DTIC ADA630186: Activity of Topical Antimicrobial Agents Against Multidrug-Resistant Bacteria Recovered from Burn Patients

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by  Defense Technical Information Center

burns 36 (2010) 1172–1184
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/burns
Activity of topical antimicrobial agents against
§
multidrug-resistant bacteria recovered from burn patients
Jessie S. Glassera, Charles H. Guymonb, Katrin Mendea,c, Steven E. Wolfa,b,d,
Duane R. Hospenthala,d,e, Clinton K. Murraya,d,e,*
aSanAntonioMilitaryMedicalCenter,FortSamHouston,TX,UnitedStates
bUSArmyInstituteofSurgicalResearch,FortSamHouston,TX,UnitedStates
cInfectiousDiseaseClinicalResearchProgram,Bethesda,MD,UnitedStates
dUniversityofTexasHealthScienceCenteratSanAntonio,SanAntonio,TX,UnitedStates
eUniformedServicesUniversityoftheHealthSciences,Bethesda,MD,UnitedStates
article i nfo abstract
Articlehistory: Background: Topical antimicrobials are employed for prophylaxis and treatment of burn
Accepted11May2010 wound infections despite no established susceptibility breakpoints,which are becoming
vital in an era of multidrug-resistant (MDR) bacteria. We compared two methods of
Keywords: determiningtopicalantimicrobialsusceptibilities.
Burn Methods: Isolates of Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus
Topical (MRSA), extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and
Acinetobacterbaumanii-calcoaceticus(ABC)fromburnpatientsweretestedusingbrothmicro-
dilutionandagarwelldiffusiontodetermineminimuminhibitoryconcentrations(MICs)
and zones of inhibition (ZI). Isolates had systemic antibiotic resistance and clonality
determined.MDRincludedresistancetoantibioticsinthreeormoreclasses.
Results: Weassessed22ESBL-producingK.pneumoniae,20ABC(75%MDR),20P.aeruginosa
(45%MDR),and20MRSAisolates.ThemostactiveagentsweremupirocinforMRSAand
mafenideacetateforthegram-negativeswithmoderateMICs/ZIfoundwithsilversulfa-
diazene,silvernitrate,andhoney.MDRandnon-MDRisolateshadsimilartopicalresistance.
Therewasnoclonalityassociatedwithresistancepatterns.
Conclusion: Despite several methods to testbacteria for topical susceptibility, no defined
breakpointsexistandstandardsneedtobeestablished.Werecommendcontinuingtouse
silverproductsforprophylaxisagainstgram-negativesandmafenideacetatefortreatment,
andmupirocinforMRSA.
PublishedbyElsevierLtdandISBI
1. Introduction surviving the initial burn insult and resuscitation are most
likelytodiefrominfectiouscomplications[1].Burnpatients
Improvements in burn care have led to longer survival but are relatively immunosuppressed and are at high risk of
have extended hospital stays. Patients who perish after infections, in particular with nosocomially-acquired multi-
§ Theopinionsorassertionscontainedhereinaretheprivateviewsoftheauthorsandarenottobeconstruedasofficialorreflectingthe
viewsoftheDepartmentoftheArmy,DepartmentofDefense,ortheUSgovernment.Thisworkwaspreparedaspartoftheirofficial
dutiesand,assuch,thereisnocopyrighttobetransferred.
* Corresponding authorat:InfectiousDisease Service, SanAntonioMilitaryMedicalCenter,Brooke ArmyMedical Center,3851Roger
BrookeDrive,FortSamHouston,TX78234,UnitedStates.Tel.:[phone];fax:[phone].
E-mailaddress:[email protected](C.K.Murray).
