incidencia y prevencion de endoftalmitis

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Endophthalmitis: incidence and preventionEduardo S. Soriano and Mauro Nishi

Purpose of review

To present current peer-reviewed articles related to the

incidence and prevention of postoperative endophthalmitis.

Recent findings

Recent literature indicates that the incidence of

postoperative endophthalmitis may be on the rise. Although

the preoperative use of antibiotics as prophylaxis is still

controversial, it is becoming more common.

Summary

The reports of endophthalmitis analyzed from peer-

reviewed ophthalmic journals suggest that the incidence ofendophthalmitis has increased, ranging from 0.1 to 0.18%

in different countries. This may be related to factors

associated with the incision. Although some resistance

has been detected, fourth-generation fluoroquinolones

seem to be a proper antibiotic for endophthalmitis

prophylaxis because of their spectrum, mode of action, and

penetration.

Keywords

cataract, endophthalmitis, incidence, prevention

Curr Opin Ophthalmol 16:6570. 2005 Lippincott Williams & Wilkins.

Cataract Institute, Federal University of Sao Paulo, Brazil

Correspondence to Eduardo S. Soriano, R. Tome de Souza, 35. Embu,SP - 06844-010, BrazilE-mail: [email protected]

Current Opinion in Ophthalmology 2005, 16:6570

Abbreviation

IOL intraocular lens

2005 Lippincott Williams & Wilkins.1040-8738

Introduction

Recently, endophthalmitis has returnedto the center of the

ophthalmologic debate on the basis of two facts: the appar-

ent increase in its incidence and the introduction of new

antibiotics that might improve its prevention [1]. Al-

though rare, this surgical complication is associated with

a poor prognosis, causing frustration to both patients and

physicians, which frequently leads to legal implications.

Preventive measures have both medical and economic im-

portance, considering the high number of cataract surgeries

performed annually in the world.

Establishing practice patterns based on scientific evidence

is essential; however, it is difficult to conduct conclusive

studies of endophthalmitis because of its low prevalence.

Prospective studies to evaluate preventive methods would

need large reference samples to establish reliable epide-

miologic results. Multicenter studies have problems in

standardizing all the potential risk factors such as the

presence of blepharitis or other ocular surface disorders,

sterilization conditions, operative environment, length of

surgery, size and location of incision, presence of suture, type

of intraocular lens (IOL), and postoperative care. Most ofthe articles related to endophthalmitis are retrospective or

laboratory studies, allowing only indirect conclusions.

The objective of this article is to review the most recent

peer-reviewed publications related to the incidence and

prevention of postcataract surgery endophthalmitis, with

a focus on practical information.

Incidence and risk factorsPhacoemulsification with topical anesthesia and a clear

corneal nonsutured temporal incision enabled a decrease

in cost and length of surgery, more operating room effi-ciency, faster recovery, reduced need for patching the eye,

and less astigmatism. With a small incision and a closed

maintained anterior chamber associated with the wide

use of antibiotics, less bacterial contamination is now ex-

pected in comparison with the extracapsular extraction

era. In the past two decades, several studies have sug-

gested that the incidence of endophthalmitis was approx-

imately 1 case in 1000 procedures, but several recent large-

scale international studies have reported significantly

higher rates of endophthalmitis: as many as 3 cases in

1000 procedures [1]. Several possible causes may con-

tribute to the development of endophthalmitis, includingincision type, surgical technique, IOL type, reuse of dis-

posable material, and emerging bacterial resistance to

existing antibiotic agents.

JOBNAME: coop 16#1 2005 PAGE: 1 OUTPUT: Wed December 22 21:01:31 2004

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The definition of endophthalmitis represents an important

factor in the comparison of incidence studies. The inclu-

sion of presumed or culture-proven cases, as well as the

specification of the time between the cataract procedureand the diagnosis, will affect estimations of incidence.

The incidence of presumed endophthalmitis in a 10-year

retrospective survey in a single United Kingdom eye unit

was 0.16%, with higher frequency in extracapsular extrac-

tion (0.31%) than in phacoemulsification (0.07%). The rate

for folded lenses (1.21%) was higher than for injectable

lenses (0.028%), suggesting that the use of injectors

reduces the incidence of infection [2]. In a prospective

study, with active surveillance of patients with clinical

diagnoses of endophthalmitis in the United Kingdom for

12 months (between 1999 and 2000), Kamalarajah et al.

