Bacillus Cereus Endophthalmitis Research Articles

Endophthalmitis Caused by Bacillus cereus: Clinical Characteristics, Outcomes and Antibiotic Susceptibility.

Bacillus cereus endophthalmitis is a severe vision-threatening disease. This study aimed to analyze the clinical characteristics, antibiotic susceptibility, and risk factors for poor final visual acuity (VA) and enucleation or evisceration (ENEV) outcomes of B. cereus endophthalmitis patients. We retrospectively reviewed 52 cases (52 eyes) of culture-proven B. cereus endophthalmitis at Zhongshan Ophthalmic Center from January 2013 to December 2023. The mean age of the patients was 38.1 ± 20.1 years, and males composed the majority (90.4%) of the sample size; laborers (32.7%) and farmers (19.2%) were the primary occupations of the patients. All cases were caused by ocular trauma. Forty-one of 51 eyes (80.4%) had a final VA worse than the ability to count fingers (CFs), and 15 of the 52 total eyes (28.8%) underwent ENEV. Binary logistic forward (LR) regression analysis demonstrated that red eye (odds ratio [OR], 13.13; 95% confidence interval [CI], 1.58-108.80; p = 0.017), eye pain (OR, 22.87; 95% CI, 1.00-522.72; p = 0.050), and corneal edema/ulcer (OR, 13.13; 95% CI, 1.58-108.80; p = 0.017) were significant risk factors for poor VA outcomes. Conjunctival sac purulent discharge (OR, 10.08; 95% CI, 2.11-48.12, p = 0.004) and white blood cell (WBC) count (OR, 1.35; 95% CI, 1.06-1.72, p = 0.016) were significant risk factors for ENEV outcomes. B. cereus showed susceptibility rates of 100.0% to vancomycin and ofloxacin; 98.0% to levofloxacin; 93.3% to ciprofloxacin; 87.5% to imipenem; and 78.9% to tobramycin. The susceptibility to azithromycin and clindamycin was 66.7% and 50.0%, respectively. In contrast, B. cereus was resistant to penicillin (susceptibility at 3.8%), cefuroxime (5.6%), and cefoxitin (37.1%).

Acute Bacillus cereus endophthalmitis caused by ocular perforation injury and occult intravitreal cilium implantation: a case report.

Acute Bacillus cereus endophthalmitis caused by ocular perforation injury and occult intravitreal cilium implantation: a case report.

Phosphatidylinositol-specific phospholipase C can decrease Müller cell viability and suppress its phagocytic activity by modulating PI3K/AKT signaling pathway.

Bacillus cereus endophthalmitis is a devastating eye infection that causes rapid blindness through the release of extracellular tissue-destructive exotoxins. The phagocytic and antibacterial functions of ocular cells are the keys to limiting ocular bacterial infections. In a previous study, we identified a new virulence gene, plcA-2 (different from the original plcA-1 gene), that was strongly associated with the plcA gene of Listeria monocytogenes. This plcA gene had been confirmed to play an important role in phagocytosis. However, how the Bc-phosphatidylinositol-specific phospholipase C (PI-PLC) proteins encoded by the plcA-1/2 genes affect phagocytes remains unclear in B. cereus endophthalmitis. Here, we found that the enzymatic activity of Bc-PI-PLC-A2 was approximately twofold higher than that of Bc-PI-PLC-A1, and both proteins inhibited the viability of Müller cells. In addition, PI-PLC proteins reduced phagocytosis of Müller cells by decreasing the phosphorylation levels of key proteins in the PI3K/AKT signaling pathway. In conclusion, we showed that PI-PLC proteins contribute to inhibit the viability of and suppress the phagocytosis of Müller cells, providing new insights into the pathogenic mechanism of B. cereus endophthalmitis.

Posttraumatic Bacillus cereus Endophthalmitis: Clinical Characteristics and Antibiotic Susceptibilities.

