Prevalence of and risk factors for nasal methicillin-resistant Staphylococcus aureus colonization among children in central Taiwan

Background/purpose

Staphylococcus aureus (S. aureus) causes diseases ranging from mild skin infections to invasive diseases. Carriage of S. aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. Several studies discussed MRSA colonization in Taiwan, but mostly in northern Taiwan. This is the first study that estimates the prevalence of MRSA nasal colonization in healthy children and identifies the potential risk factors in central Taiwan.

Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization in HIV-infected ambulatory patients

BACKGROUND: Estimates of the prevalence of colonization with methicillin-resistant Staphylococcus aureus (MRSA) vary in HIV-infected patients. METHODS: HIV clinic patients were prospectively cultured. Bilateral nasal and axillary swabs were plated on BBL CHROMagar MRSA media. Molecular typing was done by pulse-field gel electrophoresis, and staphylococcal cassette chromosomemec typing was determined. A patient questionnaire was conducted to ascertain potential MRSA risk factors; medical records were reviewed. RESULTS: Fifteen of 146 (10.3%) patients had MRSA nasal colonization; 1 also had axillary colonization. Twelve of 15 isolates were staphylococcal cassette chromosomemec type IV, and 8 of 14 were USA300 or USA400 genotype. MRSA colonization was associated with lower CD4 cell count, not receiving current or recent antibiotics, history of prior MRSA or methicillin-susceptible Staphylococcus aureus infection (P < 0.05 for all), and a trend toward history of hospitalization or emergency department visit in the past year (P = 0.064). Current use of trimethoprim-sulfamethoxazole was protective for colonization: 0 of 29 trimethoprim-sulfamethoxazole recipients were colonized versus 15 of 117 nonrecipients, P = 0.04. In a multivariate logistic regression model, prior infection with either methicillin-susceptible S. aureus (odds ratio = 32.4, 95% confidence interval 3.04 to 345.42) or MRSA (odds ratio = 9.71, 95% confidence interval 2.20 to 43.01), not receiving current or recent antibiotics (odds ratio = 0.026, 95% confidence interval 0.002 to 0.412), and lower CD4 count (odds ratio 0.996, 95% confidence interval 0.992 to 0.999) were associated with MRSA colonization. DISCUSSION: The prevalence of MRSA nasal colonization was relatively high compared with prior studies; axillary colonization was rare. Prior staphylococcal infection (methicillin-susceptible S. aureus or MRSA), not receiving antibiotics, and lower CD4 count were associated with MRSA nasal colonization. Trimethoprim-sulfamethoxazole seemed to be protective of MRSA colonization.     

Induction of antibodies by Staphylococcus aureus nasal colonization in young children

In order to develop novel antlstaphylococcal strategies, understanding the determinants of carriage and how humans respond to Staphylococcus aureus exposure is essential. Here, the primary S. aureus-specific humoral immune response and its association with nasal colonization was studied in young children. Sera from 57 colonized or non-colonized children, serially collected at birth and at 6, 14 and 24 months, were analysed for IgG, IgA and IgM binding to 19 staphylococcal proteins, using flow cytometry-based technology. The antibody responses showed extensive inter-individual variability. On average, the levels of antistaphylococcal IgA and IgM increased from birth until the age of 2 years (p <0.05), whereas the levels of IgG decreased (p <0.001). Placentally transferred maternal IgG did not protect against colonization. In colonized children, IgG and IgA levels for a number of proteins were higher than in non-colonized children. At both 14 and 24 months, the levels of IgG against chemotaxis inhibitory protein of S. aureus (at 24 months; median fluorescence intensity, 4928 vs. 24, p <0.05), extracellular fibrinogen-binding protein (987 vs. 604, p <0.05), and iron-responsive surface determinant H (62 vs. 5, p <0.05) were significantly higher in colonized children. The levels of IgA against CHIPS, IsdH and IsdA were higher (p <0.05). Therefore, CHIPS, Efb, IsdA and IsdH seem to play a role in nasal colonization of young children.     

