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Endogenous Serratia marcescens Endophthalmitis with Dark Hypopyon
SURVEY OF OPHTHALMOLOGY VOLUME 46 • NUMBER 3 • NOVEMBER–DECEMBER 2001
CLINICAL PATHOLOGIC REVIEWS STEFAN SEREGARD AND MILTON BONIUK, EDITORS
Endogenous Serratia marcescens Endophthalmitis with Dark Hypopyon: A Case Report and Review Robert A. Equi, MD, and W. Richard Green, MD The Wilmer Ophthalmological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Abstract. A case of endogenous Serratia marcescens endophthalmitis in a patient with diabetes, endstage renal disease, and an indwelling venous catheter is reported. The patient presented with a tan hypopyon and elevated intraocular pressure. Diagnosis was established by positive blood, vitreous, conjunctival, and catheter tip cultures. After a deteriorating course the eye was enucleated. Gross and histopathologic examination revealed the presence of a dark hypopyon with iris necrosis and pigment dispersion and possible spontaneous globe perforation. This is the eleventh reported case of endogenous Serratia endophthalmitis. Previous association of a pink hypopyon and of pigmented vitreous fluid and Serratia endophthalmitis has been reported. This is the first case of dark hypopyon in endogenous Serratia marcescens endophthalmitis reported in the medical literature. Previous entities associated with dark hypopyon have been limited to intraocular melanoma and Listeria monocytogenes endophthalmitis. Dark hypopyon in the appropriate clinical setting may be useful in aiding diagnostic and therapeutic decisions. (Surv Ophthalmol 46:259–268, 2001. © 2001 by Elsevier Science Inc. All rights reserved.) Key words. dark hypopyon • endogenous endophthalmitis • pigment dispersion • Serratia marcescens
Endogenous bacterial endophthalmitis is a rare disease with a potentially devastating outcome. Serratia marcescens is a motile, Gram-negative coccobacillus of the division of the Enterobacteriaceae, which includes Klebsiella and Enterobacter. It is pervasive in the environment and found in soil, water, and food. It is most commonly a cause of respiratory infections, urinary tract infections, and wound infections in certain patients that may be predisposed.40 Serratia is invariably resistant to multiple classes of antimicrobials, with aminoglycosides showing the most consistent efficacy. It is a rare cause of exogenous and endogenous endophthalmitis. A total of 25
cases of Serratia marcescens endophthalmitis have been reported.2,4,8,10,12,16,18,24,25,31,33–36,41 Of these, 10 were endogenous or metastatic in nature,2,4,12,16,24,25, 31,33,35,41 and none had a dark hypopyon. A pink hypopyon was observed in one case2 and one had a “red-brown” fluid in the vitreous.12 Dark hypopyon has previously been associated with intraocular melanoma3 and Listeria monocytogenes endophthalmitis.1,9,15,29 We report a case of endogenous Serratia marcescens endophthalmitis with dark hypopyon, elevated intraocular pressure, iris necrosis, pigment dispersion, and spontaneous globe perforation. Culture of vitreous aspirate as well as cultures of blood, 259
© 2001 by Elsevier Science Inc. All rights reserved.
0039-6257/01/$–see front matter PII S0039-6257(01)00263-6
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catheter tip, and conjunctival discharge established the diagnosis of Serratia marcescens endophthalmitis.
Case Report A 54-year-old African-American woman presented to an ophthalmologist with a 1-week history of a dull ache in the right eye, associated with blurred vision that had gotten progressively worse developing into an intense pain, redness of the right eye, and loss of vision 1 day prior to her examination. She was promptly referred for evaluation and management of endophthalmitis. Her past ocular history is notable for cataract extraction with placement of a posterior chamber intraocular lens in the left eye and panretinal photocoagulation of the left eye for proliferative diabetic retinopathy. Her past medical history is notable for type II diabetes mellitus for 15 years and insulin treatment for 5 years, end-stage renal failure dependent on dialysis, and hypertension. A temporary central venous catheter for dialysis had been placed in the right subclavian vein after surgical creation of an arterio-venous fistula of the right arm 10 days prior to her ophthalmic examination. One month prior to the onset of her current symptoms she underwent surgical debridement and skin grafting of a diabetic foot ulcer. She has a history of a hysterectomy, cholecystectomy, and an exploratory laparotomy. She is allergic to penicillin and to sulfa. Review of systems revealed a 1-day history of subjective fever, chills, and night sweats, as well as pain and tenderness at the insertion of the venous catheter. She denied cough, shortness of breath, headache, flank pain, abdominal pain, nausea, vomiting, or diarrhea. On examination, she was afebrile with normal and stable vital signs. Visual acuity was no light perception in the right eye and 20/30 in the left eye. The right pupil was not visible and the left pupil was 3 mm 1 reactive to light. There was a relative afferent pupillary defect OD by reverse testing. Intraocular pressures were 33 OD and 14 OS. External examination showed blepharoptosis OD with normal levator function and mild edema of the right upper eyelid. There was no lymphadenopathy, ocular discharge, or exophthalmos. She was orthophoric in primary gaze and her ductions and versions were full and comitant. Slit-lamp examination of the right eye revealed 4 bulbar and palpebral hyperemia and corneal surface irregularity without staining with fluoroscein. There was 4 dense cell and flare with fibrin in the anterior chamber with no gross hypopyon visible. The iris, lens, and anterior vitreous were not visible. Slit-lamp examination of the left eye was notable for pseudophakia. Dilated fundoscopic examination of the right eye was not possible because of the poor view; there was no red reflex. Di-
EQUI AND GREEN
lated fundoscopic examination of the left eye showed evidence of panretinal photocoagulation in the periphery with normal disk, slightly narrowed vessels, flat macula, and no evidence of neovascularization. In the emergency department she was given a retrobulbar injection of 2% lidocaine to the right eye. Five minutes later she developed a tonic-clonic seizure with respiratory arrest. She was intubated, stabilized, and extubated over the next 15 minutes. The vitreous was aspirated and placed on culture media (chocolate, blood, and sabouraud’s agar and thioglycolate broth) followed by intravitreal injection of vancomycin (1 mg), ceftazidime (2 mg), and amphotericin B (5 mg). There were no organisms visible on Gram stain of the vitreous aspirate. She was subsequently started on intravenous vancomycin (1 g IV repeated when serum vancomycin level dropped below 10 g/ml), gentamicin (100 mg IV after each dialysis), and amphotericin B (50 mg IV qd) as well as topical vancomycin (50 mg/ml, 1 drop QID). The next day, she developed marked periorbital edema and limitations of ductions of the right eye (Fig. 1). She had a corneal ring infiltrate of the right eye with a central corneal epithelial defect (Fig. 2). Topical ciprofloxacin (0.3%, 1 drop q 1 hr) was started. There was a mucopurulent ocular discharge and a 1-mm tan hypopyon. A culture of the mucopurulent discharge was obtained. Cultures of the vitreous, conjunctiva, blood, and venous catheter tip were positive for two separate isolates of Serratia marcescens. The first isolate, taken from vitreous on the day of admission and conjunctiva on hospital day number one, was sensitive to cefotetan, ciprofloxacin, gentamicin, imipenem, ofloxacin, tobramycin, trimethoprim/sulfa, and aztreonam (Kirby– Bauer method). The second isolate was taken from blood and catheter tip obtained on admission and was sensitive to the above antibiotics as well as ceftazidime, ceftriaxone, piperacillin, piperacillin, ticarcillin, and aztreonam. An echocardiogram, chest x-ray, and computed tomography of the abdomen and pelvis were normal. Stool studies were unremarkable for signs of infection. Systemic therapy was changed to intravenous aztreonam. Computed tomography of the orbits revealed “stranding” of the orbital fat (Fig. 3). Prednisone was started at 60 mg orally once per day. After discussion of treatment options with the patient, the decision was made to eviscerate the right eye. Intraoperatively a small perforation was noted anterior to the insertion of the medial rectus muscle. The procedure was converted to an enucleation. Postoperatively she improved with resolution of periorbital edema. She was discharged and given levofloxacin 250 mg orally twice a day for 2 weeks.
