Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics (NCT02223338), a non-randomized na study. The primary outcome is Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics.

2. Clinical Question

The clinical question concerns antibiotic resistance in organisms cultured from the eye, rather than a clinical infection outcome. The study planned to compare resistance between patients receiving ciprofloxacin and those receiving standard aseptic technique. Its stated objective was to help determine how to prevent infection while limiting antibiotic resistance in patients receiving eye injections.

The registry describes a single-practice-site study and a non-randomized, parallel-group design. Since allocation was not randomized, differences between the groups could reflect differences in the patients or their care, as well as any difference related to the intervention. The registry explicitly cautions that the arms are not a like-for-like control comparison. The record does not report methods for adjusting for such differences.

The primary endpoint focuses on resistance among specified organisms that grew in culture. It therefore does not describe resistance among all participants, all bacteria, or all eye infections. The registry record does not report how many samples grew the target organisms or how many participants met the resistance endpoint.

3. Trial Design

This completed study is registered as NCT02223338, with the title “Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics.” Its official title describes conjunctival flora resistance in a single practice site comparing povidone-iodine preparation with or without post-intravitreal injection second generation fluoroquinolones. Loma Linda University is listed as the sponsor. The study began in 2014-10, had primary completion in 2016-05, and has a status of completed. The phase is listed as NA.

The registry lists an enrollment of 120 and two parallel arms: ciprofloxacin and standard aseptic technique. Allocation is non-randomized and masking is none. These design features matter when interpreting a between-group comparison. Without random allocation, measured and unmeasured differences between participants may be associated with both group membership and the outcome. The record does not report a statistical adjustment plan or details that would establish that the groups were otherwise comparable.

The listed population includes adults over 18 with specified retinal conditions who had received at least 3 monthly intravitreal injections. The arm descriptions are incomplete, ending during a description of anti-Vascular Endothelial G... treatment. Full eligibility criteria and complete intervention procedures are not reported in the registry record. The study description says ocular samples were collected before ophthalmic medications, cultured, and assessed for organisms and antibiotic susceptibility. The described culture follow-up was 7 days.

The primary outcome is the number of participants with resistance of ocular flora to commonly used post-injection prophylactic antibiotics. The secondary outcome is the average number of antibiotics to which isolated organisms were resistant. The registry lists two outcome measures in total but does not provide an analysis record for either. No outcome estimates, group comparison, confidence intervals, or p-values are reported in the registry record. Completion status alone does not establish what results were found or how the study findings were analyzed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All culture positive samples growing Staphylococcus aureus or coagulase negative Staphylococcus species.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Resistance of Ocular Flora to Commonly Used Post-injection Prophylactic Antibiotics, measured over 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..

The primary endpoint counts participants whose ocular flora met the registry’s definition of antibiotic resistance. Resistance testing was planned for Staphylococcus aureus and coagulase negative Staphylococcus species. The stated analysis population for this endpoint is all culture-positive samples growing one of those organisms. The endpoint is therefore restricted to participants and organisms meeting those culture conditions; it is not a count of all enrolled participants with any bacterial growth or infection.

The registry describes laboratory susceptibility testing using minimum inhibitory concentrations and interpretations categorized as susceptible, intermediate, or resistant under Clinical and Laboratory Standards Institute guidelines. It also describes ciprofloxacin testing with an E test strip. These laboratory procedures are intended to classify how susceptible an organism is to antibiotics, rather than to measure symptoms, vision, or clinical infection.

A participant count can communicate how many people met a defined resistance criterion, but its interpretation depends on the number of eligible culture-positive participants and the rule used to classify participant-level resistance across organisms and antibiotics. The registry record does not report those detailed aggregation rules or the resulting counts. It also does not state which specific antibiotics beyond ciprofloxacin were included in the panel; the description directs readers to contact the investigator for more information. Thus, the endpoint’s planned meaning is identifiable, while the observed result and some operational details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a parallel-group study with non-randomized allocation and no masking. A parallel design means participants are assigned to one of the study groups for comparison rather than crossing through both interventions. In a randomized trial, allocation by chance is used to help balance known and unknown participant characteristics on average. Here, allocation was not randomized, so group differences can be entangled with differences in participant characteristics or clinical care. The registry explicitly cautions that the arms are not a like-for-like control comparison. The assignment mechanism and any methods to address confounding are not reported in the registry record.

