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Group B Streptococcus endogenous endophthalmitis
Group B Streptococcus Endogenous Endophthalmitis Case Reports and Review of the Literature Shu-Yen Lee, MRCS(Ed), MMed (Ophth), Soon-Phaik Chee, FRCS(G), FRCOphth Purpose: To report five cases of group B Streptococcus endogenous endophthalmitis (GBSEE) and to review the literature. Design: Retrospective, noncomparative, interventional case series and literature review. Patients: All patients with this condition treated at the Singapore National Eye Centre from 1994 through 2001. Interventions: Core or complete vitrectomy and intravitreal and systemic antibiotics. Methods: A review of the systemic and ocular characteristics and treatment. Main Outcome Measure: Visual outcome. Results: Group B Streptococcus endogenous endophthalmitis developed in four patients after the onset of septic arthritis and in one patient with cervical epidural abscess after acupuncture, presenting as a diffuse endophthalmitis. Group B Streptococcus was isolated in the blood, vitreous, and joints. Despite the use of high-dose intravenous antibiotics within 72 hours of ocular presentation, intravitreal antibiotic injection, and vitrectomy (two eyes), all eyes lost light perception and became phthisical. A survey of the literature revealed that GBSEE is rare and that 17 cases have been reported since 1985. For purposes of analysis, four of these cases were excluded because of inadequate details and our five cases were included. Group B Streptococcus endogenous endophthalmitis was found to arise from hematogenous spread from cutaneous sites of infection (16.7%), pharyngitis (11.1%), and pneumonia (11.1%). Septic arthritis (38.9%) and endocarditis (33.3%) were concomitant sites of infection along with endophthalmitis. The septic arthritis typically involved multiple joints. Four patients (22.2%) had diabetes mellitus and three had other underlying predisposing illness. Although most patients received intravenous (83.3%) and intravitreal (55.6%) antibiotics and four eyes underwent therapeutic vitrectomy, useful vision was preserved in only four eyes. Two patients died of sepsis. Conclusions: Group B Streptococcus endogenous endophthalmitis is a devastating condition often associated with septic arthritis. The visual prognosis is poor, despite therapy. Ophthalmology 2002;109:1879 –1886 © 2002 by the American Academy of Ophthalmology. Endogenous bacterial endophthalmitis is a rare but visually devastating disease. It arises as a result of hematogenous spread from a septic focus distant to the eye. Immunocompromised states such as diabetes mellitus, malignancy, and chemotherapy are associated with a reduced host defense and are risk factors for developing endogenous endophthalmitis (EE). Wong et al1 reported the East Asian experience of predominantly gram-negative organisms, in particular Klebsiella pneumoniae, as the leading cause of EE. In the West, grampositive organisms such as Staphylococcus aureus and Streptococcus pneumoniae are responsible for most cases.2,3 HowOriginally received: December 17, 2001. Accepted: March 28, 2002. Manuscript no. 211038. From the Singapore National Eye Centre, Singapore, Republic of Singapore. The authors have no proprietary interests in the equipment or drugs used in this paper. Correspondence to Soon-Phaik Chee, FRCS(G), FRCOphth, Singapore National Eye Centre, 11, Third Hospital Avenue, Singapore 168751, Republic of Singapore. Email: [email protected]. © 2002 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
ever, group B Streptococcus endogenous endophthalmitis (GBSEE) is rare in adults, and to date, only 17 cases have been reported in the literature. We present five cases seen at the Singapore National Eye Centre and review the literature.
Materials and Methods We reviewed the records of all patients seen at the Singapore National Eye Centre with a diagnosis of GBSEE between January 1994 and September 2001. The ocular and systemic characteristics, treatment, and final outcome of cases with GBSEE were studied. A MEDLINE literature search of all years available (1966 through 2001) was performed, and all reported cases were reviewed and tabulated (Table 1), together with our series of patients, in this report.
Case Reports Patient 1 A 55-year-old, previously fit Malay male (shown as patient 18 in Table 1) reported floaters in the left eye of 2 days duration, ISSN 0161-6420/02/$–see front matter PII S0161-6420(02)01225-3
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Ophthalmology Volume 109, Number 10, October 2002 Table 1. Clinical Summary of Group B Streptococcus Endogenous
Authors
Patient Nos.
Age (yrs)
Gender
Predisposing illness
Source of Infection
Other Sites of Infection
Time to Eye Signs
Farber et al
1
42
M
Congenital heart disease
Sore throat
Infective endocarditis
5 days
Eykyn et al O’Brart
2–5 6
55
M
Renal calculi, multiple myeloma
UTI
Septic arthritis (right elbow)
Concurrent
7
76
F
UTI
2 days
8
65
M
9
60
M
Pharyngitis
Galloway et al
10
70
F
Unknown
Infective endocarditis (two-dimensional echo), pneumonia Septic arthritis (right knee), Infective endocarditis (two-dimensional echo), Septic arthritis (left wrist) Septic arthritis (left wrist, right shoulder)
Ing et al
11
74
F
Nagelberg et al
12
62
F
DM
13
48
M
HIV, splenectomy for ITP
Cellulitis, chronic foot ulcer Cellulitis, gangrene of the right foot Unknown
14
81
15
56
Buglass et al
16
80
F
Unknown
Matsuo et al
17
83
M
Pneumonia
Lee, Chee
18
55
M
Foot abscess
19
67
M
20
53
M
DM
Cervical epidural abscess Unknown
21
82
M
DM
Unknown
22
63
F
Okada et al
DM (undiagnosed)
Unknown
Diverticulitis
Unknown
Concurrent
Concurrent 4 days 2 days 1 wk
Meningitis
1 day
Infective endocarditis (possible) Infective endocarditis (possible) Infective endocarditis, meningitis (autopsy)
NA NA 12 hrs 4 days
Septic arthritis (bilateral wrists, left ankle, right shoulder) Osteomyelitis
2 wks
Septic arthritis (bilateral wrists, left knee, left shoulder, bilateral MCP, right MTP) Septic arthritis (bilateral knees, left elbow) Septic arthritis (right shoulder, right knee, right ankle, left wrist)
5 days
1 wk
Concurrent 2 days
CF ⫽ counting fingers; CSF ⫽ cerebrospinal fluid; DM ⫽ diabetes mellitus; F ⫽ female; HIV ⫽ human immunodeficiency virus; HM ⫽ hand motion; not applicable; NLP ⫽ no perception of light; OD ⫽ right eye; OS ⫽ left eye; UTI ⫽ urinary tract infection.
