Exclusive throat carriage among Staphylococcus aureus carriers in relation to level of exposure to the health care system. See the “Methods” section for a detailed explanation of the groups. HCWs indicates health care workers.
Decreasing Staphylococcus aureus colonization with increasing age. For all 3 carriage groups, P < .001 for age dependence of carriage rates using the Mann-Whitney test.
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Mertz D, Frei R, Periat N, et al. Exclusive Staphylococcus aureus Throat CarriageAt-Risk Populations. Arch Intern Med. 2009;169(2):172–178. doi:10.1001/archinternmed.2008.536
Copyright 2009 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2009
Approximately 25% of Staphylococcus aureus carriers have exclusive throat carriage. We aimed to identify the populations at risk for exclusive throat carriage to improve sensitivity to detect carriers.
Four groups underwent nasal and throat screening for S aureus. Three groups of individuals in the community (n = 2632) with different estimated levels of exposure to the health care system (HCS) were screened, including 1500 healthy blood donors, 498 patients from a school of dental medicine, and 634 health care workers (HCWs) at a trade fair. The fourth group comprised in-hospital patients and HCWs (n = 832) and was considered the group with the highest estimated exposure to the HCS. As a primary outcome, we analyzed risk factors for exclusive throat carriage in exclusive throat carriers vs all nasal c arriers.
Of 3464 individuals screened, 428 (12.4%) had exclusive throat carriage, and 1260 (36.4%) had carriage in the nares only or in the nares and the throat. The most important independent risk factor for exclusive throat carriage was age 30 years or younger (odds ratio, 1.66; P < .001). Exposure to the HCS was a significant protective factor for exclusive throat carriage (odds ratio, 0.67; P = .001). Healthy blood donors were almost twice as likely to have exclusive throat carriage than in-hospital patients and HCWs (30.2% vs 18.4% of all carriers, P < .001).
Absence of exposure to the HCS and younger age predicted exclusive throat carriers, a population at high risk for community-onset methicillin-resistant S aureus. Screening for S aureus should include swabs from the anterior nares and from the throat to improve the likelihood of detecting carriers.
Staphylococcus aureus is the most common nosocomial pathogen, accounting for approximately 20% of all nosocomial pathogens.1 Carriers are at higher risk for staphylococcal infections after invasive medical or surgical procedures than noncarriers2 and are 2 to 9 times as likely to have surgical site infections.3 Similarly, nonsurgical S aureus nasal carriers have a significantly higher risk of developing a nosocomial S aureus bacteremia,4 which was found to be caused by the same strain as in their nares in 80%.5 The ecologic niche of S aureus is the anterior nares, and 25% to 30% of the adult population have colonization at a given time.6 Treatment of nasal carriers reduced the risk of nosocomial S aureus infection.7 Therefore, several approaches were developed to identify carriers and to treat the carriage stage before infection develops.
The emergence of methicillin-resistant S aureus (MRSA)8 increased the importance of screening to avoid subsequent infection and epidemic spread of MRSA. More recently, spread of community-onset MRSA (CO-MRSA)9 amplified the demand for accurate S aureus screening. In fact, MRSA is more common than methicillin-susceptible S aureus (MSSA) among skin and soft-tissue infections due to S aureus in US emergency departments,10 and a rapid increase in MRSA colonization was observed between 2001 and 2004.11
The Centers for Disease Control and Prevention has recently recommended routine admission screening for high-risk areas,12 and general screening of all admitted patients is debated in the United States. Screening focuses mainly on MRSA rather than on S aureus. However, the principles of S aureus screening are almost identical whether searching for MSSA or MRSA.13
Screening is restricted to the nares at most institutions, and additional screening of the throat is considered unnecessary because the anterior nares are recognized as the primary colonization site of S aureus.3 Previous investigations have found a variable frequency of S aureus throat carriage ranging from 4% up to 64%.14 Studies15-17 have shown that individuals may have colonization exclusively in the throat who would be missed on screening limited to the anterior nares. In 2 studies,15,16 the yield of throat swabs was higher than the yield of nasal swabs. The importance of additional throat swabs was recently confirmed by our group.18 The analysis (consisting of part of the data set of the present study) demonstrated an S aureus colonization rate of 37.1% in the anterior nares, with an additional yield of 12.8% from swabs of the throat. Recent studies13,15 supported these findings for MRSA.