What does the endpoint count?

The primary endpoint is a participant count: the number of participants with resistance of ocular flora to commonly used post-injection prophylactic antibiotics. The described target organisms are Staphylococcus aureus and coagulase negative Staphylococcus species, and the endpoint population is culture-positive samples growing those organisms. This distinction matters because a laboratory result for an organism is not automatically equivalent to a participant-level endpoint. A participant might have more than one isolate or susceptibility result, so an analysis needs a rule for translating laboratory observations into a participant count. That rule is not reported in the registry record.

The secondary outcome is the average number of antibiotics to which isolated organisms were resistant. A mean summarizes a set of counts, but its interpretation depends on which organisms and antibiotics are included, how multiple isolates are handled, and whether the measure is calculated per participant or per isolate. Those details are not reported in the registry record. The outcome description also does not include the resulting average.

How should laboratory susceptibility be understood?

The registry describes minimum inhibitory concentration testing, which assesses the lowest concentration of an antibiotic that inhibits visible growth under specified laboratory conditions. The registry says testing is to be interpreted as susceptible, intermediate, or resistant using Clinical and Laboratory Standards Institute guidelines. It describes Siemens MicroScan testing by doubling broth dilutions for the specified staphylococcal species, and ciprofloxacin testing with a Biomerieux E test strip. The E test produces discrete minimum inhibitory concentration values along a continuous gradient strip. These laboratory classifications characterize isolate susceptibility; they are not direct measures of whether a participant developed an infection or experienced a clinical benefit.

The record says cultures would be followed for 7 days and considered sterile if no growth was recorded at that time. This defines a culture observation period, but it does not tell readers how many cultures were positive, how many were sterile, or whether all participants posted an analyzable sample. Those counts and details are not reported in the registry record.

What does statistical uncertainty mean?

In general, an estimate describes a quantity calculated from observed data, while a confidence interval describes a range of values reasonably compatible with the data under the statistical model and its assumptions. A narrower interval indicates greater precision, and a wider interval indicates greater uncertainty. A p-value, in general, measures how unusual the observed data would be under a specified null hypothesis and model; it does not measure the probability that a treatment is effective. The registry record reports no estimates, confidence intervals, or p-values for the outcomes, so these concepts cannot be applied to a reported treatment comparison.

For a binary participant outcome such as whether resistance was identified, comparisons may be expressed using counts, proportions, or measures of association. The choice of measure, the statistical test, any covariate adjustment, and the handling of sparse outcome counts are not reported in the registry record. No particular method should be presumed from the endpoint type alone.

Why can over-dispersion matter?

In general, over-dispersion occurs when count data vary more than a statistical model expects. For example, participants may differ substantially in their number of resistant isolates or in the number of antibiotics for which resistance is observed. If a model assumes less variability than the data contain, standard errors may be too small and uncertainty intervals may be too narrow. A suitable analysis may need to account for the way observations cluster within participants or for extra variability. The registry does not report a count model or an over-dispersion assessment; this general issue should not be mistaken for a description of the trial’s actual analysis.

The planning assumptions described for sample-size calculations are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The calculations are described as planning illustrations based on a stated fraction of an observed effect. General planning calculations of this kind can explore the sample size needed under an assumed effect and model. They are not observed power, and they do not demonstrate that the study had a particular probability of detecting an effect after the data were collected. The registry does not report the observed effect or the calculated sample-size values.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Ciprofloxacin", "Standard Aseptic Technique")
n      <- c(18, 22)
events <- c(10, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Ciprofloxacin  18  10  55.6  30.8  78.5  33.7  75.4  33.5  75.6
ARM  Standard Aseptic Technique  22  6  27.3  10.7  50.2  13.2  48.2  13.2  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and a secondary outcome, but it does not report an analysis plan or analysis records. It does not state whether there were additional comparisons, subgroup analyses, interim analyses, or a prespecified hierarchy for interpreting multiple outcomes. Those details are not reported in the registry record.

