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 [14]. 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 [14] 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 [7]. 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 [8]. 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 [26]. In a recent literature review, [16] 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 [16]. BCC isolates often display significant antibiotic resistance profiles in vitro [35]. 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 [13].

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, [36] biofilm formation [9], and phase of growth [21] affect the resistance profile. Various studies have shown potential BCC resistance to all the major antibiotic classes, including polymyxins, aminoglycosides [5], ß-lactams [22], fluoroquinolones [36] and tetracyclines [3]. These factors might support an earlier surgical intervention with vitrectomy [25].

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 [2]. And while prior studies comparing outcomes of acute vs delayed onset endophthalmitis found better outcomes with the more insidious forms, [29] 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 [14]. These cases along with a report by Okonkwo [18] 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) [21]. 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.