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Fig. 1. Orbital cellulitis secondary to endogenous Serratia marcescens endophthalmitis.
Fig. 2. Mucopurulent discharge and ring corneal infiltrate in an eye with Serratia marcescens endogenous endophthalmitis.
Gross examination of the enucleated globe showed a 2 2-mm full-thickness defect in the sclera located 8 mm posterior to the limbus at 3 o’clock nasally (Fig. 4) anterior to the insertion of the medial rectus. The cornea was diffusely hazy with a ring-shaped opacity at the periphery. The eye was opened horizontally and disclosed detached vitreous and necrotic retina (Fig. 5). The choroid was distended with a white infiltrate along the inner aspect in some areas. Histopathologic evaluation disclosed a moderately intense diffuse neutrophilic infiltrate throughout the cornea with slight preponderance in the midperiphery. The iris was necrotic and a large pool of free melanin pigment was present in the posterior chamber (Figs. 6 and 7). A fibrinous material with neutrophils and much pigment, both free and in macrophages, was present in the anterior chamber angle and along the anterior surface of the iris (Figs. 6A and 8). The angles were closed by periph-
eral anterior synechiae and fibrinous exudate. The vitreous contained an intense neutrophillic infiltrate. An intense neutrophillic infiltrate was present in both frayed margins of the scleral defect (Fig. 9). The choroid was distended in areas with an intense neutrophillic infiltrate at its internal aspect with ruptures in Bruch’s membrane and extension of the abscess into the subretinal space. The retina was necrotic (Fig. 10). The central retinal artery was occluded with a fibrinous, neutrophillic aggregate. There was partial atrophy of the optic nerve with one area of total loss of nerve fiber bundles. Numerous coccobacillary organisms, seen best with the giemsa stain, were present at the posterior aspect of the remaining formed vitreous (Fig. 11), in the iris (Fig. 7B), and in the sclera (Fig. 9B), adjacent to the perforation.
Fig. 3. Proptosis, periorbital edema, and orbital “fatstranding” demonstrated on computed tomography.
Fig. 4. Scleral defect (arrow) located 8 mm posterior to the limbus nasally (asterisk cornea).
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Fig. 5. Gross appearance of the eye with dense vitreous infiltrate, necrotic detached retina, and thickened choroid with an infiltrate along its inner surface.
Discussion SERRATIA MARCESCENS
Serratia marcescens, first described by Bartolomeo Bizio in 1823, is a motile, Gram-negative coccobacillus of the Enterobacteriacea family along with Klebsiella and Enterobacter. It is ubiquitous in the environment found in food, water, and soil. Because some
Fig. 6. A: Area shows iris necrosis (asterisk), fibinopurulent exudate with pigment along the anterior surface of the iris (arrow) and pool of free melanin pigment granules in posterior chamber (arrowhead [ 134]). B: Higher power view of the pool of free pigment granules in the posterior chamber ( 544) (hematoxylin and eosin).
strains have the ability to produce a red pigment (prodigiosin), it became originally known as Bacterium prodigiosum. It was reportedly responsible for the propagation of superstition in the Middle Ages because of its ability to produce this blood-red pigment on food. The occurrence of blood on bread was taken as an omen that spurred Alexander the Great and his army to victory at the siege of Tyre in 332 B.C.17 Initially felt not to be of pathogenic importance, Serratia marcescens had been used as a bac-
Fig. 7. A: Higher power view of necrotic iris (asterisk), pigmented hypopyon (arrow), and pool of free pigment in posterior chamber, (hemotoxylin and eosin, 340). B: Coccobacillary forms in the iris (arrows), (giemsa, 1340).
Fig. 8. Dark hypopyon with neutrophils and melanin pigment that is free and in macrophages, (hematoxylin and eosin, 1340).
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SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON
Fig. 9. A: Area of scleromalacia with adjacent acute inflammatory cell infiltrate and rare clusters of coccobacillary organisms (hematoxylin and eosin, 136). B: Higher power view of the same area (giemsa, 1360).
teriologic marker in experiments investigating bacteremia following dental extractions and pyuria associated with urinary catheters.20,27 Laboratory identification of Enterobacteriaceae includes indole-negativity, an acid/acid or alkaline/ acid reaction on triple sugar iron (TSI), and variable fermentation of sugars to produce gas. Further differentiation involves evaluation for elaboration of deoxyribonuclease, utilization of malonate, liquefaction of gelatin, fermentation of arabinose, rhamnose, and raffinose, urea hydrolysis, lysine decarboxylase activity, arginine dihydrolase activity, methyl red test, Voges–Proskauer test, and phenylalanine deaminase production.40 Pigment production, al-
though traditionally considered a hallmark of Serratia marcescens, cannot be relied upon as an identifying characteristic as the minority of biotypes elaborate pigment. In one study examining 176 strains of Serratia marcescens isolated from patients with disease attributed to the organism, only 7% produced pigment.40 In the case presented here, the organisms isolated from vitreous, blood, and from the venous catheter tip were identified with use of the Vitek Gram-Negative Identification Card (bioMerieux Vitek, Inc.) by the following features: DP-300 positive, urease negative, maltose fermentation positive, inositol fermentation positive, L-arabinose fermentation negative, malonate fermentation negative, xylose fermentation negative, p-coumaric positive (based on glucose fermentation in the presence of specific inhibitors), arginine dihydrolase positive, negative acetamide utilization, tryptophan deaminase negative, raffinose fermentation negative, hydrogen sulfide negative, lysine decarboxylase positive, esculin hydrolase positve, positive growth in the presence of polymyxin B, sorbitol fermentatin positive, ornithine decarboxylase positive, plant indican positive, lactose fermentation negative, sucrose fermentation positive, rhamnose fermentation negative, and beta-galactosidase negative. SYSTEMIC DISEASE AND PATHOGENESIS
Fig. 10. Area shows necrosis of retina and optic nerve head, (hematoxylin and eosin, 136).
Wilkowske and associates summarized 176 cases of infections associated with Serratia marcescens isolated from various sites.40 The majority of cases were respi-
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Fig. 11. A: Posterior aspect of the formed vitreous (arrow) (giemsa, 544). B: Numerous coccobacillary organisms that are Gram-negative (modified Gram, 1360). C: Same organism stained with the giemsa technique (giemsa, 1360).
