Intracameral antibiotics during cataract surgery: efficacy, safety, and cost-benefit considerations.

PURPOSE OF REVIEW: We summarize evidence-based considerations regarding the use of intracameral antibiotics during cataract surgery. RECENT FINDINGS: The use of intraoperative intracameral antibiotics reduced the incidence of postcataract surgery endophthalmitis 3.5-fold, with an odds ratio ranging from 0.14 to 0.19. A survey of the American Society of Cataract and Refractive Surgery showed usage of intracameral injections of antibiotics increased by 16% in the United States between 2014 and 2021. The frequency of vancomycin usage has sharply dropped to 6%, while moxifloxacin is now the dominant choice at 83% among respondents. One analysis showed that 2500 patients need to be treated with intracameral antibiotics to prevent one case of endophthalmitis. A 500 µg intracameral moxifloxacin at $22 dollars per dose is cost-effective, including for patients with posterior capsular rupture (PCR). SUMMARY: Studies substantiate the safety and efficacy of intracameral antibiotics for endophthalmitis prophylaxis. Intracameral moxifloxacin and cefuroxime are the most common choices. While vancomycin shows potential for efficacy, further studies evaluating clinical outcomes are needed. Adverse events are rare and commonly due to errors in preparation. Topical antibiotics do not provide additional prophylactic benefits to intracameral regimens. Intracameral antibiotics given alone are cost-effective.

Cefuroxime (Aprokam®) in the Prophylaxis of Postoperative Endophthalmitis After Cataract Surgery Versus Absence of Antibiotic Prophylaxis: A Cost-Effectiveness Analysis in Poland.

OBJECTIVE: The analysis aims to assess the cost-effectiveness of cefuroxime (Aprokam®) in the prophylaxis of postoperative endophthalmitis (POE) after cataract surgery compared with the absence of antibiotic prophylaxis from the National Health Fund perspective in Poland. METHODS: We performed a cost-effectiveness and cost-utility analysis using the decision tree and Markov model, respectively, for patients after cataract surgery. The efficacy of Aprokam was 0.21 (95% confidence interval [CI], 0.08-0.55) and is based on the results of the European Society of Cataract and Refractive Surgery study. According to the epidemiological data from Poland, the risk of POE is 0.377%. The costs associated with the Aprokam administration and POE treatment costs were included. We determined the utilities of the health states in the model depending on visual loss due to POE. To determine the uncertainty of estimates parameters, a one-way deterministic and probabilistic sensitivity analysis were performed. RESULTS: Using Aprokam allows avoiding 0.003 POEs per patient. The benefit from the intervention is 0.0007 quality-adjusted life years per patient in the lifetime horizon. The total costs of prophylaxis are higher at about €1.70. The cost of avoiding one POE (incremental cost-effectiveness ratio) is about €569.85. The estimated incremental cost-effectiveness utility ratio is equal to €2427.72/quality-adjusted life-years, and it is significantly lower than the cost-effectiveness threshold in Poland in 2019 (about 7.5% of the threshold). In all scenarios of performed one-way sensitivity analyses, Aprokam is cost-effective. CONCLUSIONS: In Poland, the use of Aprokam is cost-effective, with the estimated incremental cost-utility ratio significantly lower than the cost-effectiveness threshold.

Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

Fluoroquinolone Antibiotic Prophylaxis to Prevent Post-Traumatic Bacterial Infectious Endophthalmitis: Using Monte Carlo Simulation to Evaluate the Probability of Success.

Purpose: Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE). Methods: Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE. Results: Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%. Conclusion: M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.

Intracameral moxifloxacin for endophthalmitis prophylaxis after cataract surgery: Cost-effectiveness analysis.

