Chlorhexidine‐Impregnated Cloths to Prevent Skin and Soft‐Tissue Infection in Marine Recruits: A Cluster‐Randomized, Double‐Blind, Controlled Effectiveness Trial • Author(s): Timothy J. Whitman, DO; Rachel K. Herlihy, MD, MPH; Carey D. Schlett, MPH; Patrick R. Murray, PhD; Greg A. Grandits, MS; Anuradha Ganesan, MD; Maya Brown, BA; James D. Mancuso, MD, MPH; William B. Adams, MD; David R. Tribble, MD, DrPH Source: Infection Control and Hospital Epidemiology, Vol. 31, No. 12 (December 2010), pp. 1207-1215 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/657136 . Accessed: 18/05/2014 15:29 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp . JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. . The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaborating with JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology. http://www.jstor.org This content downloaded from 91.229.248.15 on Sun, 18 May 2014 15:29:26 PM All use subject to JSTOR Terms and Conditions
Transcript
Chlorhexidine‐Impregnated Cloths to Prevent Skin and Soft‐Tissue Infection in MarineRecruits: A Cluster‐Randomized, Double‐Blind, Controlled Effectiveness Trial • Author(s): Timothy J. Whitman, DO; Rachel K. Herlihy, MD, MPH; Carey D. Schlett, MPH;Patrick R. Murray, PhD; Greg A. Grandits, MS; Anuradha Ganesan, MD; Maya Brown, BA;James D. Mancuso, MD, MPH; William B. Adams, MD; David R. Tribble, MD, DrPHSource: Infection Control and Hospital Epidemiology, Vol. 31, No. 12 (December 2010), pp.1207-1215Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/657136 .
Accessed: 18/05/2014 15:29
Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at .http://www.jstor.org/page/info/about/policies/terms.jsp
.JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range ofcontent in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new formsof scholarship. For more information about JSTOR, please contact [email protected].
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The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaboratingwith JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology.
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infection control and hospital epidemiology december 2010, vol. 31, no. 12
o r i g i n a l a r t i c l e
Chlorhexidine-Impregnated Cloths to Prevent Skinand Soft-Tissue Infection in Marine Recruits:
A Cluster-Randomized, Double-Blind, Controlled Effectiveness Trial
Timothy J. Whitman, DO; Rachel K. Herlihy, MD, MPH; Carey D. Schlett, MPH; Patrick R. Murray, PhD;Greg A. Grandits, MS; Anuradha Ganesan, MD; Maya Brown, BA; James D. Mancuso, MD, MPH;
William B. Adams, MD; David R. Tribble, MD, DrPH
(See the commentary by Popovich, on pages 1216–1218.)
background. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes skin and soft-tissue infection (SSTI)in military recruits.
objective. To evaluate the effectiveness of 2% chlorhexidine gluconate (CHG)–impregnated cloths in reducing rates of SSTI and S.aureus colonization among military recruits.
design. A cluster-randomized (by platoon), double-blind, controlled effectiveness trial.
intervention. Application of CHG-impregnated or control (Comfort Bath; Sage) cloths applied over entire body thrice weekly.
measurements. Recruits were monitored daily for SSTI. Baseline and serial nasal and/or axillary swabs were collected to assess S.aureus colonization.
results. Of 1,562 subjects enrolled, 781 (from 23 platoons) underwent CHG-impregnated cloth application and 781 (from 21 platoons)underwent control cloth application. The rate of compliance (defined as application of 50% or more of wipes) at 2 weeks was similar(CHG group, 63%; control group, 67%) and decreased over the 6-week period. The mean 6-week SSTI rate in the CHG-impregnated clothgroup was 0.094, compared with 0.071 in the control group (analysis of variance model rate difference, 0.025 � 0.016; P p .14). At baseline,43% of subjects were colonized with methicillin-susceptible S. aureus (MSSA), and 2.1% were colonized with MRSA. The mean incidenceof colonization with MSSA was 50% and 61% (P p .026) and with MRSA was 2.6% and 6.0% (P p .034) for the CHG-impregnated andcontrol cloth groups, respectively.
conclusions. CHG-impregnated cloths applied thrice weekly did not reduce rates of SSTI among recruits. S. aureus colonization ratesincreased in both groups but to a lesser extent in those assigned to the CHG-impregnated cloth intervention. Antecedent S. aureus colonizationwas not a risk factor for SSTI. Additional studies are needed to identify effective measures for preventing SSTI among military recruits.
