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Previous Article | Next Article 
Journal of Clinical Microbiology, January 1998, p. 48-51, Vol. 36, No. 1
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Enterobacter cloacae Endophthalmitis:
Report of Four Cases
N.
Okhravi,1,2,*
L.
Ficker,1
M. M.
Matheson,2 and
S.
Lightman1,2
Moorfields Eye Hospital, London EC1V
2PD,1 and
The Institute of
Ophthalmology, London EC1V 9EL,2 United Kingdom
Received 5 June 1997/Returned for modification 17 July
1997/Accepted 9 October 1997
 |
ABSTRACT |
Members of the genus Enterobacter are commensal
organisms of the gastrointestinal tract and are considered pathogenic
only for patients with lowered resistance to infection (e.g., chronic infection, cancer, or diabetes mellitus) or those with impaired immunity (congenital, acquired, or impaired immunity secondary to
therapy). We report on four cases of endophthalmitis caused by
Enterobacter cloacae: two in patients with acute
postoperative endophthalmitis, one in a patient with delayed
bleb-related endophthalmitis, and one in a patient presenting with
presumed posttraumatic endophthalmitis. Each patient presented with
severe disease many days after the onset of ocular symptoms, and two
patients had systemic risk factors accounting for a reduced resistance
to infection. Endophthalmitis caused by gram-negative bacilli is
characterized by acute onset, rapid progression, and poor final visual
outcome. Each of these patients was treated by a standard protocol with
intravitreal, systemic, and topical antibiotics and systemic steroids.
Despite treatment, the final visual outcomes for three of these
patients was no perception of light, and that for one patient remained perception of hand movements only. In common with endophthalmitis caused by other gram-negative organisms, intraocular infection secondary to Enterobacter cloacae infection is a
devastating disease which, despite treatment, results in extensive
ocular damage and severe visual loss. Since 1966, only four cases of
endophthalmitis secondary to infection with members of this genus have
been reported. This report presents four cases which occurred over a
period of 14 months and, to the best of our knowledge, the first case
of bleb-related endophthalmitis secondary to E. cloacae
infection.
| |
INTRODUCTION |
Gram-negative organisms are the
causes of 16 to 18.5% of all cases of culture-proven postsurgical
endophthalmitis (1, 3, 4, 11) and of up to 30% of
posttraumatic cases in rural areas (2). A variety of
gram-negative bacilli have been reported to cause postsurgical
endophthalmitis; the most common include Pseudomonas spp.,
Haemophilus influenzae, Proteus spp.,
Serratia marcescens, Morganella morganii,
Citrobacter spp., Escherichia coli, and
Klebsiella pneumoniae.
The earliest case reports of postsurgical endophthalmitis caused by
Enterobacter cloacae were published in 1966 (12)
and 1975 (5). Other than these two cases, only two other
separate cases of postsurgical endophthalmitis secondary to E. cloacae infection have been reported, and those were in 1992 (4) and 1993 (6). E. cloacae has more
commonly been reported as a causative agent of posttraumatic
endophthalmitis, often as part of a mixed infection (2, 11).
Irrespective of the etiology, the clinical picture at presentation is
usually that of a severe, rapidly progressive disease with acute onset
which results in a poor final visual outcome and often loss of the eye.
We report on four cases of endophthalmitis in patients treated at
Moorfields Eye Hospital between June 1995 and August 1996.
| |
CASE REPORTS |
The patients' clinical details are presented in Table
1. The details of the standard treatment
protocol have been reported previously (8), and brief
descriptions are provided in Table 1.
Patient 1.
An 89-year-old lady underwent uncomplicated
cataract surgery and was admitted 3 days later with a clinical picture
of endophthalmitis. She was treated with intensive topical gentamicin,
cefuroxime, and dexamethasone hourly, and she received one
subconjunctival injection of gentamicin and cefuroxime and intravenous
flucoxacillin and ciprofloxacin over the next 5 days. At 10 days
postsurgery, clinical deterioration was evidenced by the visual acuity
in the left eye, which was perception of light and the presence of a dense relative afferent pupillary defect (RAPD). Examination revealed pus in the anterior chamber and a dense fibrin plaque over the pupil.
No fundal details or red reflex was visible.
Gram staining and microscopy were not performed because the sample
volume obtained was small. Two days later culture of aqueous fluid in
cooked meat broth revealed gram-negative bacilli identified as E. cloacae by using the Analytical Profile Index Biochemical Identification System for members of the family
Enterobacteriaceae (API 20 E system; Biómerieux Vitek
Products Incorporated). Culture of the vitreous fluid sample was
negative.
