Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics

Bacterial Resistance Clinical Trial

Official title:

Conjunctival Floral Resistance in a Single Practice Site Comparing Povidone- Iodine Prep With or Without Post-Intravitreal Injection Second Generation Fluoroquinolones.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02223338
• Other study ID #: 5140215
• Status: Completed
• Phase: N/A
• First received: July 28, 2014
• Last updated: October 29, 2017
• Start date: October 2014
• Est. completion date: May 2016

Study information

• Verified date: October 2017
• Source: Loma Linda University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacterial Resistance

Intervention

Drug:
• Ciprofloxacin
Use of topical ciprofloxacin 4x daily for 3 days after intravitreal injection using standard aseptic techniques with Povidone-Iodine is a common practice intervention in the United States, and is thought by some to reduce the risk of post-injection endophthalmitis.
• Standard Aseptic Technique
Patients in this group will have received Povidone-Iodine Only following injections of anti-VEGF agents at least 3 times in the last 6 months.

Locations

Country	Name	City	State
United States	Loma Linda University of Health Sciences Faculty Medical Offices	Loma Linda	California

Sponsors (1)

Lead Sponsor	Collaborator
Loma Linda University

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Miño De Kaspar H, Hoepfner AS, Engelbert M, Thiel M, Ta CN, Mette M, Schulze-Schwering M, Grasbon T, Sesma-Vea B, Casas JM, Iturralde-Goñi 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. — View 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. Erratum in: Retina. 2012 Jul;32(7):1441. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics	Resistance of all coagulase negative staph and staph aureus species to a panel of commonly used antibiotics will be determined and compared between groups. Resistance will be measured using minimum inhibitory concentrations which will be tested on the Siemens MicroScan instrument by doubling broth dilutions. Antibiotic susceptibility interpretations using the categories "S" for susceptible, "I" for Intermediate and "R" for Resistance based on the Clinical and Laboratory Standards Institute (CLSI) guidelines.; Ciprofloxacin will be tested using the Biomerieux "E test" strip. The test directly quantifies antimicrobial susceptibility in terms of discrete MIC values on a continuous gradient strip. The MIC values are also based on the CLSI guidelines giving interpretations of "S", "I" or "R".; For information on other antibiotics to be tested, please contact the investigator or provide more characters for input.	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	Average Number of Antibiotics to Which Isolated Organisms Were Resistant	Average number of antibiotics to which isolated organisms were resistant, isolated organisms include only coagulase negative Staphylococcus species and Staphylococcus aureus. Antibiotics are those described in the methods section.	Through study completion, average of 4 weeks