Prevalence of Nasal Colonization Among Patients With Community‐Associated Methicillin‐Resistant Staphylococcus aureus Infection and Their Household Contacts
Objective. To evaluate the prevalence of colonization among patients with community‐associated methicillin‐resistant Staphylococcus aureus (CA‐MRSA) infection and their household contacts.
Design. Prospective, observational laboratory study of nasal colonization among patients and their household members from September 15, 2004, to February 20, 2006.
Setting. A 600‐bed, urban, academic medical center.
Patients. Fifty‐one patients who presented with CA‐MRSA infections and 49 household members had cultures of nasal swab specimens performed.
Results. Skin and soft‐tissue infections were seen in 50 patients (98%) and 2 household members. Twenty‐one (41%) of 51 patients and 10 (20%) of 49 household members were colonized with MRSA. An additional 5 patients (10%) and 12 household members (24%) were colonized with methicillin‐susceptible Staphylococcus aureus. Most MRSA isolates (95%; infective and colonizing) carried the staphylococcal cassette chromosome mec type IV complex, and 67% represented a single clone, identical to USA 300. Of the colonized household members, 5 had isolates related to the patients’ infective isolate.
Conclusions. The frequency of CA‐MRSA colonization among household members of patients with CA‐MRSA infections is higher than rates reported among the general population. Among colonized household members, only half of the MRSA strains were related to the patients’ infective isolate. Within the same household, multiple strains of CA‐MRSA may be present.
Received October 10, 2006; accepted January 25, 2007; electronically published June 19, 2007.
The epidemiology of methicillin‐resistant Staphylococcus aureus (MRSA) is changing, with an increasing frequency of community‐associated MRSA (CA‐MRSA) causing predominantly skin and soft tissue infections and necrotizing pneumonias.1 These infections have been associated with the spread of well‐characterized strains with preserved susceptibility to non–β‐lactam antibiotics and carriage of Staphylococcus cassette chromosome (SCC) mec type IV complex and genes encoding Panton‐Valentine leukocidin toxin.1
Colonization with S. aureus is a known risk factor for subsequent infections.2,3 Prior studies have identified the anterior nares as the most consistent site of S. aureus colonization.4 A recent survey of S. aureus nasal carriage in the US population in 2001‐2002 showed that the national S. aureus colonization prevalence was 32.4%; MRSA colonization was uncommon (0.8%).5 S. aureus may also be transmitted from person to person, especially in the setting of close physical contact.6 Although family outbreaks of CA‐MRSA infection have been reported to cause severe disease,7 only limited studies have systematically estimated the spread of MRSA among household contacts.8 The prevalence of nasal colonization with CA‐MRSA among members of the households of infected patients is unknown. We evaluated the frequency of nasal colonization among patients who presented with CA‐MRSA infections and their household contacts.
Methods
Patient Information
We conducted a prospective, observational study to assess the prevalence of nasal colonization of S. aureus among patients who presented to St. John Hospital and Medical Center (Detroit, MI) with infections due to CA‐MRSA and their household members from September 15, 2004, to February 20, 2006. Patients were identified through prospective monitoring of culture findings by the microbiology laboratory. All patients with MRSA isolates were screened. Inclusion criteria were infection, defined as isolation of MRSA from a patient who presented with a localized infection in an outpatient setting or within 48 hours of admission; community onset of infection, defined as no admission to a short‐term or long‐term healthcare facility within the last 2 years and no receipt of antibiotics active against S. aureus within the past year; and agreement to participate, confirmed by signing an informed consent document. Household members were given $25 if they agreed to participate. Patient information was collected, including age, race, sex, and number of household members. Data were entered into an Excel file. Statistical analysis was performed using the computer software program SPSS, release 10 (SPSS).