Purpose To report the clinical characteristics, antibiotic susceptibilities, and visual outcomes of patients with posttraumatic endophthalmitis caused by Bacillus cereus. Methods In this retrospective, noncomparative case series, the medical records of eyes with culture-proven Bacillus cereus endophthalmitis treated from January 2016 to December 2019 at a referral center were reviewed. Clinical features, antibiotic susceptibilities, and visual outcomes were assessed. Results A total of 19 eyes of 19 patients were identified. Three patients progressed to orbital cellulitis. Vitrectomy was performed in 13 eyes, and 11 required silicone oil tamponade. Finally, seven eyes underwent silicone oil removal surgery during follow-up. Only two patients retained a visual acuity better than FC. Four patients underwent evisceration, and three patients had NLP. The cultured Bacillus cereus was sensitive to levofloxacin, ofloxacin, tobramycin, and neomycin at 100%. Conclusions The visual outcomes of posttraumatic Bacillus cereus endophthalmitis were generally poor regardless of the prophylactic and therapeutic measures administered. Vitrectomy combined with silicone oil tamponade could help to save the eyeball. Bacillus cereus has a good susceptibility to ofloxacin, levofloxacin, tobramycin, and neomycin; therefore, fluoroquinolones and aminoglycosides can be used to treat Bacillus cereus infection.

TLR4 modulates inflammatory gene targets in the retina during Bacillus cereus endophthalmitis

BackgroundEndophthalmitis is a serious intraocular infection that frequently results in significant inflammation and vision loss. Because current therapeutics are often unsuccessful in mitigating damaging inflammation during endophthalmitis, more rational targets are needed. Toll-like receptors (TLRs) recognize specific motifs on invading pathogens and initiate the innate inflammatory response. We reported that TLR4 contributes to the robust inflammation which is a hallmark of Bacillus cereus endophthalmitis. To identify novel, targetable host inflammatory factors in this disease, we performed microarray analysis to detect TLR4-dependent changes to the retinal transcriptome during B. cereus endophthalmitis.ResultsC57BL/6 J and TLR4−/− mouse eyes were infected with B. cereus and retinas were harvested at 4 h postinfection, a time representing the earliest onset of neutrophil infiltration. Genes related to acute inflammation and inflammatory cell recruitment including CXCL1 (KC), CXCL2 (MIP2-α), CXCL10 (IP-10), CCL2 (MCP1), and CCL3 (MIP1-α)) were significantly upregulated 5-fold or greater in C57BL/6 J retinas. The immune modulator IL-6, intercellular adhesion molecule ICAM1, and the inhibitor of cytokine signal transduction SOCS3 were upregulated 25-, 11-, and 10-fold, respectively, in these retinas. LIF, which is crucial for photoreceptor cell survival, was increased 6-fold. PTGS2/COX-2, which converts arachidonic acid to prostaglandin endoperoxide H2, was upregulated 9-fold. PTX3, typically produced in response to TLR engagement, was induced 15-fold. None of the aforementioned genes were upregulated in TLR4−/− retinas following B. cereus infection.ConclusionsOur results have identified a cohort of mediators driven by TLR4 that may be important in regulating pro-inflammatory and protective pathways in the retina in response to B. cereus intraocular infection. This supports the prospect that blocking the activation of TLR-based pathways might serve as alternative targets for Gram-positive and Gram-negative endophthalmitis therapies in general.

CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection.