[3] estimated the incidence of endophthalmitis at

0.14% after adjustment for underreporting data. The num-

ber of cataract extractions for the study period was approx-

imately 230,000, and gram-positive organisms were

identified in 93% of the isolates and gram-negative organ-

isms in only 7%.

In an Australian retrospective survey of 117,083 cataract

procedures, the incidence of confirmed postoperative

endophthalmitis was 0.18%, remaining relatively constant

despite a threefold increase in cataract surgery over the 21

years studied. Besides the decrease of endophthalmitis af-

ter extracapsular extraction over the whole period (and not

after phacoemulsification over the past 12 years), the inci-dence was similar for extracapsular extraction and phaco-

emulsification. However, a significantly higher risk was

found in patients older than 80 years, those having surgery

in private hospitals, those receiving same-day surgery, and

those undergoing the procedure in winter. A prolonged stay,

at least 2 days, could optimize perioperative prophylactic

protocols, mainly in private hospitals. Cataract surgery with

lacrimal or eyelid procedures increased the risk of endoph-

thalmitis. No association was found between gender,

comorbidity, or volume of cataract surgery performed at

each hospital [4,5].

A 3-year survey between 1996 and 1998, conducted by use

of a national registry in Norway, showed that the incidence

of suspected postoperative endophthalmitis was 0.16%

for a total of 71,190 cases over the 3-year period, when

phacoemulsification was estimated to be used in more

than 90% of the cases. Microbial growth occurred in

75% of the cases and was an important predictor of the

visual outcome [6]. In a prospective study, the Swedish

National Cataract Register identified a 0.1% rate of pre-

sumed endophthalmitis in 54,666 cataract operations. In

this study, acrylic IOLs were seen to decrease the risk

of endophthalmitis in comparison with hydrogel and poly-methylmethacrylate lenses, although surgical complica-

tions could have occurred with a bias in the IOL

selection [7].

In a retrospective case-control study of Asian patients per-

formed in Singapore, silicone IOLs (compared with poly-

methylmethacrylate or acrylic IOL) and rupture of the

posterior capsule were independently associated withacute endophthalmitis, although the authors pointed out

that information and selection (nonrandom allocation of

patients) biases could have accentuated some associations

and attenuated others [8].

Table 1 summarizes the incidence of endophthalmitis in

different countries.

Cataract surgery and incision type: dosutureless corneal incisions increasethe risk for endophthalmitis?Wound abnormality has been identified as a risk factor for

endophthalmitis, but attention has recently been brought

to the role of the incision location in the genesis of endoph-

thalmitis. A case-control study by Cooper et al. [9] sug-

gests a possible relation between clear corneal wounds

and an increased risk of endophthalmitis. In this retrospec-

tive review, surgical technique was compared between 38

culture-proven cases of endophthalmitis and 371 randomly

selected uncomplicated cataract surgery cases. The

authors observed that clear cornea wounds were associated

with a threefold greater risk of endophthalmitis than was

scleral tunnel incision. Of all the patients in whom the in-

tegrity of the cataract wound was checked, about half re-ceived diagnoses of wound abnormality. In addition, the

presence or absence of a suture was not significant in in-

creasing the risk of endophthalmitis. However, case

patients and control patients were not matched, and statis-

tical analysis determined that if the proportion of clear cor-

neal incisions in the control group was increased to 40%

(instead of 20% in the control group in this study), the as-

sociation of type of incision and endophthalmitis might not

have been significant.

In Japan, a multicenter study evaluated 11,595 eyes pro-

spectively to assess the association between incision typein phacoemulsification and endophthalmitis. Fifteen eyes

(0.13%) had clinically diagnosed endophthalmitis. The

relative risk of endophthalmitis in eyes where an acrylic

IOL (MA60BM, Alcon) or a silicone IOL (SI-40NB,

Allergan) was implanted via a superior sclerocorneal

Table 1. Incidence of endophthalmitis in differentcountries during the phacoemulsification era

Study Place Period Incidence (%)

Mayer et al. [2] UK 19912001 0.16Kamalarajah et al. [3] UK 19992000 0.14

Semmens et al. [4] Australia 19801998 0.18Sandvig and Dannevig [6] Norway 19961998 0.16Montan et al. [7] Sweden 1998 0.10Nagaki et al. [10] Japan 19982001 0.13

66 Cataract surgery and lens implantation




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incision was 4.8-fold lower than in eyes with an acrylic

IOL (MA60BM, Alcon) implanted through a temporal cor-

neal incision. The wounds remained sutureless, and only

the sclerocorneal incisions were covered with the conjunc-tival flap. There was no significant difference in the inci-

dence of endophthalmitis between patients with or

without diabetes mellitus, nasolacrimal duct obstruction,

or eyelid disorders [10].

