The
Brazilian
Journal
of
INFECTIOUS
DISEASES
w w w. e l s e v ie r . c o m / l o c a t e / b j i d
Original
article
Microbial
contamination
of
single-
and
multiple-dose
vials
after
opening
in
a
pulmonary
teaching
hospital
Shadi
Baniasadi
a,∗,
Atosa
Dorudinia
b,
Mandana
Mobarhan
b,
Masoumeh
Karimi
Gamishan
c,
Fanak
Fahimi
d,eaVirologyResearchCenter,NationalResearchInstituteofTuberculosisandLungDiseases(NRITLD),ShahidBeheshtiUniversityof
MedicalSciences,Tehran,Iran
bPediatricRespiratoryDiseasesResearchCenter,NationalResearchInstituteofTuberculosisandLungDiseases(NRITLD),Shahid
BeheshtiUniversityofMedicalSciences,Tehran,Iran
cFoodandDrugOrganization,MinistryofHealthandMedicalEducation,Tehran,Iran
dChronicRespiratoryDiseasesResearchCenter,NationalResearchInstituteofTuberculosisandLungDiseases(NRITLD),Shahid
BeheshtiUniversityofMedicalSciences,Tehran,Iran
eClinicalPharmacyDepartment,SchoolofPharmacy,ShahidBeheshtiUniversityofMedicalSciences,Tehran,Iran
a
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t
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Articlehistory:
Received18June2012 Accepted12September2012 Availableonline5January2013
Keywords: Hospital Infectioncontrol Injection Intravenous
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b
s
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r
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c
t
Objectives: Intravenoustherapyisacomplexprocedureusuallyrequiringthepreparationof
themedicationintheclinicalareabeforeadministrationtothepatient.Breachesinaseptic techniquemayresultinmicrobialcontaminationsofvialswhichisapotentialcauseof dif-ferentavoidableinfections.Weaimedtoinvestigatetheprevalenceandpatternofmicrobial contaminationofsingle-andmultiple-dosevialsinthelargestpulmonaryteachinghospital inIran.
Methods:Inaperiodof2months,openedsingle-andmultiple-dosevialsfromdifferent
wardsweresampledbyapharmacist.Thenameofthemedication,ward,labelingofthe vials,thedateofopening,andstoringtemperaturewererecordedforeachvial.Remained contentsofeachvialwereculturedusingappropriatebacterialandfungalgrowthmedia.
Results:Microbialcontaminationwasidentifiedin11of205(5.36%)ofvials.Thehighest
contaminationratewas14.28%forvialsusedininterventionalbronchoscopyunit.Themost frequentcontaminatedmedicationwasinsulin.Gram-positivebacteria(81.82%)weremore significantlyinvolvedthangram-negativeones(9.09%)andfungi(9.09%),withthehighest frequencyforStaphylococcusepidermidis.
Conclusions: Ourdata demonstratethatrepeateduse ofvialsespecially ifbasic sterility
measuresaredisobeyedcancausemicrobialcontaminationofadministeredproductsto thepatients.Infectionpreventionistsareresponsibletotrainhealthcareworkersregarding aseptictechniquesandapplyguidelinesforaseptichandlingofintravenoussolutions.
©2013ElsevierEditoraLtda.Allrightsreserved.
∗ Correspondingauthorat:PediatricRespiratoryDiseasesResearchCenter,NationalResearchInstituteofTuberculosisandLungDiseases
(NRITLD),MasihDaneshvariHospital,ShahidBahonarAve,Darabad,Tehran,Iran.Tel.:+982126109503;fax:+982126109484. E-mailaddresses:[email protected](S.Baniasadi),[email protected](A.Dorudinia).
