Effect of Antibiotics on Community-Associated Staphylococcus Aureus Colonization and Recurrent Infection in Patients With Uncomplicated S. Aureus Skin Abscesses
Conditions: MRSA
Sponsor: Southern Illinois University

Effect of Antibiotics on Community-Associated Staphylococcus aureus 
Colonization and Recurrent Infection in Patients with Uncomplicated S. 
aureus Skin Abscesses 
PI: Marcela Rodriguez, MD 
Sub-I’s: Myto Duong, MB, BCh, BAO, MS 
Stephanie Fritz, MD 
NCTI:  NCT02690415 
January 9, 2015

 
 
SIGNIFICANCE 
 
CA-S. aureus burden 
 
Community-associated S. aureus infections have become a significant public health problem 
throughout the United States.  These infections span a wide range in severity from superficial skin 
abscesses to invasive pyomyositis, severe necrotizing pneumonia and fatal septicemia [7-11].  Recurrent S. 
aureus SSTI are problematic and recurrence rates have been reported in up to 50% of pediatric patients 
[12-16]. Recurrent S. aureus infections requiring emergency center care is common and accounts for 
significant utilization of hospital resources [17].  The incidence of S. aureus SSTI has risen dramatically over 
the past decade [18], such that cellulitis and soft tissue abscesses are the most frequent primary diagnoses 
associated with S. aureus.  In 2005, there were 14.2 million outpatient clinic visits for SSTI (48.1 visits/1000 
in the US) compared with just 8.6 million visits (32.1 visits/1000) in 1997 [18].  Due to this substantial 
burden, MRSA is a top priority for the Institute of Medicine’s Comparative Effectiveness Research Program 
[19].  The annual economic burden of MRSA infection in the United States is approximately $14 billion [20].  
At SJH and MMC in Springfield, Illinois, we have seen a significant increase in the number of pediatric ED 
and EC visits. In the last five years there has been an average of 1400 visits a year for SSTI, which counts 
for more than a fifty percent increase during this time period.  
 
Determinants of CA-S. aureus infections 
 
Traditionally, S. aureus skin colonization occurs most frequently in the anterior nares, but it can also 
colonize the axilla, inguinal fold, rectum, and throat [5, 21].  S. aureus nasal colonization is a risk factor for 
SSTI development [22-25].  Multiple sites of S. aureus colonization have been found to be related to higher 
recurrence rates [26].  Increased rates of SSTI have been described among U.S. military personnel 
colonized with CA-MRSA;  soldiers with CA-MRSA nasal colonization had a 10-fold greater risk of 
developing SSTI than soldiers colonized with Methicillin susceptible S. aureus (MSSA) [23].  Endogenous 
colonization is important in the transmission and pathogenesis of CA-MRSA infection but behavioral and 
environmental factors may be equally important [27].   
 
Management of CA-S. aureus abscesses 
 
It is controversial whether abscesses requiring incision and drainage also require antibiotics [28].  
The frequency of antibiotic prescription in S. aureus SSTI is still common as described in the literature [29]. 
Creech et al surveyed over 100 Pediatric Infectious Diseases Consultants and found that all of them 
(N=197) prescribed antibiotics; no provider reported using incision and drainage alone without antibiotic 
therapy [30]. Mc Neil et al reported an almost 95% rate of antibiotic prescription among children with S. 
aureus SSTI at Texas Children’s Hospital [31].  
In a study done by Ruhe et al, patients with SSTIs caused by MRSA benefited from antibiotic 
treatment.  Patients with CA-MRSA SSTI who received antibiotics in addition to incision and drainage had a 
greater treatment success rate (infection cure) than those managed with incision and drainage alone (95% 
versus 87%, P =.001) [32].  In a randomized trial by Duong et al, treatment failure rates for CA-MRSA skin 
abscesses were similar after incision and drainage between patients who received antibiotics and those 
given a placebo.  However, at 10-day follow-up, new lesions formed in 26.4% of cases in the placebo group 
and only 12.9% of cases in the antibiotic group [12].  Schmitz et al showed a similar incidence of treatment 
failure in adult patients with uncomplicated abscesses receiving trimethoprim-sulfamethoxazole versus 
placebo (17% vs 26%, P=.12); but at 30-day follow-up the incidence of new lesions was lower in the 
antibiotic group compared to the placebo group (9% vs 28%, P=.02) [33].  
 