0305-4179/$36.00.PublishedbyElsevierLtdandISBI
doi:10.1016/j.burns.2010.05.013
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1. REPORT DATE 2. REPORT TYPE 3. DATES COVERED
01 DEC 2010 N/A -
4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER
Activity of topical antimicrobial agents against multidrug-resistant
5b. GRANT NUMBER
bacteria recovered from burn patients
5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S) 5d. PROJECT NUMBER
Glasser J. S., Guymon C. H., Mende K., Wolf S. E., Hospenthal D. R.,
5e. TASK NUMBER
Murray C. K.,
5f. WORK UNIT NUMBER
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION
United States Army Institute of Surgical Research, JBSA Fort Sam REPORT NUMBER
Houston, TX 78234
9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S)
11. SPONSOR/MONITOR’S REPORT
NUMBER(S)
12. DISTRIBUTION/AVAILABILITY STATEMENT
Approved for public release, distribution unlimited
13. SUPPLEMENTARY NOTES
14. ABSTRACT
BACKGROUND: Topical antimicrobials are employed for prophylaxis and treatment of burn wound
infections despite no established susceptibility breakpoints, which are becoming vital in an era of
multidrug-resistant (MDR) bacteria. We compared two methods of determining topical antimicrobial
susceptibilities. METHODS: Isolates of Pseudomonas aeruginosa, methicillin-resistant Staphylococcus
aureus (MRSA), extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and
Acinetobacter baumanii-calcoaceticus (ABC) from burn patients were tested using broth microdilution
and agar well diffusion to determine minimum inhibitory concentrations (MICs) and zones of inhibition
(ZI). Isolates had systemic antibiotic resistance and clonality determined. MDR included resistance to
antibiotics in three or more classes. RESULTS: We assessed 22 ESBL-producing K. pneumoniae, 20 ABC
(75% MDR), 20 P. aeruginosa (45% MDR), and 20 MRSA isolates. The most active agents were mupirocin
for MRSA and mafenide acetate for the gram-negatives with moderate MICs/ZI found with silver
sulfadiazene, silver nitrate, and honey. MDR and non-MDR isolates had similar topical resistance. There
was no clonality associated with resistance patterns. CONCLUSION: Despite several methods to test
bacteria for topical susceptibility, no defined breakpoints exist and standards need to be established. We
recommend continuing to use silver products for prophylaxis against gram-negatives and mafenide acetate
for treatment, and mupirocin for MRSA.
15. SUBJECT TERMS
16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER 19a. NAME OF
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a. REPORT b. ABSTRACT c. THIS PAGE UU 13
unclassified unclassified unclassified
Standard Form 298 (Rev. 8-98)
Prescribed by ANSI Std Z39-18
burns 36 (2010) 1172–1184 1173
drug-resistant(MDR)organisms[2].Burnsresultinlossofthe antimicrobialagentsusingtwomethods,brothmicrodilution
firstlineofimmunologicdefense,theskin,andburnescharis andagarwelldiffusion,inconjunctionwithphenotypicand
avascular. This can result in an increased risk for bacterial genotypictestingtoevaluateforclonaldifferencesinactivity
colonizationandsubsequentinvasion,whichcanultimately andcorrelationwithsystemicresistanceprofilesandtopical
resultinburnwoundinfection.Thismaybedifficulttocontrol agentactivity.
duetodifficultyimmunecellsandsystemicantibioticshavein
arrivingtoanavascularsite[3].Burnwoundinfectionsarea
significant andseriouscomplicationoccurringafterthermal 2. Methods
injury. Though the rate of burn wound infections has
decreased, burn wound sepsis remains a substantial source 2.1. Bacterialisolates
ofinfectioninthispopulation[4].
Improvementsinburnwoundcare,suchasearlyexcision Acollectionofbacterialisolateswereobtainedfrompatients
and grafting, have resulted in decreased mortality [5]. Early admitted to the US Army Institute of Surgical Research
excisionandgraftingisthestandardofcareatspecializedburn (USAISR) Burn Center. The USAISR Burn Center is a 40-bed
centersintheUnitedStates.Thebenefitoftopicalantimicro- unitlocatedwithinBrookeArmyMedicalCenterthatserves
bials,however,isthattheycanbeusedatalllevelsofcare,even Department of Defense beneficiaries worldwide and the
whensurgeryforexcisionandgraftingisnotavailable.Topicals civilianpopulationfromwithinthesouthern Texasregional
suchashoneyhavebeeninusesinceantiquity,andothersfor traumasystem.Standardburnpatientcareincludesresusci-
decades[4–11].Therearebothanimalstudiesandclinicalstudies tation and stabilization upon arrival with earlyburn wound
that provide data about the morbidity and mortality benefits excision and skin grafting. Vancomycin and amikacin are
associatedwithuseofvarioustopicalantimicrobialagentsinthe administered routinely peri-operatively and various topical
preventionandtreatmentofburnwoundinfections[5,12–17]. antimicrobialsare usedtoincludesilversulfadiazine,mafe-
Anotherbenefitoftopicalagentsisthattheycanbedelivered nide acetate, silver nitrate solution, and silver-impregnated
directlytothesiteofcolonizationorinfectionandcanbeusedfor dressings.Thechoiceofthespecifictopicalagentusedisat
boththeprophylaxisandtreatmentofburnwoundinfections staffdiscretion.Aggressiveinfectioncontrolispracticedinthe
[18].Agentssuchassilversulfadiazine,silvernitrate,mupirocin, center to include individual patient rooms, use of contact
honey,mafenideacetate,andneomycinhavebeeninusefor precautions,andstrictlyenforcedhandwashing.