followed by sudden, painless loss of vision. He had multiple joint pains and swelling accompanied by febrile episodes for 2 weeks. At presentation, his visual acuities were 20/40 in the right eye and light perception (LP) in the left eye. The right eye was normal. The left conjunctiva was injected and the anterior chamber was shallow. Anterior chamber cells, fibrin, hypopyon, and iris bombe secondary to seclusio and occlusio pupillae were present. The hypopyon was noted to shift with changing head position. A reverse relative afferent pupillary defect (RAPD) was present and the intraocular pressure was normal. View of the posterior segment
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was not possible, but ultrasonography showed diffuse vitreous opacities without choroidal abscesses. The patient was toxic and febrile (38° C). Multiple joints, including both wrists, the right shoulder, and the left ankle, were red and swollen. An abscess involving the dorsum of the left foot, requiring incision and drainage, was the source of sepsis. He had a leukocyte count of 33.4 ⫻ 109/l with polymorph predominance of 86%. With a diagnosis of EE, a pars plana vitrectomy was performed. A pus-filled vitreous cavity with a pale, necrotic, friable but
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis Endophthalmitis from the Literature Review Laterality and Visual Acuity
Type of Endogenous Endophthalmitis
Other Culturepositive Sites
Blood Culture
Vitreous Culture
OD-LP
Posterior
Positive
Not performed
OD-HM; OS-6/36
OD-diffuse OS-anterior
Positive
Positive
Aqueous
Cefuroxime
OD-LP; OS-LP
OU-panophthalmitis
Positive
Not performed
Urine, conjunctiva
NA
OD-LP; OS-6/5
OD-diffuse
Positive
Positive
Synovial aspirate
Cefuroxime
OS-6/60
Panophthalmitis
Positive
Not performed
OD-6/18; OS-6/36 OS-LP
Not stated
Positive
Not performed
Synovial fluid
Panophthalmitis
NA
Positive
Foot ulcer
OD-20/70; OS-LP OD-CF; OS-20/20 NA
OD-posterior, OS-diffuse OD-panophthalmitis Panophthalmitis
Positive
Positive
Foot ulcer
Positive
Not performed
CSF
Positive
Not performed
NA
Panophthalmitis
Positive
Not performed
OS-LP
Diffuse
Positive
Positive
OD-LP; OS-NLP OS-LP
OU-posterior
Negative
Positive
Diffuse
Positive
Negative
OS-CF
Posterior
Positive
Positive
OD-LP
Diffuse
Positive
Positive
OD-NLP
Diffuse
Positive
Positive
OD-LP
Diffuse
Positive
Positive
Vitrectomy
Intravitreal Antibiotics NA
Final Visual Acuity
Cefazolin, gentamicin, penicillin Amoxicillin, gentamicin
Died
Benzylpenicillin, gentamicin, acyclovir Amoxicillin, gentamicin, benzylpenicillin
OD-LP; OS-NLP
NA
Benzylpenicillin
Evisceration
NA
Benzylpenicillin
Amikacin, vancomycin Vancomycin, amikacin
Cefazolin, gentamicin Penicillin G
OD-NLP; OS-20/20
OD- phthisis; OS-good
NA
NA
Normal visual acuity OU-NLP, phthisis bulbi OD-20/100; OS-LP OD-NLP; OS-20/20 NLP
Antibiotics (unspecified) NA
NA
20/40
NA
Died
NA
Cefotiam, cefdinir
Enculeated
Performed
Vancomycin, gentamicin
Vancomycin, penicillin
NLP, phthisis bulbi
Performed
Vancomycin, gentamicin Vancomycin, ceftazidime
Penicillin
NLP, phthisis bulbi NLP, enucleation
Vancomycin, ceftazidime Vancomycin, amikacin
Penicillin, ciprofloxacin Ceftriaxone
Performed
Penicillin G
Performed CSF
Foot abscess
Systemic Antibiotics
Synovial aspirate
Penicillin, gentamicin
NLP, phthisis bulbi NLP, phthisis bulbi
ITP ⫽ idiopathic thrombocytopaenia; LP ⫽ perception of light; M ⫽ male; MCP ⫽ metacarpophalangeal joint; MTP ⫽ metatarsophalangeal joint; NA ⫽
undetached retina was found. The retinal vessels appeared sheathed and occluded. Vitreous was sent for culture and sensitivity. Intravitreal gentamicin (0.1 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were administered. Gram stain of the vitreous showed gram-positive cocci and polymorphs. Blood and foot abscess cultures grew group B Streptococcus (GBS) sensitive to penicillin, ampicillin, cephalexin, and vancomycin. Intravenous (1 g/day) and topical vancomycin (50 mg/ml) administrations were commenced on day 3. The vitreous failed to culture any organism.
Although the septicemia and arthritis were controlled after 4 weeks of intravenous vancomycin, vision in the left eye did not recover and the eye eventually became phthisical.
Patient 2 A 67-year-old non-diabetic Chinese male (Patient 19, Table 1) had fever, chills, rigors, and neck pain of a week’s duration at presentation several weeks after undergoing acupuncture treatment to his neck. There was no neurologic deficit and he did not report any
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Ophthalmology Volume 109, Number 10, October 2002 trauma. He was toxic looking and febrile (38.3° C), and he developed progressive neck stiffness during his hospitalization. Magnetic resonance imaging of the cervical spine revealed an extensive anterolateral epidural abscess involving the second to the sixth cervical vertebra with moderately severe cord compression, as well as a prevertebral pus collection extending from the fourth to eighth thoracic vertebra. Osteomyelitis of the fifth and sixth cervical vertebrae was present. He had severe leucocytosis of 24.1 ⫻ 109/l, with polymorphs constituting 86%. In view of his stable neurologic status, medical .therapy with intravenous crystalline penicillin (12 MU/day) was commenced. On day 2 of his hospitalization, sudden, painful visual loss developed in the left eye. Vision was 20/30 in the right eye and counting fingers in the left eye. The right eye was normal. A left RAPD was present and the intraocular pressure was normal. There was left iritis (cells 3⫹ and flare). Multiple Roth spots and severe retinal vasculitis were noted through the hazy vitreous. Ultrasonography of the left eye confirmed the presence of diffuse vitreous debris. A diagnosis of left EE was made. The patient underwent a left therapeutic core vitrectomy, with intravitreal vancomycin (1 mg/0.1 ml) and gentamicin (0.1 mg/0.1 ml) within 24 hours of diagnosis. Blood and vitreous specimens cultured GBS sensitive to penicillin, ampicillin, and vancomycin. However, his vision deteriorated to LP secondary to a dense cataract and thick preretinal vitreal membranes. Extracapsular cataract extraction and vitrectomy with repeat intravitreal vancomycin (1 mg/0.1 ml) injection were performed 3 weeks after the first surgery. During surgery, organized vitreous gel with necrotic, atrophic retina and obliterative retinal vasculitis were found. The eye eventually lost perception of light and became phthisical. After 7 weeks of intravenous crystalline penicillin (12 MU/ day), the extradural abscess resolved (documented on serial magnetic resonance imaging scans), and the patient recovered without neurologic deficit.
Patient 3 A 53-year-old Chinese male (Patient 20, Table 1) with poorly controlled diabetes mellitus had fever, chills, and rigor at presentation accompanied by pain and stiffness in his left wrist and knee of 5 days duration. He also experienced pain and blurring of vision in the right eye for 1 day. On examination, he was febrile with a temperature of 38.2° C. The left wrist and knee were red, warm, and swollen. During his hospitalization, there was progressive joint involvement with painful swelling of his right wrist, left shoulder, bilateral metacarpophalangeal, and right metatarsophalangeal joints. Vision in the right eye was 20/25 and in the left eye was LP. A left reverse RAPD was present. There was corneal haze, and fibrin over the pupil, and a thick yellow–white hypopyon filled one third of the anterior chamber. This “sliding hypopyon” moved with a change of head position (Fig 1). There was no view of the fundus, but ultrasonography of the posterior segment revealed diffuse vitreous debris and a large inferotemporal choroidal abscess with an overlying exudative retinal detachment. The right eye was normal. Blood counts revealed a leukocytosis 13.13 ⫻ 109/l, with polymorphs accounting for 82.6%. The serum glucose level was 13.3 mmol/l. Results of the renal and liver function tests were normal. With a diagnosis of EE, aqueous and vitreous taps were performed, and intravitreal vancomycin (1 mg/0.1 ml), ceftazidime (2 mg/0.1 ml), and dexamethasone (0.1 mg/0.1 ml) were injected. Group B Streptococcus sensitive to penicillin, ampicillin, and vancomycin was cultured from the blood, aqueous, vitreous, and knee aspirates. The patient was treated with intravenous crystalline
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Figure 1. Patient 3. The photographs demonstrate the “sliding hypopyon.” A, The hypopyon with head in the upright position. B, The hypopyon with head tilted to the right after 30 seconds.
penicillin (24 MU/day) for 4 weeks and with gentamicin (3 mg/kg daily) for 1 week. He recovered systemically but the left eye became phthisical and required enucleation for pain relief. Histopathologic analysis of the enucleated globe showed mild chronic inflammation with proliferation of congested capillaries at the corneoscleral junction and edematous uvea. In addition, a degenerate lens was also present, together with osseous metaplasia posteriorly, disruption of the retina, marked fibrosis, and associated chronic inflammation. The optic nerve was normal.
