Keywords

Ocular infection; Post-operative endophthalmitis; Vision; Cystic fibrosis

Abbreviations

CE: Cataract Extraction; PKP: Penetrating Kerato Plasty; T: Topical; IVI: Intravitreal Injection; IV: Intravenous; SC: Sub Conjunctival; IOL: Intraocular Lens; PPV: Pars Plana Vitrectomy; NLP: No Light Perception; LP: Light Perception; HM: Hand Motion

Introduction

Post-operative endophthalmitis is a devastating intraocular complication of ocular surgery [1]. It occur atimes as a result of exogenous inoculation of the infective microbe(s) into the eye during the peri operative or post-operative stages of surgery, but can also occur as a result of endogenous spread of the infective organism from foci of infection within the patient.

The more common causes of post operative infective endophthalmitis are gram-positive microbes, coagulase negative staphylococci such as Staphylococcus epidermidis accounting for most of the cases [2]. However, there are other rare causes of infection. Infection due to rare species also results in significant ocular disease. Several of the rare microbes are gramnegative organisms [3], including pseudomonas species such as Burkholderia cepacia (previously known as Pseudomonas cepacia) [4-14].

Burkholderia cepacia is a rare gram-negative rod, oxidasepositive, non-fermenting bacillus. It is known to cause infection in cystic fibrosis, chronic granulomatous diseases and immunocompromised patients. It can also be the cause of infection in healthy individuals, though it is less virulent in immuno competent hosts. Known to be a cause of nosocomial infection, it can colonize antiseptic including benzalkonium chloride and chlorhexidine [15,16].

There are currently several reports of B. cepacia causing post cataract surgery endophthalmitis, one case report of post intravitreal antiVEGF injection, one report of post penetrating keratoplasty infections and one case series of post vitrectomy endophthalmitis in which B. cepacia was isolated from 3 eyes. It has been isolated from a case of post traumatic endophthalmitis [17]. Lastly, there is a case report of B. cepacia keratitis post Lasik [18] and another report of B. gladioli causing keratitis and consecutive recurrent endophthalmitis post penetrating keratoplasty [19].

Infection with B. cepacia has been reported to be difficult to treat and may also be associated with recurrence, making it a unique infection and one to note. Mechanism of this intra ocular infection and resistance to antimicrobial include the fact that the organism has an unusually large genetic make up that accounts for its microbiological versatility. It also produces lipopolysaccharide and β lactamase that renders some antibiotics ineffective against it [20].

Magnitude of Problem

Gram negative endophthalmitis in general is less common than gram positive. However they constitute a more fatal disease with poorer prognosis following treatment. Irvine et al. [17] reported 52 patients (53 eyes) with culture-proven gram-negative endophthalmitis between January 1982 and December 1990 and noted that Pseudomonas aeruginosa was isolated in 12 out of 53 and Haemophilus influenzae in 10 out of 53 were the most frequent isolates in this series.

In one report Burkholderia cepacia was the causative agent in 14 (1.8%) of 744 culture-positive cases seen in the endophthalmitis registry over a 5 years period [8].

Our search using popular search engines including Google scholar and Medline revealed eight reports including three case reports and five case series, of culture proven B. cepacia post-operative endophthalmitis between 1992 and 2018 (over a 26 year period). Majority of the cases (N=28 eyes, 82%) occurred following cataract extraction. Other cases were post filtering and cataract surgery 1 eye, post vitrectomy 3 eyes, post penetrating keratoplasty 1 eye and post intravitreal antiVEGF 1 eye. Within these reports, there were a total of 34 post operative endophthalmitis cases. This may not represent all the cases of post operative B. cepacia endophthalmitis that occurred during this period, since some cases may have gone un-reported and some may have been undiagnosed as culture was not sensitive to detect B. cepacia or culture was not done.

Predisposition

Aside from its contamination of know antiseptics, B. cepacia has also been known to contaminate ophthalmic solutions such as balanced salt solution, hyaluronic acid trypan blue [14] phacoemulsification machine fluid units and hand piece. Also there has been a report of contamination of topical anesthetic eye drops resulting in a series of post-operative infections [7].

It is know that infection with B. cepacia is seen in cystic fibrosis and other debilitating chronic infection such as in the presence of granulomatous disease [21].

