Inappropriate surgical chemoprophylaxis and surgical site infection rate at a tertiary care teaching hospital

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The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w .e l s e v i e r . c o m / l o c a t e / b j i d

Original

article

Inappropriate

surgical

chemoprophylaxis

and

surgical

site

infection

rate

at

a

tertiary

care

teaching

hospital

Devang

Ashwinkumar

Rana

∗

,

Supriya

Deepak

Malhotra,

Varsha

Jitendra

Patel

DepartmentofPharmacology,Smt.N.H.LMuni,Medicalcollege,Ahmedabad,Gujarat,India

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Articlehistory:

Received4August2012 Accepted6September2012 Availableonline1January2013

Keywords:

Kunin’scriteria Rationality

Surgicalchemoprophylaxis Surgicalsiteinfection(SSI)

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Objectives:Thisstudyaimedtoanalyzethepatternofsurgicalchemoprophylaxis,surgical siteinfectionrate,andtocheckrationalityofsurgicalchemoprophylaxisbasedonKunin’s criteria.

Materialsandmethods:Aprospective,observationalstudywasperformedonpatients under-goingsurgery,inatertiarycareteachinghospital.Datawerecollectedinapro-formawhich includedthepatients’details,prescriptionsfromdateofadmissiontodischargeoranyother outcomeandoperativenotes.SurgicalsiteinfectionasdeﬁnedbyCentreforDiseaseControl criteriawasrecorded.RationalitywasassessedbasedonKunin’scriteria.

Results:Total220patientswereenrolledoveraperiodofoneyear.Meanhospitalstaywas 8.67±5.17days. A totalof2294 drugswereprescribedout ofwhich840 (36.61%)were antimicrobials. Meanduration forpre-operativeintravenousantimicrobial therapywas 0.75±0.45dayandforpost-operative intravenousantimicrobialtherapywas3.33±2.24 dayswhile post-operativeoralantimicrobialtherapywas4.58±3.34days.Third genera-tioncephalosporinswereprescribedmostfrequently64.74%and64.40%pre-operativelyand post-operativelyrespectively.Antimicrobialprescribingwasinappropriatein52.28%.Total of19patientsdevelopedsurgicalsiteinfection.Surgicalsiteinfectionratewassigniﬁcantly higher(13.04%) inpatientsreceiving inappropriatechemoprophylaxis(p<0.01). Surgical siteinfectionadds9.98daysofhospitalstay(p<0.0001)and3.57extradrugs(p<0.0001) comparedtogroupwithoutsurgicalsiteinfection.

Conclusion:Inappropriateuseofantimicrobialsishighlyprevalentinsurgical chemoprophy-laxisleadingtohighersurgicalsiteinfectionrate.Adoptionofinternationalstandardand formulationoflocallyfeasibleguidelinescanhelpovercomethissituation.

Introduction

As Sir Alexander Fleming predicted in his Nobel Lecture, “Antimicrobials, sincetheir introduction have been pivotal

∗ _{Corresponding}_author._Tel.:₊₉₁_{9426418842/079}_27622834.

E-mailaddresses:devangandu@gmail.com(D.A.Rana),supriyadmalhotra@gmail.com(S.D.Malhotra),drvarsha4@rediffmail.com

(V.J.Patel).

inthepreventionandtreatmentofinfections.However,the increasinguseofantimicrobialshasledtoasituationof appro-priateandinappropriateuse.”1_A_surgical_site_infection_(SSI)2

is aninfection that occurs aftersurgery inthe part ofthe body wherethe surgerytook place.Surgical site infections

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remainamongthemaincausesofpost-operativemorbidity, prolonginghospitalizationandincreasingthecostofmedical treatmentinsurgicalunits.3–4_{Antimicrobials}_play_an

impor-tantroleinpreventingand treatingsurgicalsiteinfections. Surgicalchemoprophylaxisisanimportantmeasurebefore anysurgerytopreventSSI.Variousguidelines5–8_are_available

fortheuseofantimicrobialsforsurgicalchemoprophylaxis. Howeveritisobservedthattheyarenotalwaysfollowed.9,10

