Endophthalmitis caused by Burkholderia cepacia complex (BCC): clinical characteristics, antibiotic susceptibilities, and treatment outcomes
Journal of Ophthalmic Inflammation and Infection volume 13, Article number: 48 (2023)
To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis.
Retrospective, observational case series.
Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed wisth culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system.
Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1 mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%).
Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.
Bacterial endophthalmitis is most often caused by gram-positive organisms, but gram-negative organisms account for up to 30 percent of cases [24, 35]. Gram-negative endophthalmitis are often associated with unfavorable VA outcomes [25, 28]. The Burkholderia cepacia complex (BCC), previously classified as part of the Pseudomonas genus, is a group of at least 20 closely related species of rare gram-negative, oxidase-positive, non-fermenting bacillary organisms [10, 15].
Found in soil, water, plants, industrial settings, and hospitals, BCC is ubiquitous in the environment and harbors a large genome encoding for many virulence factors which provide natural antibiotic resistance [34, 36]. BCC has been implicated in outbreaks from contaminated surgical compounds, [12, 31] as well as pharmaceutical products such as nebulization solutions, hand sanitizers and mouthwash [1, 14, 32]. Tavares and colleagues reported viable BCC isolates from pharmaceutical-grade, nutrient-deficient, saline solutions containing biocidal preservatives as much as 16 months later in two BCC species .
Clinical and ecological distinction among the various BCC species remain to be described, and indeed, many clinical laboratories struggle with species specific identification using standard automated commercial systems [10, 13]. Cystic fibrosis, chronic granulomatous disease, and other causes of immune compromise have been cited as predisposing risk factors for BCC infections , although no such association has been reported yet for ocular infections.
Ocular BCC infections are rare and present with a significant degree of clinical variation. In a recent report of 6 cases of B. contaminans endophthalmitis following cataract surgery, time to onset of symptoms was 12–112 days, with 5 of 6 cases having at least one recurrence of symptoms following treatment . Most case series of BCC endophthalmitis reported poor visual outcomes that often result in phthisis, enucleation or visual acuity of light perception [6, 11, 12, 16, 17, 20, 26, 31]. Deb et al. reported an outbreak of 5 cases of post-operative BCC endophthalmitis all of which failed to respond following vitreous tap and injection of vancomycin and ceftazidime, despite subsequent demonstration of ceftazidime susceptibility. 4 cases underwent vitrectomies with additional injection of meropenem, all achieving vision of 20/200 or better, of which 2 cases attained final vision of 20/60 . In significant contrast . reported all 6 cases having good visual outcomes of ≥ 0.8 . Two other case reports of BCC endophthalmitis by Okonkwo  and Saffra  following anti-VEGF injections with relatively quick onset (4 days  and 11 days  following injection), treated with pars plana vitrectomy and intravitreal antibiotic injections also reported favorable visual outcomes (20/60  and 20/30  respectively). In a large review, BCC accounted for 1.8% (14/744)  of culture positive cases of endophthalmitis, which occurred after cataract surgery in 85% of cases (29/34),  and post-penetrating keratoplasty (PKP), LASIK,  intravitreal anti-VEGF injection, and filtering surgery in the remainder of cases.
Herein we report 3 cases of B. cepacia endophthalmitis evaluated and treated at our institution. We also review the literature of the other BCC endophthalmitis with particular attention to the reported antibiotic susceptibilities and clinical outcomes.
Patients and methods
This retrospective consecutive case series conducted at Bascom Palmer Eye Institute examined the bacterial isolates of patients with culture-positive B. cepacia endophthalmitis (Table 1). Data collected from charts included patient demographics, preexisting ocular and systemic conditions, exam findings, treatment administered, operative reports, and microbiology laboratory results (Table 2). Phenotypic antibiotic resistance patterns reported here were obtained from minimum inhibitory concentration values using the automatic system Vitek 2 (bioMérieux, Durham, NC).
