Beruflich Dokumente
Kultur Dokumente
248]
Original Article
Website:
Abstract:
www.meajo.org BACKGROUND: Endophthalmitis after cataract surgery is a rare but visionthreatening complication.
Intracameral cefuroxime(ICC) has been reported to be effective at reducing the risk, but concerns
DOI:
10.4103/meajo. regarding the risks associated with this intervention remain.
MEAJO_255_16 METHODS: Systematic review and synthesis of the literature on ICC, with a focus on the risks of
therapy.
RESULTS: Level 2a evidence was found to support the use of cefuroxime in penicillinallergic patients.
Compounding or dilutional errors are associated with ocular toxicity, but the incidence and risk of this
occurrence are unknown. Level 4 evidence supports interventions that reduce the risk of dilutional
errors. The association of cefuroxime injection with toxic anterior segment syndrome(TASS) is not
established; Level 5 evidence supports standard measures to reduce the incidence of TASS related
to cefuroxime administration.
CONCLUSION: Cefuroxime can be administered safely to penicillinallergic patients, and steps
should be taken to reduce the risk of compounding or dilutional errors to avoid negating the benefits
of this intervention. Recommended practice patterns for endophthalmitis prophylaxis should consider
the risks and benefits of ICC.
Keywords:
Cataract, cefuroxime, endophthalmitis, practice pattern, risk
antibiotics are not costeffective compared with avoided. However, cephalosporins with different side
ICC, even under optimistic assumptions about their chains(such as cefuroxime) may be given.[22]
efficacy. [18] Another economic analysis comparing
different prophylaxis regimens concluded that ICC It should be noted that the ESCRS study excluded patients
provided the best costeffectiveness ratio.[19] Therefore, with penicillin or cephalosporin allergy,[4] as did several
the decision to adopt this therapy is supported by studies other large studies.[7,11,23] ICC injection during cataract
demonstrating efficacy and costeffectiveness. surgery was well tolerated in a prospective study of forty
penicillinallergic patients with a negative preoperative
The final variable that must be included when cefuroxime skin test.[24] The use of ICC in patients with
determining practice patterns is risk. One weakness penicillin allergy was explored between 2004 and 2012 in
inherent in any meticulously performed clinical trial a casecontrol registry study; the control group was the
is that the results may not be generalizable to a more cohort of patients undergoing cataract surgery under a
diverse patient population and varying scenarios of care. hospital policy of excluding patients with selfreported
Most clinical trials make great effort to reduce the risk of penicillin allergy. After a critical review of the literature
enrollment in the study, and therefore the safety profile and pilot study in 817patients with reported penicillin
reported may be a bestcase scenario. The purpose of allergy, this policy was altered, and all patients without
this review is to provide an evidencebased review and a specific history of cephalosporin anaphylactic reaction
synthesis of the literature regarding the risks of ICC were administered ICC. Out of 13,592 subsequent cataract
when administered for the prevention of postcataract surgeries, there were no reported cases of anaphylaxis or
surgery endophthalmitis, thereby informing decisions allergic reaction.[25] This study is limited by the registry
regarding best practices for cataract surgery. design, which may underreport or miscategorize adverse
events. Asimilar longitudinal observational study by
The categories of risk to be reviewed are: Shorstein etal. reported a decreasing endophthalmitis
1. Risk of anaphylaxis, especially in penicillin or rate after instituting a standard ICC protocol; there
cephalosporin allergic patients were no reports of anaphylaxis or allergic reaction
2. Risk of toxicity at routine clinical doses among 12,609 surgeries, but some patients received
3. Risk of toxicity at increased doses due to compounding other intracameral antibiotics, and it is unclear if
errors penicillinallergic patients routinely received cefuroxime
4. Idiosyncratic reactions, including toxic anterior or other antibiotics such as moxifloxacin or vancomycin.
segment syndrome(TASS). Barreau et al. reported a similar casecontrol study
comparing the endophthalmitis rates before and after
Methods instituting a standard ICC regimen; patients with
cefuroxime allergy were excluded, but penicillinallergic
We performed a systematic review of the existing patients received ICC. There were no cases of anaphylaxis
scientific literature using PubMed and Google among 2289patients receiving ICC, but the prevalence
Scholar. The key words used were Cefuroxime, of penicillin allergy was not reported.[5]
endophthalmitis and cataract surgeries. There
were no date or language restrictions in the electronic There are two case reports of an anaphylactic reaction
searches. After reviewing the abstracts for relevance in penicillin or cephalosporin allergic patients who
44 articles were included for review. All articles were received ICC.[26,27] The number of patients from these
read in full by both authors with the exception of two centers that had received ICC were not reported,
that were available only as abstracts. The highest level preventing an estimation of the incidence of this
of evidence for each aspect of the intervention was complication.