During intraocular bacterial infections, the primary innate responders are neutrophils, which may cause bystander damage to the retina or perturb the clarity of the visual axis. We hypothesized that cytokine IL-6 and chemokine CXCL1 contributed to rapid neutrophil recruitment during Bacillus cereus endophthalmitis, a severe form of intraocular infection that is characterized by explosive inflammation and retinal damage that often leads to rapid vision loss. To test this hypothesis, we compared endophthalmitis pathogenesis in C57BL/6J, IL-6-/-, and CXCL1-/- mice. Bacterial growth in eyes of CXCL1-/-, IL-6-/-, and C67BL/6J mice was similar. Retinal function retention was greater in eyes of IL-6-/- and CXCL1-/- mice compared with that of C57BL/6J, despite these eyes having similar bacterial burdens. Neutrophil influx into eyes of CXCL1-/- mice was reduced to a greater degree compared with that of eyes of IL6-/- mice. Histology confirmed significantly less inflammation in eyes of CXCL1-/- mice, but similar degrees of inflammation in IL6-/- and C57BL/6J eyes. Because inflammation was reduced in eyes of infected CXCL1-/- mice, we tested the efficacy of anti-CXCL1 in B. cereus endophthalmitis. Retinal function was retained to a greater degree and there was less overall inflammation in eyes treated with anti-CXCL1, which suggested that anti-CXCL1 may have therapeutic efficacy in limiting inflammation during B. cereus endophthalmitis. Taken together, our results indicate that absence of IL-6 did not affect overall pathogenesis of endophthalmitis. In contrast, absence of CXCL1, in CXCL1-/- mice or after anti-CXCL1 treatment, led to an improved clinical outcome. Our findings suggest a potential benefit in targeting CXCL1 to control inflammation during B. cereus and perhaps other types of intraocular infections.

Fulminant course with dismal outcomes in cases of Bacillus cereus endophthalmitis

Bacillus cereus (B. cereus) endophthalmitis is a serious and rare ocular infection. Infection with B. cereus needs to be suspected in penetrating injuries sustained with retention of intraocular foreign bodies (IOFBs) and in agricultural settings. Additionally, it can be a cause of endogenous endophthalmitis in intravenous (IV) drug abusers and in dialysis patients. It is characterized by acute onset and a rapid fulminant course, often leading to enucleation or evisceration of the involved eye. Intravitreal and IV vancomycin has good coverage against B. cereus. Though associated with poor outcomes, high index of suspicion with early initiation of treatment might improve prognosis. Case reports of two patients with fulminating B. cereus endophthalmitis treated in our hospital in the last 1 year are reported.

Treatment of Experimental Bacillus cereus Endophthalmitis Using Intravitreal Moxifloxacin With or Without Dexamethasone

To evaluate the effects of intravitreal moxifloxacin with or without dexamethasone on experimental Bacillus cereus endophthalmitis. The right eyes of 21 New Zealand albino rabbits weighing 2-3 kg were used in this study. Each eye was inoculated with 1×10(6) colony-forming units of B. cereus microorganisms via intravitreal injection into the vitreous cavity, and an experimental model of B. cereus endophthalmitis was formed. The rabbits were separated into 3 groups: Group 1 was given 0.1 mL of balanced saline solution intravitreally, group 2 was given 50 μg of moxifloxacin, and group 3 was given 50 μg of moxifloxacin plus 400 μg of dexamethasone 24 h after the inoculation. Vitreous aspirates were taken for microbiological examination on the 3rd day. Clinical inflammation scores were evaluated on days 1, 7, and 14. The rabbits were killed on the 14th day, and the eyes were enucleated for histopathological examination. On the 7th day, only the vitreous scores of the treatment groups were significantly low compared with those of the control group (P<0.05). On day 14, the clinical scores of vitreous inflammation were 2.43±0.79, 1.43±0.53, and 1.29±0.49 in Groups 1, 2, and 3, respectively. The clinical scores of the treatment groups were significantly lower compared with those of the control group on day 14 (P<0.05). Histopathological scores were 2.43±0.79, 1.43±0.53, and 1.43±0.79 for the iris and 2.14±0.69, 1.57±0.53, and 1.14±0.38 for the vitreous in Groups 1, 2, and 3, respectively. Apart from the conjunctiva, the histopathological scores of the other tissues in the treatment groups were significantly lower compared with those of the control group (P<0.05). No significant differences were found in the histopathological or clinical scores among the treatment groups (P>0.05). Microbiological scores at day 14 were 151±6.43, 125.43±13.44, and 131.14±16.99 for Groups 1, 2, and 3, respectively. The microbiological scores of the treatment groups were significantly lower compared with those of the control group (P<0.05). Intravitreal moxifloxacin injection is effective in experimental B. cereus endophthalmitis. The addition of intravitreal dexamethasone may not significantly affect treatment efficacy.