Over the next 4 weeks the inflammation continued to settle, but despite
this, the visual acuity remained perception of light. Two weeks later,
the patient presented with a painful red eye and a visual acuity of no
perception of light and was treated symptomatically.
Patient 2.
A 50-year-old man with poorly controlled
insulin-dependent diabetes was referred for management of recurrent and
persistent vitreous hemorrhage in his left eye. Vitrectomy with
delamination and endolaser treatment were undertaken on 25 May 1996. At
the end of surgery Betamethasone (0.1%) and cefuroxime were injected subconjunctivally. The patient was then seen 1 week later with a
clinical picture suggestive of endophthalmitis, but he had in fact
suffered ocular pain and rigors since the first postoperative day.
Ocular examination revealed visual acuity of poor perception of light,
evidence of intraocular inflammation, no fundal view, or a RAPD.
Ultrasound examination at this stage revealed no evidence of retinal
detachment.
Blood tests performed on admission revealed a random glucose level of
22.5 mmol, with hemoglobin A1 and hemoglobin A1c levels elevated 9.4 and 7.2%, respectively. The oral Prednisolone therapy was gradually
reduced and was stopped after 4 weeks. Microscopy and staining were not
performed because the volumes of the samples obtained were too small.
Gram-negative organisms later identified as E. cloacae by
using the API system were isolated from two of three broths for aqueous
fluid culture and one of three broths for vitreous fluid culture.
Although the initial improvement was encouraging, with the best visual
acuity at 6/60, deterioration of clinical signs with development of
rubeotic glaucoma resulted in a final vision of no light perception.
Patient 3.
A 24-year-old man had suffered a shotgun injury to
his right eye 2 months previously. After primary repair in Nigeria, he was left with perception of light vision in a comfortable eye. According to the patient, two pellets seen on orbital X ray at the time
were not found at the time of surgery. Shortly after his arrival in the
United Kingdom, 17 days prior to admission to Moorfields Eye Hospital,
his right eye was red and tender with a visual acuity of no light
perception.
On admission, the patient denied a history of recent trauma to the eye.
Ocular examination revealed visual acuity of no perception of light, a
RAPD, a central corneal wound and epithelial defect, corneal and
scleral sutures through the old wounds, a shallow anterior chamber
containing pus but no evidence of fluid leaking from the eye, a normal
intraocular pressure, and no view of the posterior pole. Ultrasound
examination revealed the lens to be absent, the presence of a
long-standing total retinal detachment, and no shotgun pellets. A
vitrectomy was deemed technically very difficult in the absence of a
red reflex and in the presence of a very inflamed and disorganized
anterior segment. Aqueous and vitreous taps were therefore attempted
but failed. Intraocular antibiotics were nevertheless injected into the
vitreous cavity, and the patient was treated by the standard protocol.
Topical treatment, in addition, included cefuroxime and gentamicin
(1.5%) hourly by day and night. The first signs of corneal infiltrates underlying the epithelial defect appeared 2 days after admission and
prompted a further attempt at ocular sampling, and we were successful
in obtaining small samples from both the vitreous cavity and the
anterior chamber. The intraocular injection of antibiotics was repeated
at the same dose (see Table 1 footnote a). Gram staining of
the vitreous sample revealed the presence of gram-negative rods. These
were isolated from brain heart infusion broth cultures of samples taken
from both the anterior chamber and the vitreous cavity 2 days later and
were identified as E. cloacae by using the API system for
members of the family Enterobacteriacae. Six weeks after
admission, the first signs of phthisis appeared. The patient was no
longer in pain and was off all treatment.
Patient 4.
Patient 4 was a 70-year-old diabetic man who had
previously undergone combined cataract extraction, lens implant, and
trabeculectomy with mitomycin C of the right eye in July 1993 and the
left eye in September of the same year. In the case of the left eye,
four subconjunctival injections of 5-fluorouracil had been administered in the early postoperative period in order to improve the chances of
success by reducing the scarring response stimulated by the surgical
procedure. Following uncomplicated surgery, postoperative visual acuity
had been recorded as 6/9 in the left eye. The patient had suffered from
diabetes mellitus since 1993, and at the time of admission with
endophthalmitis he was poorly controlled on oral hypoglycemic
medication, with a random glucose level of 17 mmol and 2% glycosuria.