assigned utilizing the Oxford Center for EvidenceBased
Medicine Guidelines.[20] Risks of cefuroxime toxicity at standard doses
Adverse effects that have rarely been reported with
Results routine clinical doses include serous macular detachment,
cystoid macular edema(CME), increased central foveal
Risk of anaphylaxis thickness, decreased bestcorrected distance visual
Crossreactivity between penicillins and most secondand acuity, anterior chamber inflammation, and vitritis.[28,29]
all thirdand fourthgeneration cephalosporins is However, a prospective study found that ICC at the
negligible. It is generally considered safe to administer standard dose of 1mg/0.1mL did not have a statistically
a cephalosporin with a side chain that is structurally significant effect on postoperative macular thickness
dissimilar to that of penicillin.[21] In patients with a compared with nonadministration of intracameral
documented IgEmediated reaction to penicillin, use antibiotic;[30] although, this study was underpowered
of cephalosporins with a similar side chain should be to detect rare events. The ESCRS study and other
Middle East African Journal of OphthalmologyVolume 24, Issue 1, January - March 2017 25
[Downloaded free from http://www.meajo.org on Monday, June 12, 2017, IP: 112.215.65.248]
longitudinal cohort studies were not designed to assess administration of increased concentrations or volumes
safety or adverse events as primary endpoints, but a of cefuroxime. Alimitation in assigning risk based on
large number of patients enrolled without a reported studies such as this is the lack of incidence data; it is
increase in these adverse events suggests that they are unknown how many patients have received increased
not associated, are masked by confounding factors, or doses of ICC, and therefore, the rate of these adverse
are exceedingly rare. events is unknown. The incidence rate of compounding
errors for ICC is also unknown and is presumably highly
Risks of cefuroxime toxicity at increased doses dependent on local factors such as the mechanisms of
A lingering concern for some ophthalmologists is the risk medication preparation and quality control measures.
of ocular toxicity attributable to inadvertent exposure to
elevated concentrations(typically due to compounding Toxic anterior segment syndrome and other
errors). High doses of cefuroxime are associated with idiosyncratic adverse events
anterior and posterior segment inflammation with fibrin TASS after cataract surgery has been reported in
formation, corneal edema, elevated intraocular pressure, association with the intracameral use of cefuroxime.[18,40]
serous macular detachment, CME, hemorrhagic retinal akr etal. reported an ongoing cluster of TASS cases at
infarction, and reduced rod photoreceptor cell function a single center, with a resolution of the outbreak after
by electroretinography. [3135] Table1 summarizes discontinuing ICC in favor of intracameral moxifloxacin.
the reported complications related to inadvertent As expected, there was no rechallenge in affected
26 Middle East African Journal of OphthalmologyVolume 24, Issue 1, January - March 2017
[Downloaded free from http://www.meajo.org on Monday, June 12, 2017, IP: 112.215.65.248]
patients to determine conclusively if cefuroxime or other include measures to audit and provide quality assurance
factor contributed to TASS. There was also no reported of the cefuroxime dilution protocol.
analysis of cefuroxime concentration to ascertain the
potential role of dilution errors or other factors related Conclusion
to preparation. No other studies were found that studied
the relationship of cefuroxime to TASS, or the effects of Half of the riskbenefit equation of ICC has been solved to
specific interventions to reduce the incidence of TASS the satisfaction of most clinicians; the efficacy is clear. The
related to cefuroxime. remaining barriers to more widespread adoption include
concerns about risks such as anaphylaxis, dilution
Discussion errors, and toxicity (especially with noncommercial
preparation[42]) and finally, the additional costs of this
The efficacy of ICC as a prophylaxis for postcataract therapy. Since endophthalmitis is a rare event, even a
surgery endophthalmitis has been well established, slight increase in the risk of prophylactic therapy may
but concerns regarding the risks of this intervention negate the potential benefits. Our review and synthesis
remain. The consensus of the literature from of the literature regarding the risks of cefuroxime therapy
systemic administration of antibiotics is that the support the following recommendations:
risk of crossreactivity between secondgeneration 1. Cefuroxime may be used safely in patients with
cephalosporins (such as cefuroxime) and penicillin is penicillin allergy(Level 2a evidence)
very low. Our review of the literature supports a low rate 2. Efforts to reduce the risk of dilution errors may
of anaphylactic reactions, even among penicillinallergic include the use of a commercially prepared product,
patients. Apostal survey conducted among consultant or strict quality assurance measures(Level 4 evidence)
ophthalmic surgeons working in the National Health 3. Routine measures to reduce TASS should also apply
Service Ophthalmic Departments in England revealed to the use of cefuroxime (Level 5 evidence); even
that of 262 consultants, 103 (37%) used cefuroxime in though, there is no proven association.