Laboratory Investigation
Infective S. aureus isolates were recovered from specimens sent to the clinical microbiology laboratory for culture. Nasal swab specimens were obtained from both anterior nares of consenting patients and household members on the day of enrollment and were cultured on trypticase soy agar with 5% sheep blood (Remel). Identification was confirmed on the basis of catalase production and results of Staphaurex latex agglutination tests (Remel). Susceptibility testing of infective isolates was performed using Vitek 2 (bioMérieux) and methicillin resistance confirmed by growth on Mueller‐Hinton agar that contained 6 μg/mL of oxacillin (Remel). Vancomycin resistance was evaluated with 6 μg/mL of vancomycin (Remel) for MRSA isolates; no resistant isolates were identified. All MRSA (infective and nasal) isolates had DNA extracted using CHEF Genomic DNA Plug Kits (Bio‐Rad Laboratories), and DNA specimens were digested with SmaI restriction endonuclease (Invitrogen). Pulsed‐field gel electrophoresis (PFGE) was performed using CHEF‐DR III (Bio‐Rad) with switch times of 1‐20 seconds at 6 V/cm for 21 hours. Gels were stained with ethidium bromide, destained in water, and photographed with ChemiImager 4000 (Alpha Innotech). The resulting band patterns for MRSA isolates were visually compared and interpreted using standard guidelines.9 A sample of MRSA strain USA 300, a common strain associated with CA‐MRSA infections in North America and our community, was also analyzed for comparison.10,11 A representative isolate from each PFGE pattern was subjected to SCC mec typing, using the protocol of Zhang et al.12
The study was approved by the St. John Hospital and Medical Center institutional review board. Colonization status was reported to the patient and household members when asked. Education and counseling were provided; however, no routine attempts were made to decolonize patients.
Results
During the 18‐month period from September 2004 through February 2006, a total of 54 patients met our selection criteria and were asked to participate in the study. Three refused to participate, and the remaining 51 patients were enrolled. Six of the infective isolates were not available for genetic analysis. The mean age (±SD) of the patients was 
years; most (69%) were male and either African American or white. Two infections occurred in the same households during the study period. All but 1 patient presented with skin and soft tissue infection. The time between CA‐MRSA identification and culture of nasal swab specimens was 0‐86 days (median, 1 day; interquartile range, 0‐3 days). Of the 51 patients, 18 (35%) reported having no household members. There were 80 household members associated with the remaining 33 patients. Forty‐nine household members (61%) from 22 households agreed to participate. The results of nasal cultures are given in the Table. The patients had high rates of colonization, as anticipated. A high rate was also found among household members. Methicillin‐susceptible S. aureus colonization was significantly more common among household members.
PFGE analysis of 76 isolates (45 infective and 31 colonizing) revealed that 68 (89%) were related: 51 isolates had indistinguishable patterns, with a 1‐2–band difference for 17 isolates. This PFGE pattern (hereafter, “strain A”) was identical to that of strain USA 300. Four additional unrelated patterns, each of which differed from the pattern of strain A by more than 3 bands, were detected among the remaining 8 isolates. Of 17 patients from whom both infecting and colonizing isolates were recovered, 16 (94%) had identical strains. The remaining patient was colonized with an unrelated strain. The isolates from the 10 colonized household members (from 8 different households) were related to the corresponding patients’ infective isolate (all of which were strain A) in 5 instances: 4 had indistinguishable patterns, and the pattern for 1 differed by 1 band (Figure). The remaining 5 isolates were unrelated. Nearly all isolates had SCC mec type IV, and 1 had SCC mec type V.13 The risk for MRSA colonization among household members was highest for parents of the patient (60%; risk ratio [RR], 3.77 [95% confidence interval (CI), 1.40‐10.10]; 
), followed by spouses (27%; RR, 1.46 [95% CI, 0.47‐4.53]) and children or siblings (19%; RR, 0.56 [95% CI, 0.15‐2.06]). The number of MRSA‐colonized household members limits our ability to draw meaningful conclusions.
Figure Pulsed‐field gel electrophoresis of representative community‐associated methicillin‐resistant Staphylococcus aureus isolates. Lanes 1 and 10, λ ladder; lanes 2 and 3, a patient‐household pair with a 1‐band difference; lanes 6 and 7, another patient‐household pair with indistinguishable band patterns; and lanes 4, 5, 8, and 9, other patient isolates. The band pattern is indistinguishable in lanes 3 and 5‐7 (strain A); 1 band is different (indicating relatedness) in lanes 2, 8, and 9; and more than 3 bands are different (indicating unrelatedness) in lane 4.