Two days prior to admission he had arrived back from Nigeria, where he
had been treated with topical medication for the previous few days for
ocular infection. On presentation, the visual acuity of the left eye
was hand movements. Advanced glaucomatous cupping and optic neuropathy
in the fellow eye precluded the accurate assessment for a RAPD. Ocular
examination revealed a thin avascular bleb inside which a fluid level
of pus could clearly be distinguished, as could evidence of severe
intraocular inflammation occluding the view of the intraocular lens,
red reflex, and fundus. Ultrasound examination revealed no evidence of
retinal detachment. The patient was treated by the standard protocol.
Topical treatment with cetazidime and gentamicin (1.5%) was also
instituted every alternating half hour. Gram staining and microscopy of
the ocular samples did not reveal the presence of any organisms. Oral
prednisolone was reduced gradually over the next 3 weeks. Broth culture
of both aqueous and vitreous samples yielded gram-negative bacilli
later identified as E. cloacae by using the API system for
members of the family Enterobacteriaceae. Staphylococcus
aureus was isolated from broth cultures of conjunctival swabs
taken before treatment. The patient attended one follow-up appointment
only 3 weeks later, at which time his eye was comfortable, but he had a
visual acuity of hand movements only.
| |
MATERIALS AND METHODS |
Methods.
The methodology for the sampling of intraocular
fluids has been reported previously (8). Briefly, at the
time of admission intraocular fluids (aqueous and vitreous fluids) were
collected under sterile conditions and were processed immediately.
Intraocular samples were examined by Gram and Giemsa staining and were
cultured on blood agar, in brain heart infusion broth, and in
Robertson's cooked meat broth. Because the volumes of the samples
obtained were often small, Gram staining was performed only if the
volume of the intraocular fluids obtained was greater than 100 µl for aqueous fluid and 200 µl for vitreous fluid. The fluids were cultured under both aerobic and anaerobic conditions. No aerobic organism was
thought to be responsible for causing endophthalmitis unless it was
isolated from an intraocular sample with heavy growth on one solid
medium or the same organism was isolated from more than one medium.
Anaerobic growth on any anaerobic medium was considered significant.
All cultures were maintained for 14 days. If no organism was grown, the
sample was considered culture negative even in the presence of
organisms seen on Gram staining.
| |
RESULTS AND DISCUSSION |
Antibiotic susceptibilities.
The antibiotic susceptibilities
of the isolates obtained from the cultures of aqueous and vitreous
fluid from patients 2, 3, and 4 were identical. Each of seven isolates
obtained from these four patients demonstrated resistance to
ampicillin, erythromycin, and vancomycin. Each of these isolates
was found to be sensitive to chloramphenicol, cefuroxime, cefotaxime,
ciprofloxacin, ofloxacin, amikacin, gentamycin, tobramycin,
ticarcillin, mezlocillin, and tetracycline.
Discussion.
Between 11% (postoperative) (15) and
30% (posttraumatic) (2) of culture-positive cases of
bacterial endophthalmitis are caused by gram-negative bacilli. The
disease usually has an acute onset and is rapidly progressive.
Gram-negative organisms are highly virulent, their toxins and proteases
cause extensive damage to ocular tissues, and ocular infections with
these organisms result in a poor final visual outcome for the majority
of patients (4-7, 13). The damage is compounded by the
sequelae of intraocular inflammation and the host's subsequent healing
response. All four patients described here were seen in a 14-month
period, and all infections were caused by E. cloacae, which
is not considered a common cause of gram-negative endophthalmitis
(1, 11, 15). The infections were characterized by a delay in
intraocular sampling and treatment, because the patients themselves did
not seek attention in the early stages of the infection. Earlier
presentation may have resulted in a better final visual outcome.
Members of the genus Enterobacter are commensal organisms of
the gastrointestinal tract and are considered pathogenic only for
patients with lowered resistance to infection (e.g., chronic infection,
cancer, or diabetes mellitus) or those with impaired immunity
(congenital, acquired, or impaired immunity secondary to therapy).
Patients with diabetes mellitus are also known to have a higher
incidence of postoperative endophthalmitis secondary to infection with
gram-negative organisms than patients who are not diabetic
(10), and it is interesting that two of our three postoperative patients (patients 2 and 4) were diabetic. Although for
each patient the diabetes was deemed under control at the time of
surgery, at the time of admission for endophthalmitis, these patients
were poorly controlled on their medication for diabetes, and may
therefore have been more prone to infection.