However, routine screening of the throat in addition to the anterior nares increases labor and costs for screening laboratories and causes discomfort for the patient. Therefore, we aimed to identify the populations at risk for exclusive throat carriage who would be missed by routine nasal screening. This would allow targeted screening programs and improve cost-effectiveness.
We collected data from 4 groups of individuals with different estimated exposures to the health care system (HCS) (Table 1). A clear-cut and validated quantification of exposure to the HCS does not exist, to our knowledge. Therefore, health care exposure was defined as treatment of a patient in an inpatient or outpatient setting within the past 12 months or regular contact of a health care worker (HCW) (ie, nurses, physicians, physiotherapists, and occupational therapists) with patients.
Group 1 (n = 1500) consisted of healthy blood donors screened for S aureus during 2005. Blood donors in Switzerland are not financially compensated for their donation, undergo an intensive laboratory workup (including routine testing for hepatitis B and hepatitis C, as well as for human immunodeficiency virus), and provide detailed health information before each donation. Group 2 (n = 498) consisted of patients at the school of dental medicine, who were screened in 2006. Group 3 (n = 634) consisted of HCWs at a national trade fair for hospital equipment (Internationale Fachmesse für Arzt und Spitalbedorf; October 26-29, 2004; Zurich, Switzerland) who volunteered to participate in a prevalence survey of S aureus carriage. Group 4 (n = 832) consisted of in-hospital patients and HCWs screened after exposure to patients with MRSA (2000-2005). Since 1997, routine screening for MRSA is part of our hospital policy for prevention of the spread of MRSA. Twenty-three MRSA carriers (0.66% of all study participants) were excluded from further analysis to avoid possible bias. Except for group 4, all study participants (in the presence of an investigator [N.P. or M.Z.]) completed and signed a questionnaire about possible risk factors for MRSA carriage. Screening was performed by infection control nurses or physicians after appropriate training.
For the primary analysis, exclusive throat carriers were compared with all nasal carriers (exclusive nasal carriers and combined carriers [ie, individuals with colonization at both the anterior nares and the throat]). In a secondary analysis, exclusive throat carriers were compared with exclusive nasal carriers and with noncarriers to further characterize exclusive throat carriers.
Screening methods are described elsewhere in detail.18 In short, swabs were obtained from the anterior nares and from the posterior wall of the throat and were cultured in a selective enrichment broth (brain-heart infusion broth with 6% sodium chloride). After incubation at 35°C overnight, the broth was subcultured onto a chromogenic agar for S aureus (Chromagar S aureus; Hy Laboratories, Rehovot, Israel) and onto a Columbia agar with 5% sheep blood. Identification of S aureus was based on typical growth in the chromogenic medium or blood agar, as well as detection of clumping factor, protein A, and capsular antigens (Pastorex Staph-Plus; Bio-Rad, Marnes-la-Coquette, France). According to guidelines of the Clinical and Laboratory Standards Institute,19S aureus isolates were tested for oxacillin resistance by using an oxacillin disk or screening agar plate or, more recently, a cefoxitin disk. For equivocal results or MRSA, additional tests were performed for the presence of aurease (Rapidec Staph; bioMérieux, Marcy l"Etoile, France), for detection of penicillin-binding protein 2a (MRSA-Screen; Denka Seiken, Tokyo, Japan), and for polymerase chain reaction of the mecA and femA genes.
