LISTERIA
MONOCYTOGENES
ENDOPHTHALMITIS
JOHN W. SNEAD, M.D., WALTER H. STERN, M.D., JOHN P. WHITCHER, M.D., AND MASAO OKUMOTO, M.D. San Francisco, California
Listeria monocytogenes, a unique bac terium, is a rare cause of endophthalmitis. To our knowledge this is the second doc umented case of human endophthalmitis associated solely with this organism. This case deserves special attention because of the rarity of the organism as a cause of endophthalmitis, because there was no discernible route by which the organism entered the eye, and because the endo phthalmitis responded to vigorous diag nostic and therapeutic measures. CASE REPORT A 62-year-old white man was noted by his wife to have an asymptomatic, red left eye. On the follow ing day, the patient noticed markedly decreased vision in that eye, but had only slight discomfort and no discharge. There was no history of trauma or infection, either periocular or removed, and no prior glaucoma, uveitis, or cataract. There was also no history of neoplasm or diabetes mellitus. He was seen by an ophthalmologist who diag nosed plastic uveitis and prescribed topically ap plied phenylephrine and cyclopentolate, along with 0.1% dexamethasone every three hours. After a large hypopyon appeared, the patient was referred to the San Francisco Veterans Administration Hospital where he was seen four days after the onset of his red eye. General medical history and physical examination were unremarkable. Specifically, there was no nu chal rigidity, abnormal breath sounds, heart mur mur, urethritis, or cutaneous lesions. Corrected visual acuity for the right eye was 6/9 (20/30) and for the left eye hand movements. Applanation tonometry was 18 mm Hg in the right eye, and 44 mm Hg in the left. There was no preauricular or submandibular adenopathy. Biomicroscopic and ophthalmoscopic examinations of the right eye were normal. The eyelids of the left eye were edematous but not red. Extensive conjunctival injection and corneal microcystic edema were present without infiltrate or From the Veterans Administration Hospital, and the Department of Ophthalmology, University of California, San Francisco, California. Reprint requests to John W. Snead, M.D., Depart ment of Ophthalmology, University of California, San Francisco, CA 94143.
ulceration of the cornea. The anterior chamber was 40% filled with a yellow-white, hypopyon-fibrin clot inferiorly (Figure). The pupil was 3 mm in diameter and fixed. The lens was poorly visible, but appeared normal; the fundus was not visualized. Laboratory studies—Hematological examination showed the following values: hemoglobin, 13.8 g/100 ml; white blood cells, 9,500/mm3, with 57% polymorphonuclear leukocytes, 2% bands, 32% lymphocytes, 1% eosinophils, and 8% monocytes. Serum glucose, electrolytes, blood urea nitrogen, and creatinine values were normal. The VDRL test was negative. The erythrocyte sedimentation rate was 11 mm/hr. Total serum protein was 6.8 g/100 ml, with a 3.9 g/100 ml globulin fraction. Serum immunoglobulins by the radial immunodiffusion method were normal. Lymphocyte function as measured by antibody-dependent cell-mediated cytotoxicity was also normal. Intermediate-strength purified-protein derivative skin test gave no reac tion, though trichophyton antigen showed approxi mately 15 mm of induration. Orbital, chest, and lumbosacral radiographs were negative. An ocular B-scan ultrasonogram showed the hypopyon but no posterior segment abnormali ties. A pars plana vitreous aspiration was performed immediately. Gram stain of the aspirate showed a moderate number of polymorphonuclear leukocytes but no organisms. Vitreous cultures by two indepen dent laboratories revealed L. monocytogenes. Anti biotic sensitivity determinations showed resistance to penicillin and methicillin but sensitivity to most other routinely tested antibiotics, including ampicillin and gentamicin. Two blood cultures were nega tive; throat, urine, and stool cultures revealed nor mal flora. Conjunctival culture showed rare coagulase-negative Staphyloccocus epidermidis and rare anaerobic diphtheroids. Immediate therapy was begun with topically ap plied bacitracin, gentamicin, atropine, and dexa methasone, along with subconjunctivally and intra venously administered methicillin and gentamicin. After culture verification and determination of the sensitivity pattern, therapy was changed to topically applied prednisolone and atropine, subconjunctiv ally administered gentamicin and dexamethasone, and intravenously administered ampicillin, 12 g/day in divided doses. The ampicillin was continued for 17 days, then changed to orally administered ampi cillin, 500 mg four times daily, for an additional 18 days. Oral administration of prednisone, 60 mg/day, was started on the 16th hospital day and continued for ten days, then tapered slowly. Orally adminis tered acetazolamide was used as needed to lower intraocular pressure. The anterior chamber inflammation slowly
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#*&&
Figure (Snead and associates). Fibrin clot in anterior chamber.
