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Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2021 ASCRS member survey

Chang, David F. MD; Rhee, Douglas J. MD

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Journal of Cataract & Refractive Surgery: January 2022 - Volume 48 - Issue 1 - p 3-7
doi: 10.1097/j.jcrs.0000000000000757
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The method and necessity of routine antibiotic prophylaxis to prevent endophthalmitis after cataract surgery remain controversial. Topical antibiotic prophylaxis has been universally used off-label for decades despite the lack of level I supporting evidence. The results from the only large, multicenter, prospective randomized controlled trial of intraocular antibiotic prophylaxis were published 15 years ago.1–3 Demonstrating clinical efficacy of intracameral (IC) cefuroxime prophylaxis for cataract surgery, the landmark ESCRS clinical trial led to European Medicines Agency but not the U.S. Food and Drug Administration (FDA) approval of a premixed intraocular cefuroxime formulation (Aprokam, Laboratoires Théa).3,4

A 2007 ASCRS member survey of antibiotic prophylaxis practice patterns for endophthalmitis was conducted less than 1 year after the publication of the ESCRS trial results.5 Of >1300 respondents, 30% were using IC antibiotic prophylaxis. Half of them directly injected the antibiotic into the anterior chamber and half placed the antibiotic in the irrigation bottle. When the ASCRS survey was repeated in 2014 with 1147 respondents, a substantial shift in opinion and practice pattern emerged.6 The percentage of surgeons using IC antibiotic prophylaxis increased from 30% to 50% and most were using direct IC injection compared with placing antibiotics in the irrigating solution (84% vs 16% in 2014; 52% vs 48% in 2007). Vancomycin was the most frequently used intraocular antibiotics in both surveys.

Additional studies on antibiotic prophylaxis have provided new information since 2014.7–17 These include a case series of hemorrhagic occlusive retinal vasculitis associated with vancomycin and large retrospective studies on IC moxifloxacin prophylaxis and the potential benefit of topical antibiotic prophylaxis given in addition to a direct IC antibiotic injection.7,8,13,15–17 After another 7-year interval, we resurveyed the ASCRS membership regarding current antibiotic prophylaxis practice patterns for endophthalmitis. Whenever possible, identical questions from the surveys conducted 7 years and 14 years earlier were posed to facilitate analysis of differences and trends over time.

METHODS

In February 2021, a link to an online survey was sent to 5052 ASCRS member email addresses on file. The online anonymous survey consisted of 19 questions that took less than 5 minutes to complete. A unique response link was generated for each member so that it was impossible to complete the survey more than once. The survey questions are reprinted in Appendix A, https://links.lww.com/JRS/A429.

RESULTS

A total of 1205 members (24%) completed the survey. This excellent response rate for an unpaid e-survey was comparable with that from the 2 earlier surveys (Table 1). Most of the respondents continued to be American (76%) but there were fewer European respondents (6%) compared with the 2 earlier surveys. The distribution of case volume among respondents was nearly identical to the 2014 survey, with 70% performing at least 300 cases annually. Residents and fellows accounted for only 2% of the respondents.

Table 1. - Respondent Demographics by Location and Surgical Volume.
Region 2021, n (%) 2014, n (%) 2007, n (%)
United States 912 (76) 740 (65) 910 (69)
Europe 72 (6) 101 (9) 138 (11)
Canada 41 (3) 54 (5) 52 (4)
Latin America/Mexico 91 (8) 152 (13) 109 (8)
Australia/Asia 79 (7) 87 (8) 98 (7)
Africa 10 (1) 10 (1) 0
Total 1205 1144 1312
Annual cataract volume 2021 2014 2007
<100 cases 70 (6) 66 (6) 143 (11)
100, 300 cases 295 (24) 315 (27) 446 (34)
300, 500 cases 310 (26) 301 (26) 361 (28)
>500 cases 533 (44) 465 (41) 362 (28)
Total 1208 1147 1312

A decreasing number of respondents report administering perioperative topical antibiotic prophylaxis for cataract surgery compared with the 2 earlier surveys (82% vs 90% and 91%, respectively) (Table 2). The topical antibiotic preferences were similar to those in 2014, with 57% (vs 60%) using gatifloxacin or moxifloxacin and 25% (vs 21%) using ofloxacin or ciprofloxacin. This was a marked reversal from 2007 when 9 times as many surgeons preferred gatifloxacin or moxifloxacin to the 2 earlier generation fluoroquinolones. The number of surgeons using preoperative topical prophylaxis decreased to 73% compared with 85% and 88% in 2014 and 2007, respectively. In all 3 surveys, approximately half of those prescribing preoperative antibiotic drops initiated them 3 days preoperatively (Table 3).

