Br J Ophthalmol: first published as 10.1136/bjo.69.10.774 on 1 October 1985. Downloaded from

British Journal of Ophthalmology, 1985, 69, 774-777

Clostridium septicum panophthalmitis with systemic complications

MICHAEL S INSLER, ZEYNEL A KARCIOGLU, AND THOMAS NAUGLE JR From the Department of Ophthalmology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA

SUMMARY A fulminant case of endophthalmitis due to septicum is described. The patient presented with spontaneous panophthalmitis, with early visual loss and an air bubble in the anterior chamber. Death ensued, and necropsy revealed changes consistent with severe arterosclerotic cardiovascular disease, a relationship not uncommon in patients with clostridium . This association as well as the histopathology of the globe are discussed.

Gas gangrene panophthalmitis is a rare condition tenderness but good bowel sounds. The white cell usually following penetrating injury to the globe. In count was 28 9x 109/1; the haemoglobin was 13 7 g/dl, most of the reported cases the infecting organism has and the packed cell volume was 40-1%. copyright. been Clostridiumn perfringens.' Later on that evening the patient became confused Characteristic findings are brawny swelling of the and hypotensive and had a respiratory arrest. She lids, coffee coloured discharge, hypopyon, ring responded to cardiorespiratory resuscitation and was abscess of the cornea, gas bubbles in the anterior transferred to the intensive care unit. The differential chamber, and early loss of vision. Systemic manifes- diagnosis at that time included a myocardial infarc- tations include and leucocytosis, malaise, tion and gastrointestinal haemorrhage. A serous nausea, and vomiting. Treatment generally consists discharge was noted from the right eye, and lid and of evisceration or enucleation of the globe and conjunctival specimens were taken for culture. http://bjo.bmj.com/ systemic antibiotics. Extraocular extension of infec- Erythromycin 500 mg intravenously six hourly was tion is prevented by well timed surgical intervention. added to the cefamandole begun on admission. To the best of our knowledge, this paper is the first Two days after admission while the patient was on report of gas gangrene panophthalmitis due to a ventilator her temperature spiked to 104-60F Clostridium septiclunm. (40 3°C) and blood cultures were obtained. A heart and a perfusion lung scan were performed, and both Case report were within normal limits. An ophthalmology con- on September 29, 2021 by guest. Protected sultation was obtained, at which time a gas bubble A 78-year-old Caucasian woman was admitted to was noted in the anterior chamber. hospital on 15 October 1981 with a 24-hour history of Ophthalmic examination on 18 October 1981 nausea, vomiting, and mild abdominal pain. The revealed an opaque cornea and a very tense globe. diagnosis on admission was dehydration and acute An anterior chamber paracentesis was performed gastroenteritis. There was a history of atherosclerotic and approximately 0 1() ml of chocolate coloured heart disease and degenerative arthritis. Vital signs at fluid was obtained. This material was plated on blood the time of admission showed a blood pressure of and chocolate agars and was submitted for anaerobic 152/80 mmHg, respiration rate of 20/min, a slight culture. tachycardia, and a temperature of 101°F (38-3°C). On 19 October 1981 the patient died. A general Examination revealed a slightly obese Caucasian necropsy, performed 21/2 hours after death, revealed woman who was vomiting and complaining of severe atherosclerotic cardiovascular disease, abdominal pain. The heart and lung examination was dissecting aortic aneurysm, severe brochopeneu- normal. The abdominal examination revealed monia, and changes consistent with sepsis. The aortic Corrcspondencc to Michael S Inslcr. MD. aneurysm was not ruptured and did not appear to be 774 Br J Ophthalmol: first published as 10.1136/bjo.69.10.774 on 1 October 1985. Downloaded from

