Asian Journal of Pharmaceutical and Clinical Research

Vol. 4, Issue 2, 2011

ISSN - 0974-2441

ResearchArticle

ACLINICALCOMPARISONOFTHEEFFICACY&PENETRATIONOFMOXIFLOCACINAND
LEVOFLOXACININCATRACTSURGERYCASES

ISMAILAM.,*SENTHAMARAIR.,RENNEYJOHN.,SHIBUVARKEY1,ANDRAJESHC
DepartmentofPharmacyPractice,PeriyarCollegeofPharmaceuticalSciencesforGirls,Tiruchirappalli,1Academics&ResearchDept.,Dr.
AgarwalVasansEyeHospital,Tiruchirappalli,Email:amesmaail04@yahoo.co.uk

ABSTRACT
Acataractisthecloudingoropacityofthenormallyclear,naturalcrystallinelensoftheeye,whichliesbehindtheirisandthepupil.Therearean
established912millionblindinIndia,halfofwhichcanbeattributedtocataract.Endophthalmitisisapotentiallysightthreateningcomplicationof
cataractsurgery.Fluroquinolonespenetratevitreousbetterthanotherantibioticsandisusedbymanyclinicians,buthavenotbeensuggestedto
rigorous,blindedclinicaltrials.
Objectives: The main objective of this study is to compare the efficacy and penetration ability of topically applied 0.5% Moxifloxacin and 0.5%
Levofloxacinophthalmicsolutionsintohumanaqueoushumorbeforeroutinecataractsurgery.
Materials and Method: Microbiological study was carried out on patients conjunctival smear before and after administration of antibiotic. Fifty
patientsthatunderwentcataractextractionweredividedrandomlyintotwogroupswithMoxifloxacin(25Patients)andLevofloxacin(25Patients).
Result:Based on the penetration study, the mean concentration of Moxifloxacin in the aqueous humor was significantly greater than that of
LevofloxacininbothtypesofregimensnamelyregimeAandB.TheMIC90valueofMoxifloxacinwasfoundtobelowerthanthatofLevofloxacinfor
mostkeyocularpathogens.
Conclusion:This study provides an evidence based conclusion that cataract surgery can be done as an out patient procedure without any
complicationtothepatientsandthatMoxifloxacinhasabetterpenetratingpowerthanLevofloxacinintheaqueoushumor.
Keywords:Moxifloxacin,Levofloxacin,Endophthalmitis.

INTRODUCTION
A cataract is the clouding or opacity of the normally clear, natural
crystalline lens of the eye, which lies behind the iris and the pupil.
Cataract is the chief cause of preventable blindness all over the
world, according to the world health organization.1 Cataract ranks
only behind arthritis and heart disease as a leading cause of
disabilityinolderadults.
There are an established 912 million blind in India, half of which
can be attributed to cataract. A huge backlog of cataract blindness
exists in the developing world.2 It is estimated that 3.8 million
peopledevelopblinding cataracteveryyearinIndia,3asagainst2.7
millioncataractsurgeriesdoneeveryyear.
The common symptoms are blurring of vision, glare, change in
colour of vision, double images, necessity for frequent change of
glasses.ThetypesofcataractsareSenileCataract,NuclearCataract,
Cortical Cataract, Posterior Subcapsualr Cataract, Congenital
Cataract,SecondaryCataract,TraumaticCataract.Theonlyeffective
treatmentforacataractissurgerytoremovethecloudedlens,which
usually includes replacing the lens with a clear lens implant.
Sometimes cataracts are removed without reinserting implant
lenses. In such cases, vision can be corrected with eyeglasses or
contactlenses.
Cataracts can't be cured with medications, dietary supplements,
exercise or optical devices. In the early stages of a cataract when
symptoms are mild, a good understanding of the condition and a
willingness to adjust your lifestyle can help. Some selfcare
approaches, such as using a magnifying glass to read or improving
the lighting in your home, may help you deal with the effects of
havingacataract4.
Endophthalmitis is an ocular inflammation resulting from the
introductionofaninfectiousagentintotheposteriorsegment ofthe
eye.Duringinfection,irreversibledamagetodelicate photoreceptor
cellsofthe retina frequently occurs. Despite aggressivetherapeutic
and surgical interventions, endophthalmitis generally results in
partial or complete loss of vision, often within a few days of
inoculation5.

