Clinical management of an outbreak of nutritionally variant streptococcus endophthalmitis following intravitreal bevacizumab injection.

BACKGROUND: The management of an outbreak of endophthalmitis associated with intravitreal bevacizumab represents a challenging real-time process involving identification of cases, treatment and mitigation measures during the outbreak. We summarize the clinical presentation and management of a cluster of endophthalmitis cases from contaminated bevacizumab, in addition to mathematical probabilistic assessment of the number of cases that define an outbreak. METHODS: A retrospective study was conducted to assess the management of an endophthalmitis outbreak after intravitreal bevacizumab (IVB) administration. Demographic data, clinical information, individual patient management and public health reporting measures were reviewed. Outcomes of patients who received prophylactic antibiotics for endophthalmitis prevention were also reviewed. Binomial tail probability calculations were performed to determine the likelihood of clusters of endophthalmitis that could inform when an outbreak was evolving that would warrant more public health notification measures and communication. RESULTS: Forty-five eyes of 42 patients who received IVB from a single batch were reviewed. Four cases of endophthalmitis from Granulicatella adiacens, a nutritionally-variant Streptococcus species, were treated successfully with intravitreal antibiotics ± vitrectomy. Thirty-four of the remaining 41 eyes were treated with prophylactic intravitreal vancomycin with no additional cases of endophthalmitis. Outbreak management also included CDC, ASRS and public health authority notification. Binominal tail probabilities demonstrated the rarity of clusters from a single batch (i.e. ~ 1/10,000 for 2 cases; 1/2 million for 3 cases). However, given the U.S. scale of IVB administration, there is an 87% chance of a cluster ≧ 2 and a 1% chance of a cluster ≧ 3 cases annually, which may guide outbreak management. A process diagram was developed to incorporate patient management and public health measures when an outbreak is suspected. CONCLUSION: Intravitreal antibiotics and vitrectomy were effective in the individual management of cases of endophthalmitis, and no serious adverse events occurred with prophylactic intravitreal vancomycin for at-risk eyes. Best practices for outbreaks should be evaluated, given their likelihood within the U.S. and the sight-threatening consequences of endophthalmitis.

Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation.

INTRODUCTION: A growing body of evidence suggests that specific, naturally occurring gut bacteria are under-represented in the intestinal tracts of subjects with type 2 diabetes (T2D) and that their functions, like gut barrier stability and butyrate production, are important to glucose and insulin homeostasis. The objective of this study was to test the hypothesis that enteral exposure to microbes with these proposed functions can safely improve clinical measures of glycemic control and thereby play a role in the overall dietary management of diabetes. RESEARCH DESIGN AND METHODS: We evaluated whether a probiotic comprised of these anaerobic bacteria would enhance dietary management by (1) manufacturing two novel probiotic formulations containing three (WBF-010) or five (WBF-011) distinct strains in a Current Good Manufacturing Practice (cGMP) facility, (2) establishing consistent live-cell concentrations, (3) confirming safety at target concentrations dispensed in both animal and human studies and (4) conducting a 12-week parallel, double-blind, placebo-controlled, proof-of-concept study in which subjects previously diagnosed with T2D (n=76) were randomly assigned to a two times a day regimen of placebo, WBF-010 or WBF-011. RESULTS: No safety or tolerability issues were observed. Compared with the placebo group, subjects administered WBF-011 (which contains inulin, Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis and Anaerobutyricum hallii) significantly improved in the primary outcome, glucose total area under the curve (AUC): -36.1 mg/dL/180 min, p=0.0500 and also improved in secondary outcomes, glycated hemoglobin (A1c): -0.6, glucose incremental-AUC: -28.6 mg/dL/180 min. CONCLUSIONS: To our knowledge, this is the first randomized controlled trial to administer four of the five strains to human subjects with T2D. This proof-of-concept study (clinical trial number NCT03893422) shows that the intervention was safe and well tolerated and that supplementation with WBF-011 improves postprandial glucose control. The limited sample size and intersubject variability justifies future studies designed to confirm and expand on these observations.