Multiplicity is a general concern when several outcomes or statistical comparisons are examined. Conducting many tests can increase the chance that at least one result appears statistically unusual even when there is no underlying effect. Study plans can address this through prespecified primary outcomes, adjustment procedures, or a clear distinction between confirmatory and exploratory analyses. No multiplicity procedure is reported, so it is not possible to determine how multiple outcomes or comparisons were handled.

The registry does not report the number of participants with evaluable cultures, the number of culture-positive samples, or the number included in the primary endpoint analysis. It also does not report reasons for missing samples, missing laboratory results, withdrawals, or exclusions after enrollment. Therefore, the completeness of outcome data and the analysis population cannot be assessed from the registry record.

In general, missing data can affect both the precision and the validity of an estimate. The consequences depend on why data are missing and whether missingness is related to participant characteristics or outcomes. A complete-case analysis, imputation, or another approach would each rely on assumptions that need to be described. The record does not report any missing-data method, and none should be inferred.

The registry states an enrollment of 120 and reports 60 participants at risk in each group for adverse-event summaries. Those safety denominators do not establish the number with usable resistance data. Outcome-specific denominators, analysis populations, exclusions, and handling of multiple isolates are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event listing reports 60 participants at risk in the ciprofloxacin group and 60 in the standard aseptic technique group. For both groups, the recorded counts are zero serious adverse events, zero other adverse events, and zero deaths. These are the counts entered in the registry safety summary.

A zero recorded count means that no events are listed in that category for the stated group. It does not establish that every possible adverse event was actively assessed in the same way, nor does it by itself show that the groups have identical safety profiles. The registry record does not report the adverse-event collection methods, event definitions, observation period for safety, or whether participants with incomplete follow-up were included.

The safety summary should also be kept separate from the study’s resistance outcomes. The absence of listed adverse events does not indicate whether cultures grew bacteria or whether organisms were resistant to antibiotics. No serious adverse-event terms are listed, and the record does not provide event narratives or additional detail. The figures are descriptive registry counts, not a reported statistical comparison or a basis for conclusions about comparative safety.

13. What the Result Does, and Does Not, Mean

The study addresses an important statistical distinction: antibiotic resistance in cultured ocular flora is not the same outcome as infection prevention. The registry’s primary endpoint concerns participants with resistant flora among samples growing specified staphylococcal species. It does not directly count endophthalmitis, other clinical infections, visual outcomes, or all bacterial organisms.

The record establishes that the study was completed, enrolled 120 participants, and compared ciprofloxacin with standard aseptic technique in a non-randomized parallel design. It also describes laboratory methods for classifying antibiotic susceptibility. These details explain what the investigators intended to study, but they do not reveal the observed resistance findings. No outcome analyses are listed, and group results are not reported in the registry record.

Accordingly, the record does not establish whether one group had more or less resistance, whether any difference was statistically distinguishable from chance, or how precisely a difference was estimated. It also cannot show whether the interventions changed the risk of infection. The registry describes the study’s rationale and objective but does not report the results needed to answer those questions.

The non-randomized design further limits causal interpretation. Even if a group difference were reported, it could reflect differences in the participants, treatment history, clinical care, or other factors. The registry does not report an adjustment strategy that would allow readers to assess how such differences were addressed. The incomplete arm descriptions also leave details of the intervention and eligibility criteria uncertain.

Any planning sample-size calculations should be read as illustrations under assumptions, not as evidence that a particular outcome was detected or not detected. A planning calculation is distinct from an observed effect estimate, and it is not a retrospective measure of observed power. Since the registry does not report the outcome estimates or planning values, neither the magnitude nor precision of a resistance comparison can be assessed.

