Highlights
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No statistical difference exists in endophthalmitis rate between moxifloxacin and cefuroxime.
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Successful endophthalmitis prophylaxis depends on intracameral moxifloxacin dose.
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Intracameral cefuroxime does not cover Enterococcus and Pseudomonas .
Purpose
To estimate the association of cefuroxime and moxifloxacin in relation to the occurrence of endophthalmitis following phacoemulsification cataract surgery.
Design
Retrospective clinical cohort study.
Methods
We studied patients with noncomplex phacoemulsification cataract surgery in Kaiser Permanente Northern California during 2014-2019. Data were obtained for acute, postoperative endophthalmitis within 90 days of phacoemulsification, including culture and antibiogram results, intracameral and topical antibiotic agent, and dose. In a post hoc analysis, we also examined preoperative anterior chamber depth (ACD) and postoperative anterior chamber volume (ACV).
Results
Of 216,141 surgeries, endophthalmitis occurred in 0.020% of moxifloxacin-injected eyes and 0.013% of cefuroxime eyes (relative risk 1.62 with 95% CI 0.82-3.20, P = .16). Of the 34 (0.016%) cases of endophthalmitis, cefuroxime 1 mg was injected into 13 eyes and moxifloxacin 0.1% into 21 eyes. Organisms with antibiograms were identified in 12 (35%) cases. Of these, bacteria recovered from cefuroxime-injected eyes were resistant to cefuroxime in all cases (4/4), with Enterococcus comprising half of these. In eyes injected with moxifloxacin 0.1%, 6 out of 7 organisms were sensitive to moxifloxacin injected with 0.1 mL and in 1 eye injected with 1 mL. Streptococcus was the most common organism recovered (6/9) in moxifloxacin-injected eyes. Preoperative ACD and postoperative calculated ACV were higher in eyes injected with moxifloxacin.
Conclusions
Endophthalmitis cases with positive cultures were generally related to organism resistance in cefuroxime eyes but to sensitive organisms in moxifloxacin eyes. Moxifloxacin doses may have been insufficient in eyes with larger ACV.
E ndophthalmitis is a rare, sight-threatening complication following cataract surgery. Recent evidence suggests that topical antibiotic instillation reduces the incidence by half, while the addition of intracameral antibiotic injection further reduces risk by up to 7-fold.
The European Medicines Agency approved cefuroxime for intracameral injection during cataract surgery in 2012. Commercial preparations of moxifloxacin have been available in India since 2013. Despite the continued lack of an FDA-approved product in the United States, surgeons are increasingly adopting this technique, requiring the sourcing of compounded antibiotic.
The established dosage of cefuroxime injection is 1 mg in 0.1 mL (1%) solution. , , Moxifloxacin is currently more commonly injected in the United States for endophthalmitis prophylaxis ; however, there is no established standard dose as yet.
On average, more than 35,000 cataract surgeries are performed annually in Kaiser Permanente Northern California. During ongoing monthly postphacoemulsification endophthalmitis surveillance in 2018, we identified a trend of increasing cases (Supplemental Figure 1; Supplemental Material available at AJO.com). We undertook this study to identify factors that could explain this trend, including antibiotic drug choice.
Methods
This study was approved by the Kaiser Foundation Research Institute’s institutional review board and the informed consent requirement was waived owing to the retrospective design. The study was conducted according to the principles described in the Declaration of Helsinki.
Setting
Kaiser Permanente Northern California is a closed, staff-model, integrated healthcare delivery system with capitated payment that provides comprehensive care to 4 million persons, or 40% of insured individuals in the region. Physicians practice in 1 medical group and use the same type of office and surgical equipment. Some techniques and practices, such as injection of an intracameral antibiotic during cataract surgery, are standardized, while others, such as antibiotic choice, are selected by the surgeon according to their own preference.
Study Population
We included phacoemulsification surgeries performed between January 1, 2014 and December 31, 2019. Cataract surgeries that were combined with planned retinal procedures, corneal transplants, or glaucoma surgery were excluded, as were surgeries performed by retinal or oculoplastic specialists.
Data Collection
Acute, postoperative, infectious endophthalmitis was defined as occurring after the first postoperative day through the 90th day after phacoemulsification and was analyzed through March 30, 2020. Preliminary endophthalmitis was defined as having 1 or more of the diagnostic codes listed in the Supplemental Table (Supplemental Material available at AJO.com). Endophthalmitis was confirmed when the diagnosis was recorded by a retina specialist within 90 days of surgery and treatment included injection of intravitreal antibiotics. Endophthalmitis cases were validated using medical record review by a study ophthalmologist (N.S.), including review of the operative report, follow-up visits, visits to retinologists, microbiology results, and other pertinent information.
Intracameral agent and dosage were obtained from electronic pharmacy records and validated from the operative report. Ambiguities in dosage were confirmed with the operating surgeon. Topical antibiotics dispensed were obtained from pharmacy records.
We conducted a post hoc analysis of preoperative biometric measurements in eyes with endophthalmitis that included preoperative anterior chamber depth (ACD), central corneal thickness (CCT), white-to-white length (WTW), axial length (AL), lens thickness (LT), and corneal radius (R), obtained from the Lenstar LS 900 (Haag-Streit, Mason, Ohio, USA). The intraocular lens (IOL) model was obtained from the operative reports. We calculated the postoperative, pseudophakic ACD using Olsen’s formula. We then calculated the estimated pseudophakic anterior chamber volume (ACV) as a dome cap using the aqueous depth (ACD – CCT) as the height and the WTW as the dome base ( https://www.fxsolver.com/browse/formulas/Volume+of+Spherical+Dome+%28or+cap%29 ).
