Determinants of Staphylococcus aureus nasal carriage

This article aims to review what is currently known of the host and bacterial factors determining S. aureus nasal carriage, including recent developments and future prospects.     

The clonality of Staphylococcus aureus nasal carriage

Nasal carriage of Staphylococcus aureus is often a prelude to infection with the same strain. The prevailing assumption has been that colonized individuals carry a single strain. The present study investigated the frequency of simultaneous nasal carriage of multiple strains of S. aureus. Three bacterial colonies from plated samples from colonized subjects were initially compared by pulsed-field gel electrophoresis. Fourteen of 148 S. aureus-positive samples demonstrated at least a difference of a single band; 7 of these 14 samples contained different strains, and 3 of these 7 also belonged to different accessory gene regulator (agr) types. The remaining 7 samples contained clonally related isolates; 3 of these 7 contained pairs that differed by the presence or absence of the staphylococcal chromosomal cassette mec type IV. A mathematical model that we developed predicted that approximately 6.6% of S. aureus-colonized individuals carry >1 strain. The present study demonstrates that carriage of discordant S. aureus strains in individuals with nasal colonization occurs regularly and suggests that the nares are likely sites for horizontal genetic exchange among strains.     

Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment

OBJECTIVE: To determine the safety and efficacy of mupirocin calcium ointment in the elimination of Staphylococcus aureus nasal and hand carriage in healthy persons. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Clinical research unit of a tertiary medical center. SUBJECTS: Health care workers with stable S. aureus nasal carriage. INTERVENTIONS: Subjects (n = 68) were randomly assigned to receive either mupirocin or placebo intranasally twice daily for 5 days. MEASUREMENTS AND MAIN RESULTS: Cultures of the hands and nares were obtained at baseline and 72 hours after therapy. The nares were also cultured 1, 2, 4, and 12 weeks after therapy. Antimicrobial susceptibility testing and restriction endonuclease analysis of plasmid DNA were used to confirm strain identity. There were no serious side effects. Mupirocin decreased the frequency of S. aureus nasal carriage at each time interval: At 3 months, 71% of subjects receiving mupirocin remained free of nasal S. aureus compared with 18% of controls. This difference (53%; 95% CI; 26% to 80%) was significant (P less than 0.0001). Additionally, analysis of plasmid patterns showed that 79% of subjects in the mupirocin group were free of the initial colonizing strain at 3 months. The proportion of hand cultures positive for S. aureus in the mupirocin group after therapy was lower than in the placebo group (2.9% compared with 57.6%). This difference (53%; 95 CI, 30% to 80%) was significant, after adjustment for the frequency of hand carriage at baseline (P less than 0.0001). CONCLUSIONS: When applied intranasally for 5 days, mupirocin calcium ointment is safe and effective in eliminating S. aureus nasal carriage in healthy persons for up to 3 months and appears to have a corresponding effect on hand carriage at 72 hours after therapy.     

The role of nasal carriage in Staphylococcus aureus infections

Staphylococcus aureus is a frequent cause of infections in both the community and hospital. Worldwide, the increasing resistance of this pathogen to various antibiotics complicates treatment of S aureus infections. Effective measures to prevent S aureus infections are therefore urgently needed. It has been shown that nasal carriers of S aureus have an increased risk of acquiring an infection with this pathogen. The nose is the main ecological niche where S aureus resides in human beings, but the determinants of the carrier state are incompletely understood. Eradication of S aureus from nasal carriers prevents infection in specific patient categories-eg, haemodialysis and general surgery patients. However, recent randomised clinical trials in orthopaedic and non-surgical patients failed to show the efficacy of eliminating S aureus from the nose to prevent subsequent infection. Thus we must elucidate the mechanisms behind S aureus nasal carriage and infection to be able to develop new preventive strategies. We present an overview of the current knowledge of the determinants (both human and bacterial) and risks of S aureus nasal carriage. Studies on the population dynamics of S aureus are also summarised.     

Nasal carriage of methicillin-resistant Staphylococcus aureus in university students

In a study of university students, the percentage nasal carriage of Staphylococcus aureus was 40.8% (102/250). Of the isolates, MIC₅₀ of methicillin was 0.5 μg/mL and MIC₉₀ was 1 μg/mL. Six (5.8%) isolates were methicillin-resistant and carried the mecA gene. These results suggest that community-associated methicillin-resistant S. aureus may be spreading in Brazil.     