1413-8670/$–seefrontmatter©2013ElsevierEditoraLtda.Allrightsreserved. http://dx.doi.org/10.1016/j.bjid.2012.09.005
Introduction
Thirty tofifty percentofhospitalize patients receive intra-venoustherapywhichrequiresthepreparationandhandling ofthe medicine beforeadministrationtothe patient.1
Par-enteral medications are usually given out in single- and multiple-dosevials(SDVsandMDVs).ASDVisavialofliquid medicationintendedforparenteraladministration(injection orinfusion)thatismeantforuseinasinglepatientforasingle case/procedure/injection.2AMDVisavialofliquidmedication
intendedforparenteraladministration(injectionorinfusion) thatcontainsmorethanonedoseofmedication.MDVsshould bededicatedtoasinglepatientwheneverpossible.3
TherevisedversionofUnitedStatesPharmacopeia(USP) Chapter 797 is a comprehensive document that describes standardsand procedures tominimizethe riskof contam-ination of compounded parenteral products. The chapter includesevidence-based instructions for pharmacy design, washing,garbing,cleaning,qualityassurance,andpersonnel training and evaluation designed to improve compound-ing practices in all pharmacies that compound parenteral products.4 However, sterile compounding procedures vary
widelyacrossthecountries.Inourcountrythemajorityofthe reconstitutionofinjectabledrugsiscarriedoutrightbeforethe administrationtothepatientbythenursingstaff.Prevalence ofbacterialcontamination ofSDVs whichwere used more thanoncehasbeenreported5.6%inoneofIranianhospitals.5
FungalcontaminationofSDVsandmicrobialcontaminationof vialscontainingpreservativewerenotexaminedinthisreport. Theinformationregardingextrinsicmicrobialcontamination ofinjectabledrugsandpotentiallyseriousadverseeventsis slightin ourcountry and still nomeasure hasbeen taken toimprovestandardsforintravenoustherapy.Wedesigned thisstudytounderstandtheprevalenceofcontaminationsof intravenousmedicationsinourhospitalandtodesignfuture interventionwhichcouldbemadebyinfectioncontrolstaffto preventthecontaminationsoftheinjectabledrugs.
Material
and
methods
Sampletaking
Injectabledrugswerepreparedinaroomwithnospecial air-conditioningonthewardorunitinwhicheverybodyeventhe patientaccompaniedpersonandcleaningstaffcouldenterin andoutliberally.Usingsteriletechnique,3mLofthe medica-tionwaswithdrawnfromopenedSDVsandMDVsdailybya pharmacistwithoutpriorwarning.Beforesampling,thevials wereshakenbriskly,andtherubberwasswabbedwith70% ethanol.Name,potencyandtotalvolumeofthevial,clinical ward,labelingornonlabelingofthevials,thedateandtimeof opening,storagecondition,expirationdate,andmanufacturer namewerethenrecorded.
Laboratorydiagnostic
Eachsamplewastestedusingthreemethods.(1)1mLwasput intoatubecontaining15mLthioglycolatebrothandincubated
at37◦Cfor10days.Thebrothwasvisuallyexaminedevery dayandsubculturedontoblood,chocolateandsabouraud dex-troseagarplateseveryotherdaywithin10daysoranytime thattheappearanceseemedturbid.5(2)1mLwascentrifuged
(3000rpm,15min),thenthepelletewasinoculatedintoblood, chocolate, MacConkey’s and sabouraud dextroseagar. Two firstmediawereevaluatedafter48handthesabouraud dex-troseagarwasevaluatedafter18days.(3)1mLwasfiltered using 0.45mfiltersandthe filterswere placedontoblood agarplates.Plateswereincubatedfor48hat37◦Cand evalu-atedforbacterialgrowth.Theywerestoredforfungalgrowth for18days.ThebacterialisolateswereidentifiedusingGram’s stainingandstandardbiochemicalmethods.