years with variable amounts of objective data available to Themostcommongram-negativepathogensrecoveredin
supporttheiruse(Table1). ourburnunitareAcinetobacterbaumannii-calcoaceticuscomplex
Thoughwehaveinvitrodataaboutthetopicalantibiotics’ (ABC), extended-spectrum beta-lactamase (ESBL) producing
generalspectrumofactivity,therearenoestablishedclinical Klebsiella pneumoniae, and P. aeruginosa, with methicillin-
breakpointstodeterminewhetheranisolateissusceptibletoa resistant Staphylococcus aureus (MRSA) being a common
particular agent at concentrations expected at the wound gram-positive organism isolated. Isolates studied had been
surface. Bacteria with resistance to multiple systemic anti- saved for performance improvement purposes and were
microbials are increasing in prevalence worldwide, which stored in Microbank1 Bacterial Preservation systems (Pro-
raises concern for a subsequent increase in resistance to Lab Diagnostics, Austin, TX) at (cid:2)208C. The P. aeruginosa
topical agents. The potential for resistant isolates makes isolates were stored at room temperature on agar deeps.
choosingempiricsystemicantimicrobialtherapyintheburn IsolateswerepassedtwiceonTrypticaseTMSoyAgarwith5%
unit more challenging and may reduce the number of Sheep Blood (TSA II) (BD Diagnostic) prior to use. Quality
available treatment options. Thus, the possibility of using control(QC)bacteria(EscherichiacoliATCC125922,Enterococcus
topicalagentsforprophylaxisandtreatmentofburnwound faecalisATCC129212,P.aeruginosaATCC127853,andS.aureus
infectionsisappealing,inparticulargiventheabilitytoapply ATCC129213)wereobtainedfromtheAmericanTypeCulture
topical agents directly at the site of infection, avoiding Collection (Manassas, VA). The QC organisms were main-
potential systemic toxicities and the risk of systemic anti- tainedandculturedinthesamemannerasthetestorganisms.
biotics not arriving through avascular tissue to the site of
infection.However,somepreviousstudieshavealreadynoted 2.2. Antimicrobialsusceptibilitytesting
concern for resistance to topical agents as well to include
emerging resistance of staphylococci to mupirocin and Using the Phoenix Automated Microbiology System (Becton,
of Pseudomonas aeruginosa to silver sulfadiazine (Table 1) Dickinson and Co., Franklin Lakes, NJ) standard systemic
[9,18–21]. antibioticprofileswere determined [25]. ForP.aeruginosa and
Prior studies assessing topical agent antimicrobial resis- ABC,wedefinedMDRasresistancetoallantimicrobialstestedin
tance profiles have used agar well diffusion and broth agroupfor3ormoregroupsamongtheaminoglycosides,beta-
microdilution methods with data indicating an increase in lactams,carbapenems,andfluoroquinolones[26].AlloftheK.
resistance of MDR pathogens to topical antimicrobials as pneumoniaeisolatesusedinthisstudywereESBL-producing.All
compared to non-MDR pathogens [8,22–24]. However, there oftheS.aureusisolatesweremethicillin-resistant.
are limited data comparing strain variability and systemic
antimicrobial resistance to topical antimicrobial activity 2.3. Pulsed-fieldgelelectrophoresis
testedbyvariousmethods.
WithMDR bacteria on the rise wedesignedthis studyto Pulsed-fieldgelelectrophoresis(PFGE)wasalsoperformedfor
compare selected bacterial isolates against various topical further clonal typing as described elsewhere [27–29]. The
1
Table1–Descriptionoftopicalantimicrobialagentsevaluated. 1
7
Topicalagent Mechanismofaction Spectrumofactivity Pros Cons Resistance/ Priorstudies 4
other
Bacitracin PolypeptideproducedbyBacillus Gram-positiveorganisms Minimalabsorption Rareanaphylaxis RareresistantS. Noneavailable
subtilisthatinhibitscellwall especiallyStaphylococciand andallergiccontact aureus[9]
synthesisanddisruptsthe beta-hemolyticStreptococci[8] dermatitis[9]
cytoplasmicmembraneby Inactiveagainstmostgram-
formingacomplexwithC55- negativeorganismsincludingP.
prenolpyrophosphate[8,9] aeruginosa[34]
Medical Variableantimicrobialactivity Bactericidalagainstgram- Managessuperficialbacteriabut Food-gradehoneyisnota Noreported Honeyhelpedburn
gradehoney amonghoneyscollectedfrom positiveandgram-negative mayalsodiffusethroughskinto sterileproduct;maycontain resistance[7] woundstoheal
naturalenvironments[7] organismsincludingP. deepertissues[36] Bacillusspp.[38]Medical-grade earlierandwith
Propertiesresponsiblefor aeruginosaandMRSA[35,37] Generallyfoundtobesoothing, honeyneedstobefilteredand fewercomplications
antimicrobialactivityinclude pain-relieving,andnon- gamma-irradiated thanconvention
highosmolarity,lowpH(3.2– irritating[36] Avoiduseinpatientswith treatment(silver
4.5),athermolabilesubstance Maypromotehealingofburn allergytohoney,beeproducts, sulfadiazine)[35]
calledinhibine,andproduction woundsandreducescarring[35] orbeestings[36] Mostdataavailableis
ofhydrogenperoxide[7,35] onLeptospermumspp.
