Trial Outcomes & Findings for Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics (NCT NCT02223338)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

120 participants

Primary outcome 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.

Results posted on

2017-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	60	60
Overall Study COMPLETED	60	60
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ciprofloxacin n=60 Participants 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.	Standard Aseptic Technique n=60 Participants 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.	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	12 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	41 Participants n=5 Participants	48 Participants n=7 Participants	89 Participants n=5 Participants
Age, Continuous	69.78 years STANDARD_DEVIATION 12.99 • n=5 Participants	74.68 years STANDARD_DEVIATION 13.96 • n=7 Participants	72.23 years STANDARD_DEVIATION 13.65 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	37 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants	60 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

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.

Population: All culture positive samples growing Staphylococcus aureus or coagulase negative Staphylococcus species.

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.

Outcome measures

Outcome measures
Measure	Ciprofloxacin n=18 Participants 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.	Standard Aseptic Technique n=22 Participants 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.
Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics	10 Participants	6 Participants

SECONDARY outcome

Timeframe: Through study completion, average of 4 weeks

Population: All isolates of coagulase negative Staphylococcus and Staphylococcus aureus

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.

Outcome measures

Outcome measures
Measure	Ciprofloxacin n=18 Participants 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.	Standard Aseptic Technique n=22 Participants 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.
Average Number of Antibiotics to Which Isolated Organisms Were Resistant	5.44 antibiotics Standard Deviation 4.29	3.23 antibiotics Standard Deviation 3.66

Adverse Events

Ciprofloxacin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard Aseptic Technique

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. David Sierpina

Loma Linda University

Phone: 9095582154

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place