Thechoiceofprophylactictopicalantibioticandtheoptimaldosing
regimen are subject to debate. An important consideration is
whether the preoperative administration of a topical antibiotic
result in drug concentrations in the aqueous humor that is greater
than the minimum inhibitory concentration (MIC) for potential
bacterial pathogens6. Additionally, the medication chosen should
haveabroadspectrumofantimicrobialactivityparticularlyagainst
grampositive organisms, cause no corneal toxicity, and have
excellentsolubility(bioavailability)sothatitreadilypenetratesthe
tissuesoftheeye.Topicalfluoroquinoloneshave beenshownto be
efficacious and well tolerated for the treatment of bacterial
conjunctivitis7,8. Fluoroquinolones are also being used for
prophylaxisinocularsurgery.
Accordingly, in a survey of ophthalmologists performing cataract
surgery in 2000 in the United States, 79% reported use of a
preoperative topical antibiotic9. Ophthalmic surgeons commonly
prescribe antibiotic for topical dosing 2 or 3 days before or pulse
doseintheoperatingroomimmediatelybeforesurgery.
This work has been necessitated due to the rising complications of
endophthalmitis and in the search to find the best fluoroquinolone
availableinthemarketbasedonefficacyandpenetration.
MATERIALSANDMETHODS
Study design: A prospective, doublemasked, parallel, randomized,
casecontrolstudy.
Studysite:VasanEyeCareHospital,Tiruchiappalli.
Studyperiod:Thestudywasconductedduringasixmonthperiod.
Inclusion/exclusioncriteria:
Thesubjectsofeithersex(otherwisehealthy)whowerescheduled
to undergo standard cataract surgery, 21years of age or older, had
the ability to understand and give signed informed consent were
included.
Those that exhibited any intraocular inflammation, was a subject
usinganyocularmedicationordrops48hoursbeforeorduringthe
study period (other than the study treatment), had a known

Ismailetal.
AsianJPharmClinRes,Vol4,Issue2,2011,7780
sensitivitytoanyoftheingredientsinthestudymedicationsorany
quinolonecompound,hadaconditionthatmayconfoundthestudy
results,ormayinterferesignificantlywiththesubjectsparticipation
inthestudy,hadabnormaleyelidfunction,hadonlyoneeye,would
require the use of any systemic antibiotic during the study period,
wasexhibitingacornealulcer,keratitis,orhadahistoryofherpetic
keratitis, had any ocular disease that would interfere with the
evaluation of the study treatments, received previous intraocular
siliconeoil,waspregnantornursingwereexcluded.

Detection :275nmusingUVVisibledetector.
Datastation

:ClassVPdatastation

CALIBRATION CURVE OF MOXIFLOXACIN

0.1
0.09
P e a k A re a R a tio (D ru g : IS )

Methodofthestudy
The clinical ethics committee of the institution approved of the
study.The50patientsundergoingcataractextractionweredivided
randomlyintotwogroupswith0.5%Moxifloxacin25patientsand
0.5%Levofloxacin25patients.
Three days before surgery the patients conjunctival smear was
takenasabaseline.Thentheassigneddrugwasgivenrandomly to
eachpatientatadoseofadropfourtimesadayforthreedays.After
threedaysofadministrationatthetimeofsurgeryasecondsmear
was taken to assess the bacterial load to find the efficacy of the
drugs.

0.08
y = 0.009x + 0.0013
R2 = 0.9979

0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
0

10

12

Drug Concentration (mcg/ml)

Conjunctival swab material was inoculated into 0.3 ml of sterile

salineinasterilevial.Theswabwasrepeatedlytwirledinthesaline.
Inthelaboratory,0.1mlofthesalinewasinoculatedontoaplateof
5%sheepbloodagarwhile0.05mleachwasinoculatedontoaplate
ofcystinetryptoneagarandaplateofMacConkeyagar.