Alsomayhavesomeanti- honey(Manuka)
inflammatoryactivity[36]
b
Mafenide Inhibitsnucleotidesynthesis[8] Bacteriostaticagainstgram- 11.1%cream,5%solution 11.1%concentrationispainful Noresistance Mortalitybenefitin u
r
acetate negativeorganismsincludingP. Rapidlypenetratesfull whenappliedtothesuperficial reportedtoP. preventionofburn n
(Sulfamylon) aeruginosaandgram-positive thicknessescharmakingit partial-thicknessburnswith aeruginosa[6] woundsepsis s
3
organisms[13,39] effectiveinheavilycolonized intactfreenerveendings[3,40] Someresistance describedinanimal 6
woundsandestablishedburn Candryintoatenaciousgum describedto models[13] (
2
woundinfection[3,5,33] (neoeschar)thatattachestothe Providencia[5] Reductionin 0
1
woundrequiringhydrotherapy mortalityandtherate 0
toremove[41] ofinvasiveburn )
1
5%aqueoussolutionisless woundinfectionsin 1
painfulanddoesnotleavea patientsfrombefore 72
residue[42] theintroductionof –
1
Absorbedsystemicallywith mafenidetoafter, 1
8
highestbloodlevelsofmafenide particularlyin 4
anditsmetabolite(p- patientswith40–79%
carboxybenzenesulfonamide)in TBSAinonestudy[5]
2nd–4thhourresultingin andbetween20and
urinaryalkalinizationfrom 59%TBSAinanother
carbonicanhydraseinhibition study[14,15]
[43] Foundtobethemost
Possiblemetabolicacidosis, effectivetopicalagent
especiallyinpatientswith againstA.baumannii
pulmonarydysfunctionsuchas [18]
atelectasisorpneumoniathat Poorcorrelation
limitsrespiratorycompensation betweenbroth
[14,40,44] microdilutionand
Electrolytedisturbances[45] agarwelldiffusion
7%incidenceof [23]
hypersensitivity,usuallyarash
[5]
Rapidabsorptionfromthe
tissuerequirestwicedaily
applicationtokeeplevelshigh
enoughforbacterialinhibition
[33]
Mupirocin Pseudomonicacid,producedby Bactericidalathigh Nosystemicabsorptionof Prolongedusemayresultin Emergenceof Applicationof
Pseudomonasfluorescens[19] concentrations(2%formulation) mupirocinoritsmajor overgrowthofnon-susceptible resistant mupirocintoburn
InhibitionofRNAandprotein andafter24–36hofexposure metabolite(monicacid)has organisms,includingfungi[9] staphylococcihas woundsrapidly
synthesisbytargetingthe [46] beendetectedwithtopicaluse beendescribed eradicatedMRSA[48]
isoleucine-bindingsiteonthe Highlyactiveagainst inhealthyvolunteersor worldwide[9,19,20] Goodcorrelation
isoleucyl-transfer-RNA streptococciandstaphylococci patientswithepidermolysis Possiblemechanism betweenbroth
synthetaseenzyme[9,46,47] includingMRSA[9].Notactive bullosa[9,46] ofresistanceisa microdilutionand
againstenterococci Canpenetrateeschar[48] transmissible agarwelldiffusion
Lesseffectiveagainstmost Hasbeenusedsuccessfullyin plasmid[46] [23]
gram-negativebacilliand thetreatmentofMRSA-infected Nocrossresistance
anaerobesincludingK. burnswounds[49] withotherantibiotics
pneumoniaeandP.aeruginosa[19] [50]
Neomycin Aminoglycosideproducedby Gram-negativesexcept Mayenhancere- Otoxicityandnephrotoxicity ResistantstrainsofE. Noneavailable
Streptomycesfradiae[51] Pseudomonasaeruginosaand epithelializationinwound withsystemicuse.Absorption coli,Klebsiella,and
Inhibitionofproteinsynthesis anaerobessuchasBacteroides healing[34] canoccurthroughinflamed Proteusspp.may
atthe30Ssubunitofthe spp.[51] skinbutisnegligiblethrough emerge[51]
bacterialribosome[9] Staphylococci,notStreptococciand normalskin[9,51] Transferofneomycin
MayalsoinhibitbacterialDNA gram-positivebacilli Allergicsensitizationespecially resistanceoccursin
polymerase whenointmentisusedfor hospital-acquired
prolongedtimeoninflamedor isolatesofS.aureus
denudedskin[51].Relatedto Resistancemaybe
mastcelldegranulationand plasmidmediated,
b
histaminerelease[9] andresistanceto u
other r
n
aminoglycosidescan s
betransferredonthe 3
6
sameplasmid[9]
(
2
PolymyxinB Inhibitsactivityofendotoxins Gram-negativeorganisms Littlesystemicabsorption[9] Nodataavailable ResistantstrainsofA. Noneavailable 0