ratory infections, followed by urinary infections, wound infections, “blood,” and miscellaneous, including ear, surgical or autopsy tissue, intravenous catheter, vagina, cerebrospinal fluid, and peritoneal dialysis fluid. Other important observations from that study were that 56% of the patients had been hospitalized at the time Serratia was isolated, indicating possible nosocomial spread, and 90% had received antibiotics prior to their positive cultures. Other factors associated with positive cultures include surgery, inhalation therapy, genitourinary instrumentation, immunosuppressive therapy, and diabetes.40 In the case presented here, predisposing factors include diabetes mellitus, indwelling venous catheter, antecedent surgery (debridement of a foot ulcer with skin grafting and creation of an arteriovenous fistula), and prior use of antibiotics (related to the aforementioned surgical procedures). In the seven cases of endogenous Serratia endophthalmitis previously reported, all were associated with multiple potential risk factors. Serratia is an organism of low virulence but may lead to severe disease in a pre-
disposed individual either because of impaired host defenses or because of an altered host environment allowing the bacteria to grow beyond a threshold number that leads to disease. OCULAR DISEASE
Serratia marcescens has been reported as an ocular pathogen as early as 1908 when Axenfeld observed ocular disease after Bacterium prodigiosum was injected into the rabbit eye.6 It has subsequently been reported as a cause of purulent conjunctivitis in premature infants37 and in a burn patient.5 Infectious keratitis caused by Serratia marcescens is well documented.5,8,13,14,21,22,28,38,39 It is most commonly reported in association with contact lens wear13,21,28,32 and has been reported in association with contaminated eye droppers38 and radial keratotomy in a health care worker.14 Suture abscess caused by Serratia marcescens was reported by Leahey et al23 following penetrating keratoplasty.23 Kamata et al19 isolated a 56K protease from a strain of Serratia marcescens that had caused a “liquefactive keratitis.” They implicated
SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON
this protease as the virulence factor responsible for the local destructive effect that Serratia marcescens has on the cornea. Davis and collegues11 have described a Serratia marcescens lacrimal infection in a severe burn patient. Orbital infection caused by Serratia marcescens was reported after insertion of an alloplastic orbital implant by Mauriello and associates.26 Bigger and associates first reported exogenous Serratia marcescens endophthalmitis in 1971.8 They describe two cases, one post-traumatic and the other postoperative, of acute, purulent endophthalmitis resulting in eventual enucleation. The second case followed an intracapsular cataract extraction, and there was an associated orbital cellulitis in addition to corneal and scleral involvement. Wyler and associates41 reported the first case of presumed metastatic Serratia marcescens endophthalmitis; the patient was an intravenous drug abuser with persistent Serratia bacteremia. In 1992, Al Hazzaa and associates2 reported a neonate with sepsis who developed a hazy cornea and a pink hypopyon with an aqueous culture positive for Serratia marcescens. There were no erythrocytes present on microscopic examination of the anterior chamber aspirate. They suggested that the presence of a pink hypopyon might indicate infection with a pigment-producing strain of Serratia marcescens. de Courten and associates12 described a case of metastatic Serratia marcescens endophthalmitis in a neonate who underwent colostomy and subsequently developed proptosis, periorbital chemosis, hazy cornea, shallow anterior chamber with a middilated pupil, and leukocoria. Gross examination of the enucleated globe showed a “red-brown fluid” in the vitreous cavity. The characteristics of the 25 previously reported cases of Serratia marcescens endophthalmitis are summarized in Table 1. Of these, only nine are endogenous in nature.2,4,12,16,24,25,31,33,35,41 Of the 24 cases in which age was reported, the mean was 57.2 (range “neonate” to age 85) with a median age of 60 years. Of the 10 cases of endogenous endophthalmitis, the mean age was 45.6 (range “neonate” to age 77) with a median age of 59. Of the 22 cases in which sex was reported, 16 were male and six were female. Of the eight cases of endogenous endophthalmitis, five were male and three were female. Hypopyon was reported present in 11 cases. Of these, one was reported as a “pink hypopyon” in the absence of red blood cells on histopathology.2 Another was described as having a “red-brown fluid” in the vitreous.12 Associated medical conditions present in the 10 cases of endogenous or metastatic endophthalmitis include the following: 1) intracavernous carotid aneurysm, indwelling catheter, and recent craniotomy; 2) chronic lymphocytic leukemia and type II diabetes mellitus, status post-transurethral resection
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of the prostate with bladder perforation, pneumonia, and diabetes;35 3) neonate status postcolostomy; 4) esophogeal surgery and probable endocarditis; 5) neonate with sepsis; 6) diabetes with renal abscess; 7) IV drug abuse with history of glomerulonephritis and a mycotic aneurysm of the superior mesenteric artery; 8) diabetes mellitus with end-stage renal failure requiring dialysis; and 9) IV drug abuse with a prior history of candida endophthalmitis in the fellow eye. In 12 cases, either evisceration or enucleation was the final outcome.8,10,12,18,25,31,33,41 In three cases phthisis or atrophy was reported as the final outcome.2,4,34,35 One eye had a final visual acuity of 20/50, one eye 20/60, one eye 20/70, one eye 20/ 200, one eye hand motion, and one eye had no light perception.10 All of the eyes in which a final visual acuity was reported better than no light perception occurred following intraocular surgery.10 There was one reported death attributed to “CNS deterioration.”16 Histopathologic specimens have been reported in only three cases.8,12 Bigger et al8 observed in one case an acute inflammatory infiltrate involving cornea, anterior chamber, iris, ciliary body, vitreous, choroid, and retina along with destruction of the retina. Gram stain was positive for Gram-negative coccobacilli. Similar findings were described in a second case observed, but no organisms were seen.8 de Courten and associates12 reported a “red-brown fluid” in the vitreous as well as polymorphonuclear lymphocytic infiltrate of the cornea, sclera, uveal tract, and optic nerve head and necrosis of the retina. Cultures of aqueous or vitreous were positive for Serratia marcescens in 21 of the 25 cases. Of the five cases that reported Gram-stain results, four showed Gram-negative rods and one showed no organisms.8,12,16,34 The presence of a dark hypopyon in this case is intriguing. Previous reports of dark hypopyon have been limited to Listeria monocytogenes1,7,9,15,29 endophthalmitis and primary and metastatic intraocular melanoma.3 Pink hypopyon in Serratia endophthalmitis was observed by Al Hazzaa and associates,2 presumably related to pigment production, and a “redbrown” fluid in the vitreous of an eye with Serratia endophthalmitis was observed by de Courten and associates.12 In the case presented here, it appears that the cause of the dark hypopyon was necrosis of the iris with dispersion of melanin into the anterior chamber. The reason for the production of dark hypopyon and iris necrosis with pigment dispersion in Listeria and Serratia endophthalmitis is unknown. The presence of a dark hypopyon may not be as specific a clinical marker as once thought but remains useful in that its presence should raise suspicion for intraocular melanoma or infection with Listeria or Serratia. It is not clear whether organisms related to Listeria or Serratia can also cause a dark hypopyon.
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TABLE 1
Reported Cases of Endophthalmitis Due to Serratia Author (Reference) 8
Age
Sex
Medical/ Surgical History
Presentation
Bigger et al
44
Male
Bigger et al8 Salceda et al34
85 53
Female S/P ICCE Male Diabetes, S/P ICCE
Gammon et al16
60
Radda33
59
de Courten et al12 10 days
Female S/P Carotid aneurysm clipping, pneumonia, indwelling foley catheter Male Chronic lymphocytic leukemia, diabetes, S/P TURP, bladder perforation, hemodialysis Male S/P colostomy
Okada et al31
77
NR
al Hazzaa et al2
Neonate NR
Shaaraway et al36 Cohen et al10
NR 50
NR Male
Cohen et al10
69
Male
Cohen et al10
64
20/300 hypopyon
Cohen et al10
71
Cohen et al10
45
Cohen et al10
51
Cohen et al10
81
Female S/P phaco-emulsification, Diabetes Male S/P ECCE, primary capsulotomy, wound leak Male S/P PKP, suture removal, wound dehiscence Male S/P PKP, anterior vitrectomy, suture abscess, diabetes Male S/P ECCE, ACIOL
Cohen et al10
77
Male
NLP
Cohen et al10
72
Dialysis, S/P Scheie procedure Female S/P scleral Buckle
Cohen et al10
73
Male
LP
Lin et al24
68
S/P ECCE, rheumatoid arthritis Female Diabetes, renal abscess
Wyler et al41
47
Male
Johnson et al18
82
Male
Marinella and Warwar25 Alvarez et al4
48
Male
32
Male
Intraocular foreign body
Diagnosis
Pain, HM vision, purulence, hypopyon Pain, hypopyon Pain, hypopyon
Outcome
Conjunctival, intraocular cultures AC aspirate Aqueous, conjunctival cultures Proptosis, discharge, Aqueous, hypopyon urine cultures
NLP, enucleation
Pain, NLP
Vitreous culture
Evisceration
Fever, proptosis, leukocoria “pan-ophthalmitis”
Vitreous culture not reported
Enucleation
Aqueous culture NR Aqueous culture Aqueous, vitreous culture Aqueous culture Aqueous, vitreous culture Aqueous culture Vitreous culture
Phthisis
S/P esophageal surgery, “probable endocarditis Sepsis Pink hypopyon NR NR Diabetes, S/P HM, hypopyon trabeculectomy S/P phaco-emulsification HM
NR 20/400, hypopyon HM LP
NLP
HM, AC exudate
Vitreous culture Vitreous culture Vitreous culture Vitreous culture Renal abscess culture Blood, urine culture
IVDU, mycotic aneurysm NR of superior mesenteric artery S/P CE and vitrectomy, LP, “white Vitreous HTN, Hypothyroid inflammatory culture material” in AC Diabetes, dialysis, LP, fibrinous Aqueous catheter exudate, hypopyon culture HIV, IVDU 20/80, hypopyon Vitreous culture
Enucleation “Atrophic” eye Death
Enucleation
NR 20/50 20/60 20/70 20/200 HM NLP Enucleated or eviscerated Eviscerated Enucleation Enucleation NLP Enucleation Evisceration NLP, enucleation Phthisis
S/P status post; ICCE intracapsular cataract extraction; TURP transurethral resection of the prostate; HM Hand motion; NLP no light perception; HIV human immunodeficiency virus; IVDU intravenous drug use; HTN hypertension; PKP penetrating keratoplasty; ECCE extracapsular cataract extraction; NR not reported.