Patient 4 An 82-year-old Chinese male (Patient 21, Table 1) with a history of diabetes mellitus had bilateral knee pain and left elbow pain of 2 days duration associated with fever at presentation. He also reported loss of vision in the right eye for a similar duration. He had a history of right cataract extraction with broad iridectomy and intraocular lens implantation 7 years prior. On examination, the right visual acuity was no light perception. A creamy-white hypopyon was present in the anterior chamber as well as within the pupil, demonstrating two different levels of pus (Fig 2). The anterior chamber also contained fibrin, and the intraocular pressure was 40 mmHg. Because any view of the fundus
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis cin (0.4 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were injected. She recovered systemically, but phthisis bulbi developed, and the eye lost perception to light.
Discussion
Figure 2. Patient 4. The photograph demonstrates the “pupillary hypopyon” in an eye with previous extracapsular cataract with intraocular lens implantation and a broad iridectomy at the 12-o’clock position. The pupillary hypopyon is a double hypopyon with one level within the anterior chamber and a second level within the pupil, in the posterior chamber.
was precluded, ultrasonography was performed and revealed the presence of diffuse vitreous debris. The left eye was normal. Leukocytosis of 17.06 ⫻ 109/l, of which polymorphs accounted for 82.6%, was present. Group B Streptococcus cultured from both the blood and vitreous was sensitive to penicillin, ampicillin, and vancomycin. He was treated with intravenous crystalline penicillin (18 MU/day) and ciprofloxacin (800 mg/day). Intravitreal ceftazidime (2 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were injected. Topical vancomycin (50 mg/ml) and antiglaucoma medications were instilled. The patient experienced a non-Q myocardial infarction during his admission and declined further intravitreal injections. He survived the myocardial infarction and recovered from the sepsis after 4 weeks of antibiotics, but the right eye eventually became phthisical.
Patient 5 A 63-year-old Chinese female (Patient 22, Table 1) with no significant medical history had fever of 5 days’ duration, multiple joint pains, loss of vision, and redness of the right eye of 3 days duration at presentation. She had a history of poor vision in the left eye secondary to severe myopia resulting in chorioretinal degeneration associated with a posterior staphyloma. On examination, she was afebrile. The right shoulder, knee, and ankle and the left wrist were tender and swollen and had restricted movements. Her visual acuities were LP in the right eye and counting fingers in the left eye. The right eye was injected and the cornea was hazy. The intraocular pressure was 19 mmHg. There were fine keratic precipitates, flare, and fibrin within the anterior chamber. A cream-colored hypopyon filled half the anterior chamber and had a level that slid and changed as the position of the head changed. Ultrasonography revealed vitreous opacities without the presence of choroidal abscesses. The patient had a leukocyte count of 15.8 ⫻ 109/l, with 98% polymorphs. Gram-stain analysis of the vitreous showed polymorphs but no organisms. Group B Streptococcus sensitive to penicillin, ampicillin, ceftriaxone, and erythromycin was cultured from blood and vitreous. She was allergic to penicillin, so she was treated with intravenous ceftriaxone (2 g/day). Intravitreal amika-
Endogenous endophthalmitis is an uncommon, devastating disease, often associated with poor visual prognosis. Frequently, an associated underlying septic focus, such as a liver abscess, cellulitis, or urinary tract infection, is present.1–3 It usually occurs in immunocompromised patients, but may occur in healthy individuals.4,5 A literature search from 1966 through 2001 using MEDLINE revealed that GBS as a cause of EE is rare. In 1986, Greenwald et al3 published a review of 72 cases of endogenous bacterial endophthalmitis, of which only one case was caused by GBS in a neonate. In 1994, Okada et al2 performed a 10-year retrospective review of EE and reported only two cases of GBSEE (7%), despite showing that 71% of the cases were caused by gram-positive organisms and 32% were identified as Streptococcus species. In East Asians, EE caused by gram-negative organisms, especially Klebsiella, is more common than that caused by gram-positive organisms.1 Two of the 33 cases of EE seen over a 4-year period were reported to be caused by GBS. These two cases are included in the series of patients reported in this paper. Whether there is a real or apparent trend toward an increase in the incidence of GBSEE in recent years is difficult to ascertain. However, GBS is still a rare cause of EE. Farber et al6 first reported GBSEE in an adult with congenital heart disease who developed septicemia and endocarditis after a throat infection in 1985. Since then, another 16 cases have been published. In this paper, we presented five cases of GBSEE. Although 22 cases in total are reported in the literature, we were able to analyze only 18 cases, because the four cases reported by Eykyn et al7 did not include adequate details. Of the 18 patients with GBSEE, there was involvement of 25 eyes. The average age of patients in whom GBSEE developed was 62.8 years (range, 42– 82 years), with a male-to-female ratio of 5 to 3. One third had a significant underlying chronic disease. These included diabetes mellitus, particularly if it was poorly controlled (4 cases; 22.2%), underlying malignancy (1 case; 5.6%), and acquired immunodeficiency syndrome (1 case; 5.6%). Group B Streptococcus is an invasive, encapsulated microorganism with the potential to produce severe disease. It is found as a commensal in the upper respiratory tract, skin, colorectum, and vagina. It is associated most frequently with neonatal sepsis during the first hours of life, resulting in a high mortality rate (30%–50%).8 In adults, it is associated with infections such as pharyngitis, cellulitis, meningitis, and pneumonia. The mortality rate is as high as 39%,12 often occurring within 48 hours of bacteremia. Diabetes, neoplastic disease, and liver failure are known predisposing factors. In this series, the presumed source of infection included cutaneous infections (3 cases; 16.7%), pharyngitis (2 cases;
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Ophthalmology Volume 109, Number 10, October 2002 11.1%), and pneumonia (1 case; 11.1%; Table 1).2,4 –7,9 –12 Although septic arthritis was the feature most commonly seen in these patients (8 cases; 44.4%), it is likely to be a sequel of pyogenic metastases rather than the cause of the sepsis. It is well established that the pathophysiologic progression of septic arthritis in normal joints is a result of hematogenous seeding during an episode of bacteremia.13 The large joints, such as the elbow, knee, and ankle, appear to be the more common sites of involvement, occurring singly or multiply. In the presence of overwhelming sepsis, the risk of polyarticular involvement is increased.13 Pischel et al14 described the polyarticular involvement of patients with GBS sepsis and septic arthritis resulting in significant functional morbidity. Of the eight patients with septic arthritis, five patients had involvement of more than one joint. As demonstrated in patient 4, joint involvement in GBS sepsis can evolve progressively involving other joints, even when the appropriate intravenous antibiotics have been administered. The wrist joint was the most frequently involved, occurring in 7 of 23 joints (30.4%), followed by the knee joint in 21.7% (5 joints). The reason the joints are so frequently involved in association with GBSEE is not clear. The synovial space is an enclosed space containing a potential culture medium, with minimal turnover of fluid and poor blood supply. As soon as bacterial seeding to the joint occurs, entrapment and proliferation of bacteria within the synovial fluid leads to the development of septic arthritis.13 This is in direct comparison with the vitreous cavity, where the organism is trapped within a culture medium, also allowing for proliferation. Although endocarditis, occurring in 6 patients (33.3%), frequently has been suggested as a possible source of infection, this is also likely to be a consequence of the septicemia.4,10 Endocarditis often affects degenerative valves,15 but in this series, only one patient had a congenital cardiac valve abnormality (patient 1). Except for the one patient in whom only endocarditis was seen in conjunction with GBSEE (patient 15), all other patients who had endocarditis had a definite septic focus. In all but one case (patient 8) in which the only other site of sepsis was in the joint, the septic focus detected was also the source. This suggests that in GBS sepsis, endocarditis is more likely to be an innocent bystander, with infection as a result of bacterial seeding to a cardiac valve, rather than as the source of sepsis. Only one patient had a history of congenital heart disease; the others had no prior valvular heart disease. It is likely that these valves, in elderly patients, have atherosclerotic changes that may predispose patients to bacterial adherence and proliferation. In seven patients (38.9%), the source of infection could not be identified conclusively (patients 8, 10, 13, 16, 20, 21, 22). The time of onset between the systemic infection and ocular manifestation was variable. In four patients, the systemic and ocular symptoms occurred concurrently. Interestingly, in all these patients, septic arthritis also developed. This may suggest that a large colony count of bacteria had been liberated from the septic focus into the circulation, enabling seeding of bacteria into multiple sites. Most patients had ocular involvement at presentation within 5 days of onset of sepsis, with 50% of the patients seeking treat-