Attempts at performing follow‐up cultures 6 months later were limited, because a large number of individuals were lost to follow‐up. Of the 5 patients and 4 household members who were colonized and underwent follow‐up testing, 3 (1 patient and 2 household members) remained colonized with the same strain originally detected on culture.
Discussion
Nasal colonization with S. aureus is a well‐established risk factor for subsequent S. aureus infection.2,3 The risk appears to be higher for patients colonized with CA‐MRSA. A recent prospective study evaluated S. aureus colonization rates among 812 military personnel and the subsequent risk for developing soft tissue infection. Although only 3% of individuals were initially colonized with CA‐MRSA, the relative risk of subsequent infection was 10.7, compared with individuals colonized with methicillin‐susceptible S. aureus.14 Additionally, the recent increase in infections attributed to the clonal spread of CA‐MRSA strains may suggest an increased risk of infection among individuals colonized with CA‐MRSA. The high frequency of soft tissue infections due to the USA 300 MRSA strain confirms its strong pathogenicity.9
The source of most CA‐MRSA cases is not always apparent. Patients may acquire infection after contact sports or other athletic activities.15 Additionally, in our study, nasal colonization was not documented in some patients with infection, suggesting colonization at different body sites or an exogenous source. In fact, to our knowledge, the rate of nasal colonization among patients with CA‐MRSA infections at the time of clinical disease has not been previously reported. In our study, we found nasal colonization in 41% of the patients. We also found that the incidence among household contacts was significantly higher than that reported for the general population,5,14,16 suggesting either frequent spread or a common source of exposure among household contacts. Other outbreaks of invasive CA‐MRSA infection among families have also been reported, suggesting intrafamilial spread or spread among close contacts.7 The frequency of colonization among household contacts is comparable to that reported elsewhere (14.5%) among contacts of nosocomial MRSA.8 No evidence based on findings from this study is available to indicate that CA‐MRSA strains are transmitted more easily than other MRSA strains. In addition, direct spread did not account for all household colonization, because only half of the colonized household members carried the same strain as the patient. Of the 5 household members colonized with strains different from the patient isolate, 4 carried SCC mec type IV. Thus, multiple strains of CA‐MRSA may colonize a household.
The natural history of CA‐MRSA colonization is not well established. In their study among military personnel, Ellis et al.14 noted a decrease from 3% to 1.6% in colonization rates during an 8‐10–week period. Our efforts to study rates of persistent colonization were limited by patient follow‐up. Larger studies should be undertaken to evaluate persistence of colonization among patients and perform household surveillance, to determine the likelihood of recurrent infection.
Our study has several limitations. The strict entry criteria for patients with CA‐MRSA infection limited our total number of participants. In addition, more than one third of study participants did not have household members, and only 61% of household members chose to participate. Because the nose was the only site from which specimens were obtained for culture, the number of colonized patients and household members is likely underestimated. A recent study that evaluated sites of MRSA colonization among patients admitted to the hospital found that cultures of swab specimens of intact skin, the rectum, and axillae identified an additional 27% of individuals colonized with MRSA.17 The addition of cultures of rectal swab specimens to routine cultures of nasal specimens in that study resulted in identification of 95% of colonized individuals. In addition, cultures of throat specimens have recently identified another area of frequent colonization with S. aureus.18 Future studies that evaluate CA‐MRSA colonization should include cultures of throat and rectal specimens to better estimate the frequency of colonization. In addition, the baseline frequency of MRSA colonization in our community is not known, and thus a comparison with rates of colonization among household members is not available. Three other large studies demonstrated rates of CA‐MRSA colonization among nonhospitalized individuals.5,14,16
As reports of intrafamilial spread of CA‐MRSA infections increase, identification of individuals from the community at risk for MRSA infection will be increasingly important. Recognition of the household spread of strains of CA‐MRSA may affect antibiotic selection in the appropriate clinical scenario.
Acknowledgments
Financial support. This study was supported by a grant from the St. John Hospital and Medical Center Graduate Medical Education.