Significance for our community 
 
Recurrent S. aureus SSTI have become a major source of morbidity in our pediatric population.  Like 
other areas of the United States, our community has seen a dramatic increase in the incidence of skin and 

soft tissue infections among previously healthy children.  At SJH the number of pediatric ED visits related to 
SSTI increased more than fifty percent in the last 5 years, from 160 visits a year from 2008-2009 to 360 
visits a year from 2013- 2014.  While many of these infections are superficial, they provoke pain and anxiety 
for children and families, lead to subsequent scarring, and pose a significant burden through lost time from 
school and work.  Decreasing the number of recurrent SSTI will decrease ED, EC and PCP clinic visits and 
will benefit our community health in general.  
 
INNOVATION 
 
Infections due to S. aureus are a major healthcare burden.  Currently there is not an effective way to 
prevent S. aureus infection.  Antibiotics are often prescribed for the treatment of CA-S. aureus SSTI.  While 
incision and drainage alone may be adequate for management of uncomplicated CA-S. aureus skin 
abscesses, there is uncertainty about the requirement of systemic antibiotics.  It is not known whether 
antibiotics are helpful in decreasing S. aureus colonization rates or preventing future S. aureus infections. 
Though resolution of acute abscess after drainage may be unchanged by antibiotic administration, the 
impact of managing S. aureus abscess without antibiotics on ongoing S. aureus colonization and recurrent 
infection requires further study.  This study seeks to examine whether the management of initial S. aureus 
abscesses with incision and drainage in addition to antibiotic therapy is an effective means of preventing 
recurrent infection.  The prolonged longitudinal follow-up of this study is a unique characteristic that will 
enable us to capture data about recurrences of infections.  
 
APPROACH/PRELIMINARY DATA 
 
Risk factors for S. aureus SSTI 
 
 
MRSA colonization confers risk for SSTI: A prevalence study of S. aureus nasal colonization in the 
St. Louis pediatric population was performed by Fritz et al.; 1300 children ages birth to 18 years were 
enrolled.  The rates of MRSA and MSSA nasal colonization were 2.5% and 25.5%, respectively [10].  To 
investigate the relationship between S. aureus nasal colonization and subsequent SSTI, the 1300 children 
enrolled in the above prevalence study were followed for one year, during which the overall incidence of 
SSTI was 13%.  Baseline MRSA colonization conferred risk for subsequent SSTI (OR 4.6, 95% CI 1.8, 
11.9) [10].  Another study performed by Kaplan et al showed that multiple S. aureus colonization sites were 
related with higher recurrence rates [26]. 
 
 
Household member with SSTI: S. aureus SSTI 
cluster in households.  In a study performed by Fritz 
et al, SSTI in a household contact was associated 
with increased risk of SSTI  in the index patient 
(Figure 1) [22].   
 
Colonization pressure is a Risk Factor for 
subsequent SSTI: Colonization pressure (CP) is a 
measure used in healthcare settings to determine the 
magnitude of the microorganism reservoir.  MRSA CP 
has been shown to predict infections in hospitals [34].  
During my fellowship at Washington University under 
the mentorship of Stephanie Fritz, MD, MSCI, I participated in a study aimed to apply the concept of CP to 
the community setting by evaluating whether the proportion of colonized household contacts increased the 
prevalence of persistent colonization or the incidence of recurrent infections in index patients with baseline 
SSTI.  We demonstrated that high MRSA CP in households was associated with persistent MRSA 
colonization in pediatric patients.  We found a relationship between S. aureus household CP and a history 
of SSTI in household contacts in the year prior [35].  
Figure 1 
Significant Risk Factors for Development of SSTI during a   
12- Month Longitudinal Study, Univariate Analysis 
Risk Factor 
OR 
95% CI 
MRSA nasal colonization 
4.6 
1.8 – 11.9 
Skin infection in year prior to 
enrollment 
4.2 
1.8 – 9.7 
Household member with skin 
infection in year prior to enrollment 
2.9 
1.2 – 6.8 
Interval skin infection in a 
household member during  
one-year follow up 
6.4 
3.4 – 12.2 
African-American race 
3.1 
1.5 – 6.4 
Crowded home  
(>2 people/bedroom) 
4.4 
1.1 – 18.2 

 
Effect of Antibiotics on CA-MRSA colonization and recurrent infection in uncomplicated skin 
abscesses  
 