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ment within 2 days. However, ocular infection was not the initial manifestation of sepsis in any patient. Both eyes had an equal chance of being affected, and one third of the cases had bilateral involvement. These patients typically experience a dramatic loss of vision, which at presentation is often counting fingers or worse. A reverse RAPD and hypopyon often are present, with diffuse posterior segment involvement; the rapidity of involvement demonstrates the virulence of the infecting organism. A characteristic feature noted in three of our patients (patients 1, 4, and 5) was the propensity for the meniscus level of the creamy-white hypopyon to shift fluidly with a change of head posture (Fig 1). We have named this phenomenon a sliding hypopyon. This unusual feature, not seen in our experience with EE caused by other microorganisms, may be a result of the many lysins, such as hemolysin and cytolysin, produced by GBS. In patient 4, we observed a double hypopyon— one in the anterior chamber and one within the pupil, that is, within the posterior chamber (Fig 2). A pupillary hypopyon is rare and has been reported in Klebsiella EE.16 We hypothesize that the ciliary body is the site of ocular seeding in such an eye, causing a rapid outpouring of pus into the anterior and posterior segments, initially filling the posterior chamber and cascading over the pupil to form a hypopyon in the anterior chamber. In this eye, there was also diffuse vitreous opacity on ultrasonography and a visual acuity of no light perception at presentation. In four of the five patients that we presented, the endophthalmitis presented as a diffuse endophthalmitis. These features again attest to the virulence of GBS. Diagnosis in these patients may be confused with rheumatologic conditions. In the presence of multiple-joint arthritis and a severely inflamed eye, GBS sepsis may be mistaken for Reiter’s syndrome or Behc¸ et’s disease and inappropriately given steroid therapy. An important differentiating point is the history of fever, chills, and rigors and the toxic appearance of the patient. The presence of a reverse RAPD, a sliding hypopyon, and diffuse panophthalmitis make the diagnosis of EE more likely. The associated septic arthritis tends to involve the wrist and other large joints. Commonly, more than one joint is involved and progressive joint involvement may occur. Ultimately, a positive culture is required to make a definitive diagnosis. Blood cultures were positive in 16 patients (not documented in one patient). Despite the fact that systemic antibiotic therapy had been commenced before the onset of ocular manifestations, vitreous cultures were nonetheless positive in 10 of the 11 cases (83.3%) in which a vitreous culture had been taken. Other sites of positive bacterial culture include joint aspirates (3 cases; 16.7%), swabs from cutaneous sites of infection (3 cases; 16.7%), and cerebrospinal fluid (2 cases; 11.1%). Intravenous high-dose antibiotics form the mainstay of management in GBSEE. Group B Streptococcus is still most frequently sensitive to crystalline penicillin, which has good ocular penetration. Other antibiotics to which GBS is susceptible include the -lactam antibiotics, cephalosporins, vancomycin, and imipenem. In this series, eleven patients were treated with intravenous high-dose penicillin, two with
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis amoxicillin, four with antibiotics of the cephalosporin group, and one with vancomycin. Unlike most other infections that can be treated with a 1-week course of intravenous antibiotics, patients with GBS septicemia and septic arthritis or endocarditis require 3 to 4 weeks of therapy or more. The use of intravitreal and topical antibiotics is controversial. Ten eyes of the 18 patients received intravitreal antibiotics in addition to the systemic therapy. Although some advocate the delivery of the antibiotic into the vitreous cavity to destroy the causative microbe directly and rapidly during a vitreous tap for culture, others have countered that, unlike postoperative bacterial endophthalmitis, the main source of infection is not the eye, but of a hematogenous origin. Thus, if the bacteria are capable of penetrating the blood– ocular barrier to infect the eye, the antibiotics should enter the eye effectively to sterilize it. This also would account for negative cultures in vitreous aspirates obtained from patients who already have been treated partially with intravenous antibiotics. The role of vitrectomy is still undefined in most series. Most authors have shown that vitrectomy for GBSEE has not been beneficial in salvaging vision. However, this may be a consequence of bias in selecting the more severely involved eyes for surgical intervention. Four eyes with GBSEE underwent vitrectomy, and in three cases, the eyes subsequently had phthisis bulbi and loss of light perception. In the two patients we presented who had undergone vitrectomy, pus-filled vitreous cavities and necrotic, friable, and opacified retinae with occlusive retinal vasculitis were encountered. Perhaps the rapid, widespread destruction of the retina by this virulent bacterium is an important factor that prevents the preservation or salvage of useful vision even with surgery. The presence of an RAPD at presentation suggests that the widespread destruction occurs early. Hypotony and phthisis bulbi frequently result, despite sterilization of the eye by vitrectomy. This is supported by the pathologic findings of Matsuo et al11 of a necrotic vitreous cavity, total retinal detachment, and a choroid that was riddled with microabscesses and destruction of Bruch’s membrane in an eye with GBSEE that had been enucleated. We suggest that the lytic enzymes released by GBS, which are likely to cause the breakdown of the ocular barriers and may account for its ocular virulence, are responsible for its presentation as a rapidly progressive and diffuse form of panophthalmic endophthalmitis.17 There were two deaths4,10 in this series of 22 cases of GBSEE, a fatality rate of 9.0%. Both of these patients (patients 1 and 16) had infective endocarditis but no prior history of any immunosuppressive illness. Patient 16 had a rapidly deteriorating clinical course and died of the overwhelming sepsis after 2 days. Although most of the patients do recover systemically from the GBS infection and septicemia, the visual prognosis is extremely poor. Of the 18 patients, 25 eyes were involved. Only six eyes recovered useful vision, whereas the remaining eyes ultimately had either LP or no light perception and phthisis bulbi (76%). Of these six eyes, there was documentation in five eyes that showed one eye with anterior endophthalmitis (patient 6), one eye with posterior endophthalmitis (patient 12), one eye with diffuse endophthalmitis (patient 8), and two eyes with
panophthalmitis (patients 13 and 15). There was delayed ocular involvement in two eyes, concurrent presentation in two eyes, and 1 day after in one eye, whereas there were insufficient details in the sixth eye. There were no distinct features that might have been useful prognostic indicators of visual outcome. However, the “advantage” in a delayed ocular involvement in terms of visual prognosis is that these patients already would be on intravenous antibiotics for the sepsis, resulting in possible containment of the GBSEE. In conclusion, GBS can cause a severe septicemic disease. Although the primary site of infection often is not identified, pharyngitis, cutaneous infections and pneumonia should be searched for. This virulent organism can metastasize and cause infection in many sites such as the heart valves and joints. We therefore would like to highlight a clinical syndrome caused by GBS of EE accompanied by septic arthritis with or without endocarditis. The GBS septic arthritis involves multiple joints, which may become involved progressively during the septicemic episode. Because there is rapid, widespread destruction of the choroid and retina in GBSEE, the visual prognosis is poor despite intravenous antibiotics, and vitrectomy does not appear to alter the visual outcome.