Statisticalanalysis
Descriptivestatistics wereusedtodetailthe distributionof contaminated vials and the contaminating microorganism. Duetothenon-normaldistributionofvalues,Mann–Whitney testwasusedtodeterminetherelationofvialcontamination andthedateofopeningofvial.Therelationoftypeofvialand contaminationratewasevaluatedusingFisher’sexacttest.A
Pvalueoflessthan0.05wasconsideredasstatistically signif-icant.StatisticalanalysiswasperformedusingSPSSversion 16.0.
Results
Atotalof205vials(165SDVsand40MDVs)weretestedfrom18 wardsandunits,with29medicationtypes.Table1shows sam-pled medications fromdifferentwards/units. Allvials were being usedwithintheir expiration period,and no vial had expired.Nostatisticaldifferencewasobservedbetween con-taminationrateandthenumberofdaysthatthevialswere opened.Atotalof115(56.10%)vialswerekeptatroom tem-perature,therestat4◦C.
Bacterialcontaminationwasidentifiedin11of205(5.36%) ofvials.ContaminationrateforSDVsandMDVswere4.85% and7.50%respectively.Therewasnosignificantdifferencein thefrequencyofcontaminationofdifferenttypeofvials. Con-taminationswerefoundinthreeinternalwards,emergency ward,IntensiveCareUnit(ICU),transplantunit,and interven-tionalbronchoscopyunit.Thehighestcontaminationratewas 14.28%(2/14)forvialsusedforinterventionalbronchoscopy unitandthelowestwas4.54%(1/22)forvialsusedforoneof theinternalwardswhichnamedasinternalward3.
ThemostfrequentcontaminatedsolutionwasinsulinNPH 100U/mL. Nomixedcontaminationwas detectedinanyof vials.Gram-positiveandgram-negativebacteriawereinvolved in9 (81.82%)and 1(9.09%)ofcontaminations, respectively. Fungal contaminationwasdetectedin onesample(9.09%). Therefore, gram-positive bacteria were more significantly involved (p<0.05) in vial contaminations. Most commonly identified microorganisms were part of the normal com-mensallyflorawiththehighestfrequencyforStaphylococcus
epidermidis(4/11or36.36%).Table2showsthedistributionof
contaminated vials indifferentwards/units ofthehospital alongwiththecontaminatingmicroorganismandthe char-acteristicsofthevials.
Table1–Medication,nameofward/unit,andnumberofsampledvials.
Medication Ward/unit Respectivenumber
ofsampledvials
Acetylcysteine200mg/10mL Pediatric 1
Aminophyline250mg Emergency,tuberculosisICU 1,1
Atracurium50mg/5mL Interventionalbronchoscopy 1
Atropin0.5mg/mL Interventionalbronchoscopy 1
Bloodcardioplegia Operationroomandanesthesiology 1
Bupivacaine100mg/20mL Operationroomandanesthesiology 3
Ceftazidim2g Emergency 1
Dextrose5% Internal(3),internal(9),emergency,surgicalICU 4,3,1,1 Dextrose3.33%+sodiumchloride0.3% Internal(9),pediatric,emergency 1,5,2
Ganciclovir500mg Transplant 2
Heparin5000U/mL Internal(3),internal(4),internal(9),tuberculosis(5),pediatric, oncology,emergency,surgicalICU,sleep,surgery
1,1,1,1,1,1,1,1,1,2
Hydrocortisone100mg TuberculosisICU 1
InsulinNPH100U/mL Internal(3),internal(4),internal(9),tuberculosis(5), tuberculosis(6),oncology,CCU,emergency,surgicalICU,post CCU,surgery,transplant