Infect Control Hosp Epidemiol 2010; 31(12):1207-1215
From the National Naval Medical Center (T.J.W., A.G.) and Infectious Disease Clinical Research Program, Uniformed Services University (R.K.H., C.D.S.,A.G., M.B., J.D.M., D.R.T.), and National Institutes of Health (P.R.M.), Bethesda, Maryland; Division of Biostatistics, University of Minnesota, Minneapolis(G.A.G.); and Marine Corps Base, Quantico, Virginia (W.B.A.).
Received March 12, 2010; accepted June 7, 2010; electronically published October 28, 2010.� 2010 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2010/3112-0001$15.00. DOI: 10.1086/657136
Community-associated methicillin-resistant Staphylococcusaureus (CA-MRSA) causes skin and soft-tissue infection(SSTI) in community settings where crowding, frequent skintrauma, and suboptimal hygiene are a concern (eg, amongprisoners, athletes, and military recruits).1-4 Hospital-associ-ated MRSA (HA-MRSA) is more commonly associated with
surgical site infections, nosocomial pneumonia, and blood-stream infection.5
Infection control and prevention measures for CA-MRSAemphasize hand hygiene, appropriate wound care, and en-vironmental cleaning.1 Data from HA-MRSA prevention re-search support use of mupirocin nasal ointment and chlor-
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1208 infection control and hospital epidemiology december 2010, vol. 31, no. 12
hexidine gluconate (CHG) body washes as MRSA decolo-nization therapy to augment disease prevention.6 This ap-proach has been extrapolated to community settings but hasyet to be validated.1
Ellis et al7 evaluated a 5-day course of intranasal mupirocinapplied to MRSA carriers at the beginning of a military train-ing session in an attempt to decrease the rate of CA-MRSASSTI. Mupirocin use decreased MRSA colonization rates;however, it did not prevent SSTI in colonized individuals orin the overall recruit cohort. In light of these findings, perhapsa more effective prevention strategy for persons at continuousrisk for SSTI (CA-MRSA or otherwise) would be the broad-based use of an ongoing decolonization regimen over an ex-tended period of time. The topical antiseptic CHG has severalcharacteristics that make it an ideal agent for ongoing de-colonization: excellent safety profile, residual antimicrobialactivity (up to 24 hours), no evidence of clinically importantacquired resistance, and proven capacity to decrease HA-MRSA acquisition.8-10
This study investigated the effectiveness of thrice-weeklyapplication of CHG in reducing rates of SSTI and in de-creasing S. aureus colonization among military recruits.
methods
Design Overview
This was a cluster-randomized, double-blind, controlled ef-fectiveness trial with the primary end point being the 6-weekplatoon SSTI rates. The study was approved by the ethicsreview committee of the Uniformed Services University.
Setting and Participants
Recruits attending Officer Candidate School (OCS) at MarineCorps Base Quantico (Virginia) during the summer and fallof 2007 (two 6-week and two 10-week training classes) wereeligible. Recruits are assigned to platoons (of 40–70 individ-uals) and reside together in open bays, share a bathroom,and have minimal contact with recruits in other platoons.The rigorous training requires recruits to perform strenuousphysical activities and periodically to live outdoors, resultingin numerous skin abrasions and insect bites.
Investigators presented the study to recruits on the firstday of training. Written informed consent was obtained fromrecruits who agreed to participate. Exclusion criteria includedthe current use of oral antibiotics (with the anticipation ofcontinued use during training—for example, minocycline foracne) and CHG allergy or intolerance. In addition, becauseCHG is inactivated by anionic emulsifiers and sulfates, re-cruits who anticipated the continued use of skin care productscontaining these substances (a list was provided to subjects)were excluded.11
Randomization and Interventions
Randomization (ratio, 1 : 1) was at the platoon level. Ran-domization schedules (within the training class) used per-
muted blocks of sizes 2 and 4. No unblinding was necessaryduring the study.