cleared within four weeks, leaving numerous pe ripheral anterior synechiae and an associated secon dary glaucoma which necessitated filtration surgery. At the present time, the patient still has chronic stromal corneal edema and recurrent breakdown of the epithelium as a result of damaged endothelium. A soft contact lens has improved the patient's com fort but not his visual acuity, which is variably 6/120 (20/400) to finger-counting at 5 ft. The lens and vitreous have remained clear, and the fundus ap pears normal. DISCUSSION
Listeria monocytogenes is a grampositive, motile rod which gives beta hemolysis on blood agar and, therefore, may be mistaken for diphtheroids or strepto cocci. For this reason, if clinical infection is present, a report of contaminating diph theroids should not be dismissed as a negative culture unless Listeria has been specifically excluded. It is predominantly an intracellular organism that derives its name from the monocytic response often elicited in the blood of an infected host. 1 A ubiquitous organism, Listeria is a saprophyte which may survive in a plant-soil environment 2 , 3 as well as in the feces of some animals. 4 A small percent
age of human beings may harbor Listeria in the intestinal tract without clinical disease. 5 Listeria infections appear more often in persons whose defense mechanisms are compromised, such as immunosuppressed patients, 6 alcoholics, diabetics, neonates, and patients with malignant neoplasms. 7 Central nervous system in fections are the most common form of Listeria-caused disease. In the United States, meningitis accounts for about three fourths of the cases of Listeria in fections. Clinically, Listeria meningitis is no different than any other bacterial men ingitis. 8 Other reported forms of Listeria infections include endocarditis, 9 enceph alitis, pneumonia, localized abscesses, and genital infections. 4 A unique form of intrauterine Listeria infection becomes a generalized neonatal sepsis known as granulomatosis infantiseptica. This disease form, which produces disseminated ab scesses and granulomas in the skin and viscera of the fetus with a high mortality, is probably transmitted to the fetus by a transplacental route following a relatively
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asymptomatic and self-limited disease in the mother. 8 Ocular forms of human Listeria infec tions include conjunctivitis, oculoglandular disease, corneal ulceration, 10 and endophthalmitis. 1 1 All of these are rare with conjunctivitis the most frequent. Cherednichenko 1 2 suggested that Listeria may play a role in iridocyclitis and chorioretinitis, but this association was shown only serologically. Because of the crossreaction of Listeria with a number of commonly occurring organisms, and be cause antibodies to Listeria may be found in apparently healthy individuals, serological results are not sufficient for diag nosis. 4 Listeria conjunctivitis is usually a pur ulent conjunctivitis or keratoconjunctivitis which is seen in neonates and adults. Corneal ulceration may sometimes oc cur. 13,14 The conjunctivitis may be isolat ed or may be the first clinically visible sign of more generalized infection. 10 In deed, in rats, conjunctivitis may be the presenting sign of sepsis after experimen tal intraperitoneal innoculation of Liste ria. 15 Other experimental results in gravid female rabbits suggest that systemic spread may occur frequently after conjunctival instillation. 16 Listeria encepha litis has occurred in a rabbit following experimental conjunctivitis. 17 Rare cases of an oculoglandular form of Listeria infection presenting as Parinaud's oculoglandular syndrome have been recorded; however, diagnosis was on the basis of hematological and serological findings alone. 18,19 Goodner and Okumoto's 1 1 case of Lis teria endophthalmitis presented as an acute anterior chamber inflammation with a fibrin clot without signs of con junctivitis. Our patient had conjunctival injection but no purulent discharge or adenopathy. Both patients could have had an initial conjunctivitis with mild clinical manifestations masked by topically ap
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plied medications. Their patient, like ours, was initially treated with corticosteroids and mydriatics for acute anterior uveitis until Listeria was demonstrated by culture after ocular paracentesis. In neither of these cases was there historical or clinical evidence for penetrat ing injury of the eye or for a distant site of infection from which hematogenous spread could have occurred. In the pres ent case, blood cultures obtained before starting antibiotic therapy were negative. Goodner and Okumoto 1 1 considered the possibility of an oral route of entry. Certain experimental evidence indicates that Listeria may spread from an intesti nal portal of entry. 20 However, the route by which the bacteria entered the eyes in both of these cases remains obscure. In both cases, the endophthalmitis respond ed to therapy, and the eyes were saved. SUMMARY
A 62-year-old white man developed an acute anterior chamber inflammation in his left eye. Listeria monocytogenes was cultured from the vitreous aspirate. There was no evidence for ocular trauma or distant site of infection from which he matogenous spread of the organism oc curred. No underlying state of immunocompromise was demonstrated. The endophthalmitis responded well to thera pyREFERENCES 1. Murray, E. G. D„ Webb, R. A., and Swann, M. B. R.: A disease of rabbits characterised by a large mononuclear leucocytosis, caused by a hither to undescribed bacillus Bacterium monocytogenes (n.sp.). J. Pathol. Bacteriol. 29:407, 1926. 2. Weis, J., and Seeliger, H. P. R.: Incidence of Listeria monocytogenes in nature. Appl. Microbiol. 30:29, 1975. 3. Botzler, R. G., Cowan, A. B., and Wetzler, T. F.: Survival of Listeria monocytogenes in soil and water. J. Wildl. Dis. 10:204, 1974. 4. Gray, M. L., and Killinger, A. H.: Listeria monocytogenes and listeric infections. Bacteriol. Rev. 30:309, 1966.