14. Why This Trial Matters Statistically

This study is statistically relevant because it asks about antibiotic resistance in a setting where local patterns of antimicrobial susceptibility may be of interest. Its endpoint is laboratory based, requiring the interpretation of culture growth and susceptibility testing before a participant-level resistance count can be defined. That chain from sample collection to organism identification to participant-level outcome makes clear endpoint definitions and denominators particularly important.

The comparison also illustrates why study design is central to interpreting clinical research. Non-randomized allocation can leave groups different before the intervention, so a simple contrast may combine intervention-related variation with baseline or care-related differences. The registry itself cautions that these are not like-for-like control arms. Statistical adjustment can sometimes address measured differences, but the registry does not report whether such methods were used, and unmeasured differences can remain.

The study’s outcomes also show why one should distinguish a biological or laboratory marker from a clinical event. Resistance among cultured organisms may be relevant to antimicrobial stewardship questions, but it is not interchangeable with infection rates or patient outcomes. A careful interpretation needs the outcome definition, the number of samples and participants contributing data, the group estimates, and their uncertainty.

Finally, the record demonstrates the difference between a completed study registration and a report of analyzed results. Study dates, enrollment, planned endpoints, and safety counts give useful context, yet they do not answer the comparative research question when outcome analyses are absent. Transparent reporting of denominators, analysis populations, estimates, uncertainty, and methods would be needed to evaluate the resistance comparison statistically.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpreting the registry record is that it contains no analysis records and no reported results for either outcome. There are no group-specific resistance counts, outcome denominators, estimates, uncertainty intervals, or statistical tests. The listed adverse-event counts do not fill this gap because they describe a different set of outcomes.

The design is non-randomized and unmasked. The registry warns that the arms are not a like-for-like control comparison, and it does not report how participants were allocated or whether differences between groups were adjusted for. This limits the ability to interpret a potential group contrast as an effect of the intervention.

The population and intervention descriptions are incomplete. The arm descriptions are truncated, and the full eligibility criteria, treatment schedules, doses, and procedural details are not reported in the registry record. The record describes the title’s comparison as involving povidone-iodine preparation with or without post-injection second generation fluoroquinolones, but the complete implementation details cannot be established from the available descriptions.

The primary endpoint is restricted to culture-positive samples growing Staphylococcus aureus or coagulase negative Staphylococcus species. The record does not report the number of positive cultures or the rules for converting multiple isolates and susceptibility results into a participant-level outcome. The full antibiotic panel is also not described; the registry directs readers to contact the investigator for more information.

Finally, the registry does not report outcome missingness, analysis populations, multiplicity handling, or statistical methods for comparing groups. Without those details and the outcome results, precision, robustness, and generalizability cannot be evaluated.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bacterial Resistance in Patients Receiving Post-Intravitreal Injection Antibiotics — NCT02223338.
• Registry record last updated 2017-11-07; status last verified 2017-10.
• Results first posted 2017-11-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT02223338 is a completed, non-randomized, parallel-group study sponsored by Loma Linda University. It enrolled 120 participants and compared ciprofloxacin with standard aseptic technique; masking is listed as none. The registry lists the primary outcome as the number of participants with resistance of ocular flora to commonly used post-injection prophylactic antibiotics and the secondary outcome as the average number of antibiotics to which isolated organisms were resistant.

The primary endpoint concerns culture-positive samples growing Staphylococcus aureus or coagulase negative Staphylococcus species. The registry describes susceptibility testing and a culture follow-up period of 7 days. The safety summary lists 60 participants at risk in each group, with zero serious adverse events, zero other adverse events, and zero deaths in both groups.

No outcome analysis records or resistance results are reported in the registry record. The allocation was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. The study question and planned laboratory endpoint can be described, but comparative resistance findings cannot be interpreted without reported outcome estimates and analysis details.