Clinical trial NCT02223338: Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics
Official title: Conjunctival Floral Resistance in a Single Practice Site Comparing Povidone- Iodine Prep With or Without Post-Intravitreal Injection Second Generation Fluoroquinolones.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacterial Resistance
Lead sponsor: Loma Linda University
Sponsor class: OTHER
First posted: 2014-08-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 1. Background: Over 1 million intravitreal injections are performed annually in the United States. The most devastating complication related to these injections is endophthalmitis, with an incidence of 0.02 - 0.1% per injection. Techniques aimed at prevention of this complication have been studied, though emergence rates of antibiotic resistant bacteria in a single clinic population comparing antiseptic technique with iodine vs. use of post-injection second generation fluoroquinolones has not been reported in the literature.
2. Objectives: The purpose of the study is to help determine the best way to prevent infection and limit antibiotic resistance in patients receiving eye injections.
3. Procedures Involved (Research Interventions): After the patient is chosen based on inclusion criteria and agrees to participate in the study, exclusion criteria will be reviewed, cognizance will be determined, informed consent and HIPAA compliance forms will be signed. At this point and prior to the instillation of ophthalmic medications, a Rayon swab will be passed along the inferior fornix of the study eye while the patient looks up and the examiner lowers the lower eyelid. The swab will then be used to inoculate chocolate agar and a blood agar culture plates and a glass slide. These will be brought to the FMO microbiology department for culture and Gram stain. All Staphylococcus aureus and coagulase negative Staphylococcus species identified will be subjected to sensitivity testing using the Gram Positive antibiotic panel available at Loma Linda, with the addition of ciprofloxacin.

Detailed description: Previous studies have demonstrated that bacteria in the eye may become resistant to antibiotics used after injections when compared to the bacteria found in untreated eyes. However, no study published to date compares resistance rates in eyes where an iodine-based preparation is used, which is standard of care, to those in which an antibiotic is also given after the injection in a single practice setting. This is an important issue, because resistant bacteria can cause infections that are more damaging and difficult to treat than non-resistant bacteria. Moreover, previous studies have focused on the emergence of resistance to fourth generation fluoroquinolones including moxifloxacin and gatifloxacin, though use of second generation fluoroquinolones is still practiced in the United States by some retina specialists, including at the investigators institution. Currently in the United States, 81% of retina specialists give antibiotics after eye injections, although the results of several large studies suggest that this practice does not reduce rates of endophthalmitis compared with use of iodine alone.

Eligibility criteria: Inclusion Criteria:

* Patients with choroidal neovascularization due to wet age-related macular degeneration or any other cause, clinically significant macular edema or cystoid macular edema over age 18 who have been treated with at least 3 monthly intravitreal injections of an anti-Vascular Endothelial Growth Factor (anti-VEGF) agent in the last 6 months. These injections must have been given in either Dr. Fan's clinic using povidone-iodine and post-injection topical ciprofloxacin 0.3% 4x daily for 3 days, or in Dr. Rauser's clinic where povidone-iodine only is applied to the injection site and conjunctival fornix but no post-injection antibiotics are given.

Exclusion Criteria:

* Administration of anti-VEGF agents outside of Dr. Fan's or Dr. Rauser's clinics
* Intraocular surgery
* Use of topical antibiotics other than ciprofloxacin 0.3%
* Infections of the eye or ocular adnexa within the last 3 months
* Use of oral antibiotics within the last 30 days
* Contact lens wear.

Primary outcomes:
measure: Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics
timeFrame: Cultured organisms will be subjected to resistance panels once they have grown and been identified. Cultures will be followed for 7 days total, and if no growth is recorded at that time they will be considered sterile.
Secondary outcomes:
measure: Average Number of Antibiotics to Which Isolated Organisms Were Resistant
timeFrame: Through study completion, average of 4 weeks
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University of Health Sciences Faculty Medical Offices
state: California
Study officials:
affiliation: Loma Linda University
name: Michael Rauser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011 Apr;31(4):654-61. doi: 10.1097/IAE.0b013e31820a67e4.
citation: Moshfeghi AA, Rosenfeld PJ, Flynn HW Jr, Schwartz SG, Davis JL, Murray TG, Smiddy WE, Berrocal AM, Dubovy SR, Lee WH, Albini TA, Lalwani GA, Kovach JL, Puliafito CA. Endophthalmitis after intravitreal vascular [corrected] endothelial growth factor antagonists: a six-year experience at a university referral center. Retina. 2011 Apr;31(4):662-8. doi: 10.1097/IAE.0b013e31821067c4.
citation: Kim SJ, Toma HS. Ophthalmic antibiotics and antimicrobial resistance a randomized, controlled study of patients undergoing intravitreal injections. Ophthalmology. 2011 Jul;118(7):1358-63. doi: 10.1016/j.ophtha.2010.12.014. Epub 2011 Mar 21.
citation: Kim SJ, Toma HS. Antimicrobial resistance and ophthalmic antibiotics: 1-year results of a longitudinal controlled study of patients undergoing intravitreal injections. Arch Ophthalmol. 2011 Sep;129(9):1180-8. doi: 10.1001/archophthalmol.2011.213.
citation: Mino De Kaspar H, Hoepfner AS, Engelbert M, Thiel M, Ta CN, Mette M, Schulze-Schwering M, Grasbon T, Sesma-Vea B, Casas JM, Iturralde-Goni R, Klauss V, Kampik A. Antibiotic resistance pattern and visual outcome in experimentally-induced Staphylococcus epidermidis endophthalmitis in a rabbit model. Ophthalmology. 2001 Mar;108(3):470-8. doi: 10.1016/s0161-6420(00)00545-5.
citation: Miller D, Flynn PM, Scott IU, Alfonso EC, Flynn HW Jr. In vitro fluoroquinolone resistance in staphylococcal endophthalmitis isolates. Arch Ophthalmol. 2006 Apr;124(4):479-83. doi: 10.1001/archopht.124.4.479.
citation: Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United States. Am J Ophthalmol. 2011 Feb;151(2):329-32. doi: 10.1016/j.ajo.2010.08.039. Epub 2010 Dec 18.
citation: Bhatt SS, Stepien KE, Joshi K. Prophylactic antibiotic use after intravitreal injection: effect on endophthalmitis rate. Retina. 2011 Nov;31(10):2032-6. doi: 10.1097/IAE.0b013e31820f4b4f.
citation: Cheung CS, Wong AW, Lui A, Kertes PJ, Devenyi RG, Lam WC. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections. Ophthalmology. 2012 Aug;119(8):1609-14. doi: 10.1016/j.ophtha.2012.02.014. Epub 2012 Apr 4.