Antibiotic Resistance, Gut Resistome, Ocular Surface Microbiome
Conditions
Brief summary
In this study, the investigators seek to determine the effect of antibiotic use post-surgery on antimicrobial resistance. The investigators will be studying adults (aged 18 or older) who will undergo eye surgery at University of California, San Francisco (UCSF). We seek to gain a better understanding of how antibiotic use during the perioperative period influences local and systemic antibiotic resistance at the individual level.
Detailed description
Antibiotic use has saved millions of lives globally. However, this comes at the cost of selecting for antibiotic-resistant organisms at the individual and the community level. It is estimated that every year, approximately 700,000 deaths are associated with drug resistance globally. This places a significant burden on the public health system and the judicious use of antibiotics is more important than ever before. The proposed masked, randomized controlled trial evaluates the effects of topical antibiotic use on the selection of antibiotic resistance determinants at the local and systemic levels. The results will provide guidance for antibiotic usage in ophthalmology and may have the potential to inform public health policies.
Interventions
DRUGMoxifloxacin (Topical)
We are using moxifloxacin as indicated and as intended for use as an antibiotic during surgery. Frequency of postoperative antibiotics dependent on group randomization.
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Over 18 years of age 2. Undergoing cataract surgeries that would benefit from intracameral antibiotics 3. Able to provide swabs 4. Able to provide consent 5. Surgery of the second eye occurs at least 8 weeks after surgery of the first eye
Exclusion criteria
1. Same-day bilateral cataract surgeries 2. On immunosuppression medication such as Prednisone, Methotrexate, Cellcept, or anti-TNF inhibitors within past 3 months 3. On systemic antibiotic within past 3 months 4. On topical antibiotics within past 8 weeks 5. Allergies to fluoroquinolone 6. Patients needing glaucoma drainage device or trabeculectomy 7. Inability to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antimicrobial Resistance (AMR) of Conjunctiva at 1 Week | 1 Week | Normalized read counts (reads per million reads or rM) for fluoroquinolone resistance determinants from DNA deep sequencing for the conjunctival swabs at 1 week, which represent the abundance of resistance in the sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antimicrobial Resistance (AMR) of Nasopharynx at 1 Week | 1 week | Normalized read counts (reads per million reads or rM) for fluoroquinolone resistance determinants from DNA deep sequencing for the nasopharyngeal swabs at 1 week, which represent the abundance of resistance in the sample. |
| Shannon's Index | 1 week | Conjunctival samples were evaluated for microbiome heterogeneity at 1 week. Shannon's index (H) represents a measure of bacteria species heterogeneity and is calculated through the following formula, H = -sum(pi\*log(b)\*pi), where pi is the proportional abundance of species and b is the base of the logarithm. Here, we are using the natural logarithm. The Shannon's Index ranges from 0 to ln(S), where S is the number of species in the community. We report the exponentiated Shannon's Index, which is expressed as the effective number of species, which ranges from 1 to S species. An effective number of species of 1 indicates that 1 species dominates the microbiome. The greater the effective number of species, the greater the heterogeneity of species abundance in the microbiome. Low heterogeneity of bacterial species in the microbiome is a proxy for a less healthy system. |
| Simpson's Index | 1 week | Conjunctival samples were evaluated for microbiome heterogeneity at 1 week. Simpson's index (D) represents a measure of bacteria species heterogeneity and is calculated through the following formula, D = sum(pi\^2), where pi is the proportional abundance of species. The Simpson's Index ranges from 0 to 1, where 0 represents infinite heterogeneity and 1 represents no heterogeneity. We report the inverse of Simpson's Index, which is expressed as the effective number of species, which ranges from 1 to S species. An effective number of species of 1 indicates that 1 species dominates the microbiome. The greater the effective number of species, the greater the heterogeneity of species abundance in the microbiome. Low heterogeneity of bacterial species in the microbiome is a proxy for a less healthy system. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics intraoperative/ intracameral antibiotic (moxifloxacin) only; no postoperative topical antibiotic drops
Moxifloxacin (Topical): We are using moxifloxacin as indicated and as intended for use as an antibiotic during surgery. Frequency of postoperative antibiotics dependent on group randomization. | 36 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week intraoperative/ intracameral antibiotic (moxifloxacin); postoperative topical antibiotic drops once a day for 1 week
Moxifloxacin (Topical): We are using moxifloxacin as indicated and as intended for use as an antibiotic during surgery. Frequency of postoperative antibiotics dependent on group randomization. | 36 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week intraoperative/ intracameral antibiotic (moxifloxacin); postoperative topical antibiotic drops four times a day for 1 week
Moxifloxacin (Topical): We are using moxifloxacin as indicated and as intended for use as an antibiotic during surgery. Frequency of postoperative antibiotics dependent on group randomization. | 36 |
| Total | 108 |
Baseline characteristics
| Characteristic | Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 6 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 31 Participants | 30 Participants | 95 Participants |
| Age, Continuous | 69 years | 69 years | 69 years | 69 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 13 Participants | 18 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 5 Participants | 4 Participants | 17 Participants |
| Race (NIH/OMB) White | 20 Participants | 17 Participants | 12 Participants | 49 Participants |
| Region of Enrollment United States | 36 Participants | 36 Participants | 36 Participants | 108 Participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 15 Participants | 49 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 21 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 0 / 36 | 0 / 36 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
Antimicrobial Resistance (AMR) of Conjunctiva at 1 Week
Normalized read counts (reads per million reads or rM) for fluoroquinolone resistance determinants from DNA deep sequencing for the conjunctival swabs at 1 week, which represent the abundance of resistance in the sample.