From 2008-2010, 852 adults and children with MRSA skin abscesses were enrolled at St. Louis 
Children’s and Barnes-Jewish Hospitals.  MRSA colonization status was determined at baseline and 
repeated 2-8 weeks later (for 194 patients).  Of the 147 patients with MRSA colonization at screening who 
provided a follow-up culture, those prescribed an antibiotic for  MRSA were less likely to be MRSA 
colonized at follow-up than those who were not prescribed an antibiotic (39% vs 100%, p=0.01).  The 
likelihood of MRSA colonization also varied depending on which antibiotic was prescribed.  Patients 
prescribed clindamycin were less likely to be MRSA colonized than those prescribed TMP-SMX (30% vs 
54%, p=0.01).  Patients prescribed an antibiotic active against MRSA were less likely to have a recurrent 
SSTI over the subsequent year than patients who were not prescribed an antibiotic (aOR=0.32, 95% CI 
0.12, 0.90) [36]. 
 
Experimental Design and Methods 
 
 
Patient recruitment:  This is a prospective case-control study that will be performed by the SIU 
Division of Pediatric Infectious Diseases in collaboration with SJH ED, MMC ED, SIU General Pediatrics 
Clinics and the Division of Pediatric Infectious Diseases at Washington University School of Medicine.  
Children who present to SJH or MMC through the ED or SIU Pediatrics clinics with a skin abscess (first 
episode or recurrent) will be assessed for study eligibility.  Cases are defined as patients with a S. aureus 
skin abscess who had incision and drainage AND had appropriate systemic antibiotic therapy.  Controls are 
defined as patients with S. aureus skin abscesses who had incision and drainage and did NOT have 
systemic antibiotic therapy.  This is a non-interventional study and treatment of skin abscesses will be at 
discretion of the treating physician.  We expect to complete patient enrollment in six months with a six 
month follow-up period (see timeline, Figure 2).  Members of the study team (Principal Investigator (PI), 
and Research Coordinator) will obtain access to SJH and MMC ED computerized patient tracking boards to 
monitor for potential candidates/participants.  In addition we also plan to approach the SIU ED residents and 
attending physicians at MMC ED and the SIU Pediatrics Residents and Faculty from General Pediatrics 
Clinics to request notification when a potentially eligible patient is treated.  We will also get access to the 
SIU Pediatrics clinic schedules to look for potential candidates.  A copy of the approved protocol will be 
given to the attending physicians and residents so that they are aware of the study requirements.  A 
member of the study team (PI or research coordinator) will then approach the patient and his or her parent 
or legal guardian to discuss his or her participation in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2:   
Timeline & Assessment     
                 Schedule                         
 
 
Activity 
Site 
Assessment 
Project Months 
 
 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Recruitment and enrollment 
SJH-MMC-PCP 
clinics 
Consent/Assent 
 
 
 
 
 
 
 
 
 
 
 
 
Colonization swabs at 
enrollment and collection of 
wound isolate 
SJH-MMC-PCP 
clinics 
Swabs x 3/ 
Wound isolate 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up visit #1 (+1 month) 
SIU Peds ID clinic  
Swabs x 3 
 
 
 
 
 
 
 
 
 
 
 
 
Culture based analysis 
WashU lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up phone call (+3 
months) 
SIUSM 
SSTI 
recurrence 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up phone call (+6 
months) 
SIUSM 
SSTI 
recurrence 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up phone call (+12 
months) 
SIUSM 
SSTI 
recurrence 
 
 
 
 
 
 
 
 
 
 
 
 
Data analysis 
SIUSM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Inclusion criteria:  (1) Children 6 months to 18 years presenting with a skin abscess.  (2) Positive 
MRSA or MSSA culture from previous or current abscess 
 
Exclusion criteria:  (1) Immunodeficiency;  (2) Hospitalization within the prior 14 days; (3) Use of 
mupirocin, clorhexidine or bleach water baths in the last month; (4) Systemic antibacterial therapy with anti-
staphylococcal activity within the prior 14 days. 
 
Assent will be obtained from children greater than 7 years of age.  Informed consent will be obtained 
from the patient’s parent or legal guardian.  The study protocol was approved by the Southern Illinois 
University (SIU) Institutional Review Board (IRB).  Risks for participating in the study are minimal; the only 
intervention that will be done is collection of body surfaces swabs. 
 