In a laboratory investigation, McDonnell et al. [11] eval-

uated the stability of the sutureless clear corneal cataract

incision, demonstrating that transient reduction of intraoc-

ular pressure might result in poor wound apposition. The

incision edges tended to gape starting at theinternalaspect

of the wound, with a potential for fluid flow across the cor-

nea and into the anterior chamber. Histologic examination

showed dye particles applied to the ocular surface pene-

trate in all incisions for up to three fourths of the length

of the wound. Using the same method (OCT) in another

study, the authors compared different incision angles (an-

gle of knife relative to ocular surface) in clear corneal,

limbal, and scleral incisions. Larger (more perpendicular)

wound angles were associated with greater wound edge

gaping as intraocular pressure was increased. By contrast,

smaller wound angles were associated with tighter apposi-

tion of incision edges at high intraocular pressures. In gen-

eral, for smaller (standard) angles, limbal incisions resulted

in better wound apposition/sealing relative to clear corneal

incisions [12].

Clear corneal sutureless temporal incisions may be more

prone to endophthalmitis because the wound is not pro-

tected by the eyelid or conjunctiva and is more exposed

to bacteria in tear film and eyelid margins. It is possible

that there is a learning curve to the construction of a wa-

tertight clear corneal incision, or a stable, self-sealing in-

cision may be technically more difficult in the cornea than

in the sclera. At least, a red flag has been raised regarding

clear corneal sutureless temporal incisions, and further

studies are necessary to clarify whether they really in-

crease the risk of endophthalmitis. So far, it is advised thatmore attention be paid to the architecture of the incisions,

and any questionable incision should be sutured.

PreventionStrategies for preventing postoperative endophthalmitis

begin with the adoption of universal prophylactic mea-

sures like preparation of the operative site with povidone-

iodine, preoperative hand scrubbing by the surgical team,

maintenance of a sterile operative field and material, and

strict hospital polices regarding infection deterrence. The

underlying principle behind prophylaxis is to decrease thechance that any pathogen will enter the eye and eradicate

the pathogens that gained access to the eye during or after

surgery.

Several studies have suggested that the patients external

tissues represent the major sources of infection, and evi-

dence has been presented that surface flora routinely gain

entry to the anterior chamber during cataract surgery[13,14]. Considering the hypothesis that the most com-

mon sources of postoperative endophthalmitis are the

patients external flora, sterilization has become a priority

in preventive measures. Until now, the only significant

measure to prevent eye infection has been the use of top-

ical povidone-iodine in the conjunctiva before the surgery.

A 5% concentration of povidone-iodine is more effective

than 1% povidone-iodine in decreasing the conjunctival

bacterial flora, according to the study conducted by

Ferguson et al. [15] that compared conjunctival cultures

taken before and after irrigation with different concentra-

tions of povidone-iodine. The 5% povidone-iodine group

showed a decrease in median colony-forming units of

96.7% compared with 40% in the 1% povidone-iodine

group. Other prophylactic measures have also been stud-

ied, like preoperative topical antibiotics, lash trimming,

saline irrigation; intracameral antibiotics or heparin, and

postoperative subconjunctival antibiotics. However, ac-

cording to an extensive review published in 2002 by Ciulla

et al. [16], none of these methods demonstrated strong ev-

idence of reducing the risk of endophthalmitis.