Results were analyzed using commercially available statistical software (SPSS 14.0; SPSS Inc, Chicago, Illinois). To test univariate statistical significance, χ2 test for categorical data and Mann-Whitney test for noncategorical data were used. For multivariate analyses, all variables were entered in a logistic regression model without stepwise elimination. χ2 Test for trend was used to analyze exclusive throat carriage in relation to the estimated level of exposure to the HCS per group. Therefore, the 4 groups were arranged according to the estimated exposure to the HCS, and the null hypothesis that there is no difference in the prevalence of exclusive throat carriage among all carriers was chosen. P < .05 (2-tailed) was considered statistically significant.
The study was approved by the Ethical Committee of the University of Basel, Basel, Switzerland. Written informed consent was obtained from all individuals who were not hospitalized.
Overall, 1688 individuals (48.7%) were identified as S aureus carriers in the screened population of 3464 (Table 1). A total of 428 individuals (12.4% of the population screened) had exclusive throat carriage, 719 (20.8%) had colonization at both sites, and 541 (15.6%) had exclusive nasal carriage. For the primary analysis, exclusive throat carriers were compared with all nasal carriers (exclusive nasal carriers and combined carriers [ie, individuals with colonization at both the anterior nares and the throat]).
Individuals without close contact to the HCS were more likely to have exclusive throat carriage (Table 2). As shown in Figure 1, the estimated absence of exposure to the HCS among the different groups significantly correlated with the percentage of exclusive S aureus throat carriage among all carriers (P < .001). The lowest additional yield of throat swabs to identify S aureus carriers was found in group 4 (18.4% of S aureus carriers). The highest additional yield was found in group 1 (30.2% of S aureus carriers). Group 3 had less exposure to the HCS than group 4; only 515 of 634 group members (81.2%) were working as nurses, physicians, physiotherapists, or occupational therapists with regular patient contact.
The univariate and multivariate analyses identified age 30 years or younger as a risk factor for exclusive throat carriage compared with all nasal carriers (Table 2). Individuals 30 years or younger more frequently had colonization in the throat than in the nares (Figure 2). In individuals older than 30 years, a significant decrease in throat colonization was observed, while nasal colonization remained stable up to the sixth decade of life. All colonization rates (nasal carriage, throat carriage, and carriage overall) were significantly influenced by age (P < .001).
All individuals in groups 1 through 3 completed the questionnaire, and their estimated exposure to the HCS (whether as inpatients, outpatients, or HCWs) was analyzed in detail. Only HCW status was a significant independent protective factor for exclusive throat carriage in this analysis (Table 3). Similar to older individuals, patients with chronic skin disease and women less frequently had exclusive colonization in the throat, and individuals living alone more frequently had exclusive throat carriage.
To further characterize 428 exclusive throat carriers (12.4% of the study population), they were compared with 541 exclusive nasal carriers (15.6%), who together comprised 969 individuals (28.0% of the study population). The same risk factors as in the primary analysis were corroborated, with age 30 years or younger being a significant independent risk factor in all groups for exclusive throat carriage (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.80-3.60; P < .001). Exposure to the HCS was again found to be an independent protective factor (OR, 0.61; 95% CI, 0.46-0.79; P < .001). An additional analysis comparing exclusive throat carriers with noncarriers confirmed the same risk factors. Multivariate analyses showed that age 30 years or younger was a significant independent risk factor for exclusive throat carriage (OR, 2.73; 95% CI, 2.09-3.56; P < .001), and exposure to the HCS was found to be a protective factor for exclusive throat carriage (0.58; 0.47-0.72; P < .001).
Identification of S aureus carriers is a key component of an infection control program, enabling treatment before infection develops. In addition, rapid identification of MRSA carriers allows initiation of appropriate control measures to prevent spread.20 The simplest approach would be screening of all patients at various body sites, but such a policy would be costly and is not supported by society recommendations (Society for Healthcare Epidemiology of America and Association for Professionals in Infection Control and Epidemiology, Inc).21 However, targeted screening depends on selection of patients at risk for carriage22 and on selection of the body site to be screened. Undoubtedly, the anterior nares are the most frequently colonized body site in hospitalized patients.3 However, screening of the anterior nares missed identification of S aureus carriage in 12.4% of the population screened, comprising mostly young healthy individuals.