All participating platoon members received the same in-tervention: either two 2% CHG-impregnated cloths (madeby Sage; 500 mg per cloth; hereafter referred to as “the CHGgroup”)12 or 2 control cloths (Comfort Bath; Sage)13 in similarpackaging. One packet (which contained 2 cloths) was dis-pensed to subjects thrice weekly on the basis of treatmentassignment. Recruits were provided instructions on theproper application of cloths (immediately after a shower, sub-jects would scrub the entire body, except the genitalia, theface, and any areas with large open wounds). These instruc-tions were reinforced on their bi-weekly visits.
Outcomes and Follow-Up
Enrollment and bi-weekly study procedures included surveycompletion and collection of nares and axillary swab samplesfor culture. Surveys collected data on demographic charac-teristics and medical history, interim medication use, hygienepractices, intervention compliance, and changes in skin con-dition (ie, irritation or burning, itching, redness, or rash).Platoon corpsmen examined recruits daily for SSTI in ac-cordance with standard OCS protocol. Recruits with an SSTIwere referred to the OCS clinic for evaluation and treatmentby healthcare providers who were blinded to the study ran-domization schedule. OCS healthcare providers were trainedto identify the following conditions as an SSTI: a lesion thatlooked like an insect or spider bite, folliculitis, furuncle orcarbuncle (boil), abscess, cellulitis, impetigo, and infectedwound.1,14 Identified SSTIs were then grouped by Interna-tional Classification of Diseases, Ninth Revision (ICD-9), codeinto the following categories: carbuncle and furuncle, cellulitisand abscess of finger and toe (eg, paronychia), other cellulitisand abscess, impetigo, unspecified local infection of skin andsubcutaneous tissue (eg, wound or infected blister), and otherspecified diseases of hair and hair follicles (eg, folliculitis).Study staff abstracted SSTI data from clinic notes.
Swab samples of the external nares and axillae were col-lected using BD BBL CultureSwabs (dual swabs) with LiquidAmies Medium (BD Diagnostic Systems). One swab was usedto inoculate a S. aureus selective enrichment medium, tryp-ticase soy broth with 6.5% NaCl, and incubated overnight at35�C. The enrichment broth was subcultured onto CHROM-agar S. aureus (BD Diagnostic Systems), incubated at 35�C,and read at 48 hours. Suspected S. aureus colonies, identifiedby colony morphology, color, Gram stain result, catalase, andcoagulase reactions, were subcultured onto a sheep blood agarplate, incubated overnight at 35�C, and frozen at �70�C forfurther evaluation.
Specimens recovered from clinical infections were obtainedfrom the base of the cutaneous lesion using a sterile polyester(Dacron; Invista) swab after the wound surface was cleaned.The specimen was transported to the National Naval MedicalCenter clinical laboratory in Bethesda, Maryland (in accor-
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figure 1. Flow diagram of the progress of Officer Candidate School (OCS) platoons and recruits through the skin and soft-tissueinfection trial.
dance with standard OCS protocol), where it was processedand cultured according to standard techniques.15
S. aureus isolates, from both screening and clinical infectionspecimens, underwent antibiotic susceptibility testing usingMicroScan standardized broth microdilution panels (SiemensHealthcare Diagnostics) with interpretative criteria in accor-dance with those of the Clinical and Laboratory StandardsInstitute.16,17
Statistical Analysis
Sample size was calculated to achieve 80% power (with a 5%type I error) to detect a reduction in SSTI rate from 5% inthe control arm (reported SSTI rate in military settings) to2% in the CHG arm using a formula for comparing 2 bi-nomial proportions for randomization at the subject level
and multiplying by an inflation factor to account for clus-tering.18-20 The inflation factor, a function of cluster (platoon)size and variability within and between clusters, was estimatedto be 1.5. This was calculated by setting the platoon size to40 persons, the within-cluster variability to 0.0475 (binomialdistribution with a P value of .05), and the between-clustervariability to 0.00062 (corresponding to a symmetrical dis-tribution centered at 0.05 [range, 0.00–0.10], with heaviertails than in a normal distribution). The total sample sizerequired was 1,840 recruits (46 platoons). With an expectednumber of recruits of 2,500, an enrollment rate of approxi-mately 75% would yield the required sample size.