References 1. Wong JS, Chan TK, Lee HM, Chee SP. Endogenous bacterial endophthalmitis. An East Asian experience and a reappraisal of a severe ocular affliction. Ophthalmology 2000;107:1483– 91. 2. Okada AA, Johnson RP, Liles WC, et al. Endogenous bacterial endophthalmitis. Report of a ten-year retrospective study. Ophthalmology 1994;101:832– 8. 3. Greenwald MJ, Wohl LG, Sell CH. Metastatic bacterial endophthalmitis: a contemporary reappraisal. Surv Ophthalmol 1986;31:81–101. 4. O’Brart DPS, Eykyn SJ. Septicaemic infection with group B streptococci presenting with endophthalmitis in adults. Eye 1992;6:396 –9. 5. Ing EB, Erasmus MJ, Chisholm LDJ. Metastatic group B streptococcal endophthalmitis from a cutaneous foot ulcer. Can J Ophthalmol 1993;28:238 – 40. 6. Farber BP, Weinbaum DL, Dummer JS. Metastatic bacterial endophthalmitis. Arch Intern Med 1985;145:62– 4. 7. Eykyn SJ, Young SEJ, Cookson BD. Increased communityacquired septicaemic infection with group B streptococci in adults [letter]. Lancet 1991;338:446. 8. Opal SM, Cross A, Palmer M, Almazan R. Group B Streptococcal sepsis in adults and infants. Contrasts and comparisons. Arch Intern Med 1988;148:641–5. 9. Galloway A, Deighton CM, Deady J, et al. Type V group B streptococcal septicaemia with bilateral endophthalmitis and septic arthritis [letter]. Lancet 1993;341:960 –1. 10. Nagelberg HP, Petashnick DE, To KW, Woodcome HA Jr. Group B streptococcal metastatic endophthalmitis. Am J Ophthalmol 1994;117:498 –500. 11. Buglass TD, Romanchuk KG. Fatal case of group B streptococcal endogenous endophthalmitis. Can J Ophthalmol 1995; 30:149 –50. 12. Matsuo K, Nakatuka K, Yano Y, et al. Group B streptococcal
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Ophthalmology Volume 109, Number 10, October 2002 metastatic endophthalmitis in an elderly man without predisposing illness. Jpn J Ophthalmol 1998;42:304 –7. 13. Goldenberg DL. Septic arthritis. Lancet 1998;351:197–202. 14. Pischel KD, Weisman MH, Cone RO. Unique features of Group B streptococcal arthritis in adults. Arch Intern Med 1985;145:97–102. 15. Gonza´ lez-Juanatey C, Gonza´ lez-Gay MA, Llorca J, et al.
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Rheumatic manifestations of infective endocarditis in non-addicts. A 12-year study. Medicine (Baltimore) 2001;80:9 –19. 16. Chee SP, Ang CL. Endogenous Klebsiella endophthalmitis—a case series. Ann Acad Med Singapore 1995;24:473– 8. 17. Pritzlaff CA, Chang JCW, Kuo SP, et al. Genetic basis for the -haemolytic/cytolytic activity of group B Streptococcus. Mol Microbiol 2001;39:236 – 47.
ever, group B Streptococcus endogenous endophthalmitis (GBSEE) is rare in adults, and to date, only 17 cases have been reported in the literature. We present five cases seen at the Singapore National Eye Centre and review the literature.
Materials and Methods We reviewed the records of all patients seen at the Singapore National Eye Centre with a diagnosis of GBSEE between January 1994 and September 2001. The ocular and systemic characteristics, treatment, and final outcome of cases with GBSEE were studied. A MEDLINE literature search of all years available (1966 through 2001) was performed, and all reported cases were reviewed and tabulated (Table 1), together with our series of patients, in this report.
Case Reports Patient 1 A 55-year-old, previously fit Malay male (shown as patient 18 in Table 1) reported floaters in the left eye of 2 days duration, ISSN 0161-6420/02/$–see front matter PII S0161-6420(02)01225-3
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Ophthalmology Volume 109, Number 10, October 2002 Table 1. Clinical Summary of Group B Streptococcus Endogenous
Authors
Patient Nos.
Age (yrs)
Gender
Predisposing illness
Source of Infection
Other Sites of Infection
Time to Eye Signs
Farber et al
1
42
M
Congenital heart disease
Sore throat
Infective endocarditis
5 days
Eykyn et al O’Brart
2–5 6
55
M
Renal calculi, multiple myeloma
UTI
Septic arthritis (right elbow)
Concurrent
7
76
F
UTI
2 days
8
65
M
9
60
M
Pharyngitis
Galloway et al
10
70
F
Unknown
Infective endocarditis (two-dimensional echo), pneumonia Septic arthritis (right knee), Infective endocarditis (two-dimensional echo), Septic arthritis (left wrist) Septic arthritis (left wrist, right shoulder)
Ing et al
11
74
F
Nagelberg et al
12
62
F
DM
13
48
M
HIV, splenectomy for ITP
Cellulitis, chronic foot ulcer Cellulitis, gangrene of the right foot Unknown
14
81
15
56
Buglass et al
16
80
F
Unknown
Matsuo et al
17
83
M
Pneumonia
Lee, Chee
18
55
M
Foot abscess
19
67
M
20
53
M
DM
Cervical epidural abscess Unknown
21
82
M
DM
Unknown
22
63
F
Okada et al
DM (undiagnosed)
Unknown
Diverticulitis
Unknown
Concurrent
Concurrent 4 days 2 days 1 wk
Meningitis
1 day
Infective endocarditis (possible) Infective endocarditis (possible) Infective endocarditis, meningitis (autopsy)
NA NA 12 hrs 4 days
Septic arthritis (bilateral wrists, left ankle, right shoulder) Osteomyelitis
2 wks
Septic arthritis (bilateral wrists, left knee, left shoulder, bilateral MCP, right MTP) Septic arthritis (bilateral knees, left elbow) Septic arthritis (right shoulder, right knee, right ankle, left wrist)
5 days
1 wk
Concurrent 2 days
CF ⫽ counting fingers; CSF ⫽ cerebrospinal fluid; DM ⫽ diabetes mellitus; F ⫽ female; HIV ⫽ human immunodeficiency virus; HM ⫽ hand motion; not applicable; NLP ⫽ no perception of light; OD ⫽ right eye; OS ⫽ left eye; UTI ⫽ urinary tract infection.