[52] includingP.aeruginosa[8] baumanniiare 10
Interactswiththeouter Noactivityagainstgram- emerging[18] )
1
membraneofthegram- positiveorganismsorfungi[9] 1
negativecellwallanddestroys 7
2
bacterialmembraneswitha –
1
detergent-likemechanism[8,52] 1
8
Silvernitrate Interfereswithelectron Gram-negativeandgram- 0.5%aqueoussolution Poorescharpenetration[3]so Acquiredresistanceis Hasbeenusedin 4
transportinhibitingcellular positiveorganismsincluding Reducesnutritionaland canbeusedforprophylaxisbut uncommon[33,58] burntreatmentsince
respirationandfunction[8,17] Pseudomonasspp.andS.aureus metaboliclossesbydecreasing nottreatmentofburnwound Resistanceisoften atleastthe18th
[8,53] evaporativewaterloss[3,33,54] infections[55] unstableandisolates century,initiallyina
SomeactivityagainstCandida Painlessonapplication[33] Turnsblackuponcontactwith canrevertbackto hardenedformcalled
spp. tissuesandcanstainlinens sensitive[59] lunarcaustic[10]
[53,54,56,57] Reducedmortalityin
Electrolytedisturbancesdueto burnedmicewithP.
leechingofcationsacrossthe aeruginosainfection
woundintothehypotonic by30%[16]
solution,‘‘sodiumsink’’ Applicationto>40%
[3,6,20,33,40,54] TBSAwounds
Aerobactercloacaeandsome delayedsepsisand
othergram-negativebacteria reducedmortality
canconvertthenitratetonitrite from81%to33%[54]
causingmethemoglobinemia[3]
Problemswithtissueirritation
anddelayedwoundhealing
havebeenreported[3,57]
1
1
7
5
1
1
7
6
Table1 (Continued)
Topicalagent Mechanismofaction Spectrumofactivity Pros Cons Resistance/ Priorstudies
other
SilverSulfadiazine Interfereswithelectron Bactericidaltogram-negative Combinationofthesilverion Poorescharpenetration Resistanttomost Reducedmortalityin
(Silvadene) transportandnucleotide andgram-positiveorganisms andsulfadiazineina1%water Reversiblegranulocyte Enterobactercloacae burnedmicewithP.
synthesis[8] includingPseudomonasspp.and solublecreamintroducedin depressionespeciallyin>30% andsome aeruginosainfection
Bindstobacterialcell S.aureus(MRSA)[3,20] 1968[3] TBSAburns[3,6,9].Thisoccurs Pseudomonasspp.[5] by60–75%[16]
membranesandcellwall, SomeactivityagainstCandida Painlessonapplication[60] earlyintherapy(postburnday Plasmid-mediated Poorcorrelation
penetratesthecell,and spp.andherpesvirusesathigh Accelerateddeepdermalwound 2)andmainlyaffectsmature resistanceagainst betweenbroth
denaturesbacterialDNAand concentrations[9] healingandreducedconversion neutrophilsthoughhasnot somegram-negatives microdilutionand
RNAresultingininhibitionof rateofdeepdermalwoundsto beenshowntoincreaseriskof includingA. agarwelldiffusion
replication[9,17] full-thicknessskinwounds[17] infectiouscomplications[61] baumanniiandP. [23] b
Delayedescharseparation[17] Notveryeffectiveinestablished aeruginosahasbeen u
r
infectionduetominimaleschar reportedinburn n
penetration[49] patients[9,18,21] s
3
Appearsasathickcreamy 6
exudatesonthewound,which (
2
canbeconfusedwithpus[3,53] 0
Rarehypersensitivityreactions 10
tosulfamoietyreported[33,62] )
1
andrarehemolysisinsettingof 1
G6PDdeficiency[21] 7
2
Systemicabsorptionespecially –
1
inmorevascularpartial- 1
thicknessburns[21,63]though 84
anexperimentalmodelusing
radioactivesilversulfadiazine
showedsilveronlyintheskin
andnotintheblood/organs[53]
Rareargyrosis[63]ifsilverlevels
aremanytimesnormal[21]
Tripleantibiotic Antimicrobialactivityhasbeen Moderateactivityagainsta Nodataavailable Nodataavailable Nodataavailable Noneavailable
ointment(Neomycin, showntoresideinthe varietyofburnisolates,buthas
PolymyxinB,bacitracin) neomycincomponent[52] pooractivityagainstP.
aeruginosa[52]
Table2–Pulsed-fieldtype,brothmicrodilution,agarwelldiffusion,andantibioticresistanceprofilesformethicillin-resistantStaphylococcusaureusisolatesfromburn
patients.