Case reports and results
An 80-year-old male presented with complaints of redness and discharge two weeks following repeat penetrating keratoplasty with amniotic membrane graft and subconjunctival bevacizumab injection for corneal decompensation in the setting of multiple prior surgeries. Ocular comorbidities included a remote history of cataract surgery and ExPRESS shunt implantation, BGI for neovascular glaucoma, and a central retinal vascular occlusion. Prior to the penetrating keratoplasty surgery, baseline VA was noted to be poor (hand motion). Exam revealed purulent discharge, hypopyon, shallow anterior chamber (AC), and dense vitritis on B-scan echography. An AC paracentesis was performed for culture after a failed vitreous tap. Intravitreal vancomycin (1.0 mg/0.1 mL) and ceftazidime (2.25 mg/0.1 mL) were injected. Topical fortified tobramycin and vancomycin were initiated. VA improved to count fingers the following day, however, exam revealed possible periorbital extension with restricted ocular movement for which oral amoxicillin-clavulanate was started. The following day, further clinical decline was noted with decrease in VA to hand motion, increasing hypopyon size, and pain. Given poor visual potential and patient preference, the eye was enucleated 2 days following initial presentation.
A 66-year-old female presented with a painful red eye for 2 weeks. Ocular history included a prior glaucoma drainage implant (GDI) at an outside facility 6 months ago. Of note, VA prior to GDI was LP. Exam at presentation included hypopyon and fibrin surrounding the tube in the AC. B-scan ultrasound showed dense vitreous membranes. A vitreous culture was performed, and vancomycin (1.0 mg/0.1 mL), ceftazidime (2.25 mg/0.1 mL), and dexamethasone were injected. Topical fortified vancomycin 25 mg/ml, tobramycin 14 mg/ml, atropine 1% solution, and 1% prednisolone acetate were also initiated and eventually deescalated to moxifloxacin following identification of B. cepacia. At 8 days following initial presentation, her pain improved but visual acuity decreased to no light perception (NLP); there was a persistent hypopyon and B-scan echography demonstrated a retinal detachment. At six weeks follow-up, infection was resolved but the eye remained NLP with 360-degree choroidal and retinal detachments with phthisical changes. The eye was enucleated 3 years following initial presentation due poor prognosis and new exposure of the GDI and IOL.
A 62-year-old male presented with a 2-week history of progressive eye pain. The patient had prior cataract surgery 3 years earlier and reported an episode of blunt trauma (an elbow to the eye) approximately 2 weeks prior to symptom onset with stable subjective vision until the day of presentation. Presenting VA was LP and initial examination revealed complete corneal opacification with central corneal ulceration and 360 choroidal detachment on B-scan echography. The patient was taken to surgery for corneoscleral debridement of necrotic tissue and implantation of a corneal patch graft. Intraoperative biopsy was performed. The patient was treated with fortified topical vancomycin, tobramycin, with the addition of moxifloxacin upon identification of B. cepacia, as well as oral levofloxacin followed by oral ciprofloxacin. Once fungal infection was ruled out, topical prednisolone was initiated with subsequent addition of oral prednisolone and subtenon’s triamcinolone. Despite aggressive topical and periorbital treatment, at two-week follow-up, B-scan ultrasound showed retinal detachment, dense vitritis, and subretinal opacities suggestive of endophthalmitis. Due to poor prognosis, early phthisis bulbi, and an unsalvageable eye, a vitreous tap was deferred. Comfort measures and enucleation were recommended. The patient was subsequently lost-to-follow-up.
In the review of the literature, 13 additional reports of BCC related endophthalmitis were identified accounting for 56 cases (Table 3). BCC related corneal ulcers or systemic infections were not included in this review. The reports range from 1992 with Irvine and colleagues to Lind and colleagues reporting 6 cases in 2021. 78% (44/56) of cases were preceded by cataract surgery, 9% (5/56) occurred after trauma, and remainder occurring after intravitreal injections, vitrectomy, and corneal transplantation. Time to onset ranged from 2 days to 6 months from the identified inciting event, with an average of 36 days and median of 20 days. Recurrent infection was described in 13 cases, of which 6 cases had more than one recurrence. Final visual outcomes also varied significantly. One quarter of cases (14/56) had visions of 20/40 or better, with 6 of the 13 cases reported by . An additional 32% (18/56) achieved a final VA between 20/40 and 20/200. The remainder had poor visual outcomes of which at least 7 ended in phthisis or enucleation and 3 had retinal detachments by the end of respective follow up periods. Recurrence was also common with reports of at least 13/56 cases.