followed by sudden, painless loss of vision. He had multiple joint pains and swelling accompanied by febrile episodes for 2 weeks. At presentation, his visual acuities were 20/40 in the right eye and light perception (LP) in the left eye. The right eye was normal. The left conjunctiva was injected and the anterior chamber was shallow. Anterior chamber cells, fibrin, hypopyon, and iris bombe secondary to seclusio and occlusio pupillae were present. The hypopyon was noted to shift with changing head position. A reverse relative afferent pupillary defect (RAPD) was present and the intraocular pressure was normal. View of the posterior segment
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was not possible, but ultrasonography showed diffuse vitreous opacities without choroidal abscesses. The patient was toxic and febrile (38° C). Multiple joints, including both wrists, the right shoulder, and the left ankle, were red and swollen. An abscess involving the dorsum of the left foot, requiring incision and drainage, was the source of sepsis. He had a leukocyte count of 33.4 ⫻ 109/l with polymorph predominance of 86%. With a diagnosis of EE, a pars plana vitrectomy was performed. A pus-filled vitreous cavity with a pale, necrotic, friable but
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis Endophthalmitis from the Literature Review Laterality and Visual Acuity
Type of Endogenous Endophthalmitis
Other Culturepositive Sites
Blood Culture
Vitreous Culture
OD-LP
Posterior
Positive
Not performed
OD-HM; OS-6/36
OD-diffuse OS-anterior
Positive
Positive
Aqueous
Cefuroxime
OD-LP; OS-LP
OU-panophthalmitis
Positive
Not performed
Urine, conjunctiva
NA
OD-LP; OS-6/5
OD-diffuse
Positive
Positive
Synovial aspirate
Cefuroxime
OS-6/60
Panophthalmitis
Positive
Not performed
OD-6/18; OS-6/36 OS-LP
Not stated
Positive
Not performed
Synovial fluid
Panophthalmitis
NA
Positive
Foot ulcer
OD-20/70; OS-LP OD-CF; OS-20/20 NA
OD-posterior, OS-diffuse OD-panophthalmitis Panophthalmitis
Positive
Positive
Foot ulcer
Positive
Not performed
CSF
Positive
Not performed
NA
Panophthalmitis
Positive
Not performed
OS-LP
Diffuse
Positive
Positive
OD-LP; OS-NLP OS-LP
OU-posterior
Negative
Positive
Diffuse
Positive
Negative
OS-CF
Posterior
Positive
Positive
OD-LP
Diffuse
Positive
Positive
OD-NLP
Diffuse
Positive
Positive
OD-LP
Diffuse
Positive
Positive
Vitrectomy
Intravitreal Antibiotics NA
Final Visual Acuity
Cefazolin, gentamicin, penicillin Amoxicillin, gentamicin
Died
Benzylpenicillin, gentamicin, acyclovir Amoxicillin, gentamicin, benzylpenicillin
OD-LP; OS-NLP
NA
Benzylpenicillin
Evisceration
NA
Benzylpenicillin
Amikacin, vancomycin Vancomycin, amikacin
Cefazolin, gentamicin Penicillin G
OD-NLP; OS-20/20
OD- phthisis; OS-good
NA
NA
Normal visual acuity OU-NLP, phthisis bulbi OD-20/100; OS-LP OD-NLP; OS-20/20 NLP
Antibiotics (unspecified) NA
NA
20/40
NA
Died
NA
Cefotiam, cefdinir
Enculeated
Performed
Vancomycin, gentamicin
Vancomycin, penicillin
NLP, phthisis bulbi
Performed
Vancomycin, gentamicin Vancomycin, ceftazidime
Penicillin
NLP, phthisis bulbi NLP, enucleation
Vancomycin, ceftazidime Vancomycin, amikacin
Penicillin, ciprofloxacin Ceftriaxone
Performed
Penicillin G
Performed CSF
Foot abscess
Systemic Antibiotics
Synovial aspirate
Penicillin, gentamicin
NLP, phthisis bulbi NLP, phthisis bulbi
ITP ⫽ idiopathic thrombocytopaenia; LP ⫽ perception of light; M ⫽ male; MCP ⫽ metacarpophalangeal joint; MTP ⫽ metatarsophalangeal joint; NA ⫽
undetached retina was found. The retinal vessels appeared sheathed and occluded. Vitreous was sent for culture and sensitivity. Intravitreal gentamicin (0.1 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were administered. Gram stain of the vitreous showed gram-positive cocci and polymorphs. Blood and foot abscess cultures grew group B Streptococcus (GBS) sensitive to penicillin, ampicillin, cephalexin, and vancomycin. Intravenous (1 g/day) and topical vancomycin (50 mg/ml) administrations were commenced on day 3. The vitreous failed to culture any organism.
Although the septicemia and arthritis were controlled after 4 weeks of intravenous vancomycin, vision in the left eye did not recover and the eye eventually became phthisical.
Patient 2 A 67-year-old non-diabetic Chinese male (Patient 19, Table 1) had fever, chills, rigors, and neck pain of a week’s duration at presentation several weeks after undergoing acupuncture treatment to his neck. There was no neurologic deficit and he did not report any
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Ophthalmology Volume 109, Number 10, October 2002 trauma. He was toxic looking and febrile (38.3° C), and he developed progressive neck stiffness during his hospitalization. Magnetic resonance imaging of the cervical spine revealed an extensive anterolateral epidural abscess involving the second to the sixth cervical vertebra with moderately severe cord compression, as well as a prevertebral pus collection extending from the fourth to eighth thoracic vertebra. Osteomyelitis of the fifth and sixth cervical vertebrae was present. He had severe leucocytosis of 24.1 ⫻ 109/l, with polymorphs constituting 86%. In view of his stable neurologic status, medical .therapy with intravenous crystalline penicillin (12 MU/day) was commenced. On day 2 of his hospitalization, sudden, painful visual loss developed in the left eye. Vision was 20/30 in the right eye and counting fingers in the left eye. The right eye was normal. A left RAPD was present and the intraocular pressure was normal. There was left iritis (cells 3⫹ and flare). Multiple Roth spots and severe retinal vasculitis were noted through the hazy vitreous. Ultrasonography of the left eye confirmed the presence of diffuse vitreous debris. A diagnosis of left EE was made. The patient underwent a left therapeutic core vitrectomy, with intravitreal vancomycin (1 mg/0.1 ml) and gentamicin (0.1 mg/0.1 ml) within 24 hours of diagnosis. Blood and vitreous specimens cultured GBS sensitive to penicillin, ampicillin, and vancomycin. However, his vision deteriorated to LP secondary to a dense cataract and thick preretinal vitreal membranes. Extracapsular cataract extraction and vitrectomy with repeat intravitreal vancomycin (1 mg/0.1 ml) injection were performed 3 weeks after the first surgery. During surgery, organized vitreous gel with necrotic, atrophic retina and obliterative retinal vasculitis were found. The eye eventually lost perception of light and became phthisical. After 7 weeks of intravenous crystalline penicillin (12 MU/ day), the extradural abscess resolved (documented on serial magnetic resonance imaging scans), and the patient recovered without neurologic deficit.
Patient 3 A 53-year-old Chinese male (Patient 20, Table 1) with poorly controlled diabetes mellitus had fever, chills, and rigor at presentation accompanied by pain and stiffness in his left wrist and knee of 5 days duration. He also experienced pain and blurring of vision in the right eye for 1 day. On examination, he was febrile with a temperature of 38.2° C. The left wrist and knee were red, warm, and swollen. During his hospitalization, there was progressive joint involvement with painful swelling of his right wrist, left shoulder, bilateral metacarpophalangeal, and right metatarsophalangeal joints. Vision in the right eye was 20/25 and in the left eye was LP. A left reverse RAPD was present. There was corneal haze, and fibrin over the pupil, and a thick yellow–white hypopyon filled one third of the anterior chamber. This “sliding hypopyon” moved with a change of head position (Fig 1). There was no view of the fundus, but ultrasonography of the posterior segment revealed diffuse vitreous debris and a large inferotemporal choroidal abscess with an overlying exudative retinal detachment. The right eye was normal. Blood counts revealed a leukocytosis 13.13 ⫻ 109/l, with polymorphs accounting for 82.6%. The serum glucose level was 13.3 mmol/l. Results of the renal and liver function tests were normal. With a diagnosis of EE, aqueous and vitreous taps were performed, and intravitreal vancomycin (1 mg/0.1 ml), ceftazidime (2 mg/0.1 ml), and dexamethasone (0.1 mg/0.1 ml) were injected. Group B Streptococcus sensitive to penicillin, ampicillin, and vancomycin was cultured from the blood, aqueous, vitreous, and knee aspirates. The patient was treated with intravenous crystalline
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Figure 1. Patient 3. The photographs demonstrate the “sliding hypopyon.” A, The hypopyon with head in the upright position. B, The hypopyon with head tilted to the right after 30 seconds.
penicillin (24 MU/day) for 4 weeks and with gentamicin (3 mg/kg daily) for 1 week. He recovered systemically but the left eye became phthisical and required enucleation for pain relief. Histopathologic analysis of the enucleated globe showed mild chronic inflammation with proliferation of congested capillaries at the corneoscleral junction and edematous uvea. In addition, a degenerate lens was also present, together with osseous metaplasia posteriorly, disruption of the retina, marked fibrosis, and associated chronic inflammation. The optic nerve was normal.