MRSA Brothmicrodilution Agarwelldiffusion Systemicantimicrobialagents
PFT MIC BAC MUP NEO POL SN SS MA H AWD BAC MUP B/N/P SN SS MA H Susc Clin Ery Gent Levo Lin Mox Q/D Rif Tet T/S Vanc
1 >256 1 64 32 8 32 1024 5 9 150 9 12 22 34 22 R R S R S R S S S S S
1 >256 2 128 16 8 32 1024 5 9 150 9 13 22 34 21 R R S R S I S S S S S
1 >256 2 64 32 16 32 1024 10 9 62 9 13 23 36 23 R R S R S I S S S S S
1 >256 1 32 16 8 32 512 5 9 150 9 11 23 35 23 R R S S I S S S S S S
1 >256 >128 64 16 16 32 512 15 9 38 9 12 22 33 23 X R R R S R S S S S S
1 >256 1 64 16 16 32 1024 5 9 150 9 13 21 36 22 R R S R S S S S S S S b
1 >256 1 64 16 16 32 1024 10 9 150 9 12 21 33 22 X R S R S I S S S S S u
r
1 >256 2 >1024 16 8 32 512 20 9 150 9 13 23 34 23 X R S R S R S S S S S n
1 >256 1 256 16 16 32 512 5 9 150 9 13 24 34 22 X R S R S R S S S S S s
1 >256 1 64 16 16 32 512 10 9 150 9 12 22 32 24 R R S R S I S S S S S 36
1a >256 2 128 16 32 64 1024 15 9 150 9 12 23 31 22 X R S R S R S S S S S (
2
1c >256 1 128 16 8 32 1024 5 9 150 9 13 24 34 23 X R S R S I S S S S S 0
1c >256 1 32 32 8 32 512 15 9 150 9 13 23 34 23 R R S R S I S S S S S 10
3 >256 2 32 16 16 64 1024 15 9 150 9 13 21 33 24 R R S S S S I S S S S )
1
4 32 0 256 32 16 32 1024 5 9 150 9 12 21 28 21 S S R R S S S S R R S 1
USA300 >256 0.12 16 64 16 32 1024 15 9 150 9 12 23 33 22 X R S I S S S S S S S 7
2
USA300 >256 0.12 512 64 16 32 1024 10 9 150 9 12 23 32 23 X R S S S S S S I S S –
1
USA300 >256 0.25 >1024 16 16 32 1024 15 9 150 9 13 22 31 23 X R S S S S S S I X S 1
USA300 >256 0.12 512 32 16 64 1024 15 9 150 9 12 23 36 23 X R S S S S S S S S S 8
4
USA300 32 0.12 <0.5 16 16 32 512 5 9 150 20 13 25 36 24 S S S S S S S S S S S
mg/ml mm
50 >256 1 64 16 16 32 1024 10 Mean 9 140 9.6 12.5 22.6 33.5 22.7 %susc 20 10 90 30 95 45 95 100 85 95 100
90 >256 2 512 32 16 64 1024 15 Range 9 38–150 9–20 11–13 21–25 28–36 21–24
50=MIC50=minimumconcentrationrequiredtoinhibitgrowthof50%ofisolatestested;90=MIC90=minimumconcentrationrequiredtoinhibitgrowthof90%ofisolatestested;PFT=pulsedfield
type; MIC=minimum inhibitory concentration; BAC=bacitracin; MUP=mupirocin; NEO=neomycin; POL=polymyxin; SN=silver nitrate; SS=silver sulfadiazine; MA=mafenide; H=honey;
AWD=agarwelldiffusion;B/N/P=bacitracin,neomycin,polymyxinintripleantibioticointment;Susc=antimicrobialsusceptibilities;Clin=clindamycin;Ery=erythromycin;Gent=gentamicin;
Levo=levofloxacin; Lin=linezolid; Mox=moxifloxacin; Q/D=quinupristin/dalfopristin; Rif=rifampin; Tet=tetracycline; T/S=trimethoprim/sulfamethoxazole; Vanc=vancomycin; %susc=%
susceptibleoutofthoseisolatestestedagainstaspecificantimicrobialagent;R=resistant;S=susceptible;I=intermediatesusceptibility;X=nottested.