PURPOSE: To determine the cost-effectiveness of intracameral moxifloxacin compared with traditional antibiotic prophylaxis in preventing endophthalmitis after cataract surgery. SETTING: Theoretical surgical center in the United States. DESIGN: Evaluation of technology. METHODS: The incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR) were calculated for patients having cataract surgery with traditional antibiotic prophylaxis (perioperative topical antibiotics) compared with perioperative topical antibiotics with intracameral moxifloxacin. The base case was a healthy binocular 73-year-old man having first-eye cataract surgery. The incidences and costs were derived from PubMed English literature searches, Medicare reimbursement rates, and average wholesale prices. All costs and benefits were adjusted 3% per annum and for inflation to 2017 United States dollars. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS: Compared with traditional prophylaxis, an adjuvant 500 µg intracameral moxifloxacin (for $20) was cost-saving from a societal perspective in the base case; in probabilistic sensitivity analyses, all the values were within the societal willingness-to-pay threshold of $50 000/quality-adjusted-life-years (QALYs), and 6142 (61%) of 10 000 iterations were cost-saving. From a healthcare sector perspective, intracameral moxifloxacin was cost-effective, with an ICUR of $8275/QALY. In cases with posterior capsule tears, a $20 intracameral moxifloxacin was cost-saving. CONCLUSIONS: From a societal perspective in the U.S., a topical perioperative antibiotic with a 500 µg intracameral moxifloxacin costing $22 dollars or less was cost-effective and cost-saving. From a healthcare sector perspective, a $20 intracameral moxifloxacin was cost-effective but not cost-saving. Adjuvant intracameral moxifloxacin had greater effectiveness in improving QALYs than topical antibiotics.

Efficacy and cost-effectiveness of intracameral vancomycin in reducing postoperative endophthalmitis incidence in Australia.

BACKGROUND: Endophthalmitis is a rare but devastating postoperative complication of cataract surgery. We aimed to describe the incidence of acute postoperative endophthalmitis in an Australian population over a 14-year period. DESIGN: This was a retrospective longitudinal cohort study performed at Westmead Hospital, a major tertiary hospital in Sydney, Australia. PARTICIPANTS: Patients who had acute postoperative endophthalmitis within 6 weeks of their cataract surgery at Westmead Hospital were included. METHODS: Endophthalmitis cases from 2000 to 2014 were identified from computerized diagnostic coding. These were cross-referenced with the cataract surgery list over this time period. The routine use of intracameral vancomycin at the end of cataract surgery was introduced in Westmead Hospital in 2004. MAIN OUTCOME MEASURES: We quantified the incidence of acute postoperative endophthalmitis pre and post the routine use of intracameral vancomycin. RESULTS: A total of 14 805 cataract cases were performed at Westmead Hospital from 2000 to 2014. Seventeen cases of endophthalmitis were within 6 weeks post cataract surgery performed at Westmead Hospital. In the period 2000 to 2003, the incidence of postoperative endophthalmitis was 0.43% (11/2539). From 2004 to 2014, there was a dramatic decrease in the incidence of postoperative endophthalmitis to 0.049% (6/12 266, P < 0.0001). CONCLUSIONS: There has been a nine-fold reduction in the rate of acute postoperative endophthalmitis with the use of intracameral vancomycin in cataract surgery. Post-cataract surgery endophthalmitis is now a relatively rare cause of endophthalmitis in this Australian population. Our study supports the routine use of intracameral vancomycin as postoperative endophthalmitis prophylaxis.

Microencapsulation of rifampicin for the prevention of endophthalmitis: In vitro release studies and antibacterial assessment.

Rifampicin encapsulated microparticles were designed for intraocular injection after cataract surgery to prevent postoperative endophthalmitis. Microparticles were formulated by emulsification diffusion method using poly(lactic acid-co-glycolic acid) (PLGA) as polymer in order to propose a new form of rifampicin that overcome its limitations in intraocular delivery. Depending on processing formulation, different types of microparticles were prepared, characterized and evaluated by in vitro release studies. Two types of microparticles were selected to get a burst release of rifampicin, to reach minimal inhibitory concentrations to inhibit 90% of Staphylococcus epidermidis mainly involved in postoperative endophthalmitis, combined with a sustained release to maintain rifampicin concentration over 24h. The antibacterial activity and antiadhesive property on intraocular lenses were evaluated on S. epidermidis. Microparticles, with a rapid rifampicin release profile, showed an effect towards bacteria development similar to free rifampicin over 48h. However, slow-release profile microparticles exhibited a similar antibacterial effect during the first 24h, and were able to destroy all the S epidermidis in the medium after 30h. The association of the two formulations allowed obtaining interesting antibacterial profile. Moreover, rifampicin-loaded microparticles have shown a very efficient anti-adherent effect of S. epidermidis on intraocular lenses at 24h. These results propose rifampicin microparticles as suitable for antibioprophylaxis of the postoperative endophthalmitis.

