasong Hospital, Ubon Ratchatani; and the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; and Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

We report three cases of corneal ulcer caused by Pseudomonas pseudomallei. In all cases corneal trauma preceded the development of extensive ulcers, subconjunctival abscesses, and hypopyon. Treatment for a total of 8 weeks with topical and/or parenteral ceftazidime followed by amoxicillin-clavulanic acid produced resolution of infection in each case.

Case Reports Case 1. A previously healthy 56-year-old male rice farmer was admitted to the hospital 5 days after being struck in the eye by a bamboo twig. Despite topical treatment with traditional medication (a mixture of turmeric and human breast milk) followed by antibiotic drops, the eye had become progressively more painful and inflamed, and his vision had become blurred. On admission there was marked chemosis and ciliary injection of the right eye and a corneal ulcer. The patient's visual acuity was 6/36 (right eye) and 6/18 (left eye), improving with pinhole to 6/12. His oral temperature was 37.2°C, but

Received 19 January 1990; revised 25 June 1990. Reprints and correspondence: Dr. Y. Suputtamongkol, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Financial support: This work was part of the Wellcome-Mahidol University, Oxford Tropical Medicine Research Programme funded by the Wellcome Trust of Great Britain. Reviews of Infectious Diseases 1991;13:335-7 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1302-0017$02.00

findings on physical examination were otherwise normal. Empiric treatment with neomycin, polymyxin, and tobramycin eyedrops together with systemic cefazolin (6 gld) and gentamicin (180 mgld) and subsequently with topical amphotericin B produced no improvement; 6 days after admission, panophthalmitis developed, with three small subconjunctival abscesses surrounding the cornea, hypopyon, and complete opacity of the cornea. A swab specimen taken from the corneal ulcer on the day of admission grew P. pseudomalleithat was sensitive to ceftazidime, amoxicillin-clavulanic acid, chloramphenicol, and doxycycline. The infection was treated with ceftazidime as follows: 200 rng by subconjunctival injection on alternate days for 7 days; eyedrops made from ceftazidime pentahydrate (Glaxo Laboratories, Greenford, Middlesex, U.K.) for injection combined with carboxymethyl cellulose (concentration, 10 mg/ mL) hourly; and 2 g of intravenous ceftazidime every 8 hours. There was no further progression of the lesions after 2 days of treatment, and symptoms became less severe after 4.days. The fever subsided in 5 days, and subconjunctival abscesses resolved 4 weeks after the start of treatment. After 2 weeks of ceftazidime therapy, oral amoxicillin-clavulanic acid (750 mg) and additional amoxicillin alone (500 mg) (Beecham Research Laboratories, Brentford, Middlesex, U.K.) were given four times daily for a further 6 weeks. The patient has now developed an anterior staphyloma, but there is no evidence of active local or systemic infection after 8 months of follow-up. Case 2. A 5-year-old boy was admitted with periorbital swelling and pain in the right eye 7 days after contact with the irritant secretions of the fruit-sucking bug (Tessaratoma javanica). His eye had been washed immediately with well water; his symptoms had not lessened during subsequent topical treatment with chloramphenicol from a local health clinic. On admission he had periorbital desquamation, mixed injection of the conjunctiva with abundant mucopurulent discharge, central corneal ulceration and opacity, and hypopyon. His oral temperature was 37.5°C, but his physical examination was otherwise unremarkable.

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Melioidosis, or infection with Pseudomonas pseudomallei, is a major cause of morbidity and mortality in Thailand [1]. The majority of patients are farmers with underlying diabetes mellitus or renal disease who present with aggressive septicemia. Metastatic abscess formation in the lungs and viscera is common. Localized forms of the infection may also occur. Primary ocular disease has not been described previously, although a case of orbital colonization following trauma and enucleation [2], a case of orbital cellulitis [3], and a case of P. pseudomallei dacrocystitis [4] have been reported. We describe three patients admitted with severe corneal ulceration caused by P. pseudomallei to Sappasitprasong Hospital in Ubon Ratehatani, northeastern Thailand, during the rainy season of 1989.

