Bacterial Resistance
Conditions
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.
Interventions
DRUGCiprofloxacin
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.
DRUGStandard 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.
Sponsors
Loma Linda University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Antibiotics to Which Isolated Organisms Were Resistant | Through study completion, average of 4 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin Ciprofloxacin:
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 patients must have been instructed to use post-injection topical ciprofloxacin 0.3% 4x daily for 3 days. On the visit of their next injection, a conjunctival swab will be taken in the inferior fornix prior to instillation of any ophthalmic drops.
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. | 60 |
| Standard Aseptic Technique Standard Aseptic Technique:
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 with povidone-iodine only applied to the injection site and conjunctival fornix prior to injection, but no post-injection antibiotics were given. On the visit of their next injection, a conjunctival swab will be taken in the inferior fornix prior to instillation of any ophthalmic drops.
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. | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Standard Aseptic Technique | Ciprofloxacin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 41 Participants | 89 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 19 Participants | 31 Participants |
| Age, Continuous | 74.68 years STANDARD_DEVIATION 13.96 | 69.78 years STANDARD_DEVIATION 12.99 | 72.23 years STANDARD_DEVIATION 13.65 |
| Region of Enrollment United States | 60 participants | 60 participants | 120 participants |
| Sex: Female, Male Female | 37 Participants | 35 Participants | 72 Participants |
| Sex: Female, Male Male | 23 Participants | 25 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 0 / 60 | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
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.
Time frame: 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.
Population: All culture positive samples growing Staphylococcus aureus or coagulase negative Staphylococcus species.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprofloxacin | Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics | 10 Participants |
| Standard Aseptic Technique | Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics | 6 Participants |
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.
Time frame: Through study completion, average of 4 weeks
Population: All isolates of coagulase negative Staphylococcus and Staphylococcus aureus
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin | Average Number of Antibiotics to Which Isolated Organisms Were Resistant | 5.44 antibiotics | Standard Deviation 4.29 |
| Standard Aseptic Technique | Average Number of Antibiotics to Which Isolated Organisms Were Resistant | 3.23 antibiotics | Standard Deviation 3.66 |