patients allergic to penicillin.[41] We propose that an
acceptable practice pattern would be to consider ICC Future studies may further define the costeffectiveness of
in all cataract surgery patients, including those with ICC, and continued efforts to reduce the risk attributable
a history of penicillin allergy; administration to those to dilution errors are indicated. Finally, comparative
patients with cephalosporin allergy may be considered, studies of the efficacy and safety of cefuroxime compared
but skin testing may be indicated to identify those to other intracameral antibiotics are needed to help define
patients that are at increased risk of anaphylaxis and the optimal endophthalmitis prophylaxis regimen for
should not receive ICC. Alternative intracameral our patients undergoing cataract surgery.
antibiotics, such as vancomycin and moxifloxacin, may
reduce the risk of anaphylaxis in cefuroximeallergic Financial support and sponsorship
patients, but the efficacy of those interventions has been Nil.
less well established.
Conflicts of interest
The latest survey of members of the American Society There are no conflicts of interest.
of Cataract and Refractive Surgeons revealed that 30%
of the United States ophthalmologists were utilizing References
intracameral antibiotics, compared to 70% of European
respondents.[42] However, many US cataract surgeons 1. MillerJJ, ScottIU, Flynn HW Jr., SmiddyWE, NewtonJ, MillerD.
Acuteonset endophthalmitis after cataract surgery(20002004):
believe that intracameral antibiotics are unnecessary, Incidence, clinical settings, and visual acuity outcomes after
based on concerns about the methodology of the treatment. Am J Ophthalmol 2005;139:9837.
ESCRS and other studies, or that the absolute benefits 2. Taban M, Behrens A, Newcomb RL, Nobe MY, Saedi G,
do not outweigh the risks of dilution errors and SweetPM, etal. Acute endophthalmitis following cataract
toxicity.[3,43] surgery: A systematic review of the literature. Arch Ophthalmol
2005;123:61320.
3. SchwartzSG, GrzybowskiA, Flynn HW Jr. Antibiotic prophylaxis:
Not surprisingly, a clinical study demonstrated that Different practice patterns within and outside the United States.
the mathematical accuracy of a dilution protocol does Clin Ophthalmol 2016;10:2516.
not ensure dosage accuracy in a realworld clinical 4. Endophthalmitis Study Group, European Society of Cataract &
scenario. [44] The authors suggest that a commercial Refractive Surgeons. Prophylaxis of postoperative endophthalmitis
preparation would likely reduce the risk of dilution following cataract surgery: Results of the ESCRS multicenter
study and identification of risk factors. JCataract Refract Surg
errors, but commercial preparations of intracameral 2007;33:97888.
antibiotic agents may not be financially viable in all 5. BarreauG, MounierM, MarinB, AdenisJP, RobertPY.
health care environments. Implementation of ICC should Intracameral cefuroxime injection at the end of cataract surgery to
Middle East African Journal of OphthalmologyVolume 24, Issue 1, January - March 2017 27
[Downloaded free from http://www.meajo.org on Monday, June 12, 2017, IP: 112.215.65.248]
reduce the incidence of endophthalmitis: French study. JCataract penicillinallergic patients: A metaanalysis. Otolaryngol Head
Refract Surg 2012;38:13705. Neck Surg 2007;136:3407.