Among the 10 reports that described antibiotic susceptibilities, each tested and reported different antibiotic sensitivity panels (Table 4). Treatment strategies generally followed EVS guidelines with intravitreal vancomycin (1 mg/0.1 mL), ceftazidime (2.25 mg/0.1 mL). Vitrectomy with silicone oil was also a common therapy when presenting VA was LP or worse. Of the antibiotics tested in at least 3 reports, there was evidence of at least one BCC strain with resistance reported by one of the remaining 8 studies analyzed. Both  and Lalitha et al. reported strains sensitive to piperacillin/tazobactam. Case 3 reported in our cohort, however, displayed resistance to piperacillin/tazobactam. Ceftazidime was the most tested, utilized, and most commonly sensitive antibiotic at 68% (30 cases were sensitive, 16 were resistant, 2 were reported as “moderate” sensitivity, 1 was not reported). Of note, Deb et al. reported 5 cases initially treated with vitreous tap and injection of vancomycin plus ceftazidime ultimately requiring additional pars plana vitrectomy and injection of meropenem due to inadequate initial response yet reported sensitivity to ceftazidime in all isolates . Fluoroquinolone sensitivities were reported by 9/10 studies, with ciprofloxacin being the most commonly tested showing 53% sensitivity among cases tested (21/40). Aminoglycosides were also commonly tested, gentamicin showing 33% sensitivity (13/40) and amikacin showing 20% sensitivity (8/41).
Reported cases of BCC endophthalmitis are rare. The first case of B. cepacia endophthalmitis was reported by Del Piero et al. in 1985 following trabeculectomy and extracapsular cataract extraction . In the largest case series to date, Sachdeva et al. reported 14 cases of BCC endophthalmitis out of 744 cases in the LV Prasad Endophthalmitis registry between 2003 – 2008: 9 cases occurred after cataract surgery, 1 following PKP, and 4 in the setting of trauma . In a recent literature review,  found 34 cases of post-surgical, culture-confirmed endophthalmitis between 1992–2018 among 8 reports, of which 85% occurred following cataract surgery and the remainder occurring after PKP, intravitreal injections [18, 27], and vitrectomies . BCC isolates often display significant antibiotic resistance profiles in vitro . A recent report of the molecular analysis of B. contaminans isolate from a polymicrobial corneal ulcer showed inherent resistance to fluoroquinolones, cephalosporins, carbapenems, monobactam, aminoglycosides, and sulfonamides while susceptible to tetracylclines, meropenem, and ceftazidime .
Outcomes for BCC endophthalmitis varied significantly across the 13 reports reviewed. Clear trends remain difficult to extrapolate as context and treatment strategies varied widely. Additionally, the wide degree of antibiotic resistance variation among the BCC strains, discussed further below, requires an individualized approach to care. Indeed, recurrence was noted in 13 cases, 6 of which had multiple episodes, while 5 cases reported by Deb et al. treated with an antibiotic subsequently noted as sensitive had an inadequate response.
Review of the susceptibilities of BCC related endophthalmitis cases published in the literature demonstrates a diversity of antibiotic sensitivities among the virulent strains described as well as diverse panels of antibiotic susceptibilities tested. Ceftazidime was the most commonly tested and most commonly sensitive antibiotic, followed by ciprofloxacin and gentamicin. Pipercillin/tazobactam stands out as sensitive in 19/19 cases. However, this represents only two reports [14, 15] which described two single outbreak clusters respectively, and case #3 described in the present report displayed piperacillin/tazobactam resistance. These results align well with the various resistance mechanisms employed by this bacterial genus. Given the broad resistance patterns seen, identification of BCC as well Pseudomonas, which is often initially misidentified for BCC, may benefit from a broader susceptibility panel examination and lower threshold to broaden therapeutic choice of agents.