Table 2. - Perioperative Use of Antibiotic Prophylaxis.
Regimen 2021, % (n) 2014, % 2007, %
Perioperative topical antibiotics 82 (987/1206) 90 91
Preop topical antibiotics 73 (882/1206) 85 88
Postop topical antibiotics 86 (1030/1204) 97 98
IC antibiotics 66 (802/1208) 50 30
Irrigation vs direct injection (if using)
Direct injection 95 (764/802) 84 52
Irrigation bottle 5 (38/802) 16 48
Preferred topical antibioticsa 2021 2014 2007
Gatifloxacin or moxifloxacin 57 (560/987) 60 81
Ofloxacin or ciprofloxacin 25 (246/987) 21 9
Levofloxacin NA 3 3
Besifloxacin 9 (86/987) NA NA
Other 10 (95/987) 15 7
NA = not asked; postop = postoperative; preop = preoperative
aAsked of the 987 respondents (82% of 1206 total) using a perioperative topical antibiotic

Table 3. - Preop and Postop Topical Antibiotic Prescribing Patterns.
Preop initiationa 2021, % (n) 2014, % 2007, %
3 d preop 47 (414/882) 48 52
1 d preop 30 (268/882) 32 26
On arrival for surgery 23 (200/882) 20 22
Postop durationb 2021 2014 2007
1 wk or less 69 (714/1030) 72 73
Several wks (no taper) 21 (213/1030) 21 19
Several wks (taper) 10 (103/1030) 7 8
postop = postoperative; preop = preoperative
aAsked of the 882 respondents (73% of 1206 total) using a preoperative topical antibiotic
bAsked of the 1030 respondents (86% of 1204 total) using a postoperative topical antibiotic

Respondents using postoperative topical prophylaxis also decreased (86% compared with 97% and 98% in 2014 and 2007, respectively) (Table 2). Approximately 70% of them discontinued postoperative topical antibiotics by 1 week in all 3 surveys, whereas the remainder continued them for several weeks (Table 3). Intraocular antibiotic prophylaxis (64%) was more frequently used than topical (57%) at the conclusion of surgery (Table 4). This reversed the trends seen in 2014 (36% vs 69%) and 2007 (14% vs 75%). Antibiotic infusion through the irrigation bottle and intravitreal antibiotic injection was each used by only 3% of all respondents; subconjunctival injection was used by 5%.

Table 4. - Surgical Antibiotic Administration.
Method at conclusion of surgerya 2021, % (n) 2014, % 2007, %
Topical 57 (682/1206) 69 75
IC injection (AC) 58 (702/1206) 36 14
Irrigation bottle infusion (AC) 3 (38/1206) NA NA
Intravitreal injectionb 3 (30/1206) NA NA
Subconjunctival injection 5 (57/1206) 8 11
None of the above 6 (68/1206) 7 10
Who prepares IC antibioticsc 2021 2014 2007
OR nursing staff 44 (357/812) 65 77
Surgeon 3 (28/812) 6 5
Commercial intraocular solution 7 (58/812) 5 0
Pharmacy (total) 45 (369/812) 24 18
Hospital or in-house 12 (101/812) 14 NA
Outside compounding 33 (268/812) 9 NA
AC = anterior chamber; IC = intracameral; NA = not asked; OR = operating room
aPercentages total >100 because respondents could check more than 1 method
bIntravitreal includes transzonular or pars plana
cAsked of the 812 respondents using an IC antibiotic

A chronologic comparison of IC antibiotic use in all 3 surveys showed a steady increase from 2007 to 2021 (30 to 50 to 66%) (Table 2). Of those using IC antibiotic prophylaxis, there was a large decrease in the proportion administering antibiotics through the irrigation bottle from 48% in 2007 to 5% in 2021. Thirty-eight percentage of respondents currently using IC antibiotics stated that they initiated this practice within the previous 2 years. Twenty-four percentage of them do not use topical antibiotics postoperatively, whereas the remainder combine both topical and IC prophylaxis. However, only 53% would continue using topical antibiotics postoperatively if they could use an approved intraocular antibiotic solution. Among IC antibiotic users, there was a decrease in mixing by operating room nurses (77 to 65 to 44%) mirrored by increasing use of pharmacies (18 to 24 to 45%) during the 2007 to 2021 period (Table 4). Among the U.S. users, mixing by operating room staff and pharmacies accounted for 36% and 57%, respectively. Overall, there was a significant increase in use of outside compounding pharmacies, which supplied one third of all IC antibiotics in 2021 compared with only 9% in 2014. In the absence of an approved commercial antibiotic solution in the United States, the number of global ASCRS respondents using a commercial source remained small (7% in 2021; 5% in 2014).