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SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON TREATMENT
Serratia marcescens typically is a multidrug-resistant organism, perhaps owing to its pervasiveness in the environment and exposure to various antibiotics that have selected for those strains that carry resistance. Miller and Buckler30 describe Serratia marcescens ability to survive and divide within in human polymorphonuclear lymphocytes after phagocytosis that may also contribute to its resistance to many antibiotics. In virtually all isolates of Serratia tested for antibiotic susceptibility, only aminoglycoside antibiotics and amikacin show consistent efficacy in inhibiting or preventing growth on inoculated media.2,4,5,8,12,18,25,40,41 Several cases reviewed here also demonstrated variable activity of third-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole, tetracycline, and synthetic penicillins against Serratia.2,4,8,18,25,40,41 Persistence of disease despite sensitivity-guided antimicrobial therapy is also reported, owing perhaps to intracellular growth, continued effect of lipopolysaccharide from destroyed bacteria, or immune-mediated destruction.5,8,18 Based on this information, aminoglycoside therapy would be most appropriate in cases of suspected or documented Serratia infection. Given the retinal toxicity of intravitreal aminoglycosides, a third-generation cephalosporin (e.g., ceftazidime) is a reasonable alternative for empiric treatment until alterations based on susceptibility can be made.
Summary Serratia marcescens endophthalmitis is a rare cause of endogenous endophthalmitis with only ten cases previously reported. The eleventh case is reported here in a patient with multiple established risk factors for Serratia endophthalmitis: diabetes mellitus, indwelling venous catheter, recent use of antibiotics, and recent surgery. This is the first known case of dark hypopyon in Serratia endophthalmitis. The devastating course of this disease is demonstrated owing in part to multidrug resistance. The combination of patient factors that predispose to the development of endogenous Serratia endophthalmitis and the presence of a dark hypopyon and elevated intraocular pressure may be useful in narrowing the differential diagnosis and aiding in therapeutic decisions for this rare but devastating entity.
Method of Literature Search A search was conducted of the MEDLINE database for all years. The search terms used were Serratia and endophthalmitis, eye, infection, ophthalmic, conjunctivitis, keratitis, ocular, disease, treatment, review, dark hypopyon, black hypopyon. All citations judged to be of clinical importance were included as were additional references listed in key articles. We wanted to review all known and published cases of Serratia
marcescens endophthalmitis. Cases with infections caused by Serratia marcescens were included in our review, and cases of dark or black hypopyon were reviewed. Citations were referenced if they came from peer-reviewed articles only and if they had English abstracts. In addition, infections caused by Serratia species other than marcescens were excluded.
References 1. Abbott RL, Forster RK, Rebell G: Listeria monocytogenes endophthalmitis with a black hypopyon. Am J Ophthalmol 86: 715–9, 1978 2. al Hazzaa SA, Tabbara KF, Gammon JA: Pink hypopyon: a sign of Serratia marcescens endophthalmitis. Br J Ophthalmol 76:764–5, 1992 3. Albert DM, Lahav M, Troczynski E, Bahr R: Black hypopyon: report of two cases. Albrecht Von Graefes Arch Klin Exp Ophthalmol 193:81–94, 1975 4. Alvarez R, Adan A, Martinez JA, et al: Haematogenous Serratia marcescens endophthalmitis in an HIV-infected intravenous drug addict. Infection 18:29–30, 1990 5. Atlee WE, Burns RP, Oden M: Serratia marcescens keratoconjunctivitis. Am J Ophthalmol 70:31–3, 1970 6. Axenfeld T: Bacteriology of the Eye (McNab A trans.). London, Bailliere, Tindall and Cox, 1908, p 91 7. Ballen PH, Loffredo FR, Painter B: Listeria endophthalmitis. Arch Ophthalmol 97:101–2, 1979 8. Bigger JF, Meltzer G, Mandell A, Burde RM: Serratia marcescens endophthalmitis. Am J Ophthalmol 72:1102–5, 1971 9. Brian GR, Treplin MC: Listeria monocytogenes endophthalmitis: a case report. Aust NZ J Ophthalmol 16:329–31, 1988 10. Cohen SM, Flynn HW, Miller D: Endophthalmitis caused by Serratia marcescens. Ophthalmic Surg Lasers 28:195–200, 1996 11. Davis JT, Foltz E, Blakemore WS: Serratia marcescens. A pathogen of increasing clinical importance. JAMA 214: 2190–2, 1970 12. de Courten C, Sancho P, BenEzra D: Metastatic Serratia marcescens endophthalmitis. J Pediatr Ophthalmol Strabismus 25:45–7, 1988 13. Donnenfeld ED, Schrier A, Perry HD, et al: Infectious keratitis with corneal perforation associated with corneal hydrops and contact lens wear in keratoconus. Br J Ophthalmol 80: 409–12, 1996 14. Duffey RJ: Bilateral Serratia marcescens keratitis after simultaneous bilateral radial keratotomy. Am J Ophthalmol 119: 233–6, 1995 15. Eliott D, OBrien TP, Green WR, et al: Elevated intraocular pressure, pigment dispersion and dark hypopyon in endogenous endophthalmitis from Listeria monocytogenes. Surv Ophthalmol 37:117–24, 1992 16. Gammon JA, Schwab I, Joseph P: Gentamicin-resistant Serratia marcescens endophthalmitis. Arch Ophthalmol 98:1221– 3, 1980 17. Gaughran E: From superstition to science: the history of a bacterium. Trans NY Acad Sci 31:3–24, 1996 18. Johnson DH, Klein NC, Cunha BA: Postoperative Serratia marcescens endophthalmitis. Heart Lung 21:300–2, 1992 19. Kamata R, Matsumoto K, Okamura R, et al: The serratial 56K protease as a major pathogenic factor in serratial keratitis. Clinical and experimental study. Ophthalmology 92:1452–9, 1985 20. Kass EH, Schneiderman LJ: Entry of bacteria into the urinary tracts of patients with inlying catheters. N Engl J Med 256:556–57, 1957 21. Lass JH, Haaf J, Foster CS, Belcher C: Visual outcome in eight cases of Serratia marcescens keratitis. Am J Ophthalmol 92:384–90, 1981 22. Lazachek GW, Boyle GL, Schwartz AL, Leopold IH: Serratia marcescens, an ocular pathogen; new considerations. Arch Ophthalmol 86:599–603, 1971