The importance of additional throat swabs was again corroborated in the present study by group 2, which served as an external control to the previous study groups.18 Similar to the 3 groups studied earlier, we found an additional yield of 9.8% by throat screening (23.6% of all carriers had exclusive throat carriage). Considering all 4 groups, 12.4% of the study population, or 25.4% of S aureus carriers, had exclusive throat carriage and would not be identified in screening limited to the anterior nares.
The estimated level of exposure to the HCS was found to independently predict the rate of exclusive throat carriage: 18.4% of S aureus carriers had exclusive throat carriage in group 4 and 30.2% in group 1. Therefore, additional throat screening is most important in the community, while nasal screening is significantly more reliable in a hospital environment, particularly in an intensive care unit.23 The low carriage rate overall in the hospital environment may be associated with the use of antimicrobial agents in this setting. One can hypothesize that exposure to antimicrobial agents leads to decolonization and reduces the colonization rates overall. On the other hand, the highest rate of combined carriage in the throat and the anterior nares was found in group 4, with the highest exposure to the HCS, which may be explained by the hypothesis that exposure to antimicrobial agents primarily results in decolonization among individuals with a low carriage burden of S aureus but not among those with colonization in both the throat and the anterior nares. Patients with diseases associated with higher prevalence of carriage such as those undergoing dialysis or HCWs with close contact to S aureus carriers may have more frequent combined carriage states due to greater exposure to S aureus. In addition, it is conceivable that there is a higher likelihood of detecting intermittent carriers in the hospital setting than in the community.3 However, screening of both the nares and the throat increases sensitivity even in this population at lowest risk for exclusive throat carriage. The finding that the rate of exclusive throat carriage is higher in individuals living alone may also be explained by the estimated exposure to S aureus: exposure in the household is probably lower among persons living alone, which contrasts with the hospital setting.
A second independent factor influencing the carriage pattern is age. The decrease of S aureus colonization in the nares with increasing age is well known and was recently corroborated.24 The results in our study are similar. The overall colonization rate of nasal carriage, throat carriage, and carriage overall decreased with age up to 75 years, with an additional increase only in the last decades of life. However, the nasal carriage rate (28%-41%) was more stable over the years than the throat carriage rate (20%-50%). We conclude that S aureus colonization decreases with age, an observation underestimated in the past by focusing on swabs from the anterior nares only, as this effect is more pronounced in the throat.
The age factor and the lesser importance of throat carriage in the hospital environment are possible reasons for the disuse of throat swabs for S aureus screening, as most testing is performed among typical hospital populations (eg, HCWs, patients, and older populations). Obviously, the colonization pattern is different in communities with less exposure to the HCS and among young healthy adults. Young healthy individuals are at highest risk for exclusive throat carriage, a population among whom CO-MRSA is commonly observed.10 Rapid spread of CO-MRSA even in countries with low prevalence of MRSA among hospitals may relate to a detection bias of carriers in the community.