In 1994, Mirza et al. (7) reported an epidemic of
postsurgical E. cloacae endophthalmitis in seven patients,
all of whom developed the disease 1 day after surgery. The disease was
traced to contaminated cotton swabs. The consequences of infection with a large inoculum of this organism were reflected in the final visual
outcomes for the patients: four of the seven patients required evisceration, two of the seven patients developed phthisis, and only
one retained any vision (reported as 9/10). In the case of the four
patients under our care, it is not possible to accurately judge the
size of the infecting inoculum, because in all cases growth was
obtained only in broth cultures and not on plates where the colonies
could be counted. The absence of growth on solid medium would suggest
low numbers, and the possibility of contaminated broth cultures or
collection vessels, or both, was considered. The ocular samples from
all the patients had, however, been dealt with by different members of
staff at different locations. Only the surgery performed on patients 2 and 4 was carried out at Moorfields Eye Hospital, and these were
performed by different surgeons and were performed 18 months apart.
Because isolates with identical antibiotic susceptibilities were
obtained from all patients, from multiple broth culture bottles
(patients 2 and 4), and from both aqueous and vitreous samples for
three patients (patients 2, 3, and 4) and because the infections in all
four patients progressed in a manner characteristic of gram-negative
endophthalmitis, it is unlikely that the isolated organisms were
contaminants. The occurrence of four cases of E. cloacae
endophthalmitis in such a short time span at different centers may
indicate an increasing incidence of this disease or may indicate
improved microbiological techniques and species-specific diagnosis.
Patient 3 demonstrated persistent endophthalmitis 2 days after
ocular and systemic antibiotic treatment had commenced. Shaarawy et al.
(14) have reported that one of five patients from whom
repeat intraocular samples were taken 3 to 8 days after initial therapy
was found to be persistently culture positive for gram-negative
organisms (Serratia spp.). The visual outcomes for all five
of these patients were less than 20/300, and only two patients showed
any improvement in visual acuity after treatment (both patients were
culture negative on repeat sampling) (14). Of the four
antibiotics used in the emergency treatment of the patients described
here, two (ciprofloxacin and amikacin) were likely to be effective.
Despite treatment, the final visual outcomes for all these patients
presenting late in the course of the infection were very poor. Perhaps
in the presence of severe infection with virulent organisms a second
intravitreal injection of antibiotics should be considered. In patient
3, it is likely that the organism gained entry via the corneal wound, although the patient denied any history of trauma. Although E. cloacae was not isolated in conjunction with other organisms, as
is usually the case for intraocular samples from patients with posttraumatic endophthalmitis (2, 11),
Enterobacter spp. have previously been reported to be the
sole species causing disease in such patients (1).
Patient 4 had a case of delayed postoperative endophthalmitis secondary
to bleb infection. This was the eye to which 5-fluorouracil as well as
intraoperative mitomycin C had been applied postoperatively (9,
16), resulting in an avascular conjunctiva which may have been
more vulnerable to infection. To our knowledge, E. cloacae has not previously been reported to be a cause of this type of endophthalmitis.
No common factor could be found to explain the increased frequency of
isolation of E. cloacae from samples from patients with endophthalmitis. Interestingly, the onset of ocular symptoms (patients 3 and 4) and time of surgery (patients 1 and 2) for all four patients was between late May and early August 1995, and patients 3 and 4 had
both recently returned from Nigeria. These observations may indicate a
possible climatic or geographic risk to infection with this organism.
In conclusion, patients should be made aware of the need to seek
medical attention should problems arise in the days following intraocular surgery, and clinicians should be aware of the devastating effects of endophthalmitis, especially when it is caused by virulent organisms such as E. cloacae, and should promptly treat all
cases of postoperative inflammation as infective endophthalmitis until proven otherwise.
| |
ACKNOWLEDGMENTS |
We thank R. Hitchings and Z. Gregor for referring two of the
patients and the Endophthalmitis Study Group at Moorfields Eye Hospital
(L. Ficker, J. Dart, S. Tuft, and S. Lightman).
This work was supported in part by Moorfields Eye Hospital Research
Funds.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Clinical Ophthalmology, The Institute of Ophthalmology, 11-43 Bath
St., London EC1V 9EL, United Kingdom. Phone: 0171-608-6872. Fax:
0171-608-6931. E-mail:
nokhravi{at}menu.hgmp.mrc.ac.uk. [Reprint requests
to S. Lightman, Department of Clinical Ophthalmology, Moorfields Eye Hospital, City Road, London EC1V 2PD, United Kingdom. Phone:
0171-253-3411, extension 2266. Fax: 0171-566-2456.]
| |
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Journal of Clinical Microbiology, January 1998, p. 48-51, Vol. 36, No. 1
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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Abstract
Introduction
