Antibiotic & Antibacterial Antibiotic & Antibacterial Resistance of Skin Bacteria from Resistance of Skin Bacteria from

Users & Non-Users of Users & Non-Users of Antibacterial Wash ProductsAntibacterial Wash Products

Eugene C. Cole, DrPHEugene C. Cole, DrPHBrigham Young Brigham Young

UniversityUniversityProvo, UtahProvo, Utah

OrganizationOrganization Study conducted through cooperative Study conducted through cooperative

efforts of two applied research efforts of two applied research organizations:organizations: Applied Environmental, Inc., Cary, NCApplied Environmental, Inc., Cary, NC Restoration Sciences, LLC, Cary, NCRestoration Sciences, LLC, Cary, NC

Study sponsored by:Study sponsored by: The Soap and Detergent Association, The Soap and Detergent Association,

Washington, DC Washington, DC

ObjectiveObjective Investigate relationship between Investigate relationship between

antibiotic and antibacterial resistance in antibiotic and antibacterial resistance in human skin bacteria:human skin bacteria: Staphylococcus aureusStaphylococcus aureus Coagulase-negative Coagulase-negative

StaphylococcusStaphylococcus sp. sp. Isolated from forearm skin of persons Isolated from forearm skin of persons

routinely using or not using body routinely using or not using body washes and bath soaps containing, washes and bath soaps containing, exclusively, either: exclusively, either: triclosantriclosan or or triclocarbantriclocarban..

SummarySummary These study results These study results

discount the speculative discount the speculative claim that the use of claim that the use of antibacterial wash antibacterial wash products contribute to the products contribute to the selection and propagation selection and propagation of drug-resistant bacteria of drug-resistant bacteria on human skin.on human skin.

ApproachApproach Randomized study with 210 Randomized study with 210

qualified male and female qualified male and female participants >18 yearsparticipants >18 years 70 that frequently use body wash products 70 that frequently use body wash products

containing only containing only TriclosanTriclosan (TCS) (TCS) 70 that frequently use body wash products 70 that frequently use body wash products

containing only containing only TriclocarbanTriclocarban (TCC)(TCC) 70 that frequently wash, but do not use 70 that frequently wash, but do not use

any antibacterial body wash products any antibacterial body wash products ((ControlsControls))

ApproachApproach Users were defined as those using TCC or Users were defined as those using TCC or

TCS wash products on a regular basis TCS wash products on a regular basis during the last 30 days for body washing.during the last 30 days for body washing.

Exclusion criteria disqualified persons Exclusion criteria disqualified persons from participating:from participating: Antibiotic therapy within last 90 daysAntibiotic therapy within last 90 days Use of topical skin medications, Use of topical skin medications,

medicated shampoos, anti-acne productsmedicated shampoos, anti-acne products Employment in health care, day-care, or Employment in health care, day-care, or

animal careanimal care Frequent swimmer or hot tub userFrequent swimmer or hot tub user Routine exposure to solvents Routine exposure to solvents

ApproachApproach Home visits confirmed qualificationHome visits confirmed qualification Forearm skin samples were collected:Forearm skin samples were collected:

Composite swab sample of both forearms, Composite swab sample of both forearms, using a 4 x 16 cm (64 cm using a 4 x 16 cm (64 cm22 template) template)

Lab processing by elution, plating on SBA Lab processing by elution, plating on SBA and incubation for 18-24 hours at 37and incubation for 18-24 hours at 37ºº C C Colonies selected by criteria: morphology, Colonies selected by criteria: morphology,

pigmentation, texture, hemolysis, etcpigmentation, texture, hemolysis, etc Presumptive ID by gram stain, catalase, Presumptive ID by gram stain, catalase,

coagulasecoagulase Confirmation by reference laboratoryConfirmation by reference laboratory

ApproachApproach Antibiotic susceptibility performed by:Antibiotic susceptibility performed by:

Standard MIC testing using MicroScan Standard MIC testing using MicroScan methodmethod

Testing conducted by LabCorp, NCTesting conducted by LabCorp, NC Antibacterial susceptibility performed by:Antibacterial susceptibility performed by:

Standard broth micro-dilution method Standard broth micro-dilution method (Barry et al, 1999), adapted from NCCLS (Barry et al, 1999), adapted from NCCLS method M7-A4 (NCCLS, 1997)method M7-A4 (NCCLS, 1997)

All isolates tested against TCC and TCSAll isolates tested against TCC and TCS All results verified through appropriateAll results verified through appropriate QA QA

procedures and microorganism control strainsprocedures and microorganism control strains

ApproachApproach Standard Antibiotic Standard Antibiotic

Susceptibility Susceptibility Panel:Panel: AmpicillinAmpicillin CiprofloxacinCiprofloxacin ClindamycinClindamycin ErythromycinErythromycin NitrofurantoinNitrofurantoin

OxacillinOxacillin PenicillinPenicillin TetracyclineTetracycline TMP/SMXTMP/SMX VancomycinVancomycin

ResultsResults 317 317 StaphylococcusStaphylococcus isolates isolates

301 CNS isolates301 CNS isolatesNon-users (n = 106)Non-users (n = 106)TCC users (n = 102TCC users (n = 102TCS users (n = 93)TCS users (n = 93)