6. DaienV, PapinaudL, GilliesMC, DomergC, NagotN, LacombeS, 23. NgAL, TangWW, LiPS, LiKK. Intracameral cefuroxime in the
etal. Effectiveness and safety of an intracameral injection of prevention of postoperative endophthalmitis: An experience from
cefuroxime for the prevention of endophthalmitis after cataract Hong Kong. Graefes Arch Clin Exp Ophthalmol 2016;254:198792.
surgery with or without perioperative capsular rupture. JAMA 24. PromelleV, JanyB, DrimbeaA, JezraouiP, MilazzoS. Tolerability
Ophthalmol 2016;134:8106. of intracameral cefuroxime during cataract surgery in case of
7. GarcaSenz MC, AriasPuenteA, RodrguezCaravacaG, penicillin allergy. JFr Ophtalmol 2015;38:2837.
Bauelos JB. Effectiveness of intracameral cefuroxime in 25. MyneniJ, DesaiSP, JayamanneDG. Reduction in postoperative
preventing endophthalmitis after cataract surgery Tenyear endophthalmitis with intracameral cefuroxime. JHosp Infect
comparative study. JCataract Refract Surg 2010;36:2037. 2013;84:3268.
8. JabbarvandM, HashemianH, KhodaparastM, JouhariM, 26. Moisseiev E, Levinger E. Anaphylactic reaction following
TabatabaeiA, RezaeiS. Endophthalmitis occurring after cataract intracameral cefuroxime injection during cataract surgery.
surgery: Outcomes of more than 480000 cataract surgeries, JCataract Refract Surg 2013;39:14324.
epidemiologic features, and risk factors. Ophthalmology 27. Villada JR, Vicente U, Javaloy J, Ali JL. Severe anaphylactic
2016;123:295301. reaction after intracameral antibiotic administration during
9. KatzG, BlumS, LeevaO, AxerSiegelR, MoisseievJ, TeslerG, cataract surgery. JCataract Refract Surg 2005;31:6201.
etal. Intracameral cefuroxime and the incidence of postcataract 28. KontosA, MitryD, AlthauserS, JainS. Acute serous macular
endophthalmitis: An Israeli experience. Graefes Arch Clin Exp detachment and cystoid macular edema after uncomplicated
Ophthalmol 2015;253:172933. phacoemulsification using standard dose subconjunctival
10. MontanP, Lundstrm M, SteneviU, ThorburnW. Endophthalmitis cefuroxime. Cutan Ocul Toxicol 2014;33:2334.
following cataract surgery in Sweden. The 1998 national
29. Xiao H, Liu X, Guo X. Macular edema with serous retinal
prospective survey. Acta Ophthalmol Scand 2002;80:25861.
detachment postphacoemulsification followed by spectral
11. RodrguezCaravacaG, GarcaSenz MC, VillarDelCampoMC, domain optical coherence tomography: A report of two cases.
AndrsAlbaY, AriasPuenteA. Incidence of endophthalmitis BMC Res Notes 2015;8:647.
and impact of prophylaxis with cefuroxime on cataract surgery.
30. GuptaMS, McKeeHD, Saldaa M, StewartOG. Macular thickness
JCataract Refract Surg 2013;39:1399403.
after cataract surgery with intracameral cefuroxime. JCataract
12. Behndig A, Cochener B, Gell JL, Kodjikian L, Mencucci R, Refract Surg 2005;31:11636.
NuijtsRM, etal. Endophthalmitis prophylaxis in cataract surgery:
31. DelyferMN, RougierMB, LeoniS, ZhangQ, DalbonF, ColinJ,
Overview of current practice patterns in 9 European countries.
etal. Ocular toxicity after intracameral injection of very high doses
JCataract Refract Surg 2013;39:142131.
of cefuroxime during cataract surgery. JCataract Refract Surg
13. KesselL, FlesnerP, AndresenJ, ErngaardD, TendalB, HjortdalJ. 2011;37:2718.
Antibiotic prevention of postcataract endophthalmitis: A
32. OlaviP. Ocular toxicity in cataract surgery because of inaccurate
systematic review and metaanalysis. Acta Ophthalmol
preparation and erroneous use of 50mg/ml intracameral
2015;93:30317.
cefuroxime. Acta Ophthalmol 2012;90:e1534.
14. RosaGD, Dez M. Prophylaxis of postoperative endophthalmitis
33. WongDC, WaxmanMD, HerrintonLJ, ShorsteinNH. Transient
with intracameral cefuroxime: Afive years experience profilaxis
macular edema after intracameral injection of a moderately
de la endoftalmitis postquirrgica con cefuroxima intracamerular:
elevated dose of cefuroxime during phacoemulsification surgery.
Experiencia de cinco aos. Arch Soc Esp Oftalmol 2009;84:8590.
JAMA Ophthalmol 2015;133:11947.