Antibiotics

The use of antibiotics to prevent endophthalmitis has

been promoted, but consistent antibiotic use is still notroutine practice. To the best of our knowledge, there

are no prospective randomized controlled studies to sup-

port this assumption. The topical administration of anti-

biotic agents preoperatively is thought to be beneficial

because of the potential effect in diminishing superficial

flora. Considering that ocular flora play a major role in the

etiology of endophthalmitis, using anti-infective agents

like povidone-iodine to lower surface bacterial contamina-

tion before surgery would prevent infection. Also, some

drugs, such as quinolones, are capable of penetrating

the cornea to achieve significant intraocular concentra-

tions sufficient to suppress the growth of infective patho-gens that might contaminate the eye during or after

a surgical procedure. A broad-spectrum, highly permeable,

inexpensive antibiotic with low toxicity is ideal.

Quinolones

Quinolones, because of their broad-spectrum activity and

favorable pharmacokinetic and safety profiles, have be-

come a popular topical agent. Unfortunately, resistance

to this class of antibacterials, particularly among gram-

positive organisms,is emerging. Resistance has been attrib-

uted in part to inappropriate sublethal dosing and slow

tapering, which have induced mutagenesis in once suscep-tible pathogens. Because of increasing resistance, newer

agents must be considered. The fourth-generation quino-

lones, such as gatifloxacin and moxifloxacin, confer a

Endophthalmitis Soriano and Nishi 67




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dual-binding mechanism of action in gram-positive organ-

isms, inhibiting both DNA gyrase and topoisomerase intra-

venously. This is believed to expand their spectrum of

activity to inhibit bacterial strains that are otherwise resis-tant to older fluoroquinolones, and they therefore hold

great promise for treating and preventing endophthalmitis

[17].

Knowledge of the most common organisms associated with

endophthalmitis and their resistance profile is important in

the decision to use antibioticprophylaxis. In a retrospective

study, the records of all patients with culture-positive

endophthalmitis caused byStreptococcus pneumoniaetreated

at the Bascom Palmer Eye Institute between 1989 and

2003 were reviewed. In a total of 27 cases, only 5 were sec-

ondary to a cataract procedure, and the rest were related to

other causes. Some resistance to fluoroquinolones was

detected: 8% to ofloxacin, 14% to levofloxacin, and 7% to

gatifloxacin. All isolates were sensitive to ciprofloxacin

and moxifloxacin, in addition to vancomycin, clindamycin,

and cefazolin. Only 8% were sensitive to gentamicin [18].

In another study from the same center, in which all cases of

endophthalmitis (cataract surgery, posttraumatic, endoge-

nous, and miscellaneous) between 1996 and 2001 were

reviewed, the sensitivities were as follows: for gram-posi-

tive organisms, vancomycin 100%, gentamicin 78.4%,

ciprofloxacin, 68.3%, ceftazidime 63.6%, and cefazolin

66.8%. For gram-negative organisms, the sensitivities were

as follows: ciprofloxacin 94.2%, amikacin 80.9%, ceftazi-dime 80.0%, and gentamicin 75.0% [19]. A recent report

compared the in vitro susceptibilities and potencies of

ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and

gatifloxacin in retrospective bacteria isolated from cases

of endophthalmitis. In general, fourth-generation fluoro-

quinolones covered bacterial resistance to the second-

and third-generation fluoroquinolones, and moxifloxacin

was the most potent fluoroquinolone for gram-positive bac-

teria, whereas all the antibiotics studied demonstrated

equivalent potencies to gram-negative bacteria [20].

Antibiotic regimenIn addition to susceptibility, other issues still need to be

discussed regarding the use of antibiotics in prophylaxis,

like best timing, frequency, and routes, including oral,

subconjunctival, and intracameral. An experimental in vivo

study investigated three different topical regimens of

moxifloxacin to prevent bacterial endophthalmitis when

Staphylococcus aureus was injected into rabbit eyes. Saline

was used as a control. The use of moxifloxacin before

and after bacterial injection showed lower clinical scores

than when the antibiotic was used either before or after

the injection. Cultures from the anterior and posterior

chambers were negative for S. aureusin all three moxiflox-acin treatment regimens, suggesting that it reached suffi-

cient intraocular levels to prevent endophthalmitis in an

animal model [21].