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23. Leahey AB, Avery RL, Gottsch JD, et al: Suture abscesses after penetrating keratoplasty. Cornea 12:489–92, 1993 24. Lin MF, Lau YJ, Hu BS, et al: Serratia marcescens renal abscess with endophthalmitis: a case report. J Microbiol Immunol Infect 31:245–8, 1998 25. Marinella MA, Warwar R: Endogenous endophthalmitis due to Serratia marcescens. South Med J 91:388–91, 1998 26. Mauriello JA Jr, Hargrave S, Yee S, et al: Infection after insertion of alloplastic orbital floor implants. Am J Ophthalmol 117:246–52, 1994 27. McEntegart M: Bacteria following dental extractions. Lancet 2:596–8, 1949 28. McLeod SD, Goei SL, Taglia DP, McMahon TT: Nonulcerating bacterial keratitis associated with soft and rigid contact lens wear. Ophthalmology 105:517–21, 1998 29. Melamed Cattan J, Kwitko S, Barcaro S: Listeria monocytogenes endogenous endophthalmitis. Ophthalmology 98 (Suppl):S114, 1991 30. Miller ME, Buckler JM: Intracellular survival and growth of Serratia marcescens following phagocytosis by human leukocytes. J Infect Dis 118:149–52, 1968 31. Okada AA, Johnson RP, Liles WC, et al: Endogenous bacterial endophthalmitis. Report of a ten-year retrospective study. Ophthalmology 101:832–8, 1994 32. Parment PA: The role of Serratia marcescens in soft contact lens associated ocular infections. A review. Acta Ophthalmol Scand 75:67–71, 1997 33. Radda TM: Metastatic Serratia marcescens endophthalmitis. Ophthalmologica 185:65–8, 1982 34. Salceda SR, Lapuz J, Vizconde R: Serratia marcescens endophthalmitis. Arch Ophthalmol 89:163–6, 1973
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35. Salminen L, Toivanen A: Bilateral uveitis during Serratia marcescens sepsis. Am J Ophthalmol 96:402–3, 1983 36. Shaarawy A, Grand MG, Meredith TA, et al: Persistent endophthalmitis after intravitreal antimicrobial therapy. Ophthalmology 102:382–7, 1994 37. Stenderup A, Faergeman O, Ingerslev M: Serratia marcescens infections in premature infants. Acta Pathol Microbiol Scand 68:157–60, 1966 38. Templeton WC 3rd, Eiferman RA, Snyder JW, et al: Serratia keratitis transmitted by contaminated eyedroppers. Am J Ophthalmol 93:723–6, 1982 39. Tokunaga T, Fujino T, Yamasoto K, Ikeda A: [A case of serpiginous corneal ulcer caused by Serratia of Enterobacteriaceae]. Nippon Ganka Kiyo 20:862–8, 1969 40. Wilkowske CJ, Washington JA 2nd, Martin WJ, Ritts RE Jr: Serratia marcescens. Biochemical characteristics, antibiotic susceptibility patterns, and clinical significance. JAMA 214: 2157–62, 1970 41. Wyler DJ, Glickman MG, Brewin A: Persistent serratia bacteremia associated with drug abuse. West J Med 122:70–3, 1975
Supported in part by the Independent Order of Odd Fellows, Winston Salem, North Carolina. The authors have no proprietary or commercial interest in any product or idea discussed in this article. Reprint address: W. Richard Green, MD, Wilmer Ophthalmological Institute, W. Richard Green Eye Pathology Laboratory, Maumenee 427, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-9248.
CLINICAL PATHOLOGIC REVIEWS STEFAN SEREGARD AND MILTON BONIUK, EDITORS
Endogenous Serratia marcescens Endophthalmitis with Dark Hypopyon: A Case Report and Review Robert A. Equi, MD, and W. Richard Green, MD The Wilmer Ophthalmological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Abstract. A case of endogenous Serratia marcescens endophthalmitis in a patient with diabetes, endstage renal disease, and an indwelling venous catheter is reported. The patient presented with a tan hypopyon and elevated intraocular pressure. Diagnosis was established by positive blood, vitreous, conjunctival, and catheter tip cultures. After a deteriorating course the eye was enucleated. Gross and histopathologic examination revealed the presence of a dark hypopyon with iris necrosis and pigment dispersion and possible spontaneous globe perforation. This is the eleventh reported case of endogenous Serratia endophthalmitis. Previous association of a pink hypopyon and of pigmented vitreous fluid and Serratia endophthalmitis has been reported. This is the first case of dark hypopyon in endogenous Serratia marcescens endophthalmitis reported in the medical literature. Previous entities associated with dark hypopyon have been limited to intraocular melanoma and Listeria monocytogenes endophthalmitis. Dark hypopyon in the appropriate clinical setting may be useful in aiding diagnostic and therapeutic decisions. (Surv Ophthalmol 46:259–268, 2001. © 2001 by Elsevier Science Inc. All rights reserved.) Key words. dark hypopyon • endogenous endophthalmitis • pigment dispersion • Serratia marcescens
Endogenous bacterial endophthalmitis is a rare disease with a potentially devastating outcome. Serratia marcescens is a motile, Gram-negative coccobacillus of the division of the Enterobacteriaceae, which includes Klebsiella and Enterobacter. It is pervasive in the environment and found in soil, water, and food. It is most commonly a cause of respiratory infections, urinary tract infections, and wound infections in certain patients that may be predisposed.40 Serratia is invariably resistant to multiple classes of antimicrobials, with aminoglycosides showing the most consistent efficacy. It is a rare cause of exogenous and endogenous endophthalmitis. A total of 25
cases of Serratia marcescens endophthalmitis have been reported.2,4,8,10,12,16,18,24,25,31,33–36,41 Of these, 10 were endogenous or metastatic in nature,2,4,12,16,24,25, 31,33,35,41 and none had a dark hypopyon. A pink hypopyon was observed in one case2 and one had a “red-brown” fluid in the vitreous.12 Dark hypopyon has previously been associated with intraocular melanoma3 and Listeria monocytogenes endophthalmitis.1,9,15,29 We report a case of endogenous Serratia marcescens endophthalmitis with dark hypopyon, elevated intraocular pressure, iris necrosis, pigment dispersion, and spontaneous globe perforation. Culture of vitreous aspirate as well as cultures of blood, 259
© 2001 by Elsevier Science Inc. All rights reserved.
0039-6257/01/$–see front matter PII S0039-6257(01)00263-6
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catheter tip, and conjunctival discharge established the diagnosis of Serratia marcescens endophthalmitis.