Prevalence of methicillin-resistant Staphylococcus aureus nasal colonization among Taiwanese children in 2005 and 2006

From July 2005 to October 2006, a total of 3,046 children, of ages between 2 months and 5 years, presented for a well-child health care visit to one of three medical centers, which are located in the northern, central, and southern parts of Taiwan, and were surveyed for nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). The overall prevalences of S. aureus and MRSA nasal carriage among the children were 23% and 7.3%, respectively (18% and 4.8% in the central region, 25% and 6.7% in the southern region, and 27% and 9.5% in the northern region). Of the 212 MRSA isolates (96%) available for analysis, a total of 10 pulsed-field gel electrophoresis (PFGE) patterns with two major patterns (C [61%] and D [28%]) were identified. One hundred forty-nine isolates (70%) contained type IV staphylococcal cassette chromosome mec (SCCmec) DNA, and 55 isolates (26%) contained SCCmec V(T). The presence of Panton-Valentine Leukocidin (PVL) genes was detected in 60 isolates (28%). Most MRSA isolates belonged to one of two major clones, characterized as sequence type 59 (ST59)/PFGE C/SCCmec IV/absence of PVL genes (59%) and ST59/PFGE D/SCCmec V(T)/presence of PVL genes (25%). We concluded that between 2005 and 2006, 7.3% of healthy Taiwanese children were colonized by MRSA in nares. MRSA harbored in healthy children indicates an accelerated spread in the community.     

Staphylococcus aureus nasal colonization level and intracellular reservoir: a prospective cohort study

European Journal of Clinical Microbiology & Infectious Diseases - Staphylococcus aureus is a major pathogen in humans. The nasal vestibule is considered as the main reservoir of S. aureus....     

Molecular epidemiology of the nasal colonization by methicillin-susceptible Staphylococcus aureus in Swiss children

Nasal carriage of Staphylococcus aureus contributes to an increased risk of developing an infection with the same bacterial strain. Genetic regulatory elements and toxin-expressing genes are virulence factors associated with the pathogenic potential of S. aureus. We undertook an extensive molecular characterization of methicillin-susceptible S. aureus (MSSA) carried by children. MSSA were recovered from the nostrils of children. The presence of Panton-Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic-shock staphylococcal toxin (TSST-1) and agr group typing were determined by quantitative PCR. A multiple-locus variable-number of tandem repeat analysis (MLVA) assay was also performed for genotyping. Five hundred and seventy-two strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0–100.8). MLVA analysis revealed a large diversity of genetic content and no clonal relationship was demonstrated among the analysed MSSA strains. Multilocus sequence typing confirmed this observation of diversity and identified ST45 as a frequent colonizer. This broad diversity in MSSA carriage strains suggests a limited selection pressure in our geographical area.     

Factors associated with nasal colonization of methicillin-resistant Staphylococcus aureus among healthy children in Taiwan

Methicillin-resistant Staphylococcus aureus (MRSA) has been identified as a major cause of community-associated (CA) S. aureus infections in the past decade. The main reservoir in the community for MRSA and the factors contributing to its worldwide spread remain poorly defined. Between July 2005 and June 2008, a total of 6,057 healthy children 2 to 60 months of age were screened for carriage of S. aureus and Streptococcus pneumoniae in Taiwan. The prevalence and epidemiological factors influencing MRSA carriage were determined. MRSA strains were tested for antimicrobial susceptibility and underwent molecular characterization. The overall prevalences of MRSA and S. aureus carriage were 7.8% and 23.2%, respectively. A majority (88%) of MRSA isolates belonged to a common Asian-Pacific CA-MRSA lineage, multilocus sequence type 59, and were resistant to multiple non-beta-lactam antibiotics. The carriage rate of MRSA was higher among subjects 2 to 6 months old (P < 0.0001), residing in northern Taiwan (P = 0.0003), and enrolled later in the study (P < 0.0001). MRSA colonization was associated with the number of children in the family (adjusted odds ratio [aOR], 1.114; 95% confidence interval [CI], 1.002 to 1.240; P = 0.0463) and day care attendance (aOR, 1.530; 95% CI, 1.201 to 1.949; P = 0.0006). Breast feeding (P < 0.0001) and colonization with S. pneumoniae (P = 0.0170) were protective against MRSA colonization. We concluded that epidemic CA-MRSA strains increasingly colonized Taiwanese children between 2005 and 2008. The carriage rate varied significantly across different demographical features. Crowding was an independent environmental risk factor that might accelerate CA-MRSA transmission in the community.     

Prevalence and risk factor analysis for methicillin-resistant Staphylococcus aureus nasal colonization in children attending child care centers