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5. Seeliger, H. P. R.: New outlook on the epide miology and epizoology of listeriosis. Acta Microbiol. Acad. Sci. Hung. 19:273, 1972. 6. Isiadinso, O. A.: Listeria sepsis and meningitis. A complication of renal transplantation. J.A.M.A. 234:842, 1975. 7. Lavetter, A., Leedom, J. M., Mathies, A. W., Jr., Ivler, D., and Wehrle, P. F.: Meningitis due to Listeria monocytogenes. A review of 25 cases. N. Engl. J. Med. 285:598, 1971. 8. Hoeprich, P. D.: Infections caused by Listeria and Erysipelothrix. In Wintrobe, M. M. (ed.): Harri son's Principles of Internal Medicine, ed. 7. New York, McGraw-Hill Book Co., 1974, p. 837. 9. Bassan, R.: Bacterial endocarditis produced by Listeria monocytogenes. Case presentation and re view of literature. Am. J. Clin. Pathol. 63:522, 1975. 10. Burdin, J. C , Pierson, M., Percebois, G., Georges, J. C , and de Lavergne, E.: Les formes oculaires de la listeriose humaine. Presse Med. 73: 1461, 1965. 11. Goodner, E. K., and Okumoto, M.: Intraocular listeriosis. Am. J. Ophthalmol. 64:682, 1967. 12. Cherednichenko, V. M.: On the role of listerellal (sic) infection in the etiology of endogenous uveitis. Vestn. Oftalmol. 4:42, 1962.
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13. Felsenfeld, O.: Diseases of poultry transmis sible to man. Iowa State Coll. Vet. 13:89, 1951. 14. Aubertin, E., Dulong de Rosnay, C , Aubertin, J., Veaux, R., Latrille, J., and Duriez, J. C : Quelques aspects des listerioses de 1'adulte. J. Med. Bordeaux 141:1243, 1964. 15. Flamm, H., and Zehetbauer, G.: Die Lister iose des Auges im Tierversuch. Albrecht von Graefe's Arch. Klin. Ophthalmol. 158:122, 1956. 16. Gray, M. L., Singh, C , and Thorp, F„ Jr.: Abortion, stillbirth, early death of young in rabbits by Listeria monocytogenes. 1. Ocular instillation. Proc. Soc. Exp. Biol. Med. 89:163, 1955. 17. Gray, M. L., Stafseth, H. J., Thorp, F., Jr., Sholl, L. B., and Riley, W. F., Jr.: A new technique for isolating listerellae from the bovine brain. J. Bacteriol. 55:471, 1948. 18. Pletneva, N. A., and Stiksova, V. N.: Oculoglandular form of listerosis. Vestn. Oftalmol. 29:17, 1950. 19. Shmeleva, V. V.: Cases of oculo-glandular listerosis. Vestn. Oftalmol. 32:46, 1953. 20. Gray, M. L., Singh, C , and Thorp, F., Jr.: Abortion, stillbirth, early death of young in rabbits by Listeria monocytogenes. 2. Oral exposure. Proc. Soc. Exp. Biol. Med. 89:169, 1955.
OPHTHALMIC MINIATURE
He was a tall man, but he had a terrible stoop, a crooked spine and a worn face like a very old man's. His eyes were so swollen, his lower eyelids so pulled down that instead of the horizontal oval everyone has in their eyes he had something more like a circle, and in each circle the white had an unhealthy reddish tinge. They were bright, brownish iridescent rings larger looking than usual because of the distended lower eyelids. With these great round eyes the old man seemed to be examining everyone with an unpleasant, attentive gaze. Alexander Solzhenitsyn, Cancer Ward Farrar, Straus, 1969