Nasal carriage of Staphylococcus aureus in healthy preschool children

To evaluate the prevalence of Staphylococcus aureus carriage among healthy preschool children in our region, nasal swabs were collected from 5- to 7-year-old healthy children who were attending a day care center. Sociodemographic features and the data related with risk factors were obtained from the children's parents. Of the 200 children, S. aureus was isolated in 36 (18%) subjects. Methicillin-resistant S. aureus was isolated in 2 (5.6%) of these subjects, neither of whom had any identified risk factors. Antimicrobial susceptibility testing revealed that all tested strains were sensitive to gentamicin, vancomycin, trimethoprim-sulfamethoxazole, rifampicin, and mupirocin. Erythromycin, clindamycin, fusidic acid, and tetracycline resistance were determined to be 16.6, 8.3, 5.6, and 8.3%, respectively.     

A study of nasal carriage of methicillin-resistant Staphylococcus aureus]

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms in nosocomial infection. The Hospital staff working in MRSA endemic wards are known to have MRSA in their nasal cavity. The nasal carriage of MRSA was detected in staff members and patients of two hospitals. In Niigata University Hospital, 10 out of 109 nurses and 8 out of 142 doctors were found to be MRSA carriers. On the other hand, in Nagaoka Red Cross Hospital, 25 out of 448 nurses were found to be MRSA carriers, however, no carrier was found in 23 doctors. These strains were also resistant to MCIPC, IPM, TFLX and OFLX, whereas they remained sensitive to VCM. The coagulase types of MRSA isolated from the hospital staff and patients were II, IV and VII, although those of Methicillin-sensitive S. aureus (MSSA) consisted of all types. Elimination of nasal MRSA from the carriers was considered for avoiding hospital outbreaks caused by this potential pathogen. Forty hospital staff and 19 patients, in who's MRSA was found persisting in their nasal cavity, were treated by povidone iodine and chloramphenicol (CP) MRSA disappeared in 44% and 84% of the nasal carriers by povidone iodine and CP, respectively.     

Risk factors for persistent carriage of methicillin-resistant Staphylococcus aureus.

We determined risk factors associated with persistent carriage of methicillin-resistant Staphylococcus aureus (MRSA) among 102 patients enrolled in a double-blind, placebo-controlled trial of nasally administered mupirocin ointment. MRSA decolonization was unsuccessful in 77 (79%) of 98 patients who met the criteria for evaluation. By univariate analysis, 4 variables were found to be associated with persistent MRSA colonization (P < .1 for all 4): absence of mupirocin treatment, previous fluoroquinolone therapy, > or = 2 MRSA-positive body sites, and low-level mupirocin resistance. After multivariable Cox proportional hazards modeling, the presence of > or = 2 positive body sites (adjusted hazard ratio [AHR], 1.7; 95% confidence interval [CI], 1.0-2.9) and previous receipt of a fluoroquinolone (AHR, 1.8; 95% CI, 1.0-3.3) were independently associated with MRSA persistence, whereas nasal mupirocin tended to confer protection (AHR, 0.6; 95% CI, 0.4-1.0). Low-level mupirocin resistance was observed in 9 genotypically different MRSA strains and was not independently associated with chronic MRSA carriage (AHR, 1.5; 95% CI, 0.9-2.5). Our findings suggest that multisite MRSA carriage and previous receipt of a fluoroquinolone are independent risk factors for persistent MRSA colonization.     

Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients

BACKGROUND: Staphylococcus aureus is a common cause of serious infection in patients infected with HIV. OBJECTIVES: To evaluate risk factors for and quantitative effect of S. aureus infection in HIV-infected patients, with special attention to nasal carriage. DESIGN: Prospective, multihospital cohort study. SETTING: Three tertiary care Veterans Affairs Medical Centers. PARTICIPANTS: 231 ambulatory HIV-infected patients. RESULTS: Thirty-four percent of patients were nasal carriers of S. aureus. Of these patients, 38% were persistent carriers and 62% were intermittent carriers. Twenty-one episodes of infection occurred in 13 patients: Ten were bacteremias (including 2 cases of endocarditis), 1 was pneumonia, and 10 were cutaneous or subcutaneous infections. Seventeen (85%) of these episodes occurred in patients with CD4 counts less than 100 cells/mm3. Recurrent infections occurred in 3 of 7 patients who survived an initial S. aureus infection. The mortality rate was higher among patients with S. aureus infection than among those without infection (P = 0.03). Factors significantly associated with S. aureus infection were nasal carriage, presence of a vascular catheter, low CD4 count, and neutropenia. Molecular strain typing indicated that for 6 of 7 infected patients, the strain of S. aureus isolated from the infected sites was the same as that previously cultured from the nares. CONCLUSION: Nasal carriage is an important risk factor for S. aureus infection in HIV-infected patients. Controlled studies are indicated to determine whether eradication of nasal carriage in a selected subset of patients (for example, those with a low CD4 cell count) might prevent invasive S. aureus infection in patients with HIV infection.     

Emergence of community-associated methicillin-resistant Staphylococcus aureus carriage in children in Cambodia

We previously described the first reported isolation of methicillin-resistant Staphylococcus aureus (MRSA) (a case series of pediatric community-associated MRSA infections) in Cambodia. We define the rate of pediatric MRSA carriage in the same population and characterize the associated bacterial genotypes by using pulsed-field gel electrophoresis and multilocus sequence typing. A prospective cohort study of MRSA carriage conducted over one month at the Angkor Hospital for Children, Siem Reap, Cambodia, identified MRSA carriage in 87 (3.5%) of 2,485 children who came to the outpatient department, and 6 (4.1%) of 145 inpatients, including at least two with cases of nosocomial acquisition. Genotyping of all 93 MRSA isolates resolved 5 genotypes. Most (91%) isolates were assigned to sequence type 834. Only 28 (32%) of 87 MRSA carriers identified in the outpatient department had no history of recent healthcare contact. The study findings have important implications for healthcare in a setting where diagnostic microbiology and access to antimicrobial drugs with efficacy against MRSA are limited.     

Staphylococcus aureus nasal carriage is associated with glucocorticoid receptor gene polymorphisms

The aim of this study was to determine whether polymorphisms of the glucocorticoid receptor gene, influencing glucocorticoid sensitivity, are associated with persistent nasal carriage of Staphylococcus aureus. Two nasal swab cultures were obtained from each of 2,929 participants. Subjects were classified as persistent carriers (n=563) if both cultures were positive. GG homozygotes of the exon 9beta polymorphism were associated with a 68% reduced risk of persistent S. aureus nasal carriage, whereas carriers of the codon 23 lysine allele displayed an 80% increased risk. Thus, genotype-dependent variation in the sensitivity to glucocorticoids is associated with tolerance toward staphylococcal nasal colonization.     

Staphylococcus aureus nasal carriage and associated factors in type 2 diabetic patients

We aimed to compare the rate of nasal carriage of Staphylococcus aureus (NCSA) between type 2 diabetic patients and non-diabetic ones and also to reveal the associated risk factors. Type 2 diabetic subjects were selected from outpatient diabetes clinics and control subjects were selected from outpatient internal medicine clinics in the same hospital. The subjects were divided into 3 groups. Group I included 68 subjects on insulin therapy and dietetic treatment, Group II included 80 subjects on oral anti-diabetic agents and dietetic treatment and Group III included 150 age- and sex-matched non-diabetic subjects. The rates of NCSA for Group I, II and III subjects were found to be 24 (35.3%), 11 (13.8%), and 16 (10.7%), respectively. Whereas there was no significant difference in NCSA positivity between Group II and Group III, a significant difference was found between Groups I and III (P < 0.01). Univariate analysis revealed that the following were significant risk factors for NCSA in our diabetic patients: insulin use, hospital admission within the last 6 months, being diabetic for more than 6 years, fasting glucose level above 111 mg/dl and antibiotic usage within the last 6 months. Furthermore, insulin use (odds ratio 3.32) and antibiotic usage within the last 6 months (odds ratio 5.75) were defined as significant risk factors for NCSA in diabetic subjects by the logistic regression method. Our results suggested that the rate of NCSA was significantly higher in type 2 diabetic patients who used insulin or antibiotics within the last 6 months.