Bacillus cereus–Induced Permeability of the Blood–Ocular Barrier during Experimental Endophthalmitis

The purpose of this study was to determine to what extent blood-retinal barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. Mice were intravitreally injected with 100 colony-forming units of B. cereus, and eyes were analyzed at specific times after infection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the retinal pigment epithelium. B. cereus induced the leakage of albumin and fibrin into the aqueous and vitreous humor by 8 hours after infection. BRB permeability occurred as early as 4 hours and increased 13.30-fold compared with uninfected controls by 8 hours. Production of proinflammatory cytokines IL-6, MIP-1alpha, IL-1beta, and KC increased over the course of infection. In the retina, ZO-1 disruption began by 4 hours and was followed by decreasing occludin and ZO-1 expression at 4 and 8 hours, respectively. Tubulin condensation and RPE65 degradation occurred by 12 hours. A quorum-sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Wild-type and mutant B. cereus sterile supernatants induced blood-ocular barrier permeability similarly to that of wild-type infection. These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 hours after infection. Disruption of tight junctions at the level of the retinal pigment epithelium may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.

The Efficacy of Intravitreal Vancomycin and Dexamethasone in the Treatment of Experimental Bacillus cereus Endophthalmitis

Purpose: Bacillus cereus causes the most virulent and refractoryform of endophthalmitis. The authors analyzed effectiveness of intravitrealvancomycin with or without dexamethasone for experimental Bacillus cereus endophthalmitis. Methods: Rabbit eyes were injected intravitreally with 1 x 106colony-forming units of Bacillus cereus organisms. At 24 hours after injection,eyes were injected intravitreally with 0.1 ml of balanced salt solution (group 1,n = 10), 1 mg vancomycin (group 2, n = 10), and antibiotic plus 0.4 mg dexamethasone(group 3, n = 10). Inflammatory scores were assessed 7 days and 14days after treatment. Furthermore, histologic grading was carried out at the conclusionof the clinical observations. Results: Eyes treated with vancomycin, withor without dexamethasone at 7 days and 14 days expressed significant less inflammationover iris and vitreous than the control group (p < 0.05). Moreover,eyes treated with vancomycin with dexamethasone showed less inflammationover the conjunctiva and vitreous at 7 days and over the iris and vitreous at14 days, compared to antibiotic treatment alone (p < 0.05). Additionally, at14 days, the histopathological changes of eyes treated with vancomycin withdexamethasone had less conjunctival inflammation, mild iridocyclitis, less vitreouscells, and less choroidal vasculitis and retinitis compared to control groupand antibiotic treatment alone, respectively (pp < 0.05). Conclusion: Intravitrealinjection of vancomycin improved the therapeutic outcome of Bacillus cereusendophthalmitis. The addition of dexamethasone to antibiotic treatment provideda therapeutic benefit over antibiotic alone.

Failure of intravitreal dexamethasone to diminish inflammation or retinal toxicity in an experimental model of Bacillus cereus endophthalmitis

Purpose. To determine whether the usual clinical dose of intravitreal dexamethasone can attenuate intraocular inflammation and retinal necrosis in a rabbit model of fulminant Bacillus cereus endophthalmitis induced by crude exotoxins. Methods. Thirty-six eyes from pigmented mongrel rabbits received intravitreal injections of varying concentrations of crude B. cereus exotoxins with or without concomitant injections of 400 µg of dexamethasone sodium phosphate (0.1% solution). After ophthalmoscopic examination at 4 or 18 hr postinjection, the animals were killed and histopathologic findings graded. Results. Intraocular inflammation and retinal necrosis scores in eyes receiving both exotoxins and dexamethasone did not differ significantly from eyes receiving exotoxins alone for any exotoxin dose at 4 or 18 hr. The severity of retinal necrosis increased with toxin dose and was nearly maximal after 4 hr. Intraocular inflammation also generally increased with dose, but continued to increase until 18 hr. Conclusions. Standard clinical doses of intravitreal dexamethasone do not appear to attenuate the intraocular inflammatory or tissue response to secreted B. cereus exotoxins. Other treatment modalities including vitrectomy, to decrease exotoxin load, and exotoxin inhibitors may be necessary for the effective treatment of B. cereus endophthalmitis.