Efficacy of Intracameral Moxifloxacin Endophthalmitis Prophylaxis at Aravind Eye Hospital.

PURPOSE: To compare the rate of postoperative endophthalmitis before and after initiation of intracameral (IC) moxifloxacin for endophthalmitis prophylaxis in patients undergoing cataract surgery. DESIGN: Retrospective, clinical registry. PARTICIPANTS: All charity and private patients (116 714 eyes) who underwent cataract surgery between February 15, 2014, and April 15, 2015, at the Madurai Aravind Eye Hospital were included. Group 1 consisted of 37 777 eyes of charity patients who did not receive IC moxifloxacin, group 2 consisted of 38 160 eyes of charity patients who received IC moxifloxacin prophylaxis, and group 3 consisted of 40 777 eyes of private patients who did not receive IC moxifloxacin. METHODS: The electronic health record data for each of the 3 groups were analyzed, and the postoperative endophthalmitis rates were statistically compared. The cost of endophthalmitis treatment (groups 1 and 2) and the cost of IC moxifloxacin prophylaxis (group 2) were calculated. MAIN OUTCOME MEASURES: Postoperative endophthalmitis rate before and after initiation of IC moxifloxacin endophthalmitis treatment cost. RESULTS: Manual, sutureless, small incision cataract surgery (M-SICS) accounted for approximately all of the 75 937 cataract surgeries in the charity population (97%), but only a minority of the 40 777 private surgeries (21% M-SICS; 79% phacoemulsification). Thirty eyes in group 1 (0.08%) and 6 eyes in group 2 (0.02%) were diagnosed with postoperative endophthalmitis (P < 0.0001). The group 3 endophthalmitis rate was 0.07% (29 eyes), which was also higher than the second group's rate (P < 0.0001). There were no adverse events attributed to IC moxifloxacin in group 2. The total cost of treating the 30 patients with endophthalmitis in group 1 was virtually identical to the total combined cost in group 2 of routine IC moxifloxacin prophylaxis and treatment of the 6 endophthalmitis cases. CONCLUSIONS: Routine IC moxifloxacin prophylaxis achieved a highly significant, 4-fold reduction in postoperative endophthalmitis in patients undergoing M-SICS. Compared with previous studies, having such a high volume of patients undergoing surgery during a relatively short 14-month time period strengthens the conclusion. This study provides further evidence that moxifloxacin is an effective IC prophylactic antibiotic and suggests that IC antibiotics should be considered for M-SICS and phacoemulsification.

Budget impact assessment of Aprokam® compared with unlicensed cefuroxime for prophylaxis of post-cataract surgery endophthalmitis.

BACKGROUND: Intracameral cefuroxime is recommended as prophylaxis against postoperative endophthalmitis (POE) following cataract surgery. Aprokam is the only licensed product for prophylaxis of POE, although unlicensed intracameral cefuroxime may be administered using pre-filled syringes (PFS), either prepared in hospital by reconstituting cefuroxime via serial dilution (prepared PFS), or commercially purchased (purchased PFS). This study aimed to estimate the potential budget impact of using Aprokam over unlicensed cefuroxime for intracameral administration. METHODS: A budget impact model (BIM) was developed from UK NHS hospital perspective to estimate the economic impact of adopting Aprokam compared with purchased PFS or prepared PFS for the prophylaxis of POE following cataract surgery over a 5-year time horizon. The BIM incorporated direct costs only, associated with the acquisition, delivery, storage, preparation, and administration of cefuroxime. Resource utilisation costs were also incorporated; resource utilisation was sourced from a panel survey of hospital pharmacists, surgeons, and theatre nurses who are involved in the delivery, storage, preparation, quality assurance, or administration of cefuroxime formulations. Unit costs were sourced from NHS sources; drug acquisition costs were sourced from BNF. The model base case used a hypothetical cohort comprising of 1000 surgeries in the first year and followed a 5.2 % annual increase each year. RESULTS: The model predicts Aprokam is cost saving compared with purchased PFS, with a modest increase compared prepared PFS over 5 years. There are total savings of £ 3490 with Aprokam compared with purchased PFS, driven by savings in staff costs that offset greater drug acquisition costs. Compared with prepared PFS, there are greater drug acquisition costs which drive an increased total cost over 5 years of £ 13,177 with Aprokam, although there are substantial savings in staff costs as well as consumables and equipment costs. CONCLUSIONS: The lower direct costs of using Aprokam compared with purchased PFS presents a strong argument for the adoption of Aprokam where purchased PFS is administered. The additional benefits of Aprokam include increased liability coverage and possible reduction in dilution errors and contaminations; as such, in hospitals where unlicensed prepared PFS is used, modest additional resources should be allocated to adoption of Aprokam.