Effect of dietary sunflower oil and coconut oil on adipose tissue gene expression, fatty acid composition and serum lipid profile of grower pigs.

The present study was conducted to assess whether the partial replacement of feed energy by vegetable oils containing high medium-chain saturated fatty acids (MCFA) and n-6 polyunsaturated fatty acids (PUFA) would modify lipogenic gene expression and other parameter of fat metabolism in pigs. Eighteen pigs (17-19 kg body weight) received one of three experimental diets for 60 days (six animals per group): (i) Control diet; (ii) a diet with sunflower oil (SO) or (iii) a diet with coconut oil (CO). In diets SO and CO, 10% of the feed energy was replaced by the respective oils. The experimental treatment did not influence the performance of the pigs. In blood serum, an increased content of total cholesterol was observed for SO and CO fed animals, whereas no significant changes for total triglycerides and different lipoprotein fractions were detected. The fatty acid composition of adipose tissue was significantly modified, with an increased content of MCFA and n-6 PUFA in CO and SO fed pigs, respectively. The gene expression for fatty acid synthase was decreased for SO and CO fed pigs; for stearoyl CoA desaturase and sterol regulatory element binding protein, a depression was observed in SO but not in CO fed pigs. The results of present study suggest that the type of dietary fat can modulate the adipose tissue gene expression and fatty acid composition differentially, with minimal effect on serum lipid profile.

Long-term retinal toxicity of intravitreal commercially available preserved triamcinolone acetonide (Kenalog) in rabbit eyes.

PURPOSE: To investigate whether intravitreal Kenalog (IVTK; Bristol Meyers Squibb Company, Princeton, NJ) produces histologic or electroretinographic changes in the rabbit retina up to 3 months after injection. METHODS: Ten Dutch-belted rabbits were injected with 4 mg/0.1 mL Kenalog in one eye and 0.1 mL physiologic salt solution (PSS) in the fellow eye. Simultaneous bilateral dark-adapted electroretinography was performed 2 weeks and 12 weeks after injection in 10 and 6 rabbits, respectively. Saturated a-wave amplitude, maximal scotopic b-wave amplitude, and individual a-wave and b-wave amplitudes of IVTK-injected and control eyes were compared at 2 and 12 weeks after injection. Light microscopy was performed on both eyes of three animals 3 months after injection. Immunohistochemistry was performed with antibodies recognizing vimentin and human alveolar macrophage (HAM)-56, markers of glial cells and macrophages, respectively. RESULTS: No significant difference was observed in the saturated a-wave or maximal scotopic b-wave amplitudes between the PSS-injected eyes and the IVTK-injected eyes at 2 weeks (P = 0.95 and P = 0.56, respectively) and 12 weeks (P = 0.82 and P = 0.17) after injection. Light microscopy and immunohistochemistry disclosed only rare macrophages in the vitreous of IVTK-injected eyes. Retinal layers, retinal pigment epithelium, and choriocapillaris in treatment and control eyes were unremarkable. CONCLUSIONS: No demonstrable electroretinographic or histologic changes occurred to suggest immediate or delayed widespread retinal toxicity of IVTK.

Short-term course of intraocular pressure after intravitreal injection of triamcinolone acetonide.