Thishasledtoaworldwideemergenceofantimicrobial resis-tance, a major public health problem and has significant impactontreatmentandoutcomes.Toproducethedesired effect, antimicrobialshaveto besafe, efficacious and have tobeusedrationally.Severalstudieshaveevaluatedpattern ofuse ofantimicrobials assurgical chemoprophylaxis, but thereare verylimitedstudiesinrecentyearsonevaluation ofrationality. Kunin’s criteria are rationality based evalua-tionofuseofantimicrobials.Thismethodologyisbasedon localprescribingpatternsandallowsforindividualevaluation ofeachprescriptionasopposedtodevelopinggeneral crite-ria/categoriesofinfectionsandappropriateantimicrobialuse toevaluatethequalityofprescribingbyaudits.Inthepast,the classificationwasmainlybasedontheauthorityofinfectious diseasesspecialistswhoperformedtheevaluation.11Several studieshavereportedSSIrateorpatternofsurgical chemo-prophylaxisbuthavenotcorrelatedSSIrateswithpatternof surgicalchemoprophylaxis.12–17

Thisstudy was undertaken toevaluatethe pattern and rationalityofantimicrobialdrugprescribingbysurgeons in perioperativepatientsusingKunin’scriteria.11 _SSI_rate_was

calculatedand difference amongpatients withappropriate andinappropriatesurgicalchemoprophylaxiswasalso ana-lyzed.Theaimofthisstudywastoevaluatethecurrentpattern ofsurgicalchemoprophylaxisamongpatientsundergoing sur-gicalproceduresinatertiarycarehospitalanditsimpacton SSIrate.

Objectivesofstudy

1. Toassessthecurrentpatternofsurgicalchemoprophylaxis anditsrationalityassessmentbasedonKunin’scriteria11

and Scottish Intercollegiate Guidelines Network (SIGN)6 coreindicatorsforauditingantimicrobialuse insurgical chemoprophylaxis.

2. ToevaluatesurgicalsiteinfectionrateanddifferenceinSSI rateifanybetweenappropriateandinappropriate prescrip-tions.

Materials

and

methods

Twohundredandtwentyprescriptionsofpatientsadmitted inthe General Surgerywards ofa tertiary teaching hospi-talwerecollectedprospectivelybetweenJune2010andMay 2011.Thestudy protocol, pro-forma, and other documents likepatientinformationsheetandinformedconsentformin Englishandlocalvernacularlanguagewereapprovedby Insti-tutional Ethics Committee.All patientsundergoing surgery irrespectiveoftheirageandgenderwereincluded.Patients whowerenotwillingtogiveinformationwereexcludedfrom the study. Case records of enrolled patients, admitted for

Table1–Kunin’scriteria11_for_rationality_assessment_of

antimicrobialprescriptions.

CategoryI:Agreewiththeuseofantimicrobial therapy/prophylaxis,theprogramisappropriate

CategoryII:Agreewiththeuseofantimicrobial

therapy/prophylaxis,butapotentiallyfatalbacterialinfection cannotberuledoutorprophylaxisisprobablyappropriate, advantagesderivedremaincontroversial

CategoryIII:Agreewiththeuseofantimicrobial

therapy/prophylaxis,butadifferent(usuallylessexpensiveor toxic)antimicrobialispreferred

CategoryIV:Agreewiththeuseofantimicrobial

therapy/prophylaxis,butamodiﬁeddoseisrecommended

CategoryV:Disagreewiththeuseofantimicrobial therapy/prophylaxis,administrationispreferred

CategoryVI:datacannotbejudgedbecauseofmissinginformation

any operative procedures were recorded in the pro-forma containingdemographicdetails,chiefcomplaints,diagnosis, details ofoperativeprocedures anddrugdetails duringthe hospital stay. Class of operationwas decided in consulta-tionwithoperatingsurgeonsandwasbasedonUSNational ResearchCouncilgroupcriteria.18_SSI_rate_was_calculated_as

deﬁned byCDC,2 _rationality _assessment_was _done

accord-ingtotheKunin’scriteria11_shown_in_Table₁_based_on_CDC

1999Guidelines5_as_reference_standard_and_also_surgical_audit

based on SIGN guideline criteria.6 _The _analysis _was _done

basedonCDCguidelinesbecauseofunavailabilityofnational orlocalguidelines.Thegenericnamesofdrugs,generic con-tentsofeach formulationwere obtainedfrom thepatient’s pharmacybills.Drugsandformulationswhichwerenot men-tionedinthebillswereobtainedfromlocalpharmacystores andcommercialpublicationslikeIndianDrugReview2010and 2011.