Benefits and risks of immediately sequential bilateral cataract surgery: a literature review.

Immediately sequential bilateral cataract surgery (ISBCS) is a highly contended issue in ophthalmology, mainly due to the risk of bilateral endophthalmitis and financial penalties that many ophthalmologists face when performing simultaneous cataract surgeries. The purpose of this review is to understand the current status of the knowledge of ISBCS, mainly its benefits and risks and how they compare with the standard of care, delayed sequential bilateral cataract surgery. Evidence, although limited, increasingly supports ISBCS for providing faster rehabilitation, improved visual outcomes, and cost and time savings. Evidence does not support the fear of bilateral endophthalmitis resulting from the simultaneous procedure. However, stronger and greater evidence is needed before ISBCSs can be considered the standard of care. Where ISBCS can potentially create the most beneficial impact is in public eye health programmes in developing countries, but this has not yet been explored.

Simultaneous bilateral cataract surgery: economic analysis; Helsinki Simultaneous Bilateral Cataract Surgery Study Report 2.

PURPOSE: To present an economic-analysis comparison of simultaneous and sequential bilateral cataract surgery. SETTING: Helsinki University Eye Hospital, Helsinki, Finland. DESIGN: Economic analysis. METHODS: Effects were estimated from data in a study in which patients were randomized to have bilateral cataract surgery on the same day (study group) or sequentially (control group). The main clinical outcomes were corrected distance visual acuity, refraction, complications, Visual Function Index-7 (VF-7) scores, and patient-rated satisfaction with vision. Health-care costs of surgeries and preoperative and postoperative visits were estimated, including the cost of staff, equipment, material, floor space, overhead, and complications. The data were obtained from staff measurements, questionnaires, internal hospital records, and accountancy. Non-health-care costs of travel, home care, and time were estimated based on questionnaires from a random subset of patients. The main economic outcome measures were cost per VF-7 score unit change and cost per patient in simultaneous versus sequential surgery. RESULTS: The study comprised 520 patients (241 patients included non-health-care and time cost analyses). Surgical outcomes and patient satisfaction were similar in both groups. Simultaneous cataract surgery saved 449 Euros (€) per patient in health-care costs and €739 when travel and paid home-care costs were included. The savings added up to €849 per patient when the cost of lost working time was included. CONCLUSION: Compared with sequential bilateral cataract surgery, simultaneous bilateral cataract surgery provided comparable clinical outcomes with substantial savings in health-care and non-health-care-related costs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Assessment of sodium hyaluronate gel as vehicle for intracameral delivery of cefuroxime in endophthalmitis prophylaxis.