1
1
7
7
1
1
7
8
Table3–Pulsed-fieldtype,brothmicrodilution,agarwelldiffusion,andantibioticresistanceprofilesforKlebsiellapneumoniaeisolatesfromburnpatients.
Kleb Brothmicrodilution Agarwelldiffusion Antimicrobialsusceptibility
PFT MIC BAC MUP NEO POL SN SS MA H AWD BAC MUP B/N/P SN SS MA H Susc Ami Gent Tobra Cefep Ceftaz P/T Levo Cipro Imi Mero
1 >256 >128 1 2 16 64 1024 25 9 32 18 12 22 26 16 S R I R X X R R S S
1C >256 >128 1 <0.5 8 32 512 25 9 27 19 12 20 27 17 S R I R R S R R S S
1C >256 >128 2 16 16 64 2048 20 9 30 17 11 18 23 16 S R R R X I R R S S
1C >256 >128 <0.5 <0.5 8 32 1024 25 9 32 20 13 21 27 17 S R I R R I R R S S
1C >256 >128 <0.5 1 8 32 1024 25 9 28 18 12 18 25 16 S R I R R R R R S S
1D >256 >128 <0.5 <0.5 8 32 512 25 9 27 18 6 9 25 17 R R R R R R R R S S
2 >256 >128 1 <0.5 8 32 1024 25 9 27 20 8 15 29 17 R R R R X R R R S S
2 >256 >128 <0.5 16 8 32 1024 25 9 34 19 13 21 25 17 R R R R X R R R S S
2 >256 >128 1 32 8 32 1024 25 9 36 20 13 20 23 19 R R R R R X S I S S b
u
2B >256 >128 1 32 16 64 1024 25 9 31 21 12 21 23 18 S R I R R R R R S S r
2C >256 >128 <0.5 <0.5 8 32 1024 25 9 31 17 6 12 24 17 S R R R R I S R S S n
s
2C >256 >128 <0.5 <0.5 8 32 2048 25 9 33 20 6 12 23 17 S R R R R R S R S S 3
2C >256 >128 <0.5 <0.5 8 32 512 25 9 24 17 6 9 32 18 S R R R R X R R S S 6
38 >256 >128 32 8 8 32 2048 25 9 43 9 9 21 23 18 R R R R R S S S S S (2
3B >256 >128 <0.5 16 8 32 2048 25 9 37 21 15 20 20 17 S R R R R R S R S S 01
5 >256 >128 2 2 8 32 1024 25 9 33 15 10 20 21 16 S R R R R R S R S S 0
)
10 >256 >128 <0.5 1 8 32 2048 25 9 30 17 10 18 19 16 S R R R R R R R S S 1
16 >256 >128 2 2 16 64 2048 25 9 28 16 10 18 26 16 S R R R R R S R S S 1
7
17 >256 >128 <0.5 16 8 32 2048 20 9 29 21 12 21 20 18 R R R R R X R R S S 2
–
18 >256 >128 2 <0.5 32 32 2048 20 9 31 15 9 15 14 17 S R R R R X R R S S 1
18A >256 >128 2 16 16 32 1024 20 9 34 16 8 13 21 17 R R R R R X S S S S 18
24 >256 >128 <0.5 1 8 32 2048 25 12 28 17 11 16 21 16 S R R R R R S S S S 4
mg/ml mm
50 >256 >128 <0.5 1 8 32 1024 25 Mean 9.1 31.1 17.8 10.2 17.3 23.5 17 %susc 68 0 0 0 0 13 41 14 100 100
90 >256 >128 2 16 16 64 2048 25 Range 9–12 24–43 9–21 6–15 9–22 14–32 16–19
50=MIC50=minimumconcentrationrequiredtoinhibitgrowthof50%ofisolatestested;90=MIC90=minimumconcentrationrequiredtoinhibitgrowthof90%ofisolatestested;PFT=pulsedfield
type; MDRO=multidrug resistant organism; MIC=minimum inhibitory concentration; BAC=bacitracin; MUP=mupirocin; NEO=neomycin; POL=polymyxin; SN=silver nitrate; SS=silver
sulfadiazine; MA=mafenide; H=honey; AWD=agar well diffusion; B/N/P=bacitracin, neomycin, polymyxin in triple antibiotic ointment; Susc=antimicrobial susceptibilities; Ami=amikacin;
Gent=gentamicin; Tobra=tobramycin; Cefep=cefepime; Ceftaz=ceftazidime; Pip/tazo=pipericillin/tazobactam; Levo=levofloxacin; Cipro=ciprofloxacin; Imi=imipenem; Mero=meropenem;
%susc=%susceptibleoutofthoseisolatestestedagainstaspecificantimicrobialagent.