Calibration curve of Levofloxacin

0.7

Followinginoculation,theplateswereincubatedinabacteriological
incubatorat370Candafterovernightincubationandafter48hours
the plates were checked. If bacterial growth was obtained on the
plates,thecolonycountwasfirstestimatedbycountingthenumber
ofcoloniesinthestreakedareaoftheplateandmultiplyingthesame
by 10. A smear of an individual colony was prepared on a
microscope slide, and this was stained by the gram method, dried
andviewedundertheoilimmersionobjectiveoralightmicroscope.
Ifpositive,withthepresenceofbetahaemolysisonbloodagarand
growth on MacConkey agar, the growth was considered to be
staphylococcus aureus. If coagulase test was negative, with no beta
haemolysis on blood agar and no growth on MacConkey agar, the
growthwasconsideredtobeacoagulasenegativestaphylococcus.

0.6

Peak Area R atio (D ru g:IS)

0.5
y = 0.0644x + 0.0123
2
R = 0.9994
0.4

0.3

0.2

0.1

Thepatientswereinstructedtousetheirantibioticdropsaccording
toregimenAorBtowhichtheywereassigned.
RegimenA:1 dropfourtimesadayforthree days(12drops)23
patientsand
Regimen B: 1 drop 6 doses delivered every 10 min in the hour
immediatelyprecedingsurgery(6drops)15patients.

0.6

MobilePhase

:Acetonitrile:Phosphatebuffer(pH5)

Mobilephaseratio :20:80%v/v
Flowrate :1.0ml/min
Samplevolume

:20l

12

DosingregimenLevofloxacin(g/ml)Moxifloxacin(g/ml)
A0.180.05(n=8)0.770.15(n=15)
B1.340.33(n=9)1.940.06(n=6)

MoxifloxacinandLevofloxacin

:Gemini5uC18(2)100A250x4.60mm

10

Table1:MeanVALUErepresentationoflevofloxacinand
Moxifloxacin

1.8

StationaryPhase

Duringsurgery0.2mlofaqueousfluidwasaspiratedwiththehelp
ofatuberculinsyringe.Theanteriorchamberfluidwasimmediately
placed into a sterilized cryogenic tube and stored at 40 C in an
Ultra Low Freezer (Remi, Remi Instruments, Mumbai) and kept
frozen untilanalysis was performed.Each tube was markedwith a
patient identification number (which indicated the antibiotic that
the subject was randomly assigned), the subject's initials, date of
surgery, and eye. Concentrations of topically applied
fluoroquinolones were determined by use of reversephase high
pressure liquid chromatography assay technique with ultraviolet
visibledetectoratawavelengthof275nm.

ChromatographicConditions

6
Drug Concentration (mcg/ml)

Penetration(Aqueous)

Levofloxacin
Moxifloxacin

1.6
1.4
1.2
1
0.8

0.4
0.2
0
A

Fig.1:BarGraph
Statisticalmethods
Thecollecteddataweresubjectedtostatisticalanalysisandresults
analysiswasdonebyusingAnovatest.
78