Regarding intraocular antibiotic preference, vancomycin use dropped from 22% in 2014 to 6%, whereas cefuroxime use decreased from 26% in 2014 to 19% (Table 5). Moxifloxacin preference more than doubled from 33% in 2014 to 73% currently. Among the U.S. respondents, moxifloxacin preference rose even higher to 83% (31% in 2014), whereas vancomycin preference fell from 52% in 2014 to 6% in 2021. Cefuroxime preference decreased from 14% in 2014 to 11% in 2021. Only 5% of all global respondents administering moxifloxacin used a commercial intraocular product, with the remainder evenly divided between using compounded moxifloxacin (49%) and using Vigamox topical solution (46%). Users were equally divided between the higher [0.5% (39%)] and lower [0.1% (41%)] moxifloxacin concentrations; the remaining 20% did not know what concentration they were using.

Table 5. - Drug Preferences for Those Using Intraocular Antibiotic Prophylaxis.
Method 2021, % (n) 2014, %
Direct IC antibiotic injection
Moxifloxacin (mixed from Vigamox) 34 (270/802) 29
Moxifloxacin (compounded) 36 (289/802) 4
Moxifloxacin (commercial; eg, Auromox) 4 (30/802) NA
Vancomycin 2 (16/802) 22
Cefuroxime (commercial; eg, Aprokam) 7 (53/802) 12
Cefuroxime (compounded) 12 (97/802) 14
Other 1 (9/802) 3
Antibiotics placed in an irrigation bottle
Vancomycin 4 (30/802) 15
Other 1 (8/802) 1
IC = intracameral

Although the number of respondents who do not inject IC antibiotics is declining, they cite mixing and compounding risk (66%), being unconvinced of the need (48%), and cost (42%) as reasons (Table 6). These same 3 reasons were cited by 45%, 89%, and 17%, respectively, in 2007. During the previous 7 years, 31 (5%) of 633 respondents using compounded IC antibiotics reported any complications, including toxic anterior segment syndrome and corneal endothelial injury (18 and 10 respondents, respectively). Another 28 (5%) of 570 using homemade (ie, mixed in the operating room) IC antibiotics reported complications (toxic anterior segment syndrome and corneal injury by 13 and 6 respondents, respectively).

Table 6. - Opinions About IC Antibiotic Prophylaxis.
Rate importance? 2021, % (n) 2014, % 2007, %
Very important 62 (743/1208) 41 NA
Important option but other methods sufficient 22 (262/1208) 26 NA
Not necessary 8 (102/1208) 14 NA
Not sure 8 (101/1208) 19 NA
Importance of an approved commercial antibiotic? 2021 2014 2007
Important 80 (962/1204) 75 54
Not important 7 (88/1204) 9 11
Not sure 13 (154/1204) 16 35
Would still not use any IC antibiotica 7 (82/1204) 17 18
Why not using IC antibiotics?b 2021 2014 2007
Mixing/compounding risk 66 (251/382) 49 45
Cost 32 (122/382) 19 17
Not convinced of need 48 (182/382) 65 89
IC = intracameral; NA = not asked
aPercentage of respondents who would still not use an approved commercial IC antibiotic
bAsked of the 382 respondents who were not using IC antibiotics; the percentages total >100 because respondents could check more than 1 reason

Sixty-two percentage believed IC antibiotic prophylaxis to be very important and 22% deemed it an important option, along with other methods (Table 6); the remaining 8% believed it was unnecessary. Eighty-percentage felt it important to have a commercially available solution for direct IC injection compared with 75% in 2014 and 54% in 2007. If an approved commercial product were available at a reasonable cost, IC antibiotics adoption would increase to 93% of respondents (compared with 83% and 82% in the earlier surveys, respectively). Of 580 respondents who were not using intraocular prophylaxis but would adopt it if a reasonably priced commercial antibiotic was approved, 452 (78%) would prefer moxifloxacin over cefuroxime (22%).

DISCUSSION

When the randomized ESCRS endophthalmitis prophylaxis clinical trial was published, topical antibiotic prophylaxis was the community standard among ASCRS members with only 16% already injecting antibiotics directly into the anterior chamber postoperatively.5 Criticisms of the ESCRS study included an unexpectedly high endophthalmitis rate in the topical-only group and concerns that the study was prematurely terminated. In the ensuing 2007 ASCRS survey, 92% of those who were not already injecting IC antibiotics were not convinced by the study to adopt this practice.5 Although the ESCRS clinical trial led to European Medicines Agency approval of Aprokam, the FDA did not accept it as a valid efficacy study.