In the current study, all three isolates were susceptible to ceftazidime (Table 1) which were given as intravitreal injections to patient 1 and patient 2. All patients received topical fortified vancomycin and tobramycin. In addition, all three patients received topical moxifloxacin upon identification of the causative organism. Despite in vitro susceptibility testing, multiple clinical and laboratory studies have substantiated the observed treatment failure seen in many patients. Although some have attributed this to inadequate antibiotic concentrations, factors like broad intrinsic antibiotic resistance,  biofilm formation , and phase of growth  affect the resistance profile. Various studies have shown potential BCC resistance to all the major antibiotic classes, including polymyxins, aminoglycosides , ß-lactams , fluoroquinolones  and tetracyclines . These factors might support an earlier surgical intervention with vitrectomy .
All 3 patients had previous intraocular surgery. Cataract surgery is the most common cited preceding factor to BCC endophthalmitis [19, 26]. Time to presentation is also quite variable, as seen among our 3 cases [12, 26]. Although cases of BCC endophthalmitis generally meet the European Society of Cataract & Refractive Surgeons (ESCRS) criteria for acute post-operative endophthalmitis of within 6 weeks of surgery, it is notable that only 14–22% of acute endophthalmitis is seen beyond 2 weeks of surgery while BCC on average presents 2–6 weeks after initial insult . And while prior studies comparing outcomes of acute vs delayed onset endophthalmitis found better outcomes with the more insidious forms,  delayed onset cases of BCC do not follow this general trend [12, 14, 26, 31]. A recent outbreak of endophthalmitis at a surgical center in Norway included 6 patients in the period from 1/4/2019 to 1/28/2019 with B. cepacia complex linked to a contaminated fresh air ventilation system [14, 30]. All 6 eyes had severe vision loss and required prolonged treatment course. In sharp contrast with other prior reports, Lind and colleagues reported good visual outcomes (final vision of 20/25 or better) among 6 cases of BCC endophthalmitis following cataract surgery treated with vitrectomy, lensectomy with complete removal of the capsular bag, and repeated intravitreal antibiotic injections . These cases along with a report by Okonkwo  suggest an important role in capsular bag removal during initial vitrectomy as means of preventing recurrence which has been documented in other prior reports.
In the non-ophthalmic literature, B. cepacia infection has also been associated with immunocompromise, particularly in patients with cystic fibrosis and chronic granulomatous disease (CGD) . None of our patients had a history of cystic fibrosis, CGD or known immunocompromise. Several case series have also found contaminated surgical or pharmacologic agents as sources of cluster infections which was not suspected as the likely cause in our case series [12, 31].
The current study adds 3 cases B. cepacia endophthalmitis, a rare clinical entity, to the body of literature. Our review of antibiotic sensitivity profiles among BCC endophthalmitis reports is the largest review to date and builds on prior reports of broad antibiotic resistances seen in BCC.
Availability of data and materials
The datasets used and/or analyzed during the current study are included in this published article and are also available from the corresponding author on reasonable request.
Amniotic membrane transplantation
Burkholderia cepacia Complex
Cataract extraction/intraocular lens placement
Chronic granulomatous disease
Choroidal neovascular membrane
Early Vitrectomy Study
Glaucoma drainage implant
No light perception
Neovascularization of the iris
Posterior chamber intraocular lens
per os Antibiotics
Pars plana lensectomy
Pars plana vitrectomy
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This study was supported in part by an unrestricted grant from Research to Prevent Blindness (New York, New York), NIH Center Core Grant P30EY014801 (Bethesda, Maryland), and the Department of Defense (DOG Grant #W81XWH-09–1-0675) (Washington, D.C.). This work received support from the Macula Foundation. The sponsor(s) or funding organization(s) had no role in the design or conduct of this study.
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Per DHHS policies as determined by the HSRO at the University of Miami, a retrospective case series of 3 patients or fewer does not meet the DHHS standard of generalizable knowledge, and therefore does not qualify the definition of research. This study was thus exempt IRB approval. Documentation attached.
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Beca, F.A., Sengillo, J.D., Robles-Holmes, H.K. et al. Endophthalmitis caused by Burkholderia cepacia complex (BCC): clinical characteristics, antibiotic susceptibilities, and treatment outcomes. J Ophthal Inflamm Infect 13, 48 (2023). https://doi.org/10.1186/s12348-023-00370-1