Patient 4 An 82-year-old Chinese male (Patient 21, Table 1) with a history of diabetes mellitus had bilateral knee pain and left elbow pain of 2 days duration associated with fever at presentation. He also reported loss of vision in the right eye for a similar duration. He had a history of right cataract extraction with broad iridectomy and intraocular lens implantation 7 years prior. On examination, the right visual acuity was no light perception. A creamy-white hypopyon was present in the anterior chamber as well as within the pupil, demonstrating two different levels of pus (Fig 2). The anterior chamber also contained fibrin, and the intraocular pressure was 40 mmHg. Because any view of the fundus
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis cin (0.4 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were injected. She recovered systemically, but phthisis bulbi developed, and the eye lost perception to light.
Discussion
Figure 2. Patient 4. The photograph demonstrates the “pupillary hypopyon” in an eye with previous extracapsular cataract with intraocular lens implantation and a broad iridectomy at the 12-o’clock position. The pupillary hypopyon is a double hypopyon with one level within the anterior chamber and a second level within the pupil, in the posterior chamber.
was precluded, ultrasonography was performed and revealed the presence of diffuse vitreous debris. The left eye was normal. Leukocytosis of 17.06 ⫻ 109/l, of which polymorphs accounted for 82.6%, was present. Group B Streptococcus cultured from both the blood and vitreous was sensitive to penicillin, ampicillin, and vancomycin. He was treated with intravenous crystalline penicillin (18 MU/day) and ciprofloxacin (800 mg/day). Intravitreal ceftazidime (2 mg/0.1 ml) and vancomycin (1 mg/0.1 ml) were injected. Topical vancomycin (50 mg/ml) and antiglaucoma medications were instilled. The patient experienced a non-Q myocardial infarction during his admission and declined further intravitreal injections. He survived the myocardial infarction and recovered from the sepsis after 4 weeks of antibiotics, but the right eye eventually became phthisical.
Patient 5 A 63-year-old Chinese female (Patient 22, Table 1) with no significant medical history had fever of 5 days’ duration, multiple joint pains, loss of vision, and redness of the right eye of 3 days duration at presentation. She had a history of poor vision in the left eye secondary to severe myopia resulting in chorioretinal degeneration associated with a posterior staphyloma. On examination, she was afebrile. The right shoulder, knee, and ankle and the left wrist were tender and swollen and had restricted movements. Her visual acuities were LP in the right eye and counting fingers in the left eye. The right eye was injected and the cornea was hazy. The intraocular pressure was 19 mmHg. There were fine keratic precipitates, flare, and fibrin within the anterior chamber. A cream-colored hypopyon filled half the anterior chamber and had a level that slid and changed as the position of the head changed. Ultrasonography revealed vitreous opacities without the presence of choroidal abscesses. The patient had a leukocyte count of 15.8 ⫻ 109/l, with 98% polymorphs. Gram-stain analysis of the vitreous showed polymorphs but no organisms. Group B Streptococcus sensitive to penicillin, ampicillin, ceftriaxone, and erythromycin was cultured from blood and vitreous. She was allergic to penicillin, so she was treated with intravenous ceftriaxone (2 g/day). Intravitreal amika-
Endogenous endophthalmitis is an uncommon, devastating disease, often associated with poor visual prognosis. Frequently, an associated underlying septic focus, such as a liver abscess, cellulitis, or urinary tract infection, is present.1–3 It usually occurs in immunocompromised patients, but may occur in healthy individuals.4,5 A literature search from 1966 through 2001 using MEDLINE revealed that GBS as a cause of EE is rare. In 1986, Greenwald et al3 published a review of 72 cases of endogenous bacterial endophthalmitis, of which only one case was caused by GBS in a neonate. In 1994, Okada et al2 performed a 10-year retrospective review of EE and reported only two cases of GBSEE (7%), despite showing that 71% of the cases were caused by gram-positive organisms and 32% were identified as Streptococcus species. In East Asians, EE caused by gram-negative organisms, especially Klebsiella, is more common than that caused by gram-positive organisms.1 Two of the 33 cases of EE seen over a 4-year period were reported to be caused by GBS. These two cases are included in the series of patients reported in this paper. Whether there is a real or apparent trend toward an increase in the incidence of GBSEE in recent years is difficult to ascertain. However, GBS is still a rare cause of EE. Farber et al6 first reported GBSEE in an adult with congenital heart disease who developed septicemia and endocarditis after a throat infection in 1985. Since then, another 16 cases have been published. In this paper, we presented five cases of GBSEE. Although 22 cases in total are reported in the literature, we were able to analyze only 18 cases, because the four cases reported by Eykyn et al7 did not include adequate details. Of the 18 patients with GBSEE, there was involvement of 25 eyes. The average age of patients in whom GBSEE developed was 62.8 years (range, 42– 82 years), with a male-to-female ratio of 5 to 3. One third had a significant underlying chronic disease. These included diabetes mellitus, particularly if it was poorly controlled (4 cases; 22.2%), underlying malignancy (1 case; 5.6%), and acquired immunodeficiency syndrome (1 case; 5.6%). Group B Streptococcus is an invasive, encapsulated microorganism with the potential to produce severe disease. It is found as a commensal in the upper respiratory tract, skin, colorectum, and vagina. It is associated most frequently with neonatal sepsis during the first hours of life, resulting in a high mortality rate (30%–50%).8 In adults, it is associated with infections such as pharyngitis, cellulitis, meningitis, and pneumonia. The mortality rate is as high as 39%,12 often occurring within 48 hours of bacteremia. Diabetes, neoplastic disease, and liver failure are known predisposing factors. In this series, the presumed source of infection included cutaneous infections (3 cases; 16.7%), pharyngitis (2 cases;
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Ophthalmology Volume 109, Number 10, October 2002 11.1%), and pneumonia (1 case; 11.1%; Table 1).2,4 –7,9 –12 Although septic arthritis was the feature most commonly seen in these patients (8 cases; 44.4%), it is likely to be a sequel of pyogenic metastases rather than the cause of the sepsis. It is well established that the pathophysiologic progression of septic arthritis in normal joints is a result of hematogenous seeding during an episode of bacteremia.13 The large joints, such as the elbow, knee, and ankle, appear to be the more common sites of involvement, occurring singly or multiply. In the presence of overwhelming sepsis, the risk of polyarticular involvement is increased.13 Pischel et al14 described the polyarticular involvement of patients with GBS sepsis and septic arthritis resulting in significant functional morbidity. Of the eight patients with septic arthritis, five patients had involvement of more than one joint. As demonstrated in patient 4, joint involvement in GBS sepsis can evolve progressively involving other joints, even when the appropriate intravenous antibiotics have been administered. The wrist joint was the most frequently involved, occurring in 7 of 23 joints (30.4%), followed by the knee joint in 21.7% (5 joints). The reason the joints are so frequently involved in association with GBSEE is not clear. The synovial space is an enclosed space containing a potential culture medium, with minimal turnover of fluid and poor blood supply. As soon as bacterial seeding to the joint occurs, entrapment and proliferation of bacteria within the synovial fluid leads to the development of septic arthritis.13 This is in direct comparison with the vitreous cavity, where the organism is trapped within a culture medium, also allowing for proliferation. Although endocarditis, occurring in 6 patients (33.3%), frequently has been suggested as a possible source of infection, this is also likely to be a consequence of the septicemia.4,10 Endocarditis often affects degenerative valves,15 but in this series, only one patient had a congenital cardiac valve abnormality (patient 1). Except for the one patient in whom only endocarditis was seen in conjunction with GBSEE (patient 15), all other patients who had endocarditis had a definite septic focus. In all but one case (patient 8) in which the only other site of sepsis was in the joint, the septic focus detected was also the source. This suggests that in GBS sepsis, endocarditis is more likely to be an innocent bystander, with infection as a result of bacterial seeding to a cardiac valve, rather than as the source of sepsis. Only one patient had a history of congenital heart disease; the others had no prior valvular heart disease. It is likely that these valves, in elderly patients, have atherosclerotic changes that may predispose patients to bacterial adherence and proliferation. In seven patients (38.9%), the source of infection could not be identified conclusively (patients 8, 10, 13, 16, 20, 21, 22). The time of onset between the systemic infection and ocular manifestation was variable. In four patients, the systemic and ocular symptoms occurred concurrently. Interestingly, in all these patients, septic arthritis also developed. This may suggest that a large colony count of bacteria had been liberated from the septic focus into the circulation, enabling seeding of bacteria into multiple sites. Most patients had ocular involvement at presentation within 5 days of onset of sepsis, with 50% of the patients seeking treat-