Table4–Pulsed-fieldtype,brothmicrodilution,agarwelldiffusion,andantibioticresistanceprofilesforPseudomonasaeruginosaisolatesfromburnpatients.
PS Brothmicrodilution Agarwelldiffusion Antimicrobialagents
PFT MDRO MIC BAC MUP NEO POL SN SS MA H AWD BAC MUP B/N/P SN SS MA H Susc Ami Gent Tobra Amp/S Cefep Ceftaz P/T Levo Cipro Imi Mero
1 Yes >256 >128 16 2 8 32 1024 10 9 17 9 9 15 26 18 S S S R R R R R R R R
1 Yes >256 >128 16 4 8 32 1024 10 9 20 9 11 20 33 21 S R S X R R X R R R I
1 No >256 >128 8 2 8 32 2048 10 9 22 10 11 16 27 15 S S S R R R R R R S S
1 Yes >256 >128 16 1 8 32 1024 10 9 18 10 10 15 10 17 S I S R R R R R R R R
1A Yes >256 >128 16 1 8 16 1024 10 9 18 9 9 17 26 15 S I S R R R R R R R R
1A Yes >256 >128 8 2 8 32 1024 10 9 23 10 10 16 30 19 S S S R R R R R R R I
2 No >256 >128 4 2 8 16 1024 10 9 17 13 14 20 27 18 S S R R R S R R R R R b
2 No >256 >128 4 2 8 16 1024 10 9 16 13 14 25 34 15 S S I R R S R R R R R u
r
2 No >256 >128 4 2 8 16 1024 10 9 18 15 14 20 27 16 S S R R R S R R R R R n
3 No >256 >128 4 2 8 16 512 15 9 16 12 14 24 35 14 S S S R S S S S S S S s
3
3 No >256 >128 4 2 8 16 256 15 9 17 11 15 22 34 16 S S S R S S S S X S S 6
4 Yes >256 >128 32 2 8 16 128 10 9 21 9 15 23 15 22 S S S R I R R R R R R (
2
5 No >256 >128 8 1 8 16 512 15 9 19 13 15 25 37 13 S S S R S S S S S S S 0
6 Yes >256 >128 8 1 8 16 1024 10 9 21 9 14 20 29 15 I I S R R R R R R R I 10
7 No >256 >128 32 2 8 16 1024 10 9 21 9 14 20 14 17 S R S R S R R R R R I )
1
8 No >256 >128 16 1 8 16 256 10 9 14 9 13 18 40 18 S R S R R R R R R I S 1
9 No >256 >128 4 2 8 16 512 15 9 18 9 15 23 36 14 S S S R S S S S S S S 72
10 Yes >256 >128 8 1 8 16 128 15 9 18 9 11 15 11 17 S S S R I R R R R R R –
1
11 No >256 >128 8 2 8 16 512 10 9 23 14 15 23 44 16 S S S X S S X S S S S 1
12 Yes >256 >128 32 2 8 32 256 10 9 21 9 7 15 42 17 R R R R R R R R R R R 84
mg/ml mm
50 >256 >128 8 2 8 16 1024 10 Mean 9 18.9 10.6 12.5 19.6 28.9 16.7 %susc 90 65 80 0 30 40 22 25 21 30 35
90 >256 >128 32 2 8 32 1024 15 Range 9 14–23 9–15 7–15 15–25 10–44 13–22
50=MIC50=minimumconcentrationrequiredtoinhibitgrowthof50%ofisolatestested;90=MIC90=minimumconcentrationrequiredtoinhibitgrowthof90%ofisolatestested;PFT=pulsedfield
type; MDRO=multidrug resistant organism; MIC=minimum inhibitory concentration; BAC=bacitracin; MUP=mupirocin; NEO=neomycin; POL=polymyxin; SN=silver nitrate; SS=silver
sulfadiazine; MA=mafenide; H=honey; AWD=agar well diffusion; B/N/P=bacitracin, neomycin, polymyxin in triple antibiotic ointment; Susc=antimicrobial susceptibilities; Ami=amikacin;
Gent=gentamicin;Tobra=tobramycin;Amp/S=ampicillin/sulbactam;Cefep=cefepime;Ceftaz=ceftazidime;Pip/tazo=pipericillin/tazobactam; Levo=levofloxacin; Cipro=ciprofloxacin;Imi=i-
mipenem;Mero=meropenem;%susc=%susceptibleoutofthoseisolatestestedagainstaspecificantimicrobialagent;S=susceptible;R=resistant;I=intermediatesusceptibility;X=nottested.
1
1
7
9