Case Report A 54-year-old African-American woman presented to an ophthalmologist with a 1-week history of a dull ache in the right eye, associated with blurred vision that had gotten progressively worse developing into an intense pain, redness of the right eye, and loss of vision 1 day prior to her examination. She was promptly referred for evaluation and management of endophthalmitis. Her past ocular history is notable for cataract extraction with placement of a posterior chamber intraocular lens in the left eye and panretinal photocoagulation of the left eye for proliferative diabetic retinopathy. Her past medical history is notable for type II diabetes mellitus for 15 years and insulin treatment for 5 years, end-stage renal failure dependent on dialysis, and hypertension. A temporary central venous catheter for dialysis had been placed in the right subclavian vein after surgical creation of an arterio-venous fistula of the right arm 10 days prior to her ophthalmic examination. One month prior to the onset of her current symptoms she underwent surgical debridement and skin grafting of a diabetic foot ulcer. She has a history of a hysterectomy, cholecystectomy, and an exploratory laparotomy. She is allergic to penicillin and to sulfa. Review of systems revealed a 1-day history of subjective fever, chills, and night sweats, as well as pain and tenderness at the insertion of the venous catheter. She denied cough, shortness of breath, headache, flank pain, abdominal pain, nausea, vomiting, or diarrhea. On examination, she was afebrile with normal and stable vital signs. Visual acuity was no light perception in the right eye and 20/30 in the left eye. The right pupil was not visible and the left pupil was 3 mm 1 reactive to light. There was a relative afferent pupillary defect OD by reverse testing. Intraocular pressures were 33 OD and 14 OS. External examination showed blepharoptosis OD with normal levator function and mild edema of the right upper eyelid. There was no lymphadenopathy, ocular discharge, or exophthalmos. She was orthophoric in primary gaze and her ductions and versions were full and comitant. Slit-lamp examination of the right eye revealed 4 bulbar and palpebral hyperemia and corneal surface irregularity without staining with fluoroscein. There was 4 dense cell and flare with fibrin in the anterior chamber with no gross hypopyon visible. The iris, lens, and anterior vitreous were not visible. Slit-lamp examination of the left eye was notable for pseudophakia. Dilated fundoscopic examination of the right eye was not possible because of the poor view; there was no red reflex. Di-
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lated fundoscopic examination of the left eye showed evidence of panretinal photocoagulation in the periphery with normal disk, slightly narrowed vessels, flat macula, and no evidence of neovascularization. In the emergency department she was given a retrobulbar injection of 2% lidocaine to the right eye. Five minutes later she developed a tonic-clonic seizure with respiratory arrest. She was intubated, stabilized, and extubated over the next 15 minutes. The vitreous was aspirated and placed on culture media (chocolate, blood, and sabouraud’s agar and thioglycolate broth) followed by intravitreal injection of vancomycin (1 mg), ceftazidime (2 mg), and amphotericin B (5 mg). There were no organisms visible on Gram stain of the vitreous aspirate. She was subsequently started on intravenous vancomycin (1 g IV repeated when serum vancomycin level dropped below 10 g/ml), gentamicin (100 mg IV after each dialysis), and amphotericin B (50 mg IV qd) as well as topical vancomycin (50 mg/ml, 1 drop QID). The next day, she developed marked periorbital edema and limitations of ductions of the right eye (Fig. 1). She had a corneal ring infiltrate of the right eye with a central corneal epithelial defect (Fig. 2). Topical ciprofloxacin (0.3%, 1 drop q 1 hr) was started. There was a mucopurulent ocular discharge and a 1-mm tan hypopyon. A culture of the mucopurulent discharge was obtained. Cultures of the vitreous, conjunctiva, blood, and venous catheter tip were positive for two separate isolates of Serratia marcescens. The first isolate, taken from vitreous on the day of admission and conjunctiva on hospital day number one, was sensitive to cefotetan, ciprofloxacin, gentamicin, imipenem, ofloxacin, tobramycin, trimethoprim/sulfa, and aztreonam (Kirby– Bauer method). The second isolate was taken from blood and catheter tip obtained on admission and was sensitive to the above antibiotics as well as ceftazidime, ceftriaxone, piperacillin, piperacillin, ticarcillin, and aztreonam. An echocardiogram, chest x-ray, and computed tomography of the abdomen and pelvis were normal. Stool studies were unremarkable for signs of infection. Systemic therapy was changed to intravenous aztreonam. Computed tomography of the orbits revealed “stranding” of the orbital fat (Fig. 3). Prednisone was started at 60 mg orally once per day. After discussion of treatment options with the patient, the decision was made to eviscerate the right eye. Intraoperatively a small perforation was noted anterior to the insertion of the medial rectus muscle. The procedure was converted to an enucleation. Postoperatively she improved with resolution of periorbital edema. She was discharged and given levofloxacin 250 mg orally twice a day for 2 weeks.
SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON
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Fig. 1. Orbital cellulitis secondary to endogenous Serratia marcescens endophthalmitis.
Fig. 2. Mucopurulent discharge and ring corneal infiltrate in an eye with Serratia marcescens endogenous endophthalmitis.
Gross examination of the enucleated globe showed a 2 2-mm full-thickness defect in the sclera located 8 mm posterior to the limbus at 3 o’clock nasally (Fig. 4) anterior to the insertion of the medial rectus. The cornea was diffusely hazy with a ring-shaped opacity at the periphery. The eye was opened horizontally and disclosed detached vitreous and necrotic retina (Fig. 5). The choroid was distended with a white infiltrate along the inner aspect in some areas. Histopathologic evaluation disclosed a moderately intense diffuse neutrophilic infiltrate throughout the cornea with slight preponderance in the midperiphery. The iris was necrotic and a large pool of free melanin pigment was present in the posterior chamber (Figs. 6 and 7). A fibrinous material with neutrophils and much pigment, both free and in macrophages, was present in the anterior chamber angle and along the anterior surface of the iris (Figs. 6A and 8). The angles were closed by periph-
eral anterior synechiae and fibrinous exudate. The vitreous contained an intense neutrophillic infiltrate. An intense neutrophillic infiltrate was present in both frayed margins of the scleral defect (Fig. 9). The choroid was distended in areas with an intense neutrophillic infiltrate at its internal aspect with ruptures in Bruch’s membrane and extension of the abscess into the subretinal space. The retina was necrotic (Fig. 10). The central retinal artery was occluded with a fibrinous, neutrophillic aggregate. There was partial atrophy of the optic nerve with one area of total loss of nerve fiber bundles. Numerous coccobacillary organisms, seen best with the giemsa stain, were present at the posterior aspect of the remaining formed vitreous (Fig. 11), in the iris (Fig. 7B), and in the sclera (Fig. 9B), adjacent to the perforation.
Fig. 3. Proptosis, periorbital edema, and orbital “fatstranding” demonstrated on computed tomography.
Fig. 4. Scleral defect (arrow) located 8 mm posterior to the limbus nasally (asterisk cornea).
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Fig. 5. Gross appearance of the eye with dense vitreous infiltrate, necrotic detached retina, and thickened choroid with an infiltrate along its inner surface.
Discussion SERRATIA MARCESCENS
Serratia marcescens, first described by Bartolomeo Bizio in 1823, is a motile, Gram-negative coccobacillus of the Enterobacteriacea family along with Klebsiella and Enterobacter. It is ubiquitous in the environment found in food, water, and soil. Because some
Fig. 6. A: Area shows iris necrosis (asterisk), fibinopurulent exudate with pigment along the anterior surface of the iris (arrow) and pool of free melanin pigment granules in posterior chamber (arrowhead [ 134]). B: Higher power view of the pool of free pigment granules in the posterior chamber ( 544) (hematoxylin and eosin).
strains have the ability to produce a red pigment (prodigiosin), it became originally known as Bacterium prodigiosum. It was reportedly responsible for the propagation of superstition in the Middle Ages because of its ability to produce this blood-red pigment on food. The occurrence of blood on bread was taken as an omen that spurred Alexander the Great and his army to victory at the siege of Tyre in 332 B.C.17 Initially felt not to be of pathogenic importance, Serratia marcescens had been used as a bac-
Fig. 7. A: Higher power view of necrotic iris (asterisk), pigmented hypopyon (arrow), and pool of free pigment in posterior chamber, (hemotoxylin and eosin, 340). B: Coccobacillary forms in the iris (arrows), (giemsa, 1340).
Fig. 8. Dark hypopyon with neutrophils and melanin pigment that is free and in macrophages, (hematoxylin and eosin, 1340).
