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

NCT03968341 | Unknown

• 1 other identifier: CINEBIOPHTA
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Endophthalmitis

Keywords

intraocular concentrations of antibiotics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of aqueous or vitreous humor samples collected by puncture from treated patients that can be used analytically

  12 months

Study Arms (1)

intraocular antibiotic concentrations determination

EXPERIMENTAL

In the event that the patient develops unfavourably, the ophthalmologist include the patient in the trial. The patient is reviewed at 48 hours after the introduction of probabilistic antibiotic therapy for clinical reassessment and the return of microbiological test results. Following this inclusion, the new samples will be taken when the patient passes through the operating room for the treatment of his pathology as part of the care. Ophthalmologists may have to adapt the patient's management (i.e. adjustment of antibiotic therapy) as part of their usual care routine. An anterior chamber puncture and a vitrectomy are performed. Eye fluids collected as part of the treatment are sent for analysis.

Other: Pharmacokinetic and pharmacodynamic study of antibiotics used in severe endophthalmitis from samples taken from treated patients

Interventions

Pharmacokinetic and pharmacodynamic study of antibiotics used in severe endophthalmitis from samples taken from treated patients OTHER

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.

intraocular antibiotic concentrations determination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patient under guardianship or curators
• Patient deprived of liberty
• Participation refusal in the study

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead
• Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts: collaborator

Study Sites (1)

Groupe Hospitalier Paris Saint Joseph

Paris, Île-de-France Region, 75014, France

Location

Related Publications (11)

• 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/j.ophtha.2013.07.016. Epub 2013 Aug 29.

  PMID: 23993357 RESULT

• 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.

  PMID: 29453989 RESULT

• 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.

  PMID: 23410853 RESULT

• 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.

  PMID: 11345344 RESULT

• 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):46. doi: 10.1186/1869-5760-3-46.

  PMID: 23607574 RESULT

• 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.

  PMID: 19107048 RESULT

• 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.

  PMID: 7950335 RESULT

• 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 vancomycin at the end of cataract surgery: a meta-analysis. Br J Ophthalmol. 2018 Sep;102(9):1268-1276. doi: 10.1136/bjophthalmol-2017-311051. Epub 2018 Jan 11.

  PMID: 29326317 RESULT

• 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.

  PMID: 19107050 RESULT

• 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.

  PMID: 11673290 RESULT

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

  PMID: 17760640 RESULT

MeSH Terms

Conditions

Endophthalmitis

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Eye Diseases

Study Officials

• François COUDORE, Professor

  Fondation Hôpital Saint-Joseph

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: May 30, 2019
• Study Start: December 9, 2020
• Primary Completion: June 8, 2022
• Study Completion: December 8, 2023
• Last Updated: March 7, 2023

Record last verified: 2023-03

Locations

FR (1)