Potential conflicts of interest. L.B.J. reports being on the speaker’s bureau for Pfizer, Wyeth, and Aventis. All other authors report no conflicts of interest.
References
- 1. Said‐Salim B, Mathema B, Kreiswirth BN. Community‐acquired methicillin‐resistant Staphylococcus aureus: an emerging pathogen. Infect Control Hosp Epidemiol 2003; 24:451‐455.
- 2. Wenzel RP, Perl TM. The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection. J Hosp Infect 1995; 31:13‐24.
- 3. Eiff CV, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med 2001; 344:11‐16.
- 4. Kenner J, O’Connor T, Piantanida N, et al. Rates of carriage of methicillin‐resistant and methicillin‐susceptible Staphylococcus aureus in an outpatient population. Infect Control Hosp Epidemiol 2003; 24:439‐444.
- 5. Kuehnert MJ, Kruszon‐Moran D, Hill HA, et al. Prevalence of Staphylococcus aureus nasal colonization in the United States 2001‐2002. J Infect Dis 2006; 193:172‐179.
- 6. Centers for Disease Control and Prevention. Methicillin‐resistant Staphylococcus aureus skin or soft tissue infections in a state prison—Mississippi, 2000. MMWR Morb Mortal Wkly Rep 2001; 50:919‐922.
- 7. Jones TF, Creech CB, Erwin P, Baird SG, Woron AM, Schaffner W. Family outbreaks of invasive community‐associated methicillin Staphylococcus aureus infection. Clin Infect Dis 2006; 42:e76‐e78.
- 8. Calfee DP, Durbin LJ, Germanson TP, Toney DM, Smith EB, Farr BM. Spread of methicillin‐resistant Staphylococcus aureus (MRSA) among household contacts of individuals with nosocomially acquired MRSA. Infect Control Hosp Epidemiol 2003; 24:422‐426.
- 9. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed‐field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995; 33:2233‐2239.
- 10. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community‐acquired methicillin‐resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft‐tissue infections. Ann Intern Med 2006; 144:309‐317.
- 11. Johnson LB, Saeed S, Pawlak J, Manzor O, Saravolatz LD. Clinical and laboratory features of community‐associated methicillin‐resistant Staphylococcus aureus: is it really new? Infect Control Hosp Epidemiol 2006; 27:133‐138.
- 12. Zhang K, McClure J, Elsayed S, Louie T, Conly JM. Novel multiplex PCR assay for characterization and concomitant subtyping of staphylococcal cassette chromosome mec types I to V in methicillin‐resistant Staphylococcus aureus. J Clin Microbiol 2005; 43:5026‐5033.
- 13. Ito T, Ma XX, Takeuchi F, Okuma K, Yuzawa H, Hiramatsu K. Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC. Antimicrob Agents Chemother 2004; 48:2637‐2651.
- 14. Ellis MW, Hospenthal DR, Dooley DP, Gray PJ, Murray CK. Natural history of community‐acquired methicillin‐resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis 2004; 39:971‐979.
- 15. Kazakova SV, Hageman JC, Matava M, et al. A clone of methicillin‐resistant Staphylococcus aureus among professional football players. N Engl J Med 2005; 352:468‐475.
- 16. Charlebois ED, Bangsberg DR, Moss NJ, et al. Population‐based community prevalence of methicillin‐resistant Staphylococcus aureus in the urban poor of San Francisco. Clin Infect Dis 2002; 34:425‐433.
- 17. Eveillard M, de Lassence A, Lancien E, Barnaud G, Ricard JD, Joly‐Guillou ML. Evaluation of a strategy of screening multiple anatomical sites for methicillin resistant Staphylococcus aureus at admission to a teaching hospital. Infect Control Hosp Epidemiol 2006; 27:181‐184.
- 18. Nilsson P, Ripa T. Staphylococcus aureus throat colonization is more frequent than colonization in the anterior nares. J Clin Microbiol 2006; 44:3334‐3339.
-
Presented in part: 45th International Conference on Antimicrobial Agents and Chemotherapy; Washington, DC; December 16‐19, 2005 (Abstract L‐145).