Statisticalanalysis

DatawereanalyzedbyusingSPSS20.0demoversion®_._Fisher’s exacttest(twotailed)wasusedtodeterminethesigniﬁcance ofSSIpositiveratesamongdifferentvariablesandunpaired

t-testwasusedtodeterminethedifferencebetweenthe inap-propriateandappropriateprescriptiongroups.Valueofp<0.05 wasconsideredasstatisticallysigniﬁcant.

Results

Atotalof220patientswereenrolled inthe studyofwhich 141(64.1%)weremales.Theagerangesfrom13to78years; with mean age 38.88±14.18(mean±S.D.). About 90%(197) underwent electivesurgeriestherest beingemergency sur-geries.Mostoftheoperativeprocedureswereopen207(94%) andtherestwerelaparoscopic.Generalanesthesiawasused in 8 patients and in the rest either spinal or local anes-thesiawas used.Herniorrhaphy(27.3%)and appendectomy (20.5%) remained the most frequentlyperformed operative procedures. Class I, i.e., clean surgeries 105 (47.73%) were mostfrequent,followedbyclassII,i.e.,clean-contaminated 53(24.09%),classIII-contaminated38(17.27%),andclass IV-dirty24(10.91%)asshowninTable2.Meanhospitalstaywas 8.67±5.17days(mean±S.D.).

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Table2–Distributionofsurgeriesaccordingtoclass18_and_surgical_site_infection_(SSI)2_rate.

Class Operativeprocedures % SSIpositivepatients %

Clean(I) 104 47.27 2 1.92

Cleancontaminated(II) 53 24.09 4 7.54

Contaminated(III) 39 17.72 3 7.69

Dirty(IV) 24 10.91 10 41.66

Total 220 100 19 8.64

Allthepatientsundergoingoperativeproceduresreceived singleintravenous dose of antimicrobial 30minbefore the surgery,followedbypost-operativeintravenoustherapyand furtheroraltherapywithantimicrobial.Meandurationfor pre-operativeintravenousantimicrobialtherapy was 0.75±0.45 days. Meanduration ofpost-operative intravenous antimi-crobial therapy was 3.33±2.24 while post-operative oral antimicrobialtherapywas4.58±3.34days.Noneofthe oper-ativeproceduresexceededmorethan4hduration.

A total of 2294 drugs were prescribed out of which 840(36.61%)wereantimicrobials.Ceftriaxone wasthemost frequently used antimicrobial pre-operatively (50.64%) and post-operatively(36.93%)asshowninFig.1.

Outof220patients,28hadsuspectedSSI.Nineteenpatients outof28hadmicrobiologicallyconﬁrmedSSI,Escherichiacoli

(9)andStaphylococcusaureus(7)beingthecommonpathogens. SSIratewashighestinclassIV(41.66%)followedbyinclassIII (7.69%),II(7.54%),andwasleastinclassI(1.92%).SSIratewas signiﬁcantlyhigherinpatientswhopresentedwithdiabetes mellitus(p<0.0001)andhypertension(p=0.0048)asshownin

Table3.SSIpositiveratein61herniapatientswas2(1.63%)

whilein45appendectomypatientstheratewas1(2.22%).In thesepatientsE.coliwasthemostcommonisolate.Meanage ofSSIpositivepatientswasfoundsigniﬁcantlyhigheras com-paredtoSSInegativepatients(p<0.001)whichisdepictedin

Table3.Patientswithageabove40yearsshowedsigniﬁcant

higherSSIpositiverateascomparedtopatientslessthan40 years.TherewasnosigniﬁcantdifferenceforSSIratebetween gender,typesofanesthesiaandbetweenopenandlaproscopic surgery,whileemergencysurgeryshowedsigniﬁcantlyhigher SSIrateincomparisonwithelectivesurgery(p=0.0073).Mean

0 50 100 150 200 250 Pre-operative Post-operative Ceftriaxone MetronidazoleCefoperazone Amikacin Gentamicin Ampicillin + Cloxacillin Levofloxacin Cefixime + Clavulanic