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Discussion

P. pseudomallei is an environmental saprophyte found in water and muddy soil in many parts of the tropics. Infections with this organism both in humans and in animals have been reported most frequently from Southeast Asia. In recent years, with greater availability of microbiology services, melioidosis has become recognized as a major disease in the ricefarming communities of northeastern Thailand [5]. Asymptomatic infection is common (as is evidenced by a high

seroprevalence of antibodies to P. pseudomallei among healthy adults) [5, 6], and in a recent study this organism accounted for ~20 % of cases and 40 % of deaths from communityacquired septicemia in a large provincial hospital [5]. The mode of acquisition is uncertain. Ingestion, inhalation, and inoculation may all lead to infection [1,5], although the weight of evidence suggests that the last-mentioned route is responsible for the majority of cases [5]. Corneal ulceration has not been reported previously as a manifestation of melioidosis. These three cases presented during one rainy season and represented 2 % of all cases of P. pseudomallei infection seen during this period. In all three cases the disease began with a corneal abrasion, although it could not be determined with certainty whether P. pseudomallei was inoculated at the time of injury or later by local application of contaminated materials. Factors predisposing to infection, such as diabetes mellitus or renal failure, are present in the majority of patients with severe melioidosis but were found in none of our cases. The ocular infections were aggressive and resulted in extensive corneal damage with consequent loss of visual acuity in one case. In this respect, they resembled ocular infections caused by Pseudomonas aeruginosa, which is known to produce rapidly progressive panophthalmitis following traumatic inoculation [7]. It is possible that the marked proteolytic activity of P. pseudomallei contributed to the destructive ocular pathology in our three patients, as is thought to be the case with P. aeruginosa [8]. Subconjunctival abscesses, which were seen in two of our cases, are an unusual manifestation of ocular infections. P. pseudomallei infections at other sites are frequently characterized by abscess formation [l, 5]. There were no other specific clinical features by which to differentiate P. pseudomallei keratitis from that caused by other bacterial or fungal pathogens. Further experience with this condition is necessary before the value of subconjunctival abscesses as a clinical indicator of the etiology can be assessed. P. pseudomallei grows readily on routine microbiologic culture media and can be identified by simple techniques. It is resistant to many [3-lactam antibiotics, polymyxin, and the aminoglycosides and is also relatively resistant to the new fluoroquinolones, Thus many empiric treatments for eye infections may be ineffective against this organism. P. pseudomallei is sensitive to tetracyclines and chloramphenicol, although these agents are only bacteriostatic. It is also sensitive to ureidopenicillins, third-generation cephalosporins, imipenem, and amoxicillin-clavulanic acid [9]. The third-generation cephalosporin ceftazidime is the treatment of choice for acute, severe melioidosis [10]. The optimal treatment for ocular melioidosis is unknown. Since inoculation with P. pseudomallei at other sites may be followed by a rapidly fatal septicemic illness [1, 5] and since all of our cases were initially pyrexial, we decided to treat the infections aggressively with systemic as well as topical antibiotics. Systemic and local treatment

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Two days after his admission, a swab specimen taken from the corneal ulcer grew P. pseudomallei sensitive to ceftazidime, amoxicillin-clavulanie acid, chloramphenicol, and doxycycline. He was treated with ceftazidime eyedrops hourly (10 mg/mL, as in case 1) and with oral amoxicillin-clavulanic acid (60 mg/[kg-d] in four divided doses). After 3 days of treatment, chemosis and purulent discharge were markedly reduced; after 1 week of treatment, only a small area of residual corneal ulceration was observed on fluorescein examination; and after 20 days oftreatment, the boy was discharged with instructions to take oral amoxicillin-clavulanie acid for 6 weeks. His visual acuity is now normal, and there has been no evidence of further infection during 6 months of follow-up. Case 3. A 43-year-old man was admitted with a week's history of increasing pain, swelling, and blurring of vision of the left eye following an electrical burn. He had washed his eye with tap water and had received eyedrops from a provincial hospital. On examination his left eyelid was markedly swollen, with severe chemosis, scleral injection, ulceration of the lower half of the cornea, and hypopyon. His visual acuity was 6/6 in the right eye, but hand movements were perceived only by the left eye. His oral temperature was 37.5°C. Physical examination was otherwise normal. Three days after his admission, a swab taken from the lesion grew a strain of P. pseudomallei sensitive to ceftazidime, chloramphenicol, doxycycline, and amoxicillin-clavulanic acid. He was given ceftazidime as eyedrops (10 mg/mL) hourly, as a subconjunctival injection (200 mg on alternate days), and as an intravenous injection (2 g every 8 hours) for 2 weeks. His fever subsided after 3 days of treatment, concurrent with lessening in the severity of the symptoms in the eye and despite the development of a subconjunctival abscess. After 2 weeks of treatment, the swelling of the eyelid, the chemosis, and the subconjunctival abscess had resolved, but some degree of hypopyon remained. The patient's visual acuity had also gradually improved. Oral amoxicillin-clavulanic acid (1,250 mg four times daily) was subsequently given to complete a total of 8 weeks of treatment. After 6 months of followup, the patient has mild residual corneal opacity, but there has been no further evidence of active infection.