Clostridium septicumpanophthalmitis with systemic complications 775 the cause of death. No recent myocardial infarction ture was left intact. The choroidal blood vessels were was found. Culture of the anterior chamber aspirate found to contain many thromboemboli (Fig. 3). Only grew a pure colony of Clostridium septicum. fragments of retinal structures showing severe could be identified in certain segments of the PATHOLOGICAL EXAMINATION OF THE EYE globe. In addition to its necrotic appearance the The globe was examined under the dissecting micro- tissue contained empty spaces possibly secondary to scope in the pathology laboratory. No penetrating gas-producing . The overall bullous appear- injury could be identified. The corneal surface was ance of the retina and choroid was also consistent opaque, extremely irregular, and thin in the centre. with extensive oedema and gas production. A few On transverse sectioning the globe was observed to clusters of Gram-positive bacteria were identified, be diffusely necrotic. A small amount of purulent, but these did not have the spindle, drumstick appear- coffee coloured fluid was found in the anterior ance of Clostridium septicum and did not contain chamber and vitreous cavity. The inner surface of the spores. eye was pale and extensively necrotic. The retina was not identified. Instead the inner surface of the globe Discussion was irregular, elevated, and bullous in appearance. Histological examination of the eye showed that all Clostridial infections of the eye are devastating. ocular tissues were involved in an acute necrotising Since Leavelle's' extensive review of 53 previously inflammatory process (Fig. 1). The cornea and sclera reported cases as well as three of his own nine (Fig. 2) were diffusely infiltrated with acute inflam- additional cases have been reviewed by Frantz et al.5 matory cells and had undergone severe collagen All previously reported cases of gas gangrene degeneration and necrosis. Scleral and episcleral panophthalmitis followed pentrating injuries to the blood vessels were surrounded by acute inflamma- eye and the offending organism was Clostridium tion and their walls were partially necrotic. The perfringens. Frantz and colleagues' report included a central cornea was extremely thin, with total absence 68-year-old white male who presented with fever, of the epithelium and more than half of the stroma. pain in the right upper quadrant of the abdomen, and copyright. The ciliary body and iris were extensively inflamed panophthalmitis of the left eye. Unlike the previously and necrotic. The choroid was detached in some described cases their case resulted from endogenous segments and was also involved in the diffuse necro- infection of the eye complicating perforation of a sis; in some areas only the framework of the vascula- gangrenous gallbladder. http://bjo.bmj.com/

Fig. I Extensive oedema and

necrosis ofretina and choroid. on September 29, 2021 by guest. Protected Retina is totally necrotic. Only a short segment ofdetached retinal pigment epithelium (RPE) is seen in thefigure. VC: vitreous chamber; C: choroid; S: sclera; EOM: extraocular muscle. (Haematoxylin and eosin, x40). Br J Ophthalmol: first published as 10.1136/bjo.69.10.774 on 1 October 1985. Downloaded from

776 Michael S Insler, Zeynel A Karcioglu, and Thomas NaugleJr

Fig. 2 Diffuse infiltration ofacute inflammatory cells and necrosis in retina (R), choroid (C), andsclera (S). (HandE, xlOO). copyright.

The clinical picture of clostridial panophthalmitis can be overlooked, as isolates may form only a thin described by Leavelle is one of severe pain and rapid film on the culture plate without the definition of loss of vision within 12 hours of injury. An explosive distinct colonies. Smears from cultures show Gram- panophthalmitis with chemosis and swelling of the lid positive sporulating rods with oval terminal and is usually apparent by 18 hours. Hypopyon, ring subterminal spores. C. septicum is differentiated

abscess of the cornea, coffee coloured discharge, gas from other by its carbohydrate fermenta- http://bjo.bmj.com/ bubbles in the anterior chamber, immobilisation of tion reactions and its lack of lecithinase or lipase the globe, and a total loss offundus reflex with loss of production. vision were signs usually evident by 24 hours. Con- An association of clostridial infections with malig- ventional antibiotic therapy has been entirely nancy, especially cancer of the colon, has been impotent against this disastrous disease, even though demonstrated by several case reports."9 In 1969 some cases were seen very early. Alpern and Dowell' reported that 23 of 27 patients For practical purposes the clostridia may. be (85%) with C. septicum infections whose cultures divided into three groups: C. botulinum causing were referred to the Center for Disease Control on September 29, 2021 by guest. Protected botulism, C. tetani causing tetanus, and several types (CDC) for identification had malignant disease. Of of clostridia causing gas gangrene, commonly C. the four patients who did not have malignant disease perfringens, C. novyi, C. septicum, C. histolyticum, three developed intestinal tumours one to two and C. fallax. All the clostridia are large Gram- months after the C. septicum was cultured. positive rod-like anaerobic bacteria with a larger Koransky et al.7 reported on the clinical signific- spore-forming end, giving them a drumstick appear- ance of C. septicum bacteraemia. The medical ance. The clostridia which may be considered as records of 59 patients were reviewed; 42 (71%) of potential causes of gas gangrene panophthalmitis these patients had malignant disease. Half had produce powerful . The most common haematological malignant disease and one half had member of this group of organisms is C. perfringens solid tumours. Of the 21 patients with solid tumours (C. welchii); next are C. novyi and C. septicum 14 (67%) had cancer of the colon. The caecum and in degree of frequency of isolation from war distal ilieum were thought to be the most probable wounds. portals of entry for C. septicum bacteraemia among C. septicum, an , is B-haemolytic the 28 patients examined at necropsies. They on blood agar and highly motile. Spreading growth reported one patient with distant metastatic infection Br J Ophthalmol: first published as 10.1136/bjo.69.10.774 on 1 October 1985. Downloaded from