1,1,2,2,1,1,1,2,1,1,2,1
Insulinregular100U/mL Internal(3),internal(4),internal(9),tuberculosis(5), tuberculosis(6),oncology,CCU,emergency,surgicalICU, tuberculosisICU,medicalICU,operationroomand anesthesiology,surgery,transplant
4,1,2,2,2,1,1,3,1,1,1,1,3,1
Ketaminehydrochloride50mg/mL Interventionalbronchoscopy,operationroomand anesthesiology
2,1
Lidocaine2% Interventionalbronchoscopy 1
Magnesiumsulfate20% Internal(3),internal(4),internal(9),tuberculosis(6), emergency,surgicalICU,tuberculosisICU,medicalICU, operationroomandanesthesiology
1,1,1,1,2,7,1,1,1
Meropenem1g SurgicalICU 2
Methylprednisolone500mg Internal(9),pediatric,emergency 1,2,3
Morphine Internal(3) 1
Omnipaque240mg/mL Radiology 1
Potassiumchloride15% Internal(4),internal(9),tuberculosis(5),tuberculosis(6), emergency,surgicalICU,tuberculosisICU,medicalICU, Operationroomandanesthesiology,transplant
1,3,2,1,1,9,2,6,1,3
Propofol1%(w/v) Interventionalbronchoscopy 1
Sodiumchloride0.45% Emergency 1
Sodiumchloride5% Internal(3),emergency,tuberculosisICU,medicalICU 2,1,1,1 Sodiumchloride0.9%
Internal(3),internal(4),internal(9),tuberculosis(5), tuberculosis(6),pediatric,oncology,CCU,emergency,heart clinic,surgicalICU,surgery,transplant
8,6,5,1,3,5,2,3,2,1,2,10,1
Succinylcholine500mg Interventionalbronchoscopy 5
Thiopentalsodium1g Interventionalbronchoscopy,Operationroomand anesthesiology
2,1
TNG100mg/mL Interventionalbronchoscopy 1
Six(54.54%)ofcontaminatedvialswerenotmarkedwith
patient’sname,whichindicatedthattheywereprobablyused formorethanonepatient.
Discussion
Ourdatashowacontaminationrateof5.36% withbacteria
andfungi,inthecontentoftheSDVsandMDVsusedin dif-ferentwards/unitsofapulmonaryteachinghospitalinIran. Inprinciple,preparation,storageandtransportationof Com-poundedSterilePreparations(CSPs)requireasepticconditions
andtrainedpersonnel.USPChapter797isacomprehensive
documentthatdescribesstandardsandproceduresto
mini-mizetheriskcontaminationofCSPs.6ButstandardsforCSPs
indevelopingcountriesmaybelimitedbylackofresources
(trainedpersonnelandfacilities).Non-standardpreparation andhandlingofvials(whichareassumedtobesterile)result incontaminationrates,rangingfrom0%to27%.7
SDVsarepreservativefreevialswhichareintendedtobe usedonlyonce.PuncturingSDVsmultipletimesandpooling preservativefreesolutionsmaycausethepotential contami-nationrisk,possiblyleadingtosevereinfectionsinpatients.8,9
Inthecurrentstudy165of205vials(80.49%)wereSDVsthat wereusedasmultiple-dosevials.Thisfindingismorethan reportedpercentageof50%intheliterature.10,11
Ontheother handMDVscontainantibacterial preserva-tives and may beused more than once when preparation and storage is according to the manufacturer’s recom-mendations. (e.g., insulin, some heparin, lignocaine and octeotride products).8 If MDVsmustbeusedformorethan
Table2–Distributionandfrequencyofcontaminatedvialsindifferentwards/units,isolatedbacteria,andthe characteristicofcontaminatedvials.