CefuroximeCefiximeLinezolidMeropenam

Piperacillin + Tazbactum

Fig.1–Pre-operativeandpost-operativeantimicrobial drugs.

hospitalstayforSSInegativepatientswas7.81±4.1andthat forSSIpositivepatientwas17.79±6.41,whichshowsa signif-icantincreaseinmeanhospitalstayby9.98days(p<0.0001). Patients withhospitalstaygreaterthan aweekhad signif-icantly higherrate (p<0.0001) ofSSI positivity.Meandrugs prescribed inSSI negative were 7.43±1.74 and that in SSI positive patientwas11±2yieldingasigniﬁcant (p<0.0001) increaseof3.57drugs.

Antimicrobialprescriptionswerecategorizedas appropri-ate(IandII)–105(47.7%)andinappropriate(III,IV,andV)– 115(52.3%)basedonKunin’scriteria11_as_shown_in_Table₄_.

SSI rate was signiﬁcantly higher (p<0.05), in inappropriate group(13.04%)incomparisonwithappropriategroup(3.8%)as showninTable4.Outof61herniapatients,19prescriptions wereinappropriateoutofwhich2patientshadSSI(p=0.0934). Outof45appendectomypatients35prescriptionswere inap-propriateandonepatienthasSSI(p=1).RateofSSIsinpatients who receive inappropriate prophylaxis (as deﬁned by CDC guideline5₎_compared_with_rate_of_this _infection_in_patients

whoreceiveappropriateprophylaxis,expressedasaratiowas foundtobe3.43.Table5depictsthe processmeasuresand outcomemeasuresaccordingtoSIGNguidelines.6

Discussion

Thisstudywasaimedtoevaluatethecurrentprescribing pat-tern along with rationality, its impact on SSI rate and on hospital stay and number ofextra drugs needed. Previous studyfromPakistan12_reported_55.7%_males_lower_compared

toours64%,meanageofthepatientswas35±17years,and somewhatlesscomparedtoourstudy,i.e.,38.8%.

In our study SSI rate was 8.64% which was similar to previousstudies.13 _In_our_study _E._coli_was_most_commonly

isolated pathogen, followedby S.aureuswhich isin accor-dance withprevious Indian study.19 _SSI _rate _for_two _most

commonlyperformedsurgeriesherniorrhaphyand appendec-tomyiscomparabletoanearlierstudycarriedoutinIndia14

and aworldwidemetaanalysisstudy.20 _There_is_no

signiﬁ-cantdifference inSSIrate betweengenders,this ﬁndingis similartoapreviousstudyreportedinIranin2006.21_SSI_rate

increaseswithageabove40years,whichwasstatistically sig-niﬁcantatp<0.0001andwassimilartostudyreportedfrom India.22_SSI_rate_among_patients_receiving_general_anesthesia

inourstudywas16.67%ascomparedtoothermodes(7.92%), whichisinaccordancewithpreviousstudydoneinUK.23_SSI

ratewashigherinemergencysurgerythaninelectiveandis comparabletoanotherIndianstudy.14_In_our_study_SSI_rate

wassigniﬁcantlyhigherindiabeticandhypertensivepatients whichwasalsoseeninapreviousIndianstudy.22_In_our_study

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Table3–Surgicalsiteinfection(SSI)rates2_and_variables.

SSInegative(n=201) SSIpositive(n=19) Total(n=220) pvaluea

Meanage 37.71±13.44 51.26±16.21 38.88±14.19 <0.0001 ≤40years 134 6 140 0.0047 >40years 67 13 80 Gender Male 131 10 141 0.32 Female 70 9 79

Daysofhospitalstay 7.81±4.1 17.79±6.41 8.67±5.17 <0.0001

≤7days 118 1 119

>7days 83 18 101

No.ofdrugsgiven 7.43±1.74 11±2 10.42±3.37 <0.0001

Typeofanesthesia General 15 3 18 0.193 OtherSAandLA 186 16 202 Modeofoperation Elective 184 13 197 0.0073 Emergency 17 6 23 Open 188 19 207 0.60 Laproscopic 13 0 13 Co-morbidconditionsb Diabetesmellitus 2 9 11 <0.0001 Hypertension 10 5 15 0.0048

UsingFischer’sexacttwotailedtestandunpairedt-test. a _p_<_0.005.

b _Four_patients_presented_with_both_diabetes_and_{hypertension.}

opensurgery.AstudybyJawienetal.15_reported_less_SSI_rate

inlaproscopicsurgerythaninopensurgery.SSIledto signiﬁ-cantlyextendedhospitalstay(9.98days)whichissimilartoa Europeanstudy(1998)24_which_reported_9.8_days.

