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Injection volume and intracameral moxifloxacin dose

Arshinoff, Steve A. MD, FRCSC; Modabber, Milad MD, MSc, FRCSC

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Journal of Cataract & Refractive Surgery: January 2020 - Volume 46 - Issue 1 - p 162-163
doi: 10.1097/j.jcrs.0000000000000007
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We read with interest the recently published article of Shorstein and Gardner,1 which highlights the importance of adequate intracameral (IC) moxifloxacin dosing and injection protocols in achieving consistent bactericidal levels for postoperative endophthalmitis prophylaxis in cataract surgery.1 In their study, mathematical models of the anterior chamber (AC) concentrations of moxifloxacin and its elimination rates were calculated following laboratory experimentation with 3 concentrations/injected volumes (0.5%/0.05 mL, 0.5%/0.10 mL, and 0.15%/0.50 mL). Two different AC volumes representing the human pseudophakic eye (0.19 mL and 0.33 mL) for each dosing method were used for their calculations. They concluded that larger injection volumes yielded more reliable aqueous concentrations.

In our recent publication,2 we share the authors' viewpoint that larger injection volumes, with similar total dosing, offer greater precision and reliability. We concluded that an IC injection dose of 600 μg moxifloxacin in 0.4 mL (yielding an AC concentration of about 1200 μg/mL), replacing most of the AC and intracapsular volume as the final step of surgery, enables more consistent antibiotic delivery into the AC. Our proposed IC injection method, after hydration of the main incision to avoid leakage, also enables slight adjustments of the intraocular lens position while injecting. It is important to understand that with IC injection, the IC drug concentration continuously accumulates within the AC by logarithmic growth throughout the injection, gradually approaching the injected solution's concentration as aqueous is replaced, rather than providing a complete exchange or wash, an overly simplistic concept.

We chose our injection technique, because our research led us to results somewhat divergent from those of Shorstein and Gardner.1 Their model's assumption of the human pseudophakic AC volume of 0.19 mL and 0.33 mL was derived from Kanellopoulos and Asimellis,3 whose Scheimpflug imaging measurements were taken 3 months after cataract surgery. This is long after postsurgical equilibration (ie, fibrosis and closure of the capsular bag) has taken place.3 Our calculation of 0.5 mL volume of the AC and a just-evacuated capsular bag after phacoemulsification was derived by summating the preoperative anterior and posterior chamber volumes with that of the mean preoperative capsular bag.2

As a result of smaller AC volume estimates, Shorstein and Gardner1 arrived at a half-life elimination of moxifloxacin from the AC of 1.2 hours. This differs from our calculation4 of 2.89 hours, as illustrated in Figure 1, which is consistent with the literature.5,6 At our calculated abatement rate, the IC moxifloxacin does not dilute to below the bactericidal level of minimum inhibitory concentration greater than 64 μg/mL (the minimum inhibitory concentration of 90% of strains tested of the most moxifloxacin-resistant endophthalmitis pathogens, published in the ARMOR [Antibiotic Resistance Monitoring in Ocular Microorganisms] study) until 7.4 hours (with efficacy to 10.4 hours due to the postantibiotic effect of fluoroquinolones) after injection. This compares favorably with Shorstein and Gardner's1 estimation of 5.4 hours for moxifloxacin levels to fall to the same level.

Figure 1
Figure 1:
Abatement rate of intracameral moxifloxacin 600 μg in 0.4 mL against the background of the MIC90s for the indicated strains from the ARMOR study. The calculated abatement of the concentration of moxifloxacin in the AC shows that the AC level will not fall below the ARMOR-reported MIC90 of MSSA, the most frequent pathogen, for almost 37 hours, or below its mutant prevention concentration for 27 hours. Even for the most resistant strains ever reported, ARMOR CoNS MIC90 = 64 and ARMOR MRSA MIC90 = 32 mg/L, the level of moxifloxacin exceeds those MICs for 7.4 and 10.4 hours, respectively (AC = anterior chamber; ARMOR = Antibiotic Resistance Monitoring in Ocular Microorganisms; CoNS = coagulase-negative Staphylococcus; MIC = minimum inhibitory concentration; MIC90 = minimum inhibitory concentration of 90% of strains tested; MPC = mutant prevention concentration = 10× MIC for dose-dependent fluoroquinolones; MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus).

Practical and ethical limitations preclude frequent postoperative AC sampling of antibiotic levels in humans. Improved understanding of moxifloxacin's complex pharmacokinetics as clinical and bacteriological data accumulate will help us refine mathematical models representing IC abatement profiles. We arrived at greater immediate postphacoemulsification AC volume and IC moxifloxacin half-life than Shorstein and Gardner.1 However, we agree that larger volume IC injection with similar total dose is a more precise and reliable method to achieve consistent antibiotic delivery.

REFERENCES

1. Shorstein NH, Gardner S. Injection volume and intracameral moxifloxacin dose. J Cataract Refract Surg 2019;45:1498–1502
2. Arshinoff SA, Modabber M. Dose and administration of intracameral moxifloxacin for prophylaxis of postoperative endophthalmitis. J Cataract Refract Surg 2016;42:1730–1741
3. Kanellopoulos AJ, Asimellis G. Clear-cornea cataract surgery: pupil size and shape changes, along with anterior chamber volume and depth changes. A Scheimpflug imaging study. Clin Ophthalmol 2014;8:2141–2150
4. Arshinoff SA, Felfeli T, Modabber M. The aqueous level abatement profiles of intracameral antibiotics: a comparative mathematical model of moxifloxacin, cefuroxime and vancomycin with determination of relative efficacies. J Cataract Refract Surg 2019;45:1568–1574
5. Asena L, Akova YA, Gokta MT, Bozkurt A, Yaşar U, Karabay G, Demiralay E. Ocular pharmacokinetics, safety and efficacy of intracameral moxifloxacin 0.5% solution in a rabbit model. Curr Eye Res 2013;38:472–479
6. Libre PE, Mathews S. Eye diseases and conditions—endophthalmitis; researchers from Norwalk hospital describe findings in endophthalmitis (endophthalmitis prophylaxis by intracameral antibiotics: in vitro model comparing vancomycin, cefuroxime and moxifloxacin). Health Med Week 2017;43:1441
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