Average rates or means were compared among platoonsreceiving CHG-impregnated cloths and platoons receivingcontrol cloths. In some cases, analyses variables were calcu-
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note. Data are no. (%) of subjects, unless otherwise indicated. CHG,chlorhexidine gluconate; OCS, Officer Candidate School.a There were 40 platoons consisting of men (20 in each treatment group)and 4 platoons consisting of women (3 in the CHG group and 1 in thecontrol group).b Study follow-up period includes weeks 2–6.c Shower frequency assessed at midpoint (week 4) of study follow-up.
lated on an individual level for simplicity of presentation.Platoon SSTI rate was calculated as the total number of SSTIepisodes divided by total number of person-weeks of follow-up (restricted to enrolled members in the platoon). The pri-mary end point was assessed at 6 weeks, with early with-drawals censored at date of withdrawal (10-week classes werecensored at 6 weeks for primary analysis). SSTI rates arereported as the number of SSTIs per 6-week period. MeanSSTI rates were compared using a 2-way weighted analysisof variance (ANOVA; class [3 degrees of freedom] and treat-ment [1 degree of freedom]); weights were the inverse of theestimated SSTI platoon rate variance to account for differentplatoon sizes.21 All SSTI episodes were counted regardless ofindividual compliance. Similar methods were used to com-pare mean platoon prevalence and cumulative incidence ofmethicillin-susceptible S. aureus (MSSA) and MRSA colo-nization (axillae, nares, or either site) between groups. Ad-verse events (categorized as mild, moderate, or severe) andserious adverse events were compared between groups. SSTIrisk factors were assessed using stratified (by platoon) Coxregression (time to first SSTI). SAS software, version 9.1 (SASInstitute), was used for all analyses.
An interim analysis of trial conduct, safety, and efficacywas performed and presented to an independent data safetymonitoring board in March 2008 to consider whether thestudy should be augmented with further enrollment. Becauseof a trend toward higher SSTI rates in the CHG group andthe low probability (P ! .01) of observing a statistically sig-nificant difference in SSTI rates favoring CHG, the data safetymonitoring board recommended study closure.
results
Study Conduct and Baseline Characteristics
There were 2,572 recruits assigned to 44 platoons (12 platoonsin each of the first 3 training classes and 8 in the last trainingclass) (Figure 1); 23 platoons were assigned to the CHGgroup, and 21 platoons were assigned to the control group.A total of 1,562 recruits (60.7%) consented to participate; themean number of recruits enrolled per platoon was 36 (range,8–52) (Table 1). There were no significant differences in base-line factors between treatment groups; overall, 24.5% re-ported recent minor skin trauma, 13.8% reported antibioticuse within the past 3 months, 2.0% were positive for MRSA,and 42.9% were positive for MSSA, with higher positivity atthe nares than axillae.
Overall, 1,032 subjects (66.1%) completed the study (6weeks), with higher rates in the first training class (83.7%) thanin later classes (range, 57.1%–66.2%), with comparable com-pletion rates between treatment groups (Figure 1). Reasons forstudy withdrawal were equally distributed between voluntarydisenrollment and OCS attrition (median duration of follow-up, 3.4 weeks). Only 6 of the withdrawals (4 in the CHG groupand 2 in the control group) involved an adverse event, de-scribed as mild skin irritation, itching, and/or redness.
