The impact of antibiotic prophylaxis with intracameral cefuroxime on postoperative infectious endophthalmitis rates in a high-volume cataract surgery center - Scientific Reports
Our purpose was to compare postoperative infectious endophthalmitis rates before and after the introduction of antibiotic prophylaxis via intracameral with cefuroxime (ATB-P IC) in a high-volume cataract surgery service. Retrospective cohort study considering patients who underwent cataract surgery at Ophthal Hospital Especializado, São Paulo, Brazil, from January/2011 to December/2019. Patients operated from 2013 to 2019 comprised the ATB-P IC group while those operated from 2011 to 2013 formed the control group without the ATB-P IC protocol. A total of 23,184 cataract surgeries were included, with 6,207 in the Control Group and 16,977 in the ATB-P Group. A significantly higher rate of endophthalmitis was observed in the control group (0.0967%) when compared to the ATB-P group (0.0177%) (p = 0.014). Surgeries performed with ATB-P showed 80% less chance of reported endophthalmitis (OR = 0.20; 95% CI 0.05–0.72; p = 0.014) than those without ATB-P. Of the six cases confirmed by culture in the control group, all tested positive for Pseudomonas aeroginosa and the only case confirmed by culture in the ATB-P group was positive for Staphylococcus epidermidis. Our findings strongly support the use of intracameral antibiotic prophylaxis with cefuroxime to reduce postoperative infectious endophthalmitis rates, and we recommend its incorporation into cataract surgery protocols. The impact of antibiotic prophylaxis with intracameral cefuroxime on postoperative infectious endophthalmitis rates in a high-volume cataract surgery center in Brazil has been noted in Scientific Reports. Despite being a rare condition with some risk factors such as prolonged surgical time, intraoperative complications, diabetes status, and service sterility breaches, there has been no increase in the overall prevalence of infectiousendophthalMITis since 2013. The study suggests that the use of antibiotic Prophylax (ATB-P) with intracseral (IC) cefurxime is the best preventive effect on preventing the disease. However, it also notes that the drug has limited action on Gram negatives, some strains of Serratia, Proteus and Bacteroides fragilis, and inactivity on Pseudomonas15. The FDA recommends not to use vancomycin for prevention and limits its use for the treatment of infection itself, especially in patients at risk.
게시됨 : 2 년 전 ~에 의해 Los Angeles, Archaeology, Canada, University of Southern California, Department of Ophthalmology, Luciane Nunes, Sao Paulo, Roski Eye Institute, University of Calgary, Meireles, Arthur Gustavo, Visual Sciences, Rodrigo Antonio Brant, Department of Anthropology, Federal University of São Paulo – UNIFESP, Keck School of Medicine, Antonio Carlos, USA, São Paulo, Brazil, Calgary, Schapira, Ophthal Hospital Especializado, Fernandes, Paulista Medical School, Evandro, de Sousa Casavechia ~에 Health
Despite being a rare condition and of difficult causal determination, endophthalmitis is associated with some risk factors such as prolonged surgical time, intraoperative complications, diabetes status, surgeons with limited practical experience, service sterility breaches, among others4,5,7,11. Our institution has launched a cataract fellowship service in 2018, however, there has been no increase in the overall prevalence of infectious endophthalmitis since then. All cases presented in the current study were reported by experienced surgeons.
Our results demonstrate a reduction in the endophthalmitis incidence following the intraoperative use of intracameral cefuroxime, corroborating other studies on the same subject, with variable levels of association between the intervention and outcome4,11,13,15,18,19,20. The only prospective and randomized study on this subject was the ESCR study and, despite some bias associated with the non complete blinding designed, it is considered the most important one on the topic and it supports our findings11.
