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Risks of Cefuroxime Prophylaxis for
Postcataract Endophthalmitis
Khaled A. AlAbduljabbar1,2, Donald U. Stone1,3

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

Introduction surgeons adopt the use of ICC,[13] and the


absence of an ICC prophylactic regimen

P ostcataract surgery endophthalmitis is


a relatively uncommon but devastating
complication of modern cataract surgery,[1,2]
at a dose of 1 mg/0.1 mL was associated
with an almost 5fold increase in the
risk of postoperative endophthalmitis.[4]
and there is not complete consensus The injection is expedient, painless, and
regarding the ideal practice patterns for achieves high antibiotic concentrations in
prophylaxis.[3] The benefits of intracameral the immediate postoperative period. In
Research Department,
1
cefuroxime(ICC) have been supported by addition, intracameral injection may be
King Khaled Eye
multiple studies. The European Society of particularly effective in patients who sustain
Specialist Hospital,
2
College of Medicine, Cataract and Refractive Surgeons(ESCRS) posterior capsule rupture [17] and would
King Saud University, prospective multicenter interventional otherwise incur an increased the risk of
Riyadh, Kingdom of Saud trial (and many other casecontrol, endophthalmitis.
Arabia, 3Department of crosssectional, and longitudinal studies)
Ophthalmology, Wilmer
supported the hypothesis that the use of When considering the implementation
Eye Institute of Johns of any intervention, costeffectiveness is
Hopkins University,
ICC at the conclusion of cataract surgery
another important variable. ICC is relatively
Baltimore, MD, USA reduces the incidence of postoperative
costeffective in preventing endophthalmitis
endophthalmitis.[416] It is estimated that
after cataract surgery. Sharifi etal. estimated
Address for two to four cases of endophthalmitis
correspondence: the costeffectiveness ratio for ICC to be $1403
per 1000 surgeries can be avoided if
Dr.Donald U. Stone, per case of postoperative endophthalmitis
King Khaled Eye Specialist This is an open access article distributed under the terms of the prevented. Many commonly used topical
Hospital, Arouba Road, Creative Commons Attribution-NonCommercial-ShareAlike 3.0
P.O. Box7191, License, which allows others to remix, tweak, and build upon How to cite this article: Al-Abduljabbar KA,
Riyadh 11462, Kingdom of the work non-commercially, as long as the author is credited Stone DU. Risks of cefuroxime prophylaxis for
Saudi Arabia. and the new creations are licensed under the identical terms. postcataract endophthalmitis. Middle East Afr J
Email:dstone25@jhmi. Ophthalmol 2017;24:24-9.
edu For reprints contact: reprints@medknow.com
24 2017 Middle East African Journal of Ophthalmology | Published by Wolters Kluwer - Medknow
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Al-Abduljabbar and Stone: Risks of cefuroxime

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

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Al-Abduljabbar and Stone: Risks of cefuroxime

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

Table1: Adverse events attributed to cefuroxime compounding errors


Authors, year of publication Dose administered Clinical description
Buyukyildiz etal., 2010[34] 2 mg/0.1 mL Serous retinal detachment
Cystoid macular edema
Delyfer etal., 2011[31] 40.0-50.0 mg/0.1 mL Anterior inflammation with fibrin formation
2 of 6patients had corneal edema
2 others had elevated IOP extensive macular edema Serous retinal
detachment Fluorescein angiograms in 5 of 6cases showed diffuse leakage
without abnormal retinal perfusion
ERG recordings showed reduced rod function
ifti etal., 2014[35] 50-70 mg/1 mL 4cases
Corneal edema
Intraretinal hemorrhages optic atrophy developed 2weeks after surgery
Herrinton etal., 2016[36] 9 mg/0.1 mL 13 eyes of 11patients
Acute macular edema
Le D and PierreKahn, 2014[37] Suspected but confirmed 6patients
cefuroxime overdose Macular edema predominantly in the outer retinal layers associated with
serous retinal detachment. In the late stage, three patients had functional
impairment related to photoreceptor damage on OCT
Olavi, 2012[32] 50 mg/0.1 mL intracameral 16patients
cefuroxime Corneal edema
Elevated IOP
Pigmented precipitates and Loss of corneal endothelial cells
Pigmentary changes of the retina
Tritanopy type color vision defect
ERG(slight slowing of the aand bwaves in the scotopic response of the
rods)
Wong etal., 2015[33] 9 mg/0.1 mL 6 of 13 eyes had visual acuity of 20/70 or worse and severe macular edema
2 of 13 eyes(15%) had mild central corneal edema
Qureshi and Clark, 2011[38] Approximately 62.5 mg A single dot hemorrhage was seen with mild vascular tortuosity
Fundus fluorescein angiography demonstrated an ischemic macula with late
leakage of dye
OCT demonstrated intraretinal edema
Final CDVA was 4/40
White sclerosed vessel was later seen in the macula
Sakarya and Sakarya, 2010[39] 3 mg/0.1 mL 6patients
No adverse reaction or inflammation was observed at postoperative
examination
ERG: Electroretinography, OCT: Optical coherence tomography, CDVA: Corrected distance visual acuity, IPO: Intraocular pressure

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Al-Abduljabbar and Stone: Risks of cefuroxime

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
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