 
Data Collection:  At study enrollment, a detailed questionnaire will be administered to identify risk 
factors for S. aureus colonization, infection, and transmission.  Clinical data will be collected as well to track 
clinical signs at the time of presentation (vital signs, body site of infection, size of abscess, presence of 
systemic symptoms, type of incision and drainage, antibiotic use, type of packing applied).  In addition, 
colonization swabs from the nose, axilla, inguinal folds and wound isolate will be collected and transported 
to Dr. Stephanie Fritz’s laboratory at Washington University.  Longitudinal study visits will be conducted at 
the SIU Pediatric Infectious Disease Clinic one month following enrollment for research purposes only by PI 
or by the research coordinator.  At this visit, a follow-up questionnaire will be administered inquiring about 
new, recurrent, or relapsed infection.  Colonization swabs will be obtained and transported to Dr. Fritz’s 
laboratory.  Also history of any household members with any recent SSTI will be asked.  Follow-up phone 
calls will be administered at 3, 6 and 12 months after enrollment to ask about recurrent infections.  If an 
interval infection did occur, we will collect data regarding whether the individual sought medical care (and if 
so, the location where medical care was sought), the date of infection, the body site of infection, the bacteria 
causing infection, if known, whether the individual required a drainage procedure, surgery, or 
hospitalization, and whether the participant received antibiotics, oral or intravenous.  If the patient sought 
medical care, records from the hospital and/or provider’s office will be obtained for verification.  Again, 
question about any household member having an SSTI will be made.  Throughout the longitudinal study, we 
will ask participants to contact us if they develop a SSTI.  The participant will be directed to seek medical 
treatment from their primary healthcare provider.   
 
Microbiology:  Colonization swabs will be obtained at enrollment and at the 1 month follow-up visit 
by the PI or the research coordinator from the nose, axilla and inguinal folds.  Four swabs will be used for 
each participant (1 each for both nostrils, both axillae, and both sides of the groin and the abscess site).  
Specimens will be collected with Copan E-swab TM Collection and Transport System to evaluate S. aureus 
colonization.  This is a liquid-based multipurpose collection and transport system that maintains viability of 
aerobic, anaerobic and fastidious bacteria for 48 hours at room and refrigerator temperature.  The research 
coordinator and I have successfully completed training for Shipping Infectious Materials and Biological 
Substances with SIU School of Medicine.  Specimens will be shipped to Washington University in St. Louis, 
to the laboratory of Dr. Stephanie Fritz for microbiologic studies.  If wound isolates from initial infection and 
a recurrence are available, they will be requested at the microbiology laboratory at SJH or MMC.  After 
arrival, specimens will be incubated overnight in tryptic soy broth with 6.5% NaCl at 35°C.  A sample of the 
broth will be plated to mannitol salt agar and incubated for 24-48 hours.  Following confirmatory testing for 
S. aureus [37], susceptibility testing for cefoxitin (a surrogate for methicillin resistance) and 9 other 
antibiotics will be determined by Kirby-Bauer disk diffusion, in accordance with published guidelines [37].  
Inducible clindamycin resistance will be tested [38].  All isolates will be stored in glycerol at -20ºC.  
 
Sample size:  This is a pilot study to determine the feasibility of recruiting patients as described, 
having them return for 1 follow-up visit, and collaborating with Washington University for future 

Figure 3:  Monthly Study Accrual Rates 
investigations. Our goal is to get preliminary data.  According to available billing records (ICD-9 codes), 
since 2010, there has been in average 130  pediatric visits per month at SJH, MMC ED and Express Cares 
secondary to SSTI.  Our goal is to recruit 50 patients in 12 months, which means that we will need about a 
30% success rate for recruitment (Figure 3).  A sample size estimate was performed to evaluate the power 
in the study.  Considering an incidence of recurrent SSTI of 50% in patients who did not receive antibiotic 
therapy, a 60-75% percent reduction of recurrent SSTI (12-20% incidence) can be shown with 50-80% 
power.  
 
Data Analysis Plan 
 
Data on S. aureus identification will be 
collected from Washington University School of 
Medicine and recorded, along with questionnaire 
and clinical variables, on a data collection form by 
the principal investigator and research coordinator 
and then transferred to an excel spreadsheet for 
statistical analysis.  Statistical Package for the 
Social Sciences (SPSS), version 20, will be used 
for data analysis. 
Descriptive Statistics will be computed for all 
study variables.  Continuous variables will be 
described with measures of central tendency 
(mean, median) and dispersion (range, standard 
deviation).  Categorical variables will be 
summarized as frequencies and percentages. 
We will calculate the frequencies/ 
percentages for patient demographics, clinical 
characteristics, baseline questionnaire, follow-up 
questionnaires, and S. aureus colonization (nose, 
axilla, and inguinal folds) for each group: 1) 
Systemic antibiotic therapy 2) No systemic antibiotic 
therapy.  Characteristics will be compared using 
independent t-tests for continuous variables and 
Chi-squared tests of independence for categorical 
variables. Significance will be assumed when p < 
0.05 or the 95% confidence interval. 
 
