Study of Intraocular Concentrations (Aqueous Humor, Vitreous Humor) of Antibiotics After Local and/or Systemic Administration in Endophthalmitis

Endophthalmitis Clinical Trial

— CINEBIOPHTA  

Official title:

Intraocular Concentrations Study (Aqueous Humor, Vitreous Humor) of Antibiotics After Local and/or Systemic Administration in Endophthalmitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03968341
• Other study ID #: CINEBIOPHTA
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 9, 2020
• Est. completion date: December 8, 2023

Study information

• Verified date: March 2023
• Source: Groupe Hospitalier Paris Saint Joseph
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endophthalmitis is an intraocular inflammation due to a serious infection of bacterial, fungal or parasitic origin, involving visual prognosis if it is not treated in time and correctly. Despite the eye isolation from the rest of the body, germs can enter the eye either exogenously, during open globe surgery, following perforating eye trauma, or following anti-VEGF antibodies intravitreal injection, or other drugs such as corticosteroids for example, or by endogenous route, haematogenic as part of sepsis, usually during immunodepression. Post-operative endophthalmitis is the most feared complication following any endo-ocular surgery. It can be acute, occurring within 6 weeks post-operatively or delayed as after poor healing, or on a glaucoma filtration bubble. Endophthalmitis after cataract surgery is a complication with a low incidence of (0.030 to 0.047%) but which, due to interventions number carried out (830,000 in 2016, in France), appears significant. There are factors that favour endophtalmitis occurrence such as a vitreous exit from eyeball during surgical procedure, poor scar coaptation, premature removal of sutures, etc... They condition emergency care. Early diagnosis and appropriate treatment are essential for safeguarding the eye and its function. Therefore, therapeutic management requires endo-ocular sampling in front of any suspicion of endophtalmitis, to be done before any treatment, to carry out microbiological analysis (direct examination on slide, culture, universal and/or targeted PCR, antibiotic susceptibility test). Vitreous puncture is more contributive than anterior chamber puncture, underlining need for these two samples to identify the responsible germ. Once samples have been taken, a broad-spectrum antibiotic therapy introduction must be performed intra-vitreously combined with systemic and local administration. Intravitreal injections allow treatment to be provided at effective concentrations directly at the infection site. On the other hand, toxic risks must be taken into account, especially since the protocol may require multiple intravitreal injections.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: December 8, 2023
• Est. primary completion date: June 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female > 18 years old

• Francophone

• Patients referred to emergencies by an ophthalmologist or doctor, or patients already hospitalized, with a unfavourable course 48 hours after introduction of broad spectrum probabilistic antibiotic therapy for the following situations:

• Cataract surgery

• Vitreoretinal surgery

• Intravitreal injection [anti-VEGF for the treatment of AMD, dexamethasone (Ozurdex®) for the treatment of cystoid macular edema]

• Physical signs presence of intraocular inflammation (Tyndall, hypopyon, cyclic membrane, hyalite)

• Presence of functional signs (Decreased Visual Acuity)

• Patients for whom a management re-evaluation is essential with obligation of new intraocular samples.

• Patient affiliated to social security or, failing that, to another health insurance system

Exclusion Criteria:

• Patient under guardianship or curators

• Patient deprived of liberty

• Participation refusal in the study

Related Conditions & MeSH terms

• Endophthalmitis

Intervention

Other:
• Pharmacokinetic and pharmacodynamic study of antibiotics used in severe endophthalmitis from samples taken from treated patients
A 5mL dry tube will be taken by puncture of the humeral vein like a conventional blood test. This tube is not usually collected unless specifically requested by the ophthalmologist. This sample will be sent quickly (within two hours) to the CHNO Medical Biology Laboratory for centrifugation, serum separation and storage at -80°C. Samples stored at -80°C will be sent weekly to the Microbiology and Anti-infectives Laboratory at Hospital Paris Saint-Joseph, with the dosage request form duly completed with the usual information.

Locations

Country	Name	City	State
France	Groupe Hospitalier Paris Saint Joseph	Paris	Ile-de-France

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Hospitalier Paris Saint Joseph	Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Country where clinical trial is conducted

France, 

References & Publications (11)

Adenis JP, Mounier M, Salomon JL, Denis F. Human vitreous penetration of imipenem. Eur J Ophthalmol. 1994 Apr-Jun;4(2):115-7. doi: 10.1177/112067219400400207. — View Citation

Bowen RC, Zhou AX, Bondalapati S, Lawyer TW, Snow KB, Evans PR, Bardsley T, McFarland M, Kliethermes M, Shi D, Mamalis CA, Greene T, Rudnisky CJ, Ambati BK. Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vanco — View Citation

Chiquet C, Labetoulle M. [Fluoroquinolones in ophthalmology: indications and current use]. J Fr Ophtalmol. 2008 Oct;31(8):803-8. doi: 10.1016/s0181-5512(08)74403-6. French. — View Citation

Clarke B, Williamson TH, Gini G, Gupta B. Management of bacterial postoperative endophthalmitis and the role of vitrectomy. Surv Ophthalmol. 2018 Sep-Oct;63(5):677-693. doi: 10.1016/j.survophthal.2018.02.003. Epub 2018 Feb 15. — View Citation

Cornut PL, Chiquet C. [Intravitreal injection of antibiotics in endophthalmitis]. J Fr Ophtalmol. 2008 Oct;31(8):815-23. doi: 10.1016/s0181-5512(08)74405-x. French. — View Citation

Du DT, Wagoner A, Barone SB, Zinderman CE, Kelman JA, MaCurdy TE, Forshee RA, Worrall CM, Izurieta HS. Incidence of endophthalmitis after corneal transplant or cataract surgery in a medicare population. Ophthalmology. 2014 Jan;121(1):290-298. doi: 10.1016 — View Citation

Gan IM, van Dissel JT, Beekhuis WH, Swart W, van Meurs JC. Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis. Br J Ophthalmol. 2001 Nov;85(11):1289-93. doi: 10.1136/bjo.85.11.1289. — View Citation

Goldschmidt P, Bensaid P, Semoun O, Chaumeil C. [Rational approach for the treatment of postoperative endophthalmitis in impoverished populations]. J Fr Ophtalmol. 2013 Mar;36(3):261-7. doi: 10.1016/j.jfo.2012.08.002. Epub 2013 Feb 11. French. — View Citation

Khera M, Pathengay A, Jindal A, Jalali S, Mathai A, Pappuru RR, Relhan N, Das T, Sharma S, Flynn HW. Vancomycin-resistant Gram-positive bacterial endophthalmitis: epidemiology, treatment options, and outcomes. J Ophthalmic Inflamm Infect. 2013 Apr 22;3(1) — View Citation

Kumar A, Sridhar MS, Dada T, Tewari HK, Gupta SK. Intravitreal pefloxacin therapy in postoperative endophthalmitis. Clin Exp Ophthalmol. 2000 Feb;28(1):38-40. doi: 10.1046/j.1442-9071.2000.00256.x. — View Citation

Thompson AM. Ocular toxicity of fluoroquinolones. Clin Exp Ophthalmol. 2007 Aug;35(6):566-77. doi: 10.1111/j.1442-9071.2007.01552.x. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the concentrations of the various antibiotics in the media tested (aqueous and vitreous humours)	Determination of the concentrations of the various antibiotics in the media tested (aqueous and vitreous humours) by liquid chromatography coupled with a high-resolution mass spectrometer (HPLC-HRMS).	48 hours
Secondary	Number of aqueous or vitreous humor samples collected by puncture from treated patients that can be used analytically		12 months