Time frame: 1 Week
Population: Enrolled patients who presented to their 1-week follow-up. 9 patients did not present to the 1 week follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Antimicrobial Resistance (AMR) of Conjunctiva at 1 Week | 0 reads per million reads | Standard Deviation 0 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Antimicrobial Resistance (AMR) of Conjunctiva at 1 Week | 0 reads per million reads | Standard Deviation 0 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Antimicrobial Resistance (AMR) of Conjunctiva at 1 Week | 0 reads per million reads | Standard Deviation 0 |
Comparison: Used the Kruskal-Wallis (nonparametric one-way ANOVA), comparing all 3 arms. Note that for each individual, a single number (normalized read) is obtained.p-value: 1Kruskal-Wallis
Secondary
Antimicrobial Resistance (AMR) of Nasopharynx at 1 Week
Normalized read counts (reads per million reads or rM) for fluoroquinolone resistance determinants from DNA deep sequencing for the nasopharyngeal swabs at 1 week, which represent the abundance of resistance in the sample.
Time frame: 1 week
Population: Enrolled patients who presented to their 1-week follow-up. 9 patients did not present to the 1 week follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Antimicrobial Resistance (AMR) of Nasopharynx at 1 Week | 0 reads per million reads | Standard Deviation 0 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Antimicrobial Resistance (AMR) of Nasopharynx at 1 Week | 0 reads per million reads | Standard Deviation 0 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Antimicrobial Resistance (AMR) of Nasopharynx at 1 Week | 0 reads per million reads | Standard Deviation 0 |
Secondary
Shannon's Index
Conjunctival samples were evaluated for microbiome heterogeneity at 1 week. Shannon's index (H) represents a measure of bacteria species heterogeneity and is calculated through the following formula, H = -sum(pi\*log(b)\*pi), where pi is the proportional abundance of species and b is the base of the logarithm. Here, we are using the natural logarithm. The Shannon's Index ranges from 0 to ln(S), where S is the number of species in the community. We report the exponentiated Shannon's Index, which is expressed as the effective number of species, which ranges from 1 to S species. An effective number of species of 1 indicates that 1 species dominates the microbiome. The greater the effective number of species, the greater the heterogeneity of species abundance in the microbiome. Low heterogeneity of bacterial species in the microbiome is a proxy for a less healthy system.
Time frame: 1 week
Population: Enrolled patients who presented to their 1-week follow-up. 9 patients did not present to the 1 week follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Shannon's Index | 14 index | Standard Deviation 5 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Shannon's Index | 14 index | Standard Deviation 5 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Shannon's Index | 17 index | Standard Deviation 6 |
Secondary
Simpson's Index
Conjunctival samples were evaluated for microbiome heterogeneity at 1 week. Simpson's index (D) represents a measure of bacteria species heterogeneity and is calculated through the following formula, D = sum(pi\^2), where pi is the proportional abundance of species. The Simpson's Index ranges from 0 to 1, where 0 represents infinite heterogeneity and 1 represents no heterogeneity. We report the inverse of Simpson's Index, which is expressed as the effective number of species, which ranges from 1 to S species. An effective number of species of 1 indicates that 1 species dominates the microbiome. The greater the effective number of species, the greater the heterogeneity of species abundance in the microbiome. Low heterogeneity of bacterial species in the microbiome is a proxy for a less healthy system.
Time frame: 1 week
Population: Enrolled patients who presented to their 1-week follow-up. 9 patients did not present to the 1 week follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Simpson's Index | 7 index | Standard Deviation 3 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Simpson's Index | 8 index | Standard Deviation 4 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Simpson's Index | 9 index | Standard Deviation 4 |
Secondary
Simpson's Index
Nasopharyngeal samples were evaluated for microbiome heterogeneity at 1 week. Simpson's index (D) represents a measure of bacteria species heterogeneity and is calculated through the following formula, D = sum(pi\^2), where pi is the proportional abundance of species. The Simpson's Index ranges from 0 to 1, where 0 represents infinite heterogeneity and 1 represents no heterogeneity. We report the inverse of Simpson's Index, which is expressed as the effective number of species, which ranges from 1 to S species. An effective number of species of 1 indicates that 1 species dominates the microbiome. The greater the effective number of species, the greater the heterogeneity of species abundance in the microbiome. Low heterogeneity of bacterial species in the microbiome is a proxy for a less healthy system.
Time frame: 1 week
Population: Enrolled patients who presented to their 1-week follow-up. 9 patients did not present to the 1 week follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intraoperative Antibiotics (Abx) Only; no Postoperative Topical Antibiotics | Simpson's Index | 6 index | Standard Deviation 5 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Four Times a Day for 1 Week | Simpson's Index | 8 index | Standard Deviation 7 |
| Intraoperative Antibiotics (Abx); Postoperative Topical Antibiotics Once a Day for 1 Week | Simpson's Index | 5 index | Standard Deviation 4 |