15. MontanPG, WejdeG, KoranyiG, RylanderM. Prophylactic
34. BuyukyildizHZ, GulkilikG, KumcuogluYZ. Early serous macular
intracameral cefuroxime. Efficacy in preventing endophthalmitis
detachment after phacoemulsification surgery. JCataract Refract
after cataract surgery. JCataract Refract Surg 2002;28:97781.
Surg 2010;36:19992002.
16. Gower EW, Lindsley K, Nanji AA, Leyngold I, McDonnell PJ.
Perioperative antibiotics for prevention of acute endophthalmitis 35. ifti S, ifti L, Dag U. Hemorrhagic retinal infarction due
after cataract surgery. Cochrane Database Syst Rev 2013;15:CD006364. to inadvertent overdose of cefuroxime in cases of complicated
cataract surgery: Retrospective case series. Am J Ophthalmol
17. ShorsteinNH, WinthropKL, HerrintonLJ. Decreased postoperative
2014;157:4215.e2.
endophthalmitis rate after institution of intracameral antibiotics
in a Northern California eye department. JCataract Refract Surg 36. Herrinton LJ, Shorstein NH, Paschal JF, Liu L, Contreras R,
2013;39:814. Winthrop KL, etal. Comparative effectiveness of
antibiotic prophylaxis in cataract surgery. Ophthalmology
18. Sharifi E, Porco TC, Naseri A. Costeffectiveness analysis of
2016;123:28794.
intracameral cefuroxime use for prophylaxis of endophthalmitis
after cataract surgery. Ophthalmology 2009;116:188796.e1. 37. Le D B, PierreKahn V. Early macular edema after
19. Linertov R, AbreuGonzlez R, GarcaPrez L, phacoemulsification and suspected overdose of cefuroxime:
AlonsoPlasencia M, CordovsDorta LM, AbreuReyes JA, Report of six cases. JFr Ophtalmol 2014;37:20210.
etal. Intracameral cefuroxime and moxifloxacin used as 38. Qureshi F, Clark D. Macular infarction after inadvertent
endophthalmitis prophylaxis after cataract surgery: Systematic intracameral cefuroxime. JCataract Refract Surg 2011;37:11689.
review of effectiveness and costeffectiveness. Clin Ophthalmol 39. SakaryaY, SakaryaR. Cefuroxime dilution error. Eur J Ophthalmol
2014;8:151522. 2010;20:4601.
20. HowickJ, ChalmersI, GlasziouP, Greenhalgh T, Heneghan C, 40. akir B, CelikE, Aksoy N, Bursali , Uak T, BozkurtE, etal.
Liberati A, et al. The Oxford 2011 Levels of Evidence. Oxford Toxic anterior segment syndrome after uncomplicated cataract
Centre EvidenceBased Medicine. Vol.1; 2011. Available from: surgery possibly associated with intracamaral use of cefuroxime.
http://www.cebm.net/index.aspx?o=1025. [Last accessed on Clin Ophthalmol 2015;9:4937.
2016Sep03]. 41. NanavatyMA, WearneMJ. Perioperative antibiotic prophylaxis
21. CampagnaJD, BondMC, SchabelmanE, HayesBD. The use of during phacoemulsification and intraocular lens implantation:
cephalosporins in penicillinallergic patients: A literature review. National survey of smaller eye units in England. Clin Exp
JEmerg Med 2012;42:61220. Ophthalmol 2010;38:4626.
22. PichicheroME, CaseyJR. Safe use of selected cephalosporins in 42. ChangDF, BragaMeleR, HendersonBA, MamalisN, Vasavada A;
28 Middle East African Journal of OphthalmologyVolume 24, Issue 1, January - March 2017
[Downloaded free from http://www.meajo.org on Monday, June 12, 2017, IP: 112.215.65.248]
ASCRS Cataract Clinical Committee. Antibiotic prophylaxis of United States based on prospective studies. JCataract Refract
postoperative endophthalmitis after cataract surgery: Results Surg 2008;34:5059.
of the 2014 ASCRS member survey. JCataract Refract Surg 44. Lockington D, Flowers H, Young D, Yorston D. Assessing the
2015;41:13005. accuracy of intracameral antibiotic preparation for use in cataract
43. Liesegang TJ. Intracameral antibiotics: Questions for the surgery. JCataract Refract Surg 2010;36:2869.
Middle East African Journal of OphthalmologyVolume 24, Issue 1, January - March 2017 29