Relative risk and 95% confidence intervals (CI) were computed to estimate the association between cefuroxime vs moxifloxacin injection and endophthalmitis. We used the Student t test to compare days to diagnosis and pseudophakic ACD and ACV between cefuroxime- and moxifloxacin-injected eyes and χ 2 test to compare complication rates between groups.
Results
There were 34 cases of endophthalmitis in 216,141 eye surgeries (0.016%) ( Table 1 ). An injected agent other than cefuroxime and moxifloxacin was injected in 7,817 eyes (3.6%), while an intracameral agent could not be identified in 3,669 surgical cases (1.7%). No eyes in these 2 groups developed endophthalmitis. The group injected with moxifloxacin experienced an infection rate of 0.020%, which was slightly higher than the cefuroxime group (0.013%) (relative risk 1.62 with 95% CI 0.82-3.20, P = .16).
| Injection Agent | Cases/Surgeries | Endophthalmitis Frequency | RR (95% CI) |
|---|---|---|---|
| Cefuroxime | 13/97,801 | 0.013% | Ref |
| Moxifloxacin | 21/106,854 | 0.020% | 1.62 (0.82-3.20) P = .16 |
| Total | 34/216,141 a | 0.016% | – |
a Includes 7,817 eyes treated with antibiotics other than cefuroxime and moxifloxacin and 3,669 eyes with no intracameral injection.
Of the 34 endophthalmitis cases, 13 eyes were injected with cefuroxime, 19 eyes with 0.1 mL of moxifloxacin 0.1%, 1 eye with 0.5 mL of moxifloxacin 0.1%, and 1 eye with 1 mL of moxifloxacin 0.1% ( Table 2 ). Laboratory testing was conducted in 33 cases and in 14 of these (42%) an organism was identified.
| Year | Organism | ICA Sensitivity | Topical Agent | Topical Sensitivity | Intraoperative Complications | Days to Diagnosis | Preop ACD | Postop ACV |
|---|---|---|---|---|---|---|---|---|
| Cefuroxime 1 mg | ||||||||
| 2014 | Enterococcus | R | None | NA | None | 3 | 2.79 | NC |
| 2015 | No growth | Tobramycin | None | 22 | 2.88 | 0.242 | ||
| 2015 | Pseudomonas | R | None | NA | None | 3 | 2.92 | 0.216 |
| 2015 | Enterococcus | R | Ofloxacin | NR | None | 6 | 2.54 | 0.228 |
| 2016 | Coag neg Staph | R | Poly/trim | R | None | 28 | 2.16 | 0.216 |
| 2017 | No growth | Poly/trim | None | 14 | 3.06 | 0.311 | ||
| 2017 | No growth | Poly/trim | None | 22 | 2.92 | 0.272 | ||
| 2017 | Strep | NR | Ofloxacin | S | None | 6 | 3.77 | 0.303 |
| 2017 | No growth | Poly/trim | Retained lens | 33 | 3.58 | 0.286 | ||
| 2017 | Not done | Poly/trim | Retained lens | 11 | 3.27 | 0.224 | ||
| 2018 | No growth | Poly/trim | None | 56 | 2.41 | 0.226 | ||
| 2018 | No growth | Poly/trim | None | 4 | 2.55 | 0.249 | ||
| 2018 | No growth | Poly/trim | None | 67 | 3.14 | 0.297 | ||
| Moxifloxacin 0.1% (0.1 mL) | ||||||||
| 2014 | No growth | Gatifloxacin | None | 49 | 3.23 | NC | ||
| 2014 | No growth | Gatifloxacin | None | 38 | 3.06 | 0.245 | ||
| 2014 | Strep | S | Gatifloxacin | S | None | 19 | 3.37 | 0.299 |
| 2014 | No growth | Poly/trim | None | 6 | 3.39 | 0.292 | ||
| 2015 | Strep | S | Ofloxacin | S | Vitreous loss | 26 | 2.95 | 0.244 |
| 2015 | No growth | Ofloxacin | None | 16 | 2.62 | 0.214 | ||
| 2016 | Enterococcus | R | Gatifloxacin | R | Retained lens | 3 | 3.03 | 0.325 |
| 2016 | Strep | NR | Gatifloxacin | NR | None | 23 | 3.63 | 0.340 |
| 2016 | No growth | Poly/trim | Retained lens | 5 | 2.56 | NC | ||
| 2017 | Strep | S | Poly/trim | NR | None | 26 | 3.95 | 0.315 |
| 2017 | Staph aureus | S | Ofloxacin | S | None | 29 | 3.81 | 0.371 |
| 2018 | No growth | Poly/trim | None | 21 | 3.32 | 0.307 | ||
| 2018 | No growth | None | None | 27 | 2.86 | 0.231 | ||
| 2018 | No growth | Gatifloxacin | None | 31 | 3.61 | 0.354 | ||
| 2018 | Staph aureus | S | Poly/trim | S | None | 32 | 2.79 | 0.255 |
| 2018 | No growth | None | None | 31 | 3.73 | 0.347 | ||
| 2019 | No growth | None | None | 5 | 3.09 | 0.276 | ||
| 2019 | Strep | S | Poly/trim | NR | None | 3 | 3.53 | 0.268 |
| 2019 | No growth | Neomycin/poly | None | 3 | 4.61 | 0.335 | ||
| Moxifloxacin 0.1% (≥0.5 mL) a | ||||||||
| 2018 | Strep | S | Poly/trim | NR | None | 7 | 3.55 | 0.343 |
| 2019 | No growth | Poly/trim | None | 3 | 5.71 | 0.572 | ||
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