Multiple subsequent retrospective trials also reported a statistically significant reduction in postcataract endophthalmitis with IC cefuroxime, including a large study in the United States.4,7–13 However, because of the requirement, cost, and logistical hurdles of conducting a new and sufficiently large randomized clinical trial, no pharmaceutical company has pursued the FDA approval of an intraocular antibiotic in the United States.11 Despite this, IC antibiotic prophylaxis has continued to increase (two thirds of ASCRS members, compared with one half in 2014 and 30% in 2007). Among IC antibiotic users, 2 major trends have emerged in the latest survey. One is the predominant shift from infusion bottle administration to direct IC injection; the latter now accounts for 95% of intraocular prophylaxis, compared with 52% in 2007. There is a 4-fold increase in the overall number of respondents using direct IC antibiotic injection (63%) compared with 2007 (16%). The off-label practice of transzonular or pars plana intravitreal injection of antibiotics, which is primarily performed in the United States, was used by fewer than 3% of all respondents.18,19

A second major trend is a pronounced shift toward moxifloxacin and away from vancomycin for intraocular prophylaxis. Avoidance of the latter is most likely due to its association with hemorrhagic occlusive retinal vasculitis, the rare but devastating type III hypersensitivity documented in a series of 36 eyes receiving vancomycin reported in 2017.14 The delayed onset of vision loss has led to cases of bilateral vancomycin injections and bilateral blindness, and routine IC vancomycin prophylaxis has been discouraged by the FDA and the Cataract Preferred Practice Pattern panel of the American Academy of Ophthalmology.20,21

Several studies, including large retrospective data analyses from Aravind have provided new and strong support for the safety and efficacy of IC moxifloxacin prophylaxis.15–17,22 This is now preferred by 73% of global respondents, and 83% of Americans, using intraocular prophylaxis. This shift in antibiotic preference has been accompanied by greater outsourcing from compounding pharmacies, which is preferred by half of the intraocular moxifloxacin users in the United States. The other half use branded topical Vigamox as the off-label source. Those who know what moxifloxacin concentration they inject are equally divided between the 0.5% and 0.1% concentrations. Our recent study found both moxifloxacin concentrations to be safe regarding corneal endothelial cell loss.23 These trends should be considered by the FDA whose proposed exclusion of moxifloxacin from the list of bulk drug substances for which there is a clinical need would curtail the ability of 503b outsourcing facilities to compound the higher concentration in the United States.24 The lack of a commercially available and FDA-approved product is a major barrier to increased IC prophylaxis adoption as mixing or compounding risk was cited by two thirds of respondents not using it. Those unconvinced of the need have dropped from 89% (2007) to 48%. This and the fact that 38% of those injecting IC antibiotics started doing so within the past 2 years suggest that opinions are being changed by the growing body of the published retrospective studies.

Another trend is the reduction in preoperative and postoperative topical antibiotic prophylaxis, which had not changed between the 2007 and 2014 surveys. Several studies reported no additional benefit to topical antibiotics if IC prophylaxis was used.7,8,16 Among those using IC antibiotics, 1 in 4 do not prescribe topical antibiotics postoperatively. Practice patterns for the timing and duration of topical antibiotic prophylaxis remain unchanged, but there continues to be a shift toward earlier generation fluoroquinolones from a much stronger preference (81%) for branded gatifloxacin and moxifloxacin in 2007.5

Despite the lack of an approved antibiotic solution in the United States, the proportion of American (65%) and global (66%) ASCRS members using intraocular antibiotic prophylaxis has continued to rise. This would increase to 93% of surgeons if a reasonably priced commercial solution were approved. For this reason, the ASCRS and the U.S. Veterans Health Administration are working to organize a multicenter, prospective randomized clinical trial in the United States. The Topical vs Intracameral Moxifloxacin to prevent Endophthalmitis study would evaluate the efficacy of IC moxifloxacin in reducing the postcataract endophthalmitis rate compared with topical moxifloxacin alone. This latest survey highlights the undeniable need for such a product and should motivate a pharmaceutical industry partner to collaborate with the ASCRS and government funding agencies (eg, Veterans Health Administration and National Institutes of Health) on the Topical vs Intracameral Moxifloxacin to prevent Endophthalmitis study and to ultimately sponsor a submission to the FDA if IC moxifloxacin efficacy was demonstrated.

WHAT WAS KNOWN

  • In the 2014 survey, approximately half of the ASCRS members were using intracameral antibiotic prophylaxis, with the most common drug being vancomycin.
  • Most of the surgeons prescribed preoperative (85%) and postoperative (97%) topical antibiotic prophylaxis.

WHAT THIS PAPER ADDS

  • The number of ASCRS members using intraocular antibiotic prophylaxis has risen to 66%, with a strong preference for moxifloxacin (73%).
  • Fewer surgeons are prescribing preoperative (73%) and postoperative (86%) topical antibiotic prophylaxis; one fourth of those surgeons injecting IC antibiotics are not prescribing postoperative topical antibiotics.

REFERENCES

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