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SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON
Fig. 9. A: Area of scleromalacia with adjacent acute inflammatory cell infiltrate and rare clusters of coccobacillary organisms (hematoxylin and eosin, 136). B: Higher power view of the same area (giemsa, 1360).
teriologic marker in experiments investigating bacteremia following dental extractions and pyuria associated with urinary catheters.20,27 Laboratory identification of Enterobacteriaceae includes indole-negativity, an acid/acid or alkaline/ acid reaction on triple sugar iron (TSI), and variable fermentation of sugars to produce gas. Further differentiation involves evaluation for elaboration of deoxyribonuclease, utilization of malonate, liquefaction of gelatin, fermentation of arabinose, rhamnose, and raffinose, urea hydrolysis, lysine decarboxylase activity, arginine dihydrolase activity, methyl red test, Voges–Proskauer test, and phenylalanine deaminase production.40 Pigment production, al-
though traditionally considered a hallmark of Serratia marcescens, cannot be relied upon as an identifying characteristic as the minority of biotypes elaborate pigment. In one study examining 176 strains of Serratia marcescens isolated from patients with disease attributed to the organism, only 7% produced pigment.40 In the case presented here, the organisms isolated from vitreous, blood, and from the venous catheter tip were identified with use of the Vitek Gram-Negative Identification Card (bioMerieux Vitek, Inc.) by the following features: DP-300 positive, urease negative, maltose fermentation positive, inositol fermentation positive, L-arabinose fermentation negative, malonate fermentation negative, xylose fermentation negative, p-coumaric positive (based on glucose fermentation in the presence of specific inhibitors), arginine dihydrolase positive, negative acetamide utilization, tryptophan deaminase negative, raffinose fermentation negative, hydrogen sulfide negative, lysine decarboxylase positive, esculin hydrolase positve, positive growth in the presence of polymyxin B, sorbitol fermentatin positive, ornithine decarboxylase positive, plant indican positive, lactose fermentation negative, sucrose fermentation positive, rhamnose fermentation negative, and beta-galactosidase negative. SYSTEMIC DISEASE AND PATHOGENESIS
Fig. 10. Area shows necrosis of retina and optic nerve head, (hematoxylin and eosin, 136).
Wilkowske and associates summarized 176 cases of infections associated with Serratia marcescens isolated from various sites.40 The majority of cases were respi-
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Fig. 11. A: Posterior aspect of the formed vitreous (arrow) (giemsa, 544). B: Numerous coccobacillary organisms that are Gram-negative (modified Gram, 1360). C: Same organism stained with the giemsa technique (giemsa, 1360).
ratory infections, followed by urinary infections, wound infections, “blood,” and miscellaneous, including ear, surgical or autopsy tissue, intravenous catheter, vagina, cerebrospinal fluid, and peritoneal dialysis fluid. Other important observations from that study were that 56% of the patients had been hospitalized at the time Serratia was isolated, indicating possible nosocomial spread, and 90% had received antibiotics prior to their positive cultures. Other factors associated with positive cultures include surgery, inhalation therapy, genitourinary instrumentation, immunosuppressive therapy, and diabetes.40 In the case presented here, predisposing factors include diabetes mellitus, indwelling venous catheter, antecedent surgery (debridement of a foot ulcer with skin grafting and creation of an arteriovenous fistula), and prior use of antibiotics (related to the aforementioned surgical procedures). In the seven cases of endogenous Serratia endophthalmitis previously reported, all were associated with multiple potential risk factors. Serratia is an organism of low virulence but may lead to severe disease in a pre-
disposed individual either because of impaired host defenses or because of an altered host environment allowing the bacteria to grow beyond a threshold number that leads to disease. OCULAR DISEASE
Serratia marcescens has been reported as an ocular pathogen as early as 1908 when Axenfeld observed ocular disease after Bacterium prodigiosum was injected into the rabbit eye.6 It has subsequently been reported as a cause of purulent conjunctivitis in premature infants37 and in a burn patient.5 Infectious keratitis caused by Serratia marcescens is well documented.5,8,13,14,21,22,28,38,39 It is most commonly reported in association with contact lens wear13,21,28,32 and has been reported in association with contaminated eye droppers38 and radial keratotomy in a health care worker.14 Suture abscess caused by Serratia marcescens was reported by Leahey et al23 following penetrating keratoplasty.23 Kamata et al19 isolated a 56K protease from a strain of Serratia marcescens that had caused a “liquefactive keratitis.” They implicated
SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON
this protease as the virulence factor responsible for the local destructive effect that Serratia marcescens has on the cornea. Davis and collegues11 have described a Serratia marcescens lacrimal infection in a severe burn patient. Orbital infection caused by Serratia marcescens was reported after insertion of an alloplastic orbital implant by Mauriello and associates.26 Bigger and associates first reported exogenous Serratia marcescens endophthalmitis in 1971.8 They describe two cases, one post-traumatic and the other postoperative, of acute, purulent endophthalmitis resulting in eventual enucleation. The second case followed an intracapsular cataract extraction, and there was an associated orbital cellulitis in addition to corneal and scleral involvement. Wyler and associates41 reported the first case of presumed metastatic Serratia marcescens endophthalmitis; the patient was an intravenous drug abuser with persistent Serratia bacteremia. In 1992, Al Hazzaa and associates2 reported a neonate with sepsis who developed a hazy cornea and a pink hypopyon with an aqueous culture positive for Serratia marcescens. There were no erythrocytes present on microscopic examination of the anterior chamber aspirate. They suggested that the presence of a pink hypopyon might indicate infection with a pigment-producing strain of Serratia marcescens. de Courten and associates12 described a case of metastatic Serratia marcescens endophthalmitis in a neonate who underwent colostomy and subsequently developed proptosis, periorbital chemosis, hazy cornea, shallow anterior chamber with a middilated pupil, and leukocoria. Gross examination of the enucleated globe showed a “red-brown fluid” in the vitreous cavity. The characteristics of the 25 previously reported cases of Serratia marcescens endophthalmitis are summarized in Table 1. Of these, only nine are endogenous in nature.2,4,12,16,24,25,31,33,35,41 Of the 24 cases in which age was reported, the mean was 57.2 (range “neonate” to age 85) with a median age of 60 years. Of the 10 cases of endogenous endophthalmitis, the mean age was 45.6 (range “neonate” to age 77) with a median age of 59. Of the 22 cases in which sex was reported, 16 were male and six were female. Of the eight cases of endogenous endophthalmitis, five were male and three were female. Hypopyon was reported present in 11 cases. Of these, one was reported as a “pink hypopyon” in the absence of red blood cells on histopathology.2 Another was described as having a “red-brown fluid” in the vitreous.12 Associated medical conditions present in the 10 cases of endogenous or metastatic endophthalmitis include the following: 1) intracavernous carotid aneurysm, indwelling catheter, and recent craniotomy; 2) chronic lymphocytic leukemia and type II diabetes mellitus, status post-transurethral resection
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of the prostate with bladder perforation, pneumonia, and diabetes;35 3) neonate status postcolostomy; 4) esophogeal surgery and probable endocarditis; 5) neonate with sepsis; 6) diabetes with renal abscess; 7) IV drug abuse with history of glomerulonephritis and a mycotic aneurysm of the superior mesenteric artery; 8) diabetes mellitus with end-stage renal failure requiring dialysis; and 9) IV drug abuse with a prior history of candida endophthalmitis in the fellow eye. In 12 cases, either evisceration or enucleation was the final outcome.8,10,12,18,25,31,33,41 In three cases phthisis or atrophy was reported as the final outcome.2,4,34,35 One eye had a final visual acuity of 20/50, one eye 20/60, one eye 20/70, one eye 20/ 200, one eye hand motion, and one eye had no light perception.10 All of the eyes in which a final visual acuity was reported better than no light perception occurred following intraocular surgery.10 There was one reported death attributed to “CNS deterioration.”16 Histopathologic specimens have been reported in only three cases.8,12 Bigger et al8 observed in one case an acute inflammatory infiltrate involving cornea, anterior chamber, iris, ciliary body, vitreous, choroid, and retina along with destruction of the retina. Gram stain was positive for Gram-negative coccobacilli. Similar findings were described in a second case observed, but no organisms were seen.8 de Courten and associates12 reported a “red-brown fluid” in the vitreous as well as polymorphonuclear lymphocytic infiltrate of the cornea, sclera, uveal tract, and optic nerve head and necrosis of the retina. Cultures of aqueous or vitreous were positive for Serratia marcescens in 21 of the 25 cases. Of the five cases that reported Gram-stain results, four showed Gram-negative rods and one showed no organisms.8,12,16,34 The presence of a dark hypopyon in this case is intriguing. Previous reports of dark hypopyon have been limited to Listeria monocytogenes1,7,9,15,29 endophthalmitis and primary and metastatic intraocular melanoma.3 Pink hypopyon in Serratia endophthalmitis was observed by Al Hazzaa and associates,2 presumably related to pigment production, and a “redbrown” fluid in the vitreous of an eye with Serratia endophthalmitis was observed by de Courten and associates.12 In the case presented here, it appears that the cause of the dark hypopyon was necrosis of the iris with dispersion of melanin into the anterior chamber. The reason for the production of dark hypopyon and iris necrosis with pigment dispersion in Listeria and Serratia endophthalmitis is unknown. The presence of a dark hypopyon may not be as specific a clinical marker as once thought but remains useful in that its presence should raise suspicion for intraocular melanoma or infection with Listeria or Serratia. It is not clear whether organisms related to Listeria or Serratia can also cause a dark hypopyon.