Ward/unit Proportion
of contami-natedvials
(%)
Organisms Medication Opened
daysbefore sampling
Storage condition
Internal(3) 1/22(4.54%) Candidasp. Insulinregular100U/mL 11 4–6◦C Internal(4) 1/11(9,09%) Micrococcussp. Magnesiumsulfate20% 0 Room
temperature Internal(9) 1/19(5.26%) Micrococcussp. InsulinNPH100U/mL 16 4–6◦C
Transplant 1/8(12.5%) Bacillussp. Potassiumchloride15% 33 Room
temperature Interventionalbronchoscopy 2/14(14.28%) S.epidermidis Succinylcholine500mg 7 4–6◦C
S.epidermidis Succinylcholine500mg 8 4–6◦C
Emergency 2/21(9.52%) S.epidermidis Methylprednisolone500mg 2 Room temperature
S.epidermidis Dextrose3.33%+sodium chloride0.3%
0 Room
temperature SurgicalICU 3/24(12.5%) Micrococcussp. Potassiumchloride15% 0 Room
temperature
Nocardiasp. Sodiumchloride0.9% 2 Room
temperature
E.coli InsulinNPH100U/mL 9 4–6◦C
immediatepatienttreatmentarea.Thisistoprevent inad-vertentcontaminationofthevialthroughdirectorindirect
contact with potentially contaminated surfaces or
equip-ment that could then lead to infections in next patients.
If aMDVs enters the immediatepatient treatment area,it
shouldbededicatedtothatpatientonlyanddiscardedafter use.3
Itmust benoticedthat apreservative doesnot prevent non-bacterialandnon-fungalcontaminations(e.g.,viral, pro-tozoa, and prion pathogens) and does not prevent growth ofmicroorganismsinlowtemperature.7MDVsremainprone
to bacterial contamination and the use of them has been reported to be a potential source of infections in differ-entstudies.12–17 Ourstudy alsoshowsthatmicroorganisms
can survive in the presence of a preservative as 3 of the contaminatedvials were insulin. Thesterilityofmultidose insulin vials was determined up to 50 days by Rathod et al. They showed bacterial contaminations in 8 of 69 insulinvialsand concludedthatantibacterialpreservatives were more effective atroom temperature than at refriger-ator temperature.18 Other study by Jackson et al. verified
that prefilled insulin syringes remained sterile for up to one month after preparation when they were prepared using good aseptic technique and stored in the patient’s refrigerator.19
Thesterility ofa CSPis directly relatedto employment ofthebestpracticeandqualitystandards.Safepreparation andhandling ofCPSswithinaproperlyoperating unidirec-tionalairflowinanISOclass5cleanroominaccordancewith USPchapter797requirementsisthebestwaytoavoid bac-terialorfungalcontamination.20,21Thestandardizationthen
thecentralization ofthe preparationsand reconstitutionof CPSs byinfection prevention and controlexperts makesit possibleto reduce contaminationrisk related toinjectable drugs.22 Although the requirements of USP chapter 797
mayappearcomplicated,expensive,andevenunattainable
in developing countries, the first step to establish qual-ity standards could be made through training of health careworkersaccordingtorecommendationsfromCDC and WHO.23,24Themostappliedrecommendationsincludedating
MDVs afteropeningand discardingthem on the manufac-ture’sdates,discardingSDVsafteropening,andemphasizing the needforproperaseptictechnique.Simpleaseptic tech-niquesthat couldbe implementedineach hospitalsetting may be summarizes as: performing hand hygiene before preparingmedicationsforadministration;usinggloves,face mask, and avoidance oftalkingduringaninjection;25
wip-ing the outsides ofvials with70% isopropyl alcoholswabs before opening and aspirating the contents of vials using a 5p.m.filter straw26; and consideringpractical guidelines
for lipid based emulsions that supports bacterial growth suchaspropofol.27Moreoverreconstitutionofhighrisklevel
intravenous treatmentsbyacentralizedhospitalpharmacy serviceundersterileconditionsisthenextmeasuretoreduce both infection risk and cost due to discarding expensive vials.
In conclusion infection preventionists in develop-ing countries should improve sterile compounding of injectable products in a hospital. Although implemen-tation of the guidelines from professional pharmacy organizations, such as the American Society of Health-System Pharmacists (ASHP) and the National Association of Boards of Pharmacy (NABP) guarantees patient safety, understanding the problems and limitations in a hospital is essential to develop a regional standard procedure.
Conflict
of
interest
Thereisnoconflictofinterestthatshouldbedisclosedbythe authors.
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