Safety Assessment and Adherence
The number of reported adverse events was similar in theCHG group (577 total in 330 subjects [42.3%]) and controlgroup (520 total in 315 subjects [40.3%]); 83.9% were ofmild severity, and 82.3% were unrelated to study product(Table 2). There were 10 serious adverse events (7 in the CHG
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note. CHG, chlorhexidine gluconate.a From a 2-way analysis of variance model comparing means rates betweenplatoons randomized to the CHG group and platoons randomized to thecontrol group.b Serious adverse events were all unrelated to use of the study product. table 3. Number and Rate of Skin and Soft-Tissue Infections
(SSTIs), by Treatment Group
Variable
CHG group Control group
No. ofSSTIs Ratea
No. ofSSTIs Ratea
Total no. of SSTI episodesb 56 0.094 44 0.071Class
note. CHG, chlorhexidine gluconate; ICD-9, International Classificationof Diseases, Ninth Revision.a Data are weighted average of individual platoon 6-week rates for total no.of SSTI episodes, class, and follow-up interval and percentage for ICD-9codes.b Summary of analysis of variance model for treatment (CHG vs control group):b � standard error, 0.025 � 0.016; b/standard error p 1.52; P p .136.c Follow-up interval includes additional SSTI episodes (not counted in thetotal SSTI rate) experienced during weeks 6- 10 in class 2.d Several SSTI episodes were categorized as having more than 1 ICD-9 code(for the CHG group, 68 ICD-9–coded infections represent 56 SSTI episodes;for the control group, 52 ICD-9–coded infections represent 44 SSTI episodes.e Paronychia.
group and 3 in the control group); all were unrelated to studyproduct. Rates of skin irritation or burning were low and ofa mild self-limited nature, but the rates were higher amongrecruits assigned to the CHG arm (5.9% vs 1.8%; P p .003)(Table 2). Self reported use (or 50% or more of the wipes)was similar between the groups and decreased from approx-imately 64.8% at 2 weeks to 48.8% at 6 weeks (Table 2). Thehighest rates of skin irritation or burning occurred at the 2-week visit, during the period of peak compliance, with sig-nificantly higher rates in the CHG group (P ! .001).
SSTI Events
There were 100 episodes (in 98 recruits) of SSTI, including56 in the CHG group and 44 in the control group. Thenumber of SSTIs in the 44 platoons ranged from 0 to 6 (4platoons had none), 80% of which occurred in the first 4weeks of the study. The weighted mean platoon rate per 6weeks was 0.083 � 0.056 (range, 0–0.25; 0.094 � 0.067 forthe CHG group and 0.071 � 0.046 for the control group);the ANOVA model rate difference was 0.025 � 0.016(P p .14) (Table 3). SSTI differences between groups werenot significant by training class (P p .31 for group-times-class interaction) or by platoon groupings (ie, using averageadherence within platoon) into lower (less than 55%) andhigher (55% or more) rates of adherence (P p .24). Overallrates of SSTI varied by follow-up interval, with highest ratesobserved at the 6–8-week and 2–4-week periods. Interval ratedifferences by group were similar, with the exception of the0–2-week period, during which higher SSTI rates among re-cruits in the CHG group were observed (P p .005).
The most common SSTI experienced was “other cellulitisand abscess” (Table 3). SSTIs in the CHG group were more
likely to involve incision and drainage (17 vs 8), to involveobtainment of samples for culture (15 vs 10), and to resultin hospitalization (3 vs 1). Positive culture results included4 MRSA and 13 MSSA isolates.
Colonization
Colonization increased from baseline in both groups but atlower rates in the CHG platoons than in the control platoons.Rates of colonization were lower in the CHG group than inthe control group at each follow-up visit (0%–2% lower forMRSA and 8%–12% lower for MSSA across visits). The meanincidence of colonization was significantly lower in those as-signed CHG than in control intervention recipients (MSSA,49.9% vs 60.8% [P p .03]; MRSA, 2.6% vs 6.0% [P p .03])through 6 weeks (Figure 2).
S. aureus colonization in the nares was more common thanin the axilla at baseline (42.3% vs 11.2%) and as an incidentsite (isolated nares, 72.2%; isolated axilla, 16.7%; and bothsites, 11.2%). Persistent colonization (at least 2 positive cul-
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1212 infection control and hospital epidemiology december 2010, vol. 31, no. 12
figure 2. Mean platoon prevalence and cumulative incidence of colonization in axilla or nares. CHG, chlorhexidine gluconate; MRSA,methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus.
tures after enrollment) was noted in 79.9% of recruits col-onized at baseline, compared with only 29.2% recruits notcolonized on enrollment.