Infective endophthalmitis caused by Bacillus cereus after cataract extraction surgery.

We describe a 72-year-old Chinese man who developed fulminant Bacillus cereus endophthalmitis 36 h after an uneventful surgery for cataract extraction. Clinical progression of disease was extremely rapid, in spite of early vitrectomy and intravitreal injection of antibiotics. Results of Gram staining showed gram-positive bacilli, and the culture was positive for B. cereus. Endophthalmitis is rare after cataract surgery (cumulative probability within 1 year, approximately 0.08%), and cases caused by B. cereus are even less common. The prognosis and plan of treatment are discussed.

Useful Visual Outcomes after Treatment of Bacillus cereus Endophthalmitis

Bacillus cereus endophthalmitis occurring after penetrating ocular trauma has been almost always associated with a poor visual outcome. The purpose of our study was to review and report patients who had useful visual acuity outcomes. The study group consisted of five patients from a single medical center with penetrating ocular trauma and endophthalmitis caused by B. cereus. The study population was derived from a review of the microbiology records, clinical records, and operative reports of patients with culture-proven, post-traumatic endophthalmitis over a 15-year period. Patients were only included if the final visual acuity outcomes were 20/200 or better. All five patients had penetrating ocular injuries, and four patients had a retained intraocular foreign body. Endophthalmitis was diagnosed preoperatively in three patients and intraoperatively in two patients. All patients underwent pars plana vitrectomy and injection of intravitreal and periocular antibiotics. Postoperatively, a rhegmatogenous retinal detachment developed in three patients between 4 weeks and 12 months after the injury (average, 19 weeks); all retinal detachments were reattached with additional vitreoretinal surgery. Final postoperative visual acuities were 20/200 (two patients), 20/30 (one patient), and 20/25 (two patients). The postoperative follow-up time interval ranged from 12 months to 30 months (average, 19.2 months). The current series adds further support to the observation that certain eyes with post-traumatic B. cereus endophthalmitis may be associated with preservation of anatomic integrity and restoration of useful visual acuity.

Extracellular virulence factors in Bacillus cereus endophthalmitis: methods and implication of involvement of hemolysin BL

Bacillus cereus is a common cause of highly fulminant posttraumatic and metastatic endophthalmitis. Exotoxins or enzymes likely contribute to the severity of the infection, but specific virulence factors have not been identified. We developed two methods for the identification of B. cereus ocular virulence factors. In an in vitro assay that allows screening of multiple samples, retinal toxicity was estimated by measuring the release of lactate dehydrogenase from retinal buttons treated with B. cereus toxins. The results from this assay were confirmed with a sterile endophthalmitis model in which the histopathologic effect of intravitreally injected toxins was assessed. We tested pure hemolysin BL (HBL), a tripartite dermonecrotic vascular permeability factor of B. cereus, and crude exotoxin (CET) preparations, consisting of concentrated, cell-free B. cereus culture supernatant. In the in vitro assay, both CET and HBL caused rapid release of lactate dehydrogenase and retinal disintegration. In vivo, the toxins caused endophthalmitis clinically characteristic of B. cereus within 4 h. Histological changes included rapid retinal necrosis and detachment, choroidal edema, detachment and disruption of the retinal pigment epithelium, and rapid infiltration of polymorphonuclear leukocytes. Neutralization of HBL in CET preparations inhibited toxicity in vitro by 54%, and pure HBL was less toxic than CET with equal HBL contents in both methods. The results suggest that B. cereus ocular virulence is multifactorial and that HBL contributes to virulence.