Two prospective randomized studies compared the admin-

istration of topical ofloxacin 1 hour before surgery with ad-

ministration four times daily for 3 days before surgery; the

results suggestedthat thelonger regimen wasbetter forde-creasing surface contamination. In the first study, 42% of

eyes in the 1-hour group had positive conjunctival culture

immediately before surgery, compared with 19% of eyes in

the 3-day group. Immediately after surgery, 34%and 14% of

eyes had positive cultures in the 1-hour and 3-day groups,

respectively. Quantitatively, fewer bacteria were isolated

from eyes in the 3-day group compared with those in the

1-hour group [22]. The second study evaluated the rate

of contamination of microsurgical knives during cataract

surgery, comparing the 3-day with the 1-hour preoperative

application of topical ofloxacin. The results showed that

26%of knivesin the1-hour group were positive forbacterial

growth compared with only 5% in the 3-day group [23].

Intraoperative use of antibiotics

In addition to preoperative use, antibiotics are also used

intraoperatively (intracamerally or subconjunctivally) and

after surgery. The effect of antibiotics in the irrigation so-

lution may be ephemeral because the half-life of any anti-

biotic is achieved approximately2 hours aftersurgery. Libre

et al. [24] designed an experiment that simulated the half-

life of vancomycin in the anterior chamber. Incubation with

vancomycin for 2 hours caused a slight decline in the

growth of methicillin-resistant S. aureusbut did not elimi-

nate it. Methicillin-resistant S. aureusgrowth in the controlgroup was higher, suggesting that the intracameral injec-

tion of antibiotic agentscould be used in prophylaxis.A ran-

domized controlled prospective clinical trial showed that

the intraoperative infusion of vancomycin and gentamicin

decreased aqueous humor contamination during phaco-

emulsification. Aqueous samples taken at the end of sur-

gery were contaminated in 21.1% of eyes in the group with

balanced salt solution only and in 6.8% eyes in the group

with balanced salt solution plus antibiotics. Capsular rup-

ture was associated with a higher rate of contamination in

both groups. Endophthalmitis developed in 2 eyes in the

group with balanced salt solution only, and these patientshad posterior capsular rupture during the surgery and had

cultures thatwerepositive for Staphylococcusepidermidis[25].

Resistance is always a concern when antibiotics are used in

prophylaxis, mainly with vancomycin, which is the first

choice for the treatment of endophthalmitis. Seppala

et al. [26] evaluated the minimal inhibitory concentra-

tions of different antimicrobials for Streptococci viridansiso-

lated from throat, nasopharyngeal, and conjunctival swabs

of 23 patients, on four sampling occasions: before cataract

surgery and 1 day, 1 month, and 3 months after surgery. For

all patients, vancomycin was used in the irrigating solutionand topical chloramphenicol as prophylaxis. Resistance

to vancomycin or chloramphenicol was not observed.

The routine use of prophylactic vancomycin in cataract





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patients should be cautiously evaluated. Although resis-

tance has not been shown, limited evidence supports

the prevention of endophthalmitis, with a risk of toxicity.

Subconjunctival antibiotic injection is probably the oldest

prophylactic regimen to use antibiotics. Many reports

showed a beneficial trend, but the strength of the data

supporting this clinical practice have not been convincing,

and the administration of subconjunctival antibiotics at

the close of surgery has been associated with risk [27]. Be-

cause topical phacoemulsification surgery permits fast re-

covery, eyedrops have replaced antibiotic injections.

Generally, the topical antibiotics are used for 1 week when

the wound epithelializes.

The preferred practice pattern guideline sponsored by the

American Academy of Ophthalmology has stated that it is

up to the ophthalmologist to decide whether to use top-

ical, intracameral, or subconjunctival antibiotics perioper-

atively because of inconclusive evidence about the risks

and benefits of antibiotics [28]. By contrast, the potenti-

ally severe consequences of endophthalmitis support the

use of precautions to minimize the risk of infection, espe-

cially when known risk factors for endophthalmitis are

present, including rupture of the capsule, long duration

of surgery, diabetes, significant periocular skin disease, oc-

clusion of the lacrimal system, immunodeficiency, or ante-

rior vitrectomy [29].

ConclusionThe reports of endophthalmitis analyzed from peer-

reviewed ophthalmic journals suggest that the incidence

of endophthalmitis has increased, ranging from 0.1 to

0.18% in different countries. This may be related to factors

associated with the incision. Although some resistance has

been detected, fourth-generation fluoroquinolones seem

to be an appropriate antibiotic for endophthalmitis prophy-

laxis to complement the use of povidone-iodine because of

their spectrum, mode of action, and penetration.