Our cataract surgeries consistently followed a protocol involving povidone-iodine eye drops, postoperative topical moxifloxacin, and moxifloxacin/dexamethasone eye drops for 30 days. Due to an increased number of infectious endophthalmitis cases in 2013, we introduced the use of antibiotic prophylaxis (ATB-P) with intracameral (IC) cefuroxime. While the literature supports the use of this drug, it is worth noting that it has some limitations including potential associations with complications derived from contamination, dilution errors, toxic anterior segment syndrome, and macular toxicity18. Furthermore, the drug has limited action on Gram negatives, including some strains of Serratia, some strains of Proteus and Bacteroides fragilis, and inactivity on Pseudomonas15. There are still references in the literature reporting worse visual results associated with the cefuroxime ATB-IC use, largely due to increased rates of infections with gram-negative cefuroxime-resistant strains11. In our work, we did not find gram-negative infection after the introduction of ATB-P but we noticed a delay in the diagnosis of endophthalmitis by one day in the ATB-IC group when compared to the control cases.
We did not consider the intracameral use of moxifloxacin or vancomycin due to potential toxicity and local regulations. The available formulations of moxifloxacin in Brazil contain preservatives and adjuvants that are toxic to ocular structures20; even the most used eye drops in our country (Vigamox®, Alcon), market as not having preservatives, has a warning that the solution should not be injected under the conjunctiva, nor introduced directly into the anterior chamber of the eye20,21. Other studies performed in other locations have, however, shown good results on its use, safety, and efficacy16,22. Vancomycin has no action on gram-negatives and has been associated with occlusive retinal vasculitis and, although few cases, its use was considered imprudent. In addition, the FDA recommends not to use vancomycin for prevention of endophthalmitis, and limits its use for the treatment of infection itself, especially in patients at risk for Methicillin-resistant Staphylococcus aureus, Methicillin-resistant Staphylococcus epidermidis12,21,23. A recent metanalysis comparing different intracameral injection has shown vancomycin (OR = 0.03, 99.6% CI 0.00–0.53, p value = 0.006) as the best preventive effect on preventing endophthalmitis, followed by intracameral injection of cefuroxime (OR = 0.18, 99.6% CI 0.09–0.35, p value < 0.001), and moxifloxacin (OR = 0.36, 99.6% CI 0.16–0.79, p value = 0.003)16. In any case, the local health regulations in Brazil do not advice the use of intracameral vancomycin or moxifloxacin.
One of our cases (case #7) was confirmed as infectious endophthalmitis by gram-positive and showed an antibiogram profile resistant to most cephalosporins. This case involved a male, elderly patient, insulin-dependent diabetic, and immunosuppressed due to metastatic neoplasia (breast and lung cancer). The bacterial resistance is related to an intrinsic property of a bacterial species or an acquired capacity, induced by mutation in native DNA or introduction of resistant DNA that can be transferred between different genera or species24. Moreover, in immunosuppressed patients there is population/colonization by species other than the usual ones, especially when they undergo prolonged hospitalization, which may explain the observed resistance.
The discussion on antibiotic use and bacterial resistance is ongoing. Cefuroxime resistance mechanisms include beta-lactamase hydrolysis, reduced penicillin-binding protein affinity, outer membrane impermeability in Gram-negative bacteria, and bacterial drug efflux pumps25. It is also known that cefuroxime exhibits time-dependent antibacterial activity, so that it needs to exceed a minimum duration (about 2 to 3 h) of exposure to the drug, in concentrations 4 to 6 times the minimum inhibitory concentration to obtain greater antibiotic efficacy and a lower risk of developing resistance26. There is also experimental evidence that suggest that exposure to antibiotics for less than 2 h may not be adequate to inhibit the growth of organisms that commonly cause postoperative infectious endophthalmitis26.
According to the concept of antibiotic prophylaxis, the maximum time of exposure to antibiotic should be up to 24 hours3,5,6,7, as a longer period would not bring benefit to the patient and would promote the risk of inducing bacterial resistance2, in addition to increase the risk of adverse events1 and costs15,27. After the intracameral injection of 1mg of cefuroxime, the levels of antibiotics in the aqueous humor remain above the inhibitory concentration for several relevant bacterial species up to 4–5 h after surgery25. Under usual conditions, the aqueous humor formation rate is 2.5–2.8 µL/min and this volume is completely replaced every 100 min28. Moreover, the turnover of cefuroxime injected into the chamber is approximately 8 h, for a concentration of 40 µg/20 µL (0.04 mg/0.02 ml)29. Taking in consideration that cefuroxime turnover follows a linear pattern of clearance regardless of injection sites (systemic versus ocular)29 and even though aqueous humor (AH) homeostasis is modified by ocular inflammation, possibly the total volume injected into the eye of cefuroxime 1 mg / 0.1 ml, is not completely eliminated within 24 hours. However, due to the low concentration injected, due to the tiny residual concentration stored in the anterior chamber and in the capsule, due to the despicable levels reached systemically, and the ethical consideration on risks related to increased risk of inducing resistance microbial activity against the benefits would justify its use.