OBJECTIVE: To describe the natural history of intraocular pressure (IOP) within the first 30 minutes after intravitreal injection of triamcinolone acetonide (TA). DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS: Thirty-eight consecutive patients who met inclusion and exclusion criteria and underwent intravitreal injection of 0.1 ml (4 mg) of TA were studied. METHODS: Intraocular pressure was measured by Goldmann applanation tonometry at baseline; immediately after injection; and at 2, 5, 10, 20, and 30 minutes after injection. MAIN OUTCOME MEASURES: Intraocular pressure measurements at baseline; immediately after intravitreal injection; and 2, 5, 10, 20, and 30 minutes after injection, and percentage of patients with IOP < or = 24 mmHg at 30 minutes. RESULTS: Patients who did not experience vitreous reflux (30/38 [78.9%]) at the site of injection had a significant initial elevation of IOP that rapidly normalized. Patients who experienced vitreous reflux (8/38 [21.1%]) at the site of injection had either no change in IOP or a small drop in IOP that rapidly normalized. The IOP measured in millimeters of mercury immediately after injection (45.9 [no reflux], 12.6 [reflux]), 2 minutes after injection (39.9 [no reflux], 13.5 [reflux]), 5 minutes after injection (33.3 [no reflux], 13.8 [reflux]), 10 minutes after injection (26.4 [no reflux], 15.1 [reflux]), and 20 minutes after injection (21.8 [no reflux], 15.0 [reflux]) showed a statistically significant difference between the 2 groups. The difference in IOP between the 2 groups was not significant at baseline or 30 minutes after injection. At 30 minutes, 90% (95% confidence interval, 85.8%-95.2%) of patients without vitreous reflux had an IOP < 24 mmHg. CONCLUSIONS: Patients undergoing intravitreal injection of TA with no vitreous reflux have a risk of short-term elevation of IOP that rapidly normalizes over 30 minutes. In patients with vitreous reflux after the injection, the IOP declines immediately after injection and rapidly normalizes over 10 minutes.

Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models.

PURPOSE: To determine whether moxifloxacin can be used safely as an intraocular antibiotic, retinal safety of intravitreal moxifloxacin was studied with electroretinography (ERG) and histopathology in animal models. METHODS: Moxifloxacin was injected into mouse eyes at intravitreal concentrations of 5 to 500 microg/mL and into rabbit eyes at 150 microg/mL. As the control, the vehicle was injected into the fellow eyes of each animal. Four weeks after injection, ERG recordings were performed, and animal eyes were processed for histologic examination. RESULTS: ERG studies showed no significant difference between control and moxifloxacin-injected eyes at any dose in either the mouse or rabbit model. Histologic examination revealed no retinal abnormality in mice at 5 to 100 microg/mL or in rabbits at 150 microg/mL intravitreal moxifloxacin. In mice at 500 microg/mL, occasional focal retinal necroses were observed, suggesting isolated retinal toxicity at this concentration of moxifloxacin. CONCLUSIONS: Intravitreal moxifloxacin, up to 100 microg/mL in mice or 150 microg/mL in rabbits, caused no ERG or retinal histologic abnormality. These results indicate that moxifloxacin is a safe intravitreal antibiotic in mouse and rabbit animal models. If proven safe and efficacious by further study in humans, intravitreal injection of moxifloxacin could be considered as an alternative to currently used antibiotics in selected patients with resistance or allergy to the more traditional antibiotics.

An eye model for practicing vitreoretinal membrane peeling.

A cost-effective, reusable practice eye model for epiretinal membrane peeling that uses easily obtained, commercially available materials was developed. A commercially available globe that is anatomically and optically similar to the human eye was modified by creating 2 ports that simulate superior sclerotomies. The model has a removable plastic anterior segment, which allows access to the posterior segment for practice membrane placement. Membranes were created on the macula by applying a coat of liquid skin bandage. Membrane peeling was performed under an ophthalmic operating microscope using a disposable flat vitrectomy lens. The basic skills required for membrane peeling can be demonstrated and acquired by practicing with this eye model. The practice eye model is expected to enhance the acquisition of skills required for epiretinal membrane peeling.

Clearance of intravitreal moxifloxacin.