It is, however, not known if the presence of other systemic disease such as diabetes and use of insulin as previously reported [1], or if immunosuppression significantly increases the risk of post operative B. cepacia endophthalmits. In one report of a case having multiple recurrence and eventual poor outcome the patient was diabetic and had a poor glycemic control [10].

Clinical Features and Diagnosis

Often, infection with B. cepacia presents within days or few weeks after surgery. Most reported cases have presented, with an acute presentation after cataract surgery characterized by loss of vision and signs of intra ocular inflammation including pain. It can rarely presents as a delayed-onset postoperative endophthalmitis [8].

The clinical signs vary considerably. There may be only a mild cellular reaction and flare initially which may progress to severe anterior chamber reaction (associated with severe pain), despite treatment. Hypopyon may be a feature and has been reported in several of the cases. The cornea may show a significant degree of involvement or only mild haze. In some cases keratitis and cornea abscess has been reported.

Rarely the patient may present in an unusual pattern too, with only a blur in vision [4]. Recurrence and persistent inflammation despite treatment is common and has been reported by several authors. This is related to its multidrug resistance.

Microbiological diagnosis is made by identification of the microbe after vitreous culture using standard biochemical techniques.

B. cepacia infection can co exist with other organisms such as Pseudomonas aeruginosa [5,13,14]. The behavior of the microbe in this polymicrobial situation may defer from what is already known in relation to its virulence and clinical presentation.

Microbial Sensitivity

Gram negative endophthalmitis in general is less common than gram positive. However they constitute a more fatal disease with poorer prognosis following treatment. Irvine et al. [17] reported 52 patients (53 eyes) with culture-proven gram-negative endophthalmitis between January 1982 and December 1990 and noted that Pseudomonas aeruginosa was isolated in 12 out of 53 and Haemophilus influenzae in 10 out of 53 were the most frequent isolates in this series.

In one report Burkholderia cepacia was the causative agent in 14 (1.8%) of 744 culture-positive cases seen in the endophthalmitis registry over a 5 years period [8].

Our search using popular search engines including Google scholar and Medline revealed eight reports including three case reports and five case series, of culture proven B. cepacia post-operative endophthalmitis between 1992 and 2018 (over a 26 year period). Majority of the cases (N=28 eyes, 82%) occurred following cataract extraction. Other cases were post filtering and cataract surgery 1 eye, post vitrectomy 3 eyes, post penetrating keratoplasty 1 eye and post intravitreal antiVEGF 1 eye. Within these reports, there were a total of 34 post operative endophthalmitis cases. This may not represent all the cases of post operative B. cepacia endophthalmitis that occurred during this period, since some cases may have gone un-reported and some may have been undiagnosed as culture was not sensitive to detect B. cepacia or culture was not done.

Predisposition

Aside from its contamination of know antiseptics, B. cepacia has also been known to contaminate ophthalmic solutions such as balanced salt solution, hyaluronic acid trypan blue [14] phacoemulsification machine fluid units and hand piece. Also there has been a report of contamination of topical anesthetic eye drops resulting in a series of post-operative infections [7].

It is know that infection with B. cepacia is seen in cystic fibrosis and other debilitating chronic infection such as in the presence of granulomatous disease [21].

It is, however, not known if the presence of other systemic disease such as diabetes and use of insulin as previously reported [1], or if immunosuppression significantly increases the risk of post operative B. cepacia endophthalmits. In one report of a case having multiple recurrence and eventual poor outcome the patient was diabetic and had a poor glycemic control [10].

Clinical Features and Diagnosis

Often, infection with B. cepacia presents within days or few weeks after surgery. Most reported cases have presented, with an acute presentation after cataract surgery characterized by loss of vision and signs of intra ocular inflammation including pain. It can rarely presents as a delayed-onset postoperative endophthalmitis [8].

The clinical signs vary considerably. There may be only a mild cellular reaction and flare initially which may progress to severe anterior chamber reaction (associated with severe pain), despite treatment. Hypopyon may be a feature and has been reported in several of the cases. The cornea may show a significant degree of involvement or only mild haze. In some cases keratitis and cornea abscess has been reported.

Rarely the patient may present in an unusual pattern too, with only a blur in vision [4]. Recurrence and persistent inflammation despite treatment is common and has been reported by several authors. This is related to its multidrug resistance.

Microbiological diagnosis is made by identification of the microbe after vitreous culture using standard biochemical techniques.