Sodium cefuroxime is a second-generation cephalosporin widely used at 10mg/mL for endophthalmitis prophylaxis after cataract surgery. Sodium cefuroxime solution is usually conditioned in pre-filled syringes then frozen for storage. In the present study, 0.2% sodium hyaluronate gel, natural extracellular polymer used in wound healing, was compared to conventional saline solution (0.9% sodium chloride) as drug delivery systems for cefuroxime loading in pre-filled syringes. Therefore, the temperature (4 and 25 degrees C) and time of storage (up to 21 days) varied in order to appreciate both cefuroxime and vehicle stability. Furthermore, the kinetics of drug release from both hyaluronate gel and saline solution were compared since in vitro sets of dialysis experiments. Results indicated that cefuroxime loaded in either saline solution or hyaluronate hydrogel was found stable in pre-filled syringes stored at 4 degrees C for 21 days, whereas cefuroxime degradations products appeared from the 2nd day of storage at 25 degrees C. Both drug delivery systems were found bioequivalent, although statistically slower cefuroxime dialysis was evidenced by using sodium hyaluronate vehicle. Noteworthy, cefuroxime concentration in drug delivery systems during dialysis experiment remained greater than the minimum inhibitory concentrations reported for resistant strains. In conclusion, the present stability and release study confirmed that sodium hyaluronate hydrogel is a promising vehicle for cefuroxime intracameral delivery in endophthalmitis prophylaxis.

Prophylaxis of postoperative endophthalmitis following cataract surgery: current status and future directions.

Endophthalmitis is an uncommon but potentially devastating intraocular infection that can occur after routine cataract surgery. Although a broad spectrum of organisms have been shown to cause acute postoperative endophthalmitis, most cases are caused by Gram-positive bacteria, which may be introduced at the time of surgery from colonization of adjacent conjunctiva or eyelid skin. Risk factors for the development of endophthalmitis following cataract surgery include patient age, intraoperative surgical complications and poor wound construction. There are several antibacterial strategies employed to prevent postoperative endophthalmitis, with topical, intracameral and subconjunctival delivery being the most common. Worldwide, there seems to be significant regional variance in the type and method of prophylactic antibacterial regimens; for example, topical fluoroquinolones are commonly used in the US, while intracameral cephalosporins are employed widely in Europe. The optimal antibacterial strategy for the prevention of endophthalmitis should be safe, inexpensive and broad in microbiological activity spectrum, while not requiring patient compliance for its effectiveness.

Cost-effectiveness analysis of intracameral cefuroxime use for prophylaxis of endophthalmitis after cataract surgery.

OBJECTIVE: To evaluate the cost-effectiveness of intracameral cefuroxime for postoperative endophthalmitis prophylaxis, and to determine the efficacy threshold necessary for alternative antibiotics to attain cost-effective equivalence with intracameral cefuroxime. DESIGN: Cost-effectiveness analysis. PARTICIPANTS: We study a hypothetical cohort of 100,000 patients undergoing cataract surgery as a part of the cost analysis. METHODS: A cost-effectiveness model was constructed to analyze different antibiotic prophylactic regimens for postoperative endophthalmitis with intracameral cefuroxime as our base case. Efficacy was defined as the absolute reduction in rate of infection from background rate of infection, which was sourced from the literature. Antibiotic cost data were derived from the Red Book 2007 edition, and salary data were taken from the United States Bureau of Labor Statistics. Multivariate sensitivity analysis assessed the performance of antibiotic options under different scenarios. MAIN OUTCOME MEASURES: Cost per case of endophthalmitis prevented; theoretical maximal cost-effectiveness; efficacy threshold necessary to achieve cost-effective equivalence with intracameral cefuroxime; ratio indicating how many times more effective or less expensive alternative antibiotics would have to be to achieve cost-effective equivalence with intracameral cefuroxime. RESULTS: The cost-effectiveness ratio for intracameral cefuroxime is $1403 per case of postoperative endophthalmitis prevented. By comparison, the least expensive topical fluoroquinolone in our study, ciprofloxacin, would have to be >8 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. The most expensive topical fluoroquinolones studied, gatifloxacin and moxifloxacin, would have to be > or =19 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. A sensitivity analysis reveals that even in the worst case scenario for intracameral cefuroxime efficacy and with a 50% reduction in the cost of 4th-generation fluoroquinolones, gatifloxacin and moxifloxacin would have to be > or =9 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. CONCLUSIONS: Administration of intracameral cefuroxime is relatively cost-effective in preventing endophthalmitis after cataract surgery. Owing to their high costs, many commonly used topical antibiotics are not cost-effective compared with intracameral cefuroxime, even under optimistic assumptions about their efficacy.