PURPOSE: To study the clearance of moxifloxacin after intravitreal injection in rabbits. METHODS: Intravitreal injections of 200 microg/0.1 mL of moxifloxacin were administered to rabbits. Four eyes per time point after injection (1 hour and 6, 12, 24, and 36 hours) and three eyes at 48 hours, respectively, were enucleated and immediately frozen and stored at -80 degrees C. Ocular dissection and isolation of frozen vitreous was performed. Vitreous samples were acquired at the various time intervals after injection. Antibiotic assays were performed with high performance liquid chromatography. RESULTS: The concentration of intravitreal moxifloxacin showed an exponential decay with a half-life of 1.72 hours. The mean vitreous concentration was 120.49 +/- 49.23 microg/mL 1 hour after injection, and declined to 20.23 +/- 5.85 microg/mL at 6 hours and 1.06 +/- 0.81 microg/mL at 12 hours, respectively. CONCLUSIONS: The vitreous concentrations achieved were several orders of magnitude greater than the MIC90 of organisms commonly involved in bacterial endophthalmitis, and therapeutic levels were maintained at 12 hours in uninflamed, phakic rabbit eyes. The pharmacokinetic data suggest that intravitreal moxifloxacin may have a role in the treatment of bacterial endophthalmitis.

Staphylococcus hominis endophthalmitis associated with a capsular hypopyon.

PURPOSE: To report a case of Staphylococcus hominis endophthalmitis associated with a capsular hypopyon. DESIGN: Interventional case report. METHODS: A 51-year-old man presented with chronic postcataract extraction inflammation and underwent vitrectomy, partial capsulectomy, and intravitreal antibiotic injections, followed by explantation of the intraocular lens and capsule. RESULTS: A capsular hypopyon in the absence of an anterior chamber hypopyon was noted. Cultures of the vitreous and capsule revealed Staphylococcus hominis, a coagulase-negative gram-positive organism. CONCLUSIONS: We are unaware of previous reports of endophthalmitis caused by Staphylococcus hominis, and could find none in a computerized search using MEDLINE. This case adds Staphylococcus hominis to the list of causative organisms in chronic endophthalmitis and illustrates the rare finding of a capsular hypopyon.

Intravitreal clearance of moxifloxacin.

PURPOSE: To study the clearance of a single dose of intravitreally injected moxifloxacin in rabbits. METHODS: Intravitreal injections of 200 microg/0.1 mL of moxifloxacin were performed in rabbits. Four eyes per time interval after injection (1, 6, 12, 24, 36 hours) and three eyes at 48 hours were enucleated, immediately frozen, and placed at -80 degrees C. Ocular dissection and isolation of frozen vitreous were performed. Antibiotic assays were performed with use of high-performance liquid chromatography. RESULTS: The concentration of intravitreal moxifloxacin showed an exponential decay with a half-life of 1.72 hours. The mean vitreous concentration was 120.49 +/- 49.23 microg/mL 1 hour after injection, which declined to 20.23 +/- 5.85 microg/mL at 6 hours and 1.06 +/- 0.81 microg/mL at 12 hours. The aqueous levels of moxifloxacin showed an exponential decay from 10 microg/mL at 1 hour after intravitreal injection to undetectable levels by 12 hours after injection. CONCLUSIONS: Moxifloxacin clearance from the vitreous is rapid and consistent with previous clearance studies of ciprofloxacin. Given that the injected dose corresponds to several times the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) of organisms commonly involved in endophthalmitis, and that therapeutic levels are present up to 12 hours after injection, intravitreal moxifloxacin may have a role in the treatment of endophthalmitis.

Subconjunctival antibiotics for acute postcataract extraction endophthalmitis--is it necessary?

PURPOSE: To evaluate the efficacy of adjunctive subconjunctival antibiotic injection in the treatment of acute postcataract extraction endophthalmitis. DESIGN: Retrospective cohort study. METHODS: Patients who presented with hand motions or better vision and received subconjunctival antibiotics (SC+ group) were compared with those who did not (SC- group) in the treatment of acute postoperative endophthalmitis. RESULTS: The rate of obtaining a final vision of 20/40 or better was 60% in the SC+ group (n = 25) compared with 72% in the SC- group (n = 18) (P =.69), and the mean change in logMAR was -1.36 (improvement) versus -1.34 (P =.93). Based on a linear regression model controlling for presenting vision, there was no statistical difference in the mean logMAR change between the two groups (P =.73). CONCLUSION: Subconjunctival antibiotic injection as an adjunct to intravitreal antibiotics was unassociated with treatment benefit in patients with acute postoperative endophthalmitis presenting with vision of hand motions or better.