Nonetheless, despite growing scientific data, there remain

many questions about the incidence, risk factors, and pre-

vention of endophthalmitis.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as: of special interest of outstanding interest

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This article reviews the studies of incidence, preventive measures, and causes ofpostoperative endophthalmitis, based on Medline searches from 1966 to 2003.

2 Mayer E, Cadman D, Ewings P, et al. A 10-year retrospective survey of cat-aract surgery and endophthalmitis in a single eye unit: injectable lenses lowerthe incidence of endophthalmitis. Br J Ophthalmol 2003; 87:867869.

In this retrospective study of cataract surgeries in a single UK eye departmentbetween 1991 and 2001, the authors investigated the potential link betweenmethod of IOL implantation and risk of endophthalmitis.

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This paper was based on a laboratory study to determine whether clear cornealcataract wounds might permit the flow of surface fluid into the wound and acrossthe cornea, using optical coherence tomography and India ink applied to the cor-neal surface.

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This laboratory study evaluated the effect of intraocular pressure, location, and

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This retrospective, observational case series investigated clinical settings, man-agement strategies, antibiotic sensitivities, and visual acuity outcomes in allpatients with endophthalmitis caused by Streptococcus pneumoniae treated at

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19 Benz MS, Scott IU, Flynn HW Jr, et al. Endophthalmitis isolates and antibioticsensitivities: a 6-year review of culture-proven cases. Am J Ophthalmol 2004;137:3842.

The authors report the bacterial pathogens isolated from all patients with endoph-thalmitis at Bascom Palmer Eye Institute between 1996 and 2001.

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21 Kowalski RP, Romanowski EG, Mah FS, et al. Topical prophylaxis with moxi-floxacin prevents endophthalmitis in a rabbit model. Am J Ophthalmol 2004;138:3337.

This in vivo laboratory investigation evaluated the prophylaxis potential of topicalmoxifloxacin to prevent endophthalmitis after the injection of S. aureus into theanterior chamber in a rabbit model.

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23 De Kaspar HM, Chang RT, Shriver EM, et al. Three-day application of topicalofloxacin reduces the contamination rate of microsurgical knives in cataractsurgery: a prospective randomized study. Ophthalmology 2004; 111:13521355.

This prospective randomized trial was conducted to determine the rate of contam-ination of microsurgical knives during cataract surgery, comparing a 3-day witha 1-hour preoperative application of topical ofloxacin.

24 Libre PE, Della-Latta P, Chin N: Intracameral antibiotic agents for endophthal-mitis prophylaxis: a pharmacokinetic model. J Cataract Refract Surg 2003;29:17911794.

This research laboratory study assessed in vitro whether intracameral antibioticagents are plausibly effective prophylaxis against S. aureus endophthalmitis.

25 Sobaci G, Tuncer K, Tas A, et al. The effect of intraoperative antibiotics inirrigating solutions on aqueous humor contamination and endophthalmitisafter phacoemulsification surgery. Eur J Ophthalmol 2003; 13:773778.

This randomized prospective clinical trial evaluated the efficacy of intraoperativeantibiotics in irrigating solutions on aqueous humor contamination during phaco-emulsification surgery.

26 Seppala H, Al-Juhaish M, Jarvinen H, et al. Effect of prophylacticantibioticsonantimicrobial resistance of viridans streptococci in the normal floraof cataractsurgery patients. J Cataract Refract Surg 2004; 30:307315.

This study evaluated the in vitro activity of 15 antibiotics for viridans-group strep-tococci isolated in the normal flora (throat, nasopharynx, and conjunctiva) ofpatients undergoing cataract surgery, prophylactically treated with vancomycinin the irrigating solution and topical chloramphenicol.

27 Schmitz S, Dick HB, Krummenauer F, et al. Endophthalmitis in cataract sur-gery: results of a German survey. Ophthalmology 1999; 106:18691877.

28 American Academy of Ophthalmology Anterior Segment Panel. PreferredPractice Pattern Cataract in the adult eye. 2001.

29 Liesegang TJ: Use of antimicrobials to prevent postoperative infection inpatients with cataracts. Curr Opin Ophthalmol 2001; 12:6874.




incidencia y prevencion de endoftalmitis

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