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AsianJPharmClinRes,Vol4,Issue2,2011,7780
RESULTS
The average age of the 50 patients under study was 60.52 years.
Malepatientsnumbered32(64%)andfemalepatientsnumbered18
(36%). Among this the patients having associated disease of
diabetes alone 22 (44%), hypertension alone 18 (36%) both
hypertensionanddiabeteswere9(18%),andpatientswithanemia
25 (50%). Microorganisms isolated were Staphylococcus aureus in
21(42%)patients,Staphylococcusepidermidisin18(36%)patients.
DISCUSSION
Amongst 50 patients undergoing cataract extraction were divided
randomlyintotwogroupswith0.5%Moxifloxacin25patientsand
0.5% Levofloxacin 25 patients.Three days before surgery the
patientsconjunctivalsmearwastakentofindthebacterialloadasa
baseline. Then the assigned drug was given to each patient at a
dosageof4timesadayforthreedays.
After3daysofadministrationasecondsmearwastakenandthere
wasnogrowthinboththegroups.Soboththedrugswerefoundto
be effective on the surface as a prophylactic prior to
phacoemulsification.Inthemicrobiologicalaspectofthisstudy,the
two antibiotics Levofloxacin and moxifloxacin were effective in
eradicating the bacterial flora from the conjunctiva after 3 days of
drugadministration.Boththedrugsregisterednogrowthafterdrug
treatment.
The new generation of fluoroquinolones addresses the problem of
emergingbacterialresistancewithabroaderspectrumofactivity10
14. Themostrecenttherapeuticagentsincludethefourthgeneration
fluoroquinolone moxifloxacin 0.5%. Unlike prior generation
fluoroquinolones that predominantly inhibit topoisomerase IV or
DNA gyrase and, therefore, only require I genetic mutation for
bacteriatodevelopresistance,15fourthgenerationfluoroquinolones
work on both bacterial DNA gyrase and topoisomerase IV16,17. To
become resistant to these agents, the bacteria must undergo 2
geneticmutations,resultinginasignificantlydecreasedchanceofan
organismdevelopingresistance18.
Theincreasedefficacyoffourthgenerationfluoroquinolonesagainst
grampositive organisms19, 20 makes these antibiotics important
agents to evaluate for prophylaxis against post cataract surgery
endophthalmitis.
In this study we have found that the mean concentration of
Moxifloxacin in the aqueous humour was significantly greater than
thatofLevofloxacininallthetreatmentgroups(p<0.0001).
In the regimen A, the mean SD for Moxifloxacin was found to be
0.770.15(n=15)andthatofLevofloxacinitwas0.180.05(n=
8). This represented a 4.28 fold difference in measured aqueous
humorantibioticconcentrationwhichwasstatisticallysignificant(p
<0.001).
In the regimen B, the mean SD for Moxifloxacin was found to be
1.940.06(n=6)andthatofLevofloxacinitwas1.340.33(n=9).
This represented a 1.45 fold difference in the antibiotic
concentrationwhichwasconsideredtobestatisticallysignificant(p
< 0.001).Regimen B delivered more drug in the aqueous than
Regimen Afor both the drugs. In Moxifloxacinthere was 2.52 fold
difference (p < 0.001) and for Levofloxacin there was 7.44 fold
difference(p < 0.001) mean valueswere shown in theTable 1and
graphicalrepresentationshowninfigure1.
No clinically evident epithelial or intraocular toxicity was noticed
withthetopicalapplicationofanyoftheantibacterialagentsusedin
thisstudy.
The strengths of this study include that it was prospective and
doublemasked. The limitations of the study include small and
uneven sample sizes and difficulty in flawlessly evaluating
preoperativeantibioticcompliance.
CONCLUSION
It is concluded that there was no difference between Moxifloxacin
andLevofloxacinophthalmicsolutionontheconjunctivalflorasince
both the drugs were effective in eradicating the bacteria from the

surface. But for a drug to be used as a prophylactic prior to

intraocular surgery continuous MIC levels must be present in the
aqueousandvitreoustopreventpostoperativeendophthalmitis. So
thedrugshouldhaveagoodpenetration.
BasedonthepenetrationthemeanconcentrationofMoxifloxacinin
the aqueous humor was significantly greater than that of
LevofloxacininboththeregimesAandB.
RegimenBdeliveredmoredrugintheaqueoushumorthanRegimen
A with both the drugs. In moxifloxacin there was 2.52 fold
difference (p < 0.001) and for Levofloxacin there was 7.44 fold
difference (p < 0.001). The fourth generation fluoroquinolone eye
drops have been developed to broaden the spectrum of antibiotic
coverage,includingresistantstrain.
So we can come to an evidence based conclusion that cataract
surgery can be done as an out patient procedure without any
complicationtothepatientbyusingregimenBandMoxifloxacinwas
foundtohaveabetterpenetrationthanLevofloxacinintheaqueous
humor.
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