The increasingly recognized importance of identification of S aureus carriers, especially MRSA, drives the search for new detection methods based on molecular rather than conventional screening.25 These methods seem to be cost-effective for screening of MRSA given the high cost of unnecessary isolation.26 However, even the most sophisticated methods that provide results in minutes fail if the appropriate body sites are not screened. One may speculate that screening of the throat to increase sensitivity may be epidemiologically more important than obtaining a rapid result with lower sensitivity. Unidentified carriers are established sources for outbreaks, particularly with CO-MRSA. Throat carriage triggered a large MRSA outbreak that was traced back to a sole HCW with colonization in the throat; routine nasal screening had failed to identify this carrier.27
As recently shown,18 the expenses of additional throat screening can be minimized by pooling cultures, without a significant decrease in sensitivity. In contrast to our data, a Slovenian group showed a false-negative rate of 14% among pooled MRSA cultures, which they did not recommend.28 In that study, a different technique with up to 5 swabs pooled into a culture was used. With every additional swab pooled, the broth was more diluted, most likely decreasing the sensitivity of pooling. In our study, only 2 swabs were pooled into a broth without additional dilution, which may explain the high yield of S aureus in our pooled cultures. If rapid detection is necessary, polymerase chain reaction may be performed using swabs from both the nares and the throat, which can significantly decrease the time to notification,25 an approach deserving further clinical trials. However, almost all studies using polymerase chain reaction–based techniques have focused on swabs from the nares only, probably missing 25% of carriers. Failure to identify throat carriage may explain the low success of decolonization efforts for MRSA, as the carriage in the throat is more difficult to eradicate than at any other body site.29
Several limitations of this study should be mentioned. First, the literature demonstrates no evidence that there is a major difference in preferential body sites between MSSA and MRSA,15 but undetected differences still may be present. In addition, no significant differences in colonization patterns were found among study populations.13,18 Nevertheless, results require confirmation from studies among other populations, especially in areas with high prevalences of MRSA. The MRSA prevalence among the population screened for the present study was low at 0.66% (23 of 3464). The results do not differ if these individuals are included in the analyses. They were excluded to avoid potential bias. Screening of 1051 consecutive patients since January 2008 in the emergency department at our hospital confirmed a prevalence of less than 0.1% of patients with MRSA at admission (data not shown).
A second limitation of the study relates to the different investigators performing the swabs. The highest yield of positive swabs from the throat was found in group 1, the healthy blood donors. In this group, a single highly motivated and skilled HCW obtained all swabs. However, the other individuals had a similar extent of training, and all individuals obtaining the swabs were well-trained HCWs. Comparative trials with differences in techniques are lacking. In addition, the same type of swab was used throughout the study, and the clear correlation between level of exposure to the HCS and colonization pattern argues for an actual difference unexplained by differences in sampling.
A third limitation concerns the estimated exposure to the HCS based on definition of the 4 groups. No clear-cut criteria for measuring the level of exposure to the HCS have been published, to our knowledge. Nevertheless, group 1 represents a healthy population, while group 4 represents a population inside the HCS. Differences between the groups were not analyzed in the multivariate model because of a significant correlation between the variable of health care exposure and the estimated level of exposure in the 4 groups. Therefore, we cannot rule out a possible bias by evaluation of these 4 groups because other factors (unavailable for analysis) could have influenced the carriage patterns between the groups.
Absence of exposure to the HCS and younger age predicted exclusive throat carriage. A population with these characteristics is also at highest risk for CO-MRSA. In this setting, screening for S aureus must include swabs from both the anterior nares and the throat to improve the likelihood of detecting carriers.
Correspondence: Andreas F. Widmer, MD, MS, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland (email@example.com).
Accepted for Publication: June 15, 2008.
Author Contributions: Drs Mertz and Widmer had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Mertz and Widmer. Acquisition of data: Frei, Periat, Zimmerli, and Widmer. Analysis and interpretation of data: Mertz, Battegay, Flückiger, and Widmer. Drafting of the manuscript: Mertz and Widmer. Critical revision of the manuscript for important intellectual content: Mertz, Frei, Periat, Zimmerli, Battegay, and Flückiger. Statistical analysis: Mertz and Widmer. Obtained funding: Widmer. Administrative, technical, and material support: Mertz, Frei, Periat, Zimmerli, and Widmer. Study supervision: Battegay, Flückiger, and Widmer.
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by grant 3200BO-104179 from the Swiss National Science Foundation (Dr Widmer).
Previous Presentation: This study was presented as an abstract at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17, 2007; Chicago, Illinois.