Patients from the current study with suspected infectious endophthalmitis in the postoperative period were directed to diagnostic confirmation. All subjects underwent through ocular ultrasound and vitrectomy via pars plana with intravitreal injection of antibiotics of Ceftazidime (2.25 mg/0.1 ml) and vancomycin (1.0 mg/0.1 ml), even those with visual acuity better than light perception, as recommended by the EVS1. In all cases, vitreous biopsies were collected and sent for staining and culture. The diagnosis of endophthalmitis is clinical and the treatment should not be delayed when signs and symptoms are indicative, as it may be occurring rapid destruction of ocular tissues and only after the third day of intraocular infection that pathogen-specific antibodies can be detected12. Consequently, laboratory results of staining and culture can be negative while severe inflammation occurs in the eye.
The prognosis for cases with negative culture is likely to be good, as sterile inflammation in the absence of bacterial toxins minimizes the risk of retinal damage30. In cases of positive culture, the severity of the intraocular infection depends on factors like inoculum, microorganism virulence, host immune responses, perioperative measures, and timing of infection presentation12. This justifies the different visual results found in the cases from 2013, as patients with early diagnosis and treatment for the virulent microorganism evolved to good visual acuity (cases #3 and #4) as opposed to patients who evolved to total blindness (cases #1 and #6) likely due to the different amount of inoculum; while one patient with a relatively late diagnosis and treatment (i.e. eighth postoperative day), evolved with low vision (case #2).
Furthermore, even with early diagnosis and institution of adequate treatment, the visual prognosis tends to be poor, as toxins produced by the microorganism and host inflammatory responses cause rapid damage to the photoreceptor and these effects can remain even after the contents eyepieces have become sterile30. Approximately fifty percent of affected patients do not restore vision of 20/40 or better and about thirty percent have visual acuity worse than 20/200 after treatment1,7,30. The cases developed prior the use of ATB-P of cefuroxime IC follow similar outcomes in terms of vision, but all the cases occurring after the introduction of ATB-P have restore vision to 20/30.
Despite the substantial sample size in the current study, there are some limitations worth noting. Firstly, there were no cases of gram-negative bacterial infections in our dataset, which may potentially overestimate the beneficial effects of intracameral antibiotic prophylaxis with cefuroxime. Additionally, in our pursuit of maximizing the sample size, we collected data from surgeries performed by a large number of surgeons. This also contributes to other potential limitations associated with the retrospective study design, including the risk of selection bias, concerns about data quality, and the presence of confounding variables. For future studies investigating the use of intracameral antibiotic prophylaxis in cataract surgeries, randomized controlled trials are advisable to address these limitations more effectively.
In conclusion, our findings indicate that the use of povidone-iodine eye drops associated with ocular topical antibiotics in the immediate postoperative period was not enough to avoid the occurrence of acute infectious endophthalmitis. After the addition of intracameral antibiotic-prophylaxis with cefuroxime into the regular protocol, the rates of infectious have drastically dropped into acceptable values within a high-volume surgical service. Considering that the conjunctiva is not sterile, the use of an ocular prosthesis (intraocular lens), the poor visual prognosis related to a postoperative acute infectious endophthalmitis, the high costs associated with treating an infectious endophthalmitis in comparison to the low cost of prophylaxis, and the visual and psychological morbidity, we strongly recommend the use of antibiotic prophylaxis to prevent infectious endophthalmitis in the postoperative period of cataract surgery.
주제: Drugs