Inourstudy asinglepre-operativedoseofantimicrobial therapy was given before the operative procedure which isin accordance with the various standard guidelines and previousstudiesalsoshowedthatsingledoseprophylaxisis notassociatedwithincreasedrateofSSIwhencomparedto multipledoseregimens.25_In_our_study_mean_duration_of

pre-operativeintravenoustherapywas0.75±0.45days,followed bymean post-operativeintravenous therapy for 3.33±2.24 andpost-oporaltherapyfor4.58±3.34days.Howevertiming ofadministrationofﬁrstdoseofantimicrobialpre-operatively wasincompliancewiththeCDCguidelines.5_Mean_duration

of post-operative antimicrobial use was 7.88 days which islonger thanreportedbyprevious studyfromIndia, i.e.,5

days16_which_may_be_due_to_differences_in_prevalent_practices.

Allpatientsreceivedantimicrobials,inboththepre-operative andpost-operativeperiod,andnoantimicrobialwasgivenin theintra-operativeperiod.Mostcommonlyuseddruggroup forprophylaxiswasthirdgenerationcephalosporins,followed bymetronidazole,andpenicillingroupsimilartoanIndian study.17_In_our_study_none_of_the_patients_received_cefazolin

asrecommendedbyvariousguidelines.5–8

Forsurgicalprophylaxisitisimportanttoselectan antimi-crobialwithnarrowestantibacterialspectrumtoreducethe emergence ofresistance,secondlytheantimicrobial antibi-otic must be active against the most likely contaminating microorganismsforthattypeofsurgery,theﬁrst-generation cephalosporinsare excellentagentsforskinandsofttissue infections owing to Streptococcus pyogenes and methicillin-susceptible S.aureus. Hencea singledose ofcefazolin just before surgery is the preferred prophylaxis for procedures

Table4–AppropriatenessofsurgicalprophylaxisbasedonKunin’scriteria11_and_surgical_site_infection_rate_(n₌_220).

Appropriatetherapy

CategoryI CategoryII Subtotal SSIpositive SSInegative

2(0.91%) 103(46.81%) 105(47.72%) 4 101

Inappropriatetherapy

CategoryIII CategoryIV CategoryV Subtotal SSIpositive SSInegative

108(49.09%) 0(0%) 7(3.19%) 115(52.28%) 15 100

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Table5–CoreindicatorsforsurgicalauditbasedonSIGNguidelines.6

(a)Processmeasures

1 Wasprophylaxisgivenforanoperationincludedinlocalguidelines? Nolocalguidelineavailable

2 Ifprophylaxiswasgivenforanoperationnotincludedinlocalguidelines, wasaclinicaljustiﬁcationforprophylaxisrecordedinthecasenotes?

Justiﬁcationwasnotrecordedinthecasenote

3 Wastheﬁrstdosageofprophylaxisgivenwithin30minofthestartof surgery?

Yes

4 Werethechoice,dosageandrouteofadministrationconsistentwithlocal guidelinesforthatprocedure?

Consistentwithoutguideline

5 Wastheprescriptionwritteninthe“once-only”sectionofthedrug prescriptionchart?

Notapplicable

6 Wasthedurationofprophylaxisgreaterthen24h? Yes (b)Outcomemeasures

1 Surgicalsiteinfectionrate=numberofSSIsoccurring postoperatively/totalnumberofoperativeprocedures

19/220=0.0864(8.64%) 2 RateofSSIsoccurringpostoperativelyinpatientswhoreceive

inappropriateprophylaxis(asdeﬁnedinguideline)comparedwithrateof thisinfectioninpatientswhoreceiveappropriateprophylaxis,expressed asaratio