Clostridium septicumpanophthalmitis with systemic complications 777

be ruled out when C. septicum is cultured from a 'metastatic' infection outside the bowel.' However, she did have severe atherosclerotic cardiovascular disease, as did six of 17 patients without malignant disease in Koransky and colleague's series.7 It has been suggested that arteriosclerosis may have a role in the development of ischaemia and tissue necrosis, which are important predisposing factors for clostri- dial growth and gangrene formation.7 Although a positive (ante-mortem) blood culture was not obtained in our case, we attribute this to antimicrobial therapy instituted prior to the sam- pling. Fever, especially when accompanied by gas gangrene, tissue necrosis, and/or the signs of shock which characterised our patient's hospital course, should suggest possible septicaemia caused by toxic bacteria such as clostridium. The importance of early recognition and prompt therapy in patients with Clostridium septicum infec- tion cannot be overemphasised. When these patients are admitted to hospital they are acutely ill and toxic. Their clinical course is usually fast downhill, and unless the appropriate antibiotics are administered soon after admission the outcome is fatal. Blood cultures, both aerobic and anaerobic, should be performed rapidly, and therapy should be instituted copyright. before the results of the cultures are received. remains the drug of choice, but some Fig. 3 Uedema, necrosis, and diffuse acute inflammatory patients may be treated successfully with chloram- cell infiltration ofthe retina, choroid, andsclera with multiple phenicol, carbenicillin, or cephalothin. thromboemboli (T) in choroidal andscleral blood vessels. R: necrotic retina; C: choroid; S: sclera. (H and E, x85). Insert: Organisms, identified in culture as Clostridium References areas septicum, within necrotic ofthe sclera. (, http://bjo.bmj.com/ x850, oil immersion). I Lcavellc RB. Gas gangrcnc panophthalmitis. Arch Ophihalmol 1955; 53: 634-42. 2 Walsh TJ. Clostridial ocular infcctions. Casc report of gas of the eye who had an enucleation and then was later gangrcnc panophthalmitis. BrJ Ophthalinol 1965; 49: 472-7. found to have adenocarcinoma of the colon. 3 Kurz GH, Wciss JF. Gas gangrcne panophthalmitis. Br J Further results of their study showed that of the 17 Ophthalmol 1969; 53: 323-6. 4 Lcvitt JM, Stam J. panophthalmitis. patients with no detectable malignancy six had severe Arch Ophthalmol 1970; 84: 227-88.

atherosclerotic cardiovascular disease with a 5 Frantz JF, Lcmp MA, Font RL, Stonc R, Eisner E. Acute on September 29, 2021 by guest. Protected gangrenous extremity or gangrenous bowel. Infec- cndogenous panophthalmitis causcd by Clostridium perfringens. Am J 78: tion with C. septicum was the apparent cause of Ophthalmol 1974; 295-3t)3. death 6 Alpern RJ, Dowell VR. Clostridium septicum infections and in 40 patients (68%). All surviving patients were malignancy. JA MA 1969; 209: 385-8. given penicillin, cephalothin, chloramphenicol, or 7 Koransky JR, Stargel MD, Dowcll VR. Clostridiuin septicum carbenicillin (antibiotics to which clostridia have bacteremia. Am J Med 1979; 66: 63-6. been found to be soon 8 Katlic MR, Derkac WM, Coleman WS. Clostridium septicum sensitive"') after they were infcction and admitted to malignancy. Ann Surg 1981: 193: 361-4. the hospital. 9 Schaaf RE, Jacobs N, Kcivin FM, et al. Clostridium septicum Post-mortem examination of our patient, who infcction associated with colonic carcinoma and hcmatologic apparently developed spontaneous gas gangrene abnormality. Radiology 198t); 137: 625-7. panophthalmitis due to Clostridium septicum, failed 1) Gabay EL, Rolfc RD, Fincgold SM. Susccptibility of Clostridium septicum to 23 antimicrobial agents. Antimicrob to disclose an occult malignant tumour, which must Agents Chemother 1981; 20: 852-3.