SSTI Risk Factors
Factors present at baseline or follow-up were not associatedwith an increased risk of SSTI (Table 1). Of recruits colonizedwith either MRSA or MSSA at baseline, 6.7% developed anSSTI, compared with 7.2% of recruits who were not colonized(hazard ratio, 0.97 [95% confidence interval, 0.66–1.43];P p .88). Using colonization as a time-updated covariateyielded a hazard ratio of 1.14 (95% confidence interval, 0.77–1.70; P p .50). Of those who developed an SSTI during thestudy, 42.7% were not colonized at the surveillance visit 2weeks prior to development of an SSTI.
discussion
In this effectiveness study, the first community-based CHGrandomized controlled trial, the thrice-weekly applicationfailed to prevent SSTIs. Our findings highlight the real-worldchallenges in generating evidence-based data from effective-ness studies as recruit attrition and logistical challenges ofintermittent self-application led to suboptimal adherence.22
The study design conservatively estimated infection rates andfactored in attrition considerations, enrollment variabilityacross platoon clusters, and adherence limitations, assuringsuccessful trial execution.
The estimated difference in SSTI rate between the CHGgroup and the control group was 0.025, with a standard errorof 0.016 and a lower bound of the 95% confidence intervalof �0.01, provide a high level of confidence that the CHGregimen evaluated was ineffective in the prevention of SSTIs.Of note, OCS clinic–based surveillance data demonstrated anSSTI rate of 0.090, providing assurance that the infection rateamong enrolled subjects was comparable to the infection ratesoccurring in the overall recruit population.
We speculate that the main reason that CHG failed toprevent SSTIs was that the thrice-weekly regimen had limitedsuccess in reducing and preventing CA-MRSA skin coloni-zation, a presumed risk factor for SSTI.19 In addition, theresidual antiseptic effect of CHG may have been compro-mised by sweating and frequent showers in this population.Although the incidence of CA-MRSA colonization was lowerin the CHG group than in the control group, differences wereonly modest.
In light of our negative findings, clinicians should note that
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1214 infection control and hospital epidemiology december 2010, vol. 31, no. 12
trials validating the use of CHG for infection control andprevention have been done entirely in hospital settings (Table4) and not in “real world” community setting.9,23-28 Therefore,the demonstrated clinical efficacy of CHG is limited to thereduction of bloodstream infection and surgical site infection.In addition, the effect of CHG on bacterial carriage is limitedto modest reductions in HA-MRSA and vancomycin-resistantenterococci eradication from baseline levels and incidentcolonization.9,24-26,28,29 Importantly, hospital-based study de-signs, CHG regimens, target populations, and disease pre-vention goals vary markedly from our community-basedstudy, making direct comparisons difficult. Thrice-weeklyCHG was selected because it was a practical dosing regimenfor a highly regimented recruit training environment and wasclinically reasonable, considering that the residual antimicro-bial activity of CHG lasts up to 24 hours.10
A progressive increase in S. aureus colonization rates (upto 80% of individuals) most likely reflects high transmissionintensity secondary to crowded conditions. In addition, wenoted that 41% of recruits were persistently colonized (withpositive results at 3 or more time points), 38% were inter-mittently colonized (positive results at 1–2 time points), and20% were never colonized. Our findings differ from previousobservations that 20% of individuals are persistently colo-nized, 30% are intermittently colonized, and 50% are nevercolonized.30 We suspect similar colonization dynamics occurin environments that approximate military settings (eg, ath-letic teams, prisons, and day care). Antecedent colonizationwas not observed to be a risk factor for SSTI in our study,lending support to Miller and Diep’s31 reconsideration of thetenet that long-standing CA-MRSA colonization must pre-cede SSTI. However, our support is limited, because somedata suggest a potentially important contribution of MRSAcolonization in sites other than the axilla or nares (eg, inguinaland rectum).32,33
CHG caused no serious adverse reactions in our cohortbut did cause infrequent, mild, self-limited skin irritation, areported adverse effect.8,23 In addition, although not statis-tically significant, we noted a greater number of SSTIs (56vs 44) and a higher likelihood that SSTI required incisionand drainage (17 vs 8) in the CHG group. To account forthis finding, we considered the possibility that the skin irri-tation secondary to CHG use, in military recruits alreadyexperiencing frequent skin abrasions, may have contributedto skin breakdown and an increased susceptibility to SSTIs.However, our findings clearly need further investigation.