RID 1991;13 (March-April)

RID 1991;13 (March-April)

Corneal Ulcers Due to P. pseudomallei

Acknowledgments The authors thank the director of Sappasitprasong Hospital and his staff; the physicians of the Department of Ophthalmology and Medicine; Ms. Vanapom Wuthiekanun, Ms. Nittaya Teerawattanasook, and the staff of the microbiology laboratory; the nursing staff of the ophthalmological ward; and Dr. T. M. E. Davis for their help during these studies. They also thank Profs. Danai Bunnag and Khunying Tranakchit Harinasuta for their support and Ms. Nucharee Cholvilai for typing the manuscript. Finally, they thank Glaxo Labora-

tories and Beecham Research Laboratories for the kind donation of ceftazidime and amoxicillin-clavulanic acid, respectively.

References 1. Leelarasamee A, Bovornkitti S. Melioidosis: review and update. Rev Infect Dis 1989;11:413-25 2. Nussbaum 11, Hull DS, Carter MJ. Pseudomonas pseudomallei in an anophthalmic orbit. Arch Ophthalmol 1980;98:1224-5 3. Yospaiboon Y, Sangveejit J. Orbital cellulitis due to Pseudomonas pseudomallei. Thai Journal of Ophthalmology 1987;1:51-4 4. Suwanwatana C. Acute dacrocystitis due to Pseudomonaspseudomallei. Srinakarin Hospital Medical Journal 1990;5:56-8 5. Chaowagul W, White NJ, Dance DAB,Wattanagoon Y, Naigowit P, Davis TME, Looareesuwan S, Pitakwatehara N. Melioidosis: a major cause of community-acquired septicemia in northeastern Thailand. J Infect Dis 1989;159:890-9 6. Nigg C. Serologic studies on subclinical melioidosis. J Immunol 1968; 91:18-28 7. Pollack M. Pseudomonasaeruginosa. In: Mandell GL, Douglas RG Jr, Bennett J, eds. Principles and practice of infectious diseases. 2nd ed. New York: Wiley, 1985:1243-4 8. Wretlind B, Pavlovskis OR. The role of proteases and exotoxin A in the pathogenicity of Pseudomonasaeruginosa infections. Scand J Infect Dis [Suppl] 1981;29:13-9 9. Dance DAB, Wuthiekanun V, Chaowagul W, White NJ. The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 1989;24: 295-309 10. White NJ, Dance DAB, Chaowagul W, Wattanagoon Y, Wuthiekanun V, Pitakwatehara N. Halving of mortality of severe melioidosis by ceftazidime. Lancet 1989;2:697-700

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with ceftazidime proved effective in our three cases, although it was started too late to prevent extensive corneal damage in one instance. Melioidosis is slow to respond to antimicrobial treatment and has a tendency to relapse [1]. Therefore, long courses of treatment are necessary (minimum, 8 weeks). Amoxicillin-c1avulanic acid was given for maintenance therapy in our cases because it is well tolerated and because we have found it to be of value for the treatment of other forms of melioidosis (authors' unpublished data). Ophthalmologists should be aware of the possibility of P. pseudomallei infection in cases of traumatic corneal abrasion in patients from endemic areas. Microbiology laboratories should be specifically requested to search for this organism in specimens taken from such cases, and treatment with local and systemic ceftazidime should be started in suspected or confirmed cases.

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Corneal ulcer caused by Pseudomonas pseudomallei: report of three cases.

We report three cases of corneal ulcer caused by Pseudomonas pseudomallei. In all cases corneal trauma preceded the development of extensive ulcers, s...
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