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TABLE 1
Reported Cases of Endophthalmitis Due to Serratia Author (Reference) 8
Age
Sex
Medical/ Surgical History
Presentation
Bigger et al
44
Male
Bigger et al8 Salceda et al34
85 53
Female S/P ICCE Male Diabetes, S/P ICCE
Gammon et al16
60
Radda33
59
de Courten et al12 10 days
Female S/P Carotid aneurysm clipping, pneumonia, indwelling foley catheter Male Chronic lymphocytic leukemia, diabetes, S/P TURP, bladder perforation, hemodialysis Male S/P colostomy
Okada et al31
77
NR
al Hazzaa et al2
Neonate NR
Shaaraway et al36 Cohen et al10
NR 50
NR Male
Cohen et al10
69
Male
Cohen et al10
64
20/300 hypopyon
Cohen et al10
71
Cohen et al10
45
Cohen et al10
51
Cohen et al10
81
Female S/P phaco-emulsification, Diabetes Male S/P ECCE, primary capsulotomy, wound leak Male S/P PKP, suture removal, wound dehiscence Male S/P PKP, anterior vitrectomy, suture abscess, diabetes Male S/P ECCE, ACIOL
Cohen et al10
77
Male
NLP
Cohen et al10
72
Dialysis, S/P Scheie procedure Female S/P scleral Buckle
Cohen et al10
73
Male
LP
Lin et al24
68
S/P ECCE, rheumatoid arthritis Female Diabetes, renal abscess
Wyler et al41
47
Male
Johnson et al18
82
Male
Marinella and Warwar25 Alvarez et al4
48
Male
32
Male
Intraocular foreign body
Diagnosis
Pain, HM vision, purulence, hypopyon Pain, hypopyon Pain, hypopyon
Outcome
Conjunctival, intraocular cultures AC aspirate Aqueous, conjunctival cultures Proptosis, discharge, Aqueous, hypopyon urine cultures
NLP, enucleation
Pain, NLP
Vitreous culture
Evisceration
Fever, proptosis, leukocoria “pan-ophthalmitis”
Vitreous culture not reported
Enucleation
Aqueous culture NR Aqueous culture Aqueous, vitreous culture Aqueous culture Aqueous, vitreous culture Aqueous culture Vitreous culture
Phthisis
S/P esophageal surgery, “probable endocarditis Sepsis Pink hypopyon NR NR Diabetes, S/P HM, hypopyon trabeculectomy S/P phaco-emulsification HM
NR 20/400, hypopyon HM LP
NLP
HM, AC exudate
Vitreous culture Vitreous culture Vitreous culture Vitreous culture Renal abscess culture Blood, urine culture
IVDU, mycotic aneurysm NR of superior mesenteric artery S/P CE and vitrectomy, LP, “white Vitreous HTN, Hypothyroid inflammatory culture material” in AC Diabetes, dialysis, LP, fibrinous Aqueous catheter exudate, hypopyon culture HIV, IVDU 20/80, hypopyon Vitreous culture
Enucleation “Atrophic” eye Death
Enucleation
NR 20/50 20/60 20/70 20/200 HM NLP Enucleated or eviscerated Eviscerated Enucleation Enucleation NLP Enucleation Evisceration NLP, enucleation Phthisis
S/P status post; ICCE intracapsular cataract extraction; TURP transurethral resection of the prostate; HM Hand motion; NLP no light perception; HIV human immunodeficiency virus; IVDU intravenous drug use; HTN hypertension; PKP penetrating keratoplasty; ECCE extracapsular cataract extraction; NR not reported.
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SERRATIA MARCESCENS ENDOPHTHALMITIS WITH DARK HYPOPYON TREATMENT
Serratia marcescens typically is a multidrug-resistant organism, perhaps owing to its pervasiveness in the environment and exposure to various antibiotics that have selected for those strains that carry resistance. Miller and Buckler30 describe Serratia marcescens ability to survive and divide within in human polymorphonuclear lymphocytes after phagocytosis that may also contribute to its resistance to many antibiotics. In virtually all isolates of Serratia tested for antibiotic susceptibility, only aminoglycoside antibiotics and amikacin show consistent efficacy in inhibiting or preventing growth on inoculated media.2,4,5,8,12,18,25,40,41 Several cases reviewed here also demonstrated variable activity of third-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole, tetracycline, and synthetic penicillins against Serratia.2,4,8,18,25,40,41 Persistence of disease despite sensitivity-guided antimicrobial therapy is also reported, owing perhaps to intracellular growth, continued effect of lipopolysaccharide from destroyed bacteria, or immune-mediated destruction.5,8,18 Based on this information, aminoglycoside therapy would be most appropriate in cases of suspected or documented Serratia infection. Given the retinal toxicity of intravitreal aminoglycosides, a third-generation cephalosporin (e.g., ceftazidime) is a reasonable alternative for empiric treatment until alterations based on susceptibility can be made.
Summary Serratia marcescens endophthalmitis is a rare cause of endogenous endophthalmitis with only ten cases previously reported. The eleventh case is reported here in a patient with multiple established risk factors for Serratia endophthalmitis: diabetes mellitus, indwelling venous catheter, recent use of antibiotics, and recent surgery. This is the first known case of dark hypopyon in Serratia endophthalmitis. The devastating course of this disease is demonstrated owing in part to multidrug resistance. The combination of patient factors that predispose to the development of endogenous Serratia endophthalmitis and the presence of a dark hypopyon and elevated intraocular pressure may be useful in narrowing the differential diagnosis and aiding in therapeutic decisions for this rare but devastating entity.
Method of Literature Search A search was conducted of the MEDLINE database for all years. The search terms used were Serratia and endophthalmitis, eye, infection, ophthalmic, conjunctivitis, keratitis, ocular, disease, treatment, review, dark hypopyon, black hypopyon. All citations judged to be of clinical importance were included as were additional references listed in key articles. We wanted to review all known and published cases of Serratia
marcescens endophthalmitis. Cases with infections caused by Serratia marcescens were included in our review, and cases of dark or black hypopyon were reviewed. Citations were referenced if they came from peer-reviewed articles only and if they had English abstracts. In addition, infections caused by Serratia species other than marcescens were excluded.
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EQUI AND GREEN
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Supported in part by the Independent Order of Odd Fellows, Winston Salem, North Carolina. The authors have no proprietary or commercial interest in any product or idea discussed in this article. Reprint address: W. Richard Green, MD, Wilmer Ophthalmological Institute, W. Richard Green Eye Pathology Laboratory, Maumenee 427, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-9248.