Optimal dose, concentration of moxifloxacin needed to prevent endophthalmitis

Randall J. Olson, MD

It was 1985 in the Middle East, and I was excited to see my one-eyed patient who had struggled with hand motion vision for decades. The penetrating keratoplasty with extracapsular cataract extraction and IOL had gone well, and I knew the bandage unveiling would be dramatic. It was, but not how I had hoped. The no light perception eye that was one sack of pus was nauseating, and I still have nightmares about this case. Turns out a bad bug can lead to a bad outcome — true in 1985 and still true today.

Clearly, our standard care for these cases has improved since 1985 with little controversy. Treatment, however, is not so good that a case avoided is a treasure accepted. So, prophylaxis is a big deal and controversial. A tight, non-leaking wound for prevention and increased surveillance after surgical complications are well understood; however, antibiotic prophylaxis, specifically, dose, route and antibiotic used, has stirred controversy. These are not easy to answer where the incidence is so low. Therefore, our gratitude to two groups, Aravind and Kaiser Permanente Northern California. There are a lot of other large databases to tap, but these two have the volume, granularity, minimal leakage and discipline to give us answers. I salute them.

The Kaiser group has published a new study in American Journal of Ophthalmology on postoperative endophthalmitis. The impressive overall results further confirm that the intraocular route is the way to go, and I sense a diminishing minority who refute this. Sadly, a definitive randomized, prospective clinical trial to eliminate all doubters would be a daunting study, and most would consider it unethical to even consider. The present study makes three interesting findings. Cefuroxime still has some juice and was not inferior to moxifloxacin, even though moxifloxacin is becoming the more commonly used antibiotic in the U.S. Secondly, culture-positive cases are generally resistant organisms for cefuroxime but not for moxifloxacin. Finally, moxifloxacin positive cases have significantly larger anterior chambers.

So, how can cefuroxime still compete with important bacterial resistance that would seem to favor moxifloxacin? Furthermore, the odds that it is superior, while not significant, are 84% with low power to detect a difference, so it has a shot of still being superior in a larger study. How can this be? Its greater therapeutic index means we can put a whole lot of the stuff in the eye so that resistance (remember, resistance is relative) is less of an issue than with moxifloxacin. The study notes that it may have better biokinetics in destroying gram-plus organisms (most of our postoperative endophthalmitis cases) than moxifloxacin, and it is likely that levels above the bacterial minimum inhibitory concentration (MIC) are retained longer than moxifloxacin even if just due to the high starting point.

The fact that positive cultures are cefuroxime resistant are the expected result. Certainly, there was exposure to many more resistant organisms than these few cases, so not is all lost, but maybe cefuroxime with a second antibiotic that fills the void could add additional clout? A lot of this work could be relatively simple in vitro work for efficacy and toxicity, but it may be time to consider this.

The finding that postoperative endophthalmitis cases in which moxifloxacin was the prophylactic agent used had bacteria that are sensitive is surprising. At any dose used in the anterior chamber, the antibiotic levels are going to be way above any MIC for any sensitive organism, so we may have a time to kill issue. Other possibilities include a dilution problem with large anterior chambers, which is indeed the case in this study. However, a larger anterior chamber usually means a myopic eye, and marked anterior chamber deepening with anterior chamber contents blown into the anterior vitreous is a common finding at the end of the case, so this may be another dilution explanation. I also feel myopic eyes are more likely to have a leaky wound and harder to seal, so maybe the antibiotic is leaking out more readily.

Answers always lead to more questions, and that is just the way it is in medicine. What I can conclude is that the Kaiser group has once again helped us understand how we can do a better job of avoiding this awful complication.