16 SA isolates16 SA isolatesNon-users (n = 4)Non-users (n = 4)TCC users (n = 7)TCC users (n = 7)TCS users (n = 5)TCS users (n = 5)

ResultsResults No isolates showed full or intermediate No isolates showed full or intermediate

resistance to vancomycinresistance to vancomycin S. aureusS. aureus - MRSA - MRSA

Rates of Rates of resistance to oxacillin was resistance to oxacillin was less than reported ratesless than reported rates for hospital- for hospital-acquired and community-acquired MRSA:acquired and community-acquired MRSA:

12.5% 12.5% 20.2% (Fridkin et al, 2002)20.2% (Fridkin et al, 2002) 50.0% (Tiemersma et al, 2004)50.0% (Tiemersma et al, 2004)

ResultsResults CNS - MRCNS - MR

Rates of Rates of resistance to oxacillin resistance to oxacillin was less than reported rateswas less than reported rates for hospital-acquired and for hospital-acquired and community-acquired MR-CNS:community-acquired MR-CNS:

20.6% 20.6% 43.6% (Fridkin et al, 2002)43.6% (Fridkin et al, 2002) 73.3% (DUMC, 2005)73.3% (DUMC, 2005)

ResultsResults MRSAMRSA

NU = 25.0% (1/4) NU = 25.0% (1/4) TCC = 0.0% (0/7)TCC = 0.0% (0/7) TCS = 20.0% (1/5)TCS = 20.0% (1/5)

MR-CNSMR-CNS NU = 17.9% (19/106) NU = 17.9% (19/106) TCC = 23.5% (24/102)TCC = 23.5% (24/102) TCS = 20.4% (19/93)TCS = 20.4% (19/93)

ResultsResults Antibiotic Resistance - SAAntibiotic Resistance - SA

Distribution across Distribution across all 10 drugs all 10 drugs showed no significant differences showed no significant differences among groupsamong groups, even when TCC and , even when TCC and TCS data were pooled and compared TCS data were pooled and compared with NU results.with NU results.

Distribution across Distribution across the 6 preferred the 6 preferred drugs showed no significant drugs showed no significant differences among groupsdifferences among groups, even , even when TCC and TCS data were pooled when TCC and TCS data were pooled and compared with NU results.and compared with NU results.

ResultsResults Antibiotic Resistance - CNSAntibiotic Resistance - CNS

Distribution across Distribution across all 10 drugs all 10 drugs showed no significant showed no significant differences among groupsdifferences among groups, , even when TCC and TCS data even when TCC and TCS data were pooled and compared with were pooled and compared with NU results.NU results. GreaterGreater tetracycline resistance tetracycline resistance in NU group isolatesin NU group isolates..

ResultsResults

Antibiotic Resistance to more Antibiotic Resistance to more than 1than 1 preferred drugpreferred drug CNS - for 69 isolates, rates of CNS - for 69 isolates, rates of resistance for each of the 3 resistance for each of the 3 groups were comparablegroups were comparable

NU = 25.5% (27/106)NU = 25.5% (27/106)TCC = 24.5% (25/102)TCC = 24.5% (25/102)TCS = 18.3% (17/93)TCS = 18.3% (17/93)

ResultsResults

Antibiotic Resistance to more Antibiotic Resistance to more than 1than 1 preferred drugpreferred drug SA - for 2 isolates, rates of SA - for 2 isolates, rates of resistance for each of the 3 resistance for each of the 3 groups were comparablegroups were comparable

NU = 25.0% (1/4)NU = 25.0% (1/4)TCC = 00.0% (0/7)TCC = 00.0% (0/7)TCS = 20.0% (1/5)TCS = 20.0% (1/5)

ResultsResults Antibacterial (TCC/TCS) Antibacterial (TCC/TCS)

ResistanceResistance All isolates (n=317) were tested for All isolates (n=317) were tested for

resistance to TCC and TCSresistance to TCC and TCSCNS isolates from all 3 groups CNS isolates from all 3 groups had comparable MIC values had comparable MIC values when tested against TCC and when tested against TCC and TCSTCS

SA isolates had comparable SA isolates had comparable MIC values when tested MIC values when tested against TCC and TCSagainst TCC and TCS

ResultsResults Antibacterial ResistanceAntibacterial Resistance

CNS – MIC ValuesCNS – MIC Values

TCCTCC TCS TCS

NUNU 0.0117-0.7500.0117-0.750 0.128-2.020 0.128-2.020

TCCTCC 0.0234-0.7500.0234-0.750 0.004-2.020 0.004-2.020

TCSTCS 0.0117-0.7500.0117-0.750 0.008-2.020 0.008-2.020

ResultsResults Antibacterial ResistanceAntibacterial Resistance

SA – MIC ValuesSA – MIC Values

TCCTCC TCS TCS

NUNU 0.0469-0.18750.0469-0.1875 0.510-2.040 0.510-2.040

TCCTCC 0.0029-0.18750.0029-0.1875 0.124-1.020 0.124-1.020

TCSTCS 0.0469-0.18750.0469-0.1875 1.020-2.040 1.020-2.040

ResultsResults Cross-Resistance TestingCross-Resistance Testing

CNS – 9 isolates most resistant CNS – 9 isolates most resistant to preferred treatment drugs (4-to preferred treatment drugs (4-5)5) Antibacterial MICs for TCC were Antibacterial MICs for TCC were comparable across all 3 groups, comparable across all 3 groups, with none showing highest MICs (as with none showing highest MICs (as did less antibiotic-resistant isolates) did less antibiotic-resistant isolates)