 
Specific Aim 1:  
Primary outcome:  
To determine overall colonization status in children presenting with S. aureus abscesses who do and do not 
receive systemic antibiotic therapy at two time points (baseline and 1 month); a hierarchical logistic 
regression model will be used with colonization status as the outcome.  Follow-up tests will be utilized when 
necessary. 
 
Secondary outcomes: 
1. To determine colonization status at each body site (nose, axilla and inguinal folds) independently in 
children presenting with S. aureus abscesses who do and do not receive systemic antibiotic therapy 
at two time points (baseline and 1 month); a hierarchical logistic regression model will be used with 
colonization status as the outcome at each body site. 
2. A chi-squared test of independence will be used to determine if there is an association between 
colonization (determined at baseline) and presence of abscess at 1 month.   
7-8 patients will enroll in the study 
per month 
12 patients eligible for study 
enrollment 
100 patients per month present 
to SJH-MMC ED or PCP clinics 
with SSTI 
Enrollment acceptance: 65% 
SSTI culture positive for S. aureus: 70% 
Screening acceptance: 
80% 
Capture rate for 
screening: 30% 
21 patients will be approached 
for study screening 
17 patients will be screened 
70 patients undergo drainage 
procedure 

 
 
Specific Aim 2: 
Primary outcome: 
To measure incidence of SA recurrent skin and soft tissue infections at 3 months in patients who did or did 
not receive systemic antibiotic therapy. A binary logistic regression will be performed to see if antibiotic 
therapy is associated with SSTI at 3 months after adjusting for covariates. 
 
Secondary outcomes:   
1. To measure incidence of SA recurrent skin and soft tissue infections at 1, 6 and 12 months 
independently in patients who did and did not receive systemic antibiotic therapy.   Separate logistic 
regressions will be performed (at each time point) to see if antibiotic therapy is associated with SSTI 
after adjusting for covariates.  
2. In order to assess the trend of SSTI’s over 1 year follow-up we will use the Cochran-Armitage test 
for trend to determine if there are more SSTI’s in the following year for patients colonized 
(determined at baseline). 
 
Specific Aim 3:  
Primary outcome:  
To measure S. aureus antibiotic resistance in patients who did and did not receive systemic antibiotics, we 
will use a chi-squared test of independence to compare antibiotic resistance between patients who did and 
did not receive antibiotic therapy. 
 
Potential limitations:  
 
Recruitment success rate is estimated to be around 30% in order to collect  the desired patient 
sample (50 patients) in a 1 year period; this is based on a  prior study in which the same population was 
targeted [39]. We recognize the complexity of having patients come to clinic for research purposes only in 
follow up.  SIU School of Medicine’s Department of Pediatrics is providing funds to complete the study 
beyond the 12 month period.  Patient reimbursement of a $20 check will be given at the follow-up visit for 
study purposes, without any charges to medical insurance.  In previous studies conducted by our team, we 
had had a high longitudinal retention rate when the same incentive was given [39, 40].  Specimens will be 
obtained by research personnel and the collection technique.  The surface area swabbed and the pressure 
used will be standardized for all participants.  We have validated the shipping procedures for specimen 
transport to our collaborators at Washington University.  We would like to evaluate whether shipment of the 
swabs can be done in a timely manner and whether the length of time required for shipment impacts the 
ability to successfully recover microorganisms.  Reaching participant for follow-up phone calls may be a 
challenge, especially at 6 and 12 months after study enrollment; thus, we will obtain multiple methods of 
contact for each participant.  A source of bias that we will have is the variability in the treating physician’s 
decision to administer antibiotics or not.  Adjusting for possible confounding factors and covariates will be 
made but these factors will not play a role in the primary outcome which is S. aureus colonization. 
 
Conclusion: The Research Seed Grant, RSG, is an important step in achieving my career goal of 
becoming an independent investigator at SIU and will offer me a tremendous opportunity to help our patient 
population.  The goal of this project is to obtain preliminary data which will allow me to apply for future 
external funding to be able to recruit more patients and to show a statistical significance.  Recurrent S. 
aureus SSTI have become a major source of morbidity in our pediatric population.  Decreasing the number 
of recurrent SSTI will decrease ED and PCP clinic visits and will benefit our public health.