13.04/3.8=3.43

3 RateofClostridiumdifﬁcileinfectionsoccurringpostoperativelyinpatients whoreceiveinappropriateprophylaxis(asdeﬁnedinguideline)compared withrateofthisinfectioninpatientswhoreceiveappropriate

prophylaxis,expressedasaratio

NoculturerecordedClostridiumdifﬁcile infection

in which skin ﬂora are the likely pathogens. For patients undergoingclean operativeprocedure for herniorrhaphy, a cleanprocedureasingledoseofcefazolin1gpreoperatively andforappendectomy,acleancontaminatedsurgerysingle preoperativeintravenousdoseofeithercefotetanorcefoxitin 1g is recommended.5–8 _Therefore, _it _is _recommended _that

the use of third generation cephalosporins such as ceftri-axoneandcefotaximebeavoidedinsurgicalprophylaxisas it may berequired later if patient developsserious sepsis For herniorrhaphyuse ofcefazolinis appropriate,whilein caseofappendectomythirdgenerationcephalosporinshave been used as substitutefor cefotetan and cefoxitin in our study asinIndia cefazolinisavailablewhilecefotetanand cefoxitinarenotmarketed.26Howeverthisisnotjustiﬁed,as thirdgeneration cephalosporinshavetobesparedfor ther-apeuticpurpose.Better optionwould beanalternativelike cefuroxime.Dirtyandcontaminatedsurgeriesrequiredbroad spectrum antimicrobials coverage. Drugs like piperacillin, tazobactum,linezolidwereusedmainlyafterdiagnosisofSSI fortherapeuticpurpose.

Inourstudy52%patientsreceivedinappropriate chemo-prophylaxis according to Kunin’s criteria.11 _This _ﬁnding _is

inaccordancewithearlierstudiesthatshowed51.5%11_and

65.6%27 _{respectively.}_Most_of_the_{antimicrobials}_were _broad

spectrum,prescribedforlongerdurationwhichwas unwar-ranted.Inappropriateprophylaxiswasassociatedwithhigher culturepositive(SSIpositive)rates(13.04%)ascomparedtothe appropriateprophylaxis(3.8%).

Toourknowledgethis studyisﬁrst ofitskind inIndia. Strength of this study was the assessment of rationality ofchemoprophylaxis based on Kunin’scriteria11 _and _SIGN

guideline6_as_well_as_comparison_of_SSI_rate_in_patients

receiv-ingappropriateandinappropriatechemoprophylaxis.Oneof thelimitationsofourstudy iscross-sectionaldesignofthe study.Alsotherewasnopatientfollowupafterdischargeup to30dayswhichisrequiredaccordingtoCDCdeﬁnitionofSSI andhencesomecasesofSSIafterdischargefromhospitalmay

bemissed.Patientpost-dischargequestionnairewasnotused andfurtheranalysisbasedonqualityoflifecouldbedone. Fur-therstudieswithlargersamplesizecanbeplannedincluding additionalcostbornebythepatientbecauseof inappropriate-ness.Indepthsubanalysisintovarioustypesofsurgeriesand variousdrugregimensandinfectionscanbedonetoselecta properandrationalregimenforanindividualsurgeryusing otherguidelines.Kunin’scriteria11_is_a_preliminary_evaluation

ofappropriateness,afurtherin-depthanalysisof antimicro-bialprescriptioncanbedoneaccordingtotheModiﬁedKunin’s criteria,25_Giessen_score,28_and_by_SWABs_score.29_Evaluation

basedonthecombinedscoresfromboththesurgicalwound judgmentandprescriptionanalysiscanalsobedone.

Conclusion

Inappropriate chemoprophylaxisasevidentinthis studyis associatedwithhigherSSIrateleadingtoprolongationof hos-pital stay and increasednumber of drugs usage. Adoption ofinternationalstandardandformulationoflocallyfeasible guidelinescanhelpovercomethissituation.Howeverthisis a singlecenter study andresults ofthisstudy may notbe generalized.

Conﬂict

of

interest

Theauthorshavenoconﬂictofinteresttodeclare.

Acknowledgements

TheauthorswouldliketoexpresstheirthankstoDr.PankajR. Patel,Dean,Smt.NHLMedicalCollegeandDr.M.H.Makwana, Superintendent,V.S.Hospitalforpermittingthemtodothis work inV.S.Hospital. Theauthorsalsoexpressgratitudeto surgerydepartmentforsupport.

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