MICs for TCS were comparable, and MICs for TCS were comparable, and with one exception, none showed with one exception, none showed highest MICs (as did less antibiotic-highest MICs (as did less antibiotic-resistant isolates)resistant isolates)

ResultsResults Cross-Resistance TestingCross-Resistance Testing

CNS – 7 isolates w/highest CNS – 7 isolates w/highest antibacterial MICs for TCCantibacterial MICs for TCCComparable antibiotic Comparable antibiotic resistance across the 3 groups resistance across the 3 groups (resistance to 0-2 preferred (resistance to 0-2 preferred drugs), as opposed to drugs), as opposed to resistance to 4-5 drugs shown resistance to 4-5 drugs shown by less TCC-resistant isolatesby less TCC-resistant isolates..

ResultsResults Cross-Resistance TestingCross-Resistance Testing

CNS – 60 isolates w/highest CNS – 60 isolates w/highest antibacterial MICs for TCSantibacterial MICs for TCSComparable antibiotic Comparable antibiotic resistance across the 3 resistance across the 3 groups, as opposed to groups, as opposed to resistance to drugs shown by resistance to drugs shown by less TCS-resistant isolates.less TCS-resistant isolates.

ResultsResults Cross-Resistance TestingCross-Resistance Testing

SASA No isolates showing highest No isolates showing highest

possible MIC value for TCC.possible MIC value for TCC. Of 3 isolates showing the Of 3 isolates showing the

highest MIC value for TCS, none highest MIC value for TCS, none were resistant to any of the were resistant to any of the preferred treatment drugs.preferred treatment drugs.

ConclusionConclusion These study results These study results

confirm similar findings confirm similar findings from recent assessments from recent assessments of antibiotic and of antibiotic and antibacterial resistance in antibacterial resistance in home environments home environments

Cole et al, J Appl Micro 2003 Cole et al, J Appl Micro 2003 Aiello et al, Emer Inf Dis 2005 Aiello et al, Emer Inf Dis 2005

ConclusionConclusion These study results further These study results further

discount the speculative discount the speculative claim that the use of claim that the use of antibacterial wash antibacterial wash products contribute to the products contribute to the selection and propagation selection and propagation of drug-resistant bacteria of drug-resistant bacteria on human skin.on human skin.

ReferencesReferences Cole et al, 20003, Investigation of antibiotic and antibacterial Cole et al, 20003, Investigation of antibiotic and antibacterial

agent cross-resistance in target bacteria from homes of agent cross-resistance in target bacteria from homes of antibacterial product users and non-users. antibacterial product users and non-users. Journal of Applied Journal of Applied MicrobiologyMicrobiology 95:664-676. 95:664-676.

Aiello et al, 2005, Antibacterial cleaning products and drug Aiello et al, 2005, Antibacterial cleaning products and drug resistance. resistance. Emerging Infectious DiseasesEmerging Infectious Diseases, 11(10):1565-1570., 11(10):1565-1570.

DUMC (2005), Summary of Antimicrobial Susceptibility Test DUMC (2005), Summary of Antimicrobial Susceptibility Test Results 1999-2004, Duke University Medical Center, Durham, Results 1999-2004, Duke University Medical Center, Durham, NC, NC, htpp://pathology.mc.duke.edu/microbiology/susceptibility.htm. htpp://pathology.mc.duke.edu/microbiology/susceptibility.htm.

Fridkin SF, Hill HA, Volkova NV, Edwards JR, Lawton RM, Gaynes Fridkin SF, Hill HA, Volkova NV, Edwards JR, Lawton RM, Gaynes RP, McGowan , Jr JE, 2002, Temporal changes in prevalence of RP, McGowan , Jr JE, 2002, Temporal changes in prevalence of antimicrobial resistance in 23 U.S. hospitals, antimicrobial resistance in 23 U.S. hospitals, Emerging Infectious Emerging Infectious DiseasesDiseases, (8)7:697-701., (8)7:697-701.

Tiemersma EW, Bronzwaer SL, Lyytikainen O, Degener JE, Tiemersma EW, Bronzwaer SL, Lyytikainen O, Degener JE, Schrijnemakers P, Bruinsma N, Monen J, Witte W, Grundmann H, Schrijnemakers P, Bruinsma N, Monen J, Witte W, Grundmann H, 2004, Methicillin-resistant Staphylococcus aureus in Europe, 2004, Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002, 1999-2002, Emerging Infectious DiseasesEmerging Infectious Diseases, 10(9):1627-1634., 10(9):1627-1634.