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ment within 2 days. However, ocular infection was not the initial manifestation of sepsis in any patient. Both eyes had an equal chance of being affected, and one third of the cases had bilateral involvement. These patients typically experience a dramatic loss of vision, which at presentation is often counting fingers or worse. A reverse RAPD and hypopyon often are present, with diffuse posterior segment involvement; the rapidity of involvement demonstrates the virulence of the infecting organism. A characteristic feature noted in three of our patients (patients 1, 4, and 5) was the propensity for the meniscus level of the creamy-white hypopyon to shift fluidly with a change of head posture (Fig 1). We have named this phenomenon a sliding hypopyon. This unusual feature, not seen in our experience with EE caused by other microorganisms, may be a result of the many lysins, such as hemolysin and cytolysin, produced by GBS. In patient 4, we observed a double hypopyon— one in the anterior chamber and one within the pupil, that is, within the posterior chamber (Fig 2). A pupillary hypopyon is rare and has been reported in Klebsiella EE.16 We hypothesize that the ciliary body is the site of ocular seeding in such an eye, causing a rapid outpouring of pus into the anterior and posterior segments, initially filling the posterior chamber and cascading over the pupil to form a hypopyon in the anterior chamber. In this eye, there was also diffuse vitreous opacity on ultrasonography and a visual acuity of no light perception at presentation. In four of the five patients that we presented, the endophthalmitis presented as a diffuse endophthalmitis. These features again attest to the virulence of GBS. Diagnosis in these patients may be confused with rheumatologic conditions. In the presence of multiple-joint arthritis and a severely inflamed eye, GBS sepsis may be mistaken for Reiter’s syndrome or Behc¸ et’s disease and inappropriately given steroid therapy. An important differentiating point is the history of fever, chills, and rigors and the toxic appearance of the patient. The presence of a reverse RAPD, a sliding hypopyon, and diffuse panophthalmitis make the diagnosis of EE more likely. The associated septic arthritis tends to involve the wrist and other large joints. Commonly, more than one joint is involved and progressive joint involvement may occur. Ultimately, a positive culture is required to make a definitive diagnosis. Blood cultures were positive in 16 patients (not documented in one patient). Despite the fact that systemic antibiotic therapy had been commenced before the onset of ocular manifestations, vitreous cultures were nonetheless positive in 10 of the 11 cases (83.3%) in which a vitreous culture had been taken. Other sites of positive bacterial culture include joint aspirates (3 cases; 16.7%), swabs from cutaneous sites of infection (3 cases; 16.7%), and cerebrospinal fluid (2 cases; 11.1%). Intravenous high-dose antibiotics form the mainstay of management in GBSEE. Group B Streptococcus is still most frequently sensitive to crystalline penicillin, which has good ocular penetration. Other antibiotics to which GBS is susceptible include the -lactam antibiotics, cephalosporins, vancomycin, and imipenem. In this series, eleven patients were treated with intravenous high-dose penicillin, two with
Lee and Chee 䡠 Group B Streptococcus Endogenous Endophthalmitis amoxicillin, four with antibiotics of the cephalosporin group, and one with vancomycin. Unlike most other infections that can be treated with a 1-week course of intravenous antibiotics, patients with GBS septicemia and septic arthritis or endocarditis require 3 to 4 weeks of therapy or more. The use of intravitreal and topical antibiotics is controversial. Ten eyes of the 18 patients received intravitreal antibiotics in addition to the systemic therapy. Although some advocate the delivery of the antibiotic into the vitreous cavity to destroy the causative microbe directly and rapidly during a vitreous tap for culture, others have countered that, unlike postoperative bacterial endophthalmitis, the main source of infection is not the eye, but of a hematogenous origin. Thus, if the bacteria are capable of penetrating the blood– ocular barrier to infect the eye, the antibiotics should enter the eye effectively to sterilize it. This also would account for negative cultures in vitreous aspirates obtained from patients who already have been treated partially with intravenous antibiotics. The role of vitrectomy is still undefined in most series. Most authors have shown that vitrectomy for GBSEE has not been beneficial in salvaging vision. However, this may be a consequence of bias in selecting the more severely involved eyes for surgical intervention. Four eyes with GBSEE underwent vitrectomy, and in three cases, the eyes subsequently had phthisis bulbi and loss of light perception. In the two patients we presented who had undergone vitrectomy, pus-filled vitreous cavities and necrotic, friable, and opacified retinae with occlusive retinal vasculitis were encountered. Perhaps the rapid, widespread destruction of the retina by this virulent bacterium is an important factor that prevents the preservation or salvage of useful vision even with surgery. The presence of an RAPD at presentation suggests that the widespread destruction occurs early. Hypotony and phthisis bulbi frequently result, despite sterilization of the eye by vitrectomy. This is supported by the pathologic findings of Matsuo et al11 of a necrotic vitreous cavity, total retinal detachment, and a choroid that was riddled with microabscesses and destruction of Bruch’s membrane in an eye with GBSEE that had been enucleated. We suggest that the lytic enzymes released by GBS, which are likely to cause the breakdown of the ocular barriers and may account for its ocular virulence, are responsible for its presentation as a rapidly progressive and diffuse form of panophthalmic endophthalmitis.17 There were two deaths4,10 in this series of 22 cases of GBSEE, a fatality rate of 9.0%. Both of these patients (patients 1 and 16) had infective endocarditis but no prior history of any immunosuppressive illness. Patient 16 had a rapidly deteriorating clinical course and died of the overwhelming sepsis after 2 days. Although most of the patients do recover systemically from the GBS infection and septicemia, the visual prognosis is extremely poor. Of the 18 patients, 25 eyes were involved. Only six eyes recovered useful vision, whereas the remaining eyes ultimately had either LP or no light perception and phthisis bulbi (76%). Of these six eyes, there was documentation in five eyes that showed one eye with anterior endophthalmitis (patient 6), one eye with posterior endophthalmitis (patient 12), one eye with diffuse endophthalmitis (patient 8), and two eyes with
panophthalmitis (patients 13 and 15). There was delayed ocular involvement in two eyes, concurrent presentation in two eyes, and 1 day after in one eye, whereas there were insufficient details in the sixth eye. There were no distinct features that might have been useful prognostic indicators of visual outcome. However, the “advantage” in a delayed ocular involvement in terms of visual prognosis is that these patients already would be on intravenous antibiotics for the sepsis, resulting in possible containment of the GBSEE. In conclusion, GBS can cause a severe septicemic disease. Although the primary site of infection often is not identified, pharyngitis, cutaneous infections and pneumonia should be searched for. This virulent organism can metastasize and cause infection in many sites such as the heart valves and joints. We therefore would like to highlight a clinical syndrome caused by GBS of EE accompanied by septic arthritis with or without endocarditis. The GBS septic arthritis involves multiple joints, which may become involved progressively during the septicemic episode. Because there is rapid, widespread destruction of the choroid and retina in GBSEE, the visual prognosis is poor despite intravenous antibiotics, and vitrectomy does not appear to alter the visual outcome.
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