The ICD-9 classification “other cellulitis and abscess” wasthe most common SSTI noted; however, in this category,abscesses were rare. Early recognition and treatment (within1 day) associated with daily skin surveys likely prevented thenatural process of abscess formation. In contrast to previousreports, clinical isolates of MSSA were more common thanclinical isolates of MRSA.7,19,34 Finally, we did not screen forStreptococcus species, but we suspect that these organismscontributed as an etiology of cellulitis.
Ammerlaan et al35 recently noted the efficacy of a shortcourse of intranasal mupirocin in eradicating MRSA colo-nization 1 week after its use, although recolonization occurredsoon afterwards. Failure of long-term eradication is secondaryto recolonization from other sources (eg, contact with fomitesand individuals who carry MRSA), or perhaps mupirocin onlysuppresses bacterial density for a brief period of time. Giventhe inability to decolonize recruits with CHG alone, futureresearch efforts to reduce SSTI may include a universallyapplied short course of intranasal mupirocin, yielding a high(more than 90%) 1-week decolonization rate,35 followed byintermittent CHG use to slow incident colonization. Thisapproach seems reasonable, because mupirocin is safe, andminimal resistance is noted following short-term use inhealthy persons.36
In conclusion, the thrice-weekly application of CHG inthis community setting failed to prevent SSTI. It did, however,slow the acquisition of S. aureus colonization, the clinicalsignificance of which is unclear. Our results draw into ques-tion the common use of CHG by clinicians to prevent re-current CA-MRSA SSTI or interrupt outbreaks. In addition,our study highlights the challenges inherent in SSTI preven-tion arguing for further investigation of multiple-componenthygiene measures directed at the individual and environmentin addition to vaccine development.
acknowledgments
We thank the Marine Officer Candidates and their leadership for participatingin this study, along with the staff of the Bradley Branch Medical Clinic,including Vicki Colapeitro, Timothy Dwyer, Agnes Bradley-Wright, FrancescaCariello, and Anna Wakefield. We are indebted to Britta Babel, Amy Kom-inski, Sasha Ottey, and Laura Ediger for their assistance in the microbiologylaboratory, as well as Duane Hospenthal and Michael Ellis for their help instudy design. We thank Yusra Talaat, Thomas Dang, Scott Wegner, and themany clinical research coordinators of the Infectious Disease Clinical Re-search Program for their dedication to this project. We would also like tothank Rachel Gorwitz, Mary Foulkes, and Daniel Freilich for their work onthe data safety monitoring board. Finally, we thank Greg Martin, John Pow-ers, and Ken Wilkins for their helpful review of the manuscript.
Financial support. Support for this work (IDCRP-001) was provided bythe Infectious Disease Clinical Research Program, a Department of Defenseprogram executed through the Uniformed Services University. This projectwas funded by the National Institute of Allergy and Infectious Diseases,National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072.
Potential conflicts of interest. All authors report no conflicts of interestrelevant to this article.
Address reprint requests to Timothy J. Whitman, DO, Division of Infec-tious Diseases, Department of Internal Medicine, National Naval MedicalCenter, 8901 Rockville Pike, Bethesda, MD ([email protected]).
The content of this publication is the sole responsibility of the authors anddoes not necessarily reflect the views or policies of the National Institutes ofHealth, the Department of Health and Human Services, the Department ofDefense, or the Departments of the Army, Navy, or Air Force. Mention of tradenames, commercial products, or organizations does not imply endorsement bythe US government.
Presented in part at the 46th Annual Meeting of the Infectious DiseasesSociety of America; October 25–28, 2008; Washington, DC (Abstract L-774).
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