B. cepacia infection can co exist with other organisms such as Pseudomonas aeruginosa [5,13,14]. The behavior of the microbe in this polymicrobial situation may defer from what is already known in relation to its virulence and clinical presentation.

Microbial Sensitivity

Often B. cepacia shows multi drug resistance to a number of commonly used antibiotics. The multi-drug resistance of B. cepacia is due to rough lipopolysaccharide encasing the organism. The organism produces lipopolysaccharide and beta lactamase that renders the antibiotics ineffective against it [22].

Resistance has been reported to a wide range of anti microbial including quinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin), ceftriaxone, cefoxitine, tobramycin, amikacin, gentamicin and vancomycin, Several authors have reported sensitivity to ceftazidime. Also reported, is sensitivity to co-trimoxazole, cefotaxime and piperacillin/tazobactam.

Ceftazidime generally has demonstrated in vitro efficacy for a good number of gram-negative organisms causing endophthalmitis and should be used when this group of organisms are suspected or isolated. It has also been recommended for use by the endophthalmitis vitrectomy study (EVS) [23].

Treatment

Strategies that have been used for treatment of cases of post operative B. cepacia endophthalmitis (Table 1). This consists of topical antibiotics (fortified in some cases) and steroids, subconjunctival injection of antibiotics, intravitreal antibiotics (administered in a tap and inject fashion), pars plana vitrectomy, explantation of intraocular lens, systemic antibiotics, as well as topical cycloplegics.

The treatment is tailored according to the microbial sensitivity pattern after culture and microscopy evaluation of vitreous samples.

Generally, it is a rare cause of intra ocular infection and may be difficult to treat. As is the general trend in post operative infections, treatment commences as soon as the patient presents and usual consists of topical preparations as well as initiating intravitreal injection of antibiotics, with or without steroids. In several case reports of B. cepacia endophthalmitis, multiple intravitreal injections have been required either on its own or at the conclusion of vitrectomy. Systemic i.e., oral or intravenous antibiotics were used in some cases. There is absence of specific evidence relating to treatment for B. cepacia endophthalmitis, except as is provided by the general knowledge and guidance of the EVS [23]. The several treatment approaches listed in Table 1 point to the fact that knowledge and treatment strategy for B. cepacia post operative endophthalmitis is lacking. This is a significant gap and need to be met. However reports on gramnegative organisms such as by Duan et al. [3] and Irvine et al.[17] provide useful information on antimicrobial sensitivity and treatment.

Outcome of Treatment

Post treatment visual outcome in eyes with post operative endophthalmitis is usually guarded. Poor vision could arise from toxins within the vitreous cavity, direct effect on the retina of the infecting microbe, toxicity from the intravitreal antibiotics and intra ocular inflammation.

In several reported cases the visual outcome following treatment of post operative B. cepacia endophthalmitis is poor (Table 1). There were 14/34 (41%) eyes in which the vision after treatment was less than 6/60. Also there was phthisis bulbi reported in three out of the 8 reports.

Prognosis

The prognosis following B. cepacia post operative endophthalmitis varies significantly. Though some of the reports have reported remarkably good vision after management [4,6,9] there are 4 reports of the 8 presented have suggested recurrence as an important feature of the presentation. The recurrence of diseases tends to occur within days or weeks and is associated with poorer anatomical and visual outcome, as 3 out of the 4 reports of recurrence also reported occurrence of phthisis bulbi or evisceration (Table 1). Therefore mechanisms to overcome this recurrence are desirable. Some known factors that could be responsible for recurrence include insensitive antibiotics given at the initial treatment, Gram-negative bacillus, multidrug resistance and inadequate exposure time to antibiotics [24].

Table 1: Summary of the 9 case reports and series from 1985-2018 in literature.

Conclusion

Post operative endophthalmitis due to B. cepacia is rare and appears to be more difficult to treat. Since the initial reports over 3 decades ago, there are presently several more reports implicating this opportunistic infection, mostly thought to be of significance in cystic fibrosis patients. It is responsible for poor visual outcome after intra ocular surgery. Going by the current trend, it is likely that the numbers of B. cepacia post operative endophthalmitis will continue to increase. It should be recognized as an important cause of gram-negative post operative infection. Since the visual outcome of therapy in 41% of eyes in this review is less than 6/60, strategies for early detection and optimum treatment should be investigated. There is still significant gap in knowledge to improve current outcomes including the treatment of possible ceftazidime resistant strains [25].

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