Children attending child care centers (CCCs) are at increased risk for infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Nasal colonization often precedes infection, and MRSA colonization has been associated with increased infection risk. Community-associated MRSA (CA-MRSA) has caused increased MRSA infections in the general population, including children. Little is known about the frequency of MRSA nasal colonization in young children, particularly in those attending CCCs where disease transmission is common. We sampled the nares of 1,163 children in 200 classrooms from 24 CCCs in North Carolina and Virginia to assess S. aureus colonization. MRSA strains were molecularly analyzed for staphylococcal cassette chromosome mec (SCCmec) type, Panton-Valentine leukocidin status, and multilocus sequence type. A case-control study was performed to identify risk factors for MRSA colonization. We found that 18.1% children were colonized with S. aureus and 1.3% with MRSA. Molecular analysis of the MRSA strains identified 47% as CA-MRSA and 53% as health care-associated MRSA (HA-MRSA). Although two centers had multiple children colonized with MRSA, genotyping indicated that no transmission had occurred within classrooms. The case-control study did not detect statistically significant risk factors for MRSA colonization. However, MRSA-colonized children were more likely to be nonwhite and to have increased exposure to antibiotics and skin infections in the home. Both CA-MRSA and HA-MRSA strains were found colonizing the nares of children attending CCCs. The low frequency of colonization observed highlights the need for a large multicenter study to determine risk factors for MRSA colonization and subsequent infection in this highly susceptible population.     

Differential roles of sortase-anchored surface proteins and wall teichoic acid in Staphylococcus aureus nasal colonization

Most of the severe bacterial infections originate from the endogenous microflora of human body surfaces. However, the molecular basis of colonization, e.g. of the human nose by Staphylococcus aureus, has remained incompletely understood. Several surface-exposed proteins and wall teichoic acid (WTA) polymers have previously been implicated in S. aureus attachment to nasal epithelial cells. Here we dissect the role of these molecules in colonization using S. aureus sortase A (srtA) and tagO mutants deficient in surface protein and WTA display, respectively. Although the two mutants were similarly affected in attachment to nasal cells they were abrogated in binding to different types of epithelial ligands. Surface protein sorting, but not WTA, were required for keratin- or fibronectin-mediated interactions while only WTA-mediated binding to nasal cells was effectively inhibited by polyinosinic acid, indicating a possible role of scavenger receptor-like molecules in WTA-dependent epithelial interactions. Both mutants exhibited profound colonization defects in a cotton rat nasal colonization model, albeit at different stages of colonization (>90% reduced bacterial counts at 24 h or several days after inoculation with the tagO or srtA mutant, respectively). These data indicate that S. aureus nasal colonization is a multifactorial process with various ligands affecting initial colonization and prolonged persistence in different ways. Our studies should be useful in the development of new preventive and therapeutic strategies.     

Sensitivities of nasal and rectal swabs for detection of methicillin-resistant Staphylococcus aureus colonization in an active surveillance program

All medical and high-risk surgical patients were screened for methicillin-resistant Staphylococcus aureus colonization over 3.5 years. The sensitivities of nasal and rectal swabs were 68% and 62%, respectively. Naris and open-skin-site swabs detected 467 (74%) of 627 adult carriers identified. Rectal swabs detected an additional 160 (26%) carriers.     

Lack of evidence for persistent nasal colonization with community-acquired methicillin-resistant Staphylococcus aureus in a central European cohort

One hundred and three patients who had previously tested positive for community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue infection, and the remainder were mostly asymptomatic carriers. Of 103 patients, only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs available, 30.9% were positive for S. aureus but only four yielded Panton–Valentine leukocidin-positive methicillin-resistant S. aureus. In summary, we were unable to find persistent health issues or nasal colonization with cMRSA in a cohort of previously cMRSA-infected/colonized patients.     

Risk factors for treatment failure in orthopedic device-related methicillin-resistant Staphylococcus aureus infection

The purpose of this study was to determine the clinical and microbiological risk factors for treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) orthopedic device-related infection (ODRI). A retrospective cohort study of patients with MRSA ODRI who were treated at Geneva University Hospitals between 2000 and 2008 was undertaken. Stored MRSA isolates were retrieved for genetic characterization and determination of the vancomycin minimum inhibitory concentration (MIC). Fifty-two patients were included, of whom 23 (44%) had joint arthroplasty and 29 (56%) had osteosynthesis. All 41 of the retrieved MRSA isolates were susceptible to vancomycin (MIC?≤?2 mg/L) and 35 (85%) shared genetic characteristics of the South German clone (ST228). During a median follow-up of 391 days (range, 4–2,922 days), 18 patients (35%) experienced treatment failure involving MRSA persistence or recurrence. Microbiological factors such as infection with the predominant clone and a vancomycin MIC of 2 mg/L were not associated with treatment failure. Using a Cox proportional hazards model, implant retention (hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.3–18.2; P?=?0.017) and single-agent antimicrobial therapy (HR, 4.4; 95% CI, 1.2–16.3; P?=?0.025) were independent predictors of treatment failure after debridement. Therapy using a combination of antimicrobials should be considered for patients with MRSA ODRI, especially when implant removal is not feasible.     

Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants

In recent years, Staphylococcus aureus has become a common bowel colonizer in Swedish infants. We aimed to identify host factors that determine such colonization. Stool samples from 100 Italian and 100 Swedish infants were obtained on seven occasions during the first year of life and cultured quantitatively for S. aureus. In a subgroup of infants in each cohort, individual strains were identified by random amplified polymorphic DNA analysis. Colonization at each time-point was related to delivery mode, siblings in family and antibiotic treatment. In total, 66% of the Italian and 78% of the Swedish infants had S. aureus in their stools on at least one time-point (p 0.08) and 4% of Italian and 27% of Swedish infants were positive on at least six of the seven time-points investigated (p 0.0001). Most infants analysed regarding strain carriage harboured a single strain in their microbiota for several months. The S. aureus stool populations in colonized infants decreased from 10⁷ to 10⁴ colony-forming units/g between 1 week and 1 year of age in both cohorts. In multivariate analysis, the strongest predictor for S. aureus colonization was being born in Sweden (OR 3.4 at 1 week of age, p 0.002). Having (an) elder sibling(s) increased colonization at peak phase (OR 1.8 at 6 months, p 0.047). Antibiotic treatment was more prevalent among Italian infants and correlated negatively with S. aureus colonization at 6 months of age (OR 0.3, p 0.01). To conclude, S. aureus is a more common gut colonizer in Swedish than Italian infants, a fact that could not be attributed to feeding or delivery mode.     

Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium

Nasal carriage of Staphylococcus aureus is an important source of nosocomial infection and community-acquired methicillin-resistant S. aureus (MRSA). Previous studies by our laboratory revealed that nasal carriage of S. aureus is accompanied by subclinical inflammation, which is insufficient to prevent colonization, and that carriage might also be a result of adaptation and selection of certain S. aureus strains to the host's nasal environment. In the present study we observed that a carrier strain of S. aureus preferentially colonizes and attaches to nasal epithelial cells (NEC) compared to a non-carrier S. aureus strain. Conversely, when naive NEC were pretreated with interleukin-1beta for 24 hr, the growth and attachment of the carrier strain of S. aureus were significantly reduced in comparison to the non-carrier strain, emphasizing the pivotal role played by host innate immunity in the initial events of nasal carriage. While both strains up-regulated the expression of the pattern recognition receptor, Toll-like receptor 2 (TLR2), NEC exposed to the nasal carrier strain had a 4-hr delay in TLR2 expression compared with NEC exposed to non-carrier S. aureus. Moreover, even after 20 hr of colonization the expression of two principal epithelial antimicrobial peptides, human beta-defensin-2 and human beta-defensin-3, was negligibly induced in NEC exposed to the nasal carrier strain of S. aureus in comparison to the non-carrier strain. These results suggest that carrier strains of S. aureus retain a competitive advantage over non-carrier strains by delaying the host's innate response to epithelial colonization and infection.     

Staphylococcus aureus nasal and pharyngeal carriage in Senegal

Nasal and pharyngeal swabs were collected from 132 patients admitted to the Principal Hospital in Dakar (Senegal), in January and February 2012. The prevalence of Staphylococcus aureus carriage was 56.1% (n = 74): 40.2% for pharyngeal samples and 36.4% for nasal samples. None of the isolates was methicillin-resistant. Carriage was independently associated with being female (p <0.01) and large households (≥15 members) (p 0.04). The luk-PV genes encoding Panton–Valentine leukocidin (PVL) were present in 26.2% of the isolates. These data highlight the importance of the oropharynx as a site of colonization, and the high prevalence of PVL-positive isolates in Senegal as compared with industrialized countries.     

Bacterial and host factors implicated in nasal carriage of methicillin-resistant Staphylococcus aureus in mice

Nasal carriage is a major risk factor for Staphylococcus aureus infection, especially for methicillin-resistant strains (MRSA). Using a mouse model of nasal carriage, we have compared several S. aureus strains and demonstrated increased colonization levels by MRSA in cystic fibrosis transmembrane conductance regulator-deficient mice and Toll-like receptor 2 (TLR2)-deficient mice but not TLR4-deficient mice.     

Risk factors and mortality of healthcare-associated and community-acquired Staphylococcus aureus bacteraemia

Staphylococcus aureus bacteraemia (SAB) is a leading cause of mortality and morbidity in both nosocomial and community settings. The objective of the study is to explore epidemiological characteristics and predisposing risk factors associated with healthcare-associated (HCA) and community-acquired (CA) SAB, and to evaluate any differences in mortality and efficacy of initial antimicrobial therapy on treatment outcome. We conducted a two-part analysis. First, a triple case-control study in which groups of HCA SAB with onset ≥ 48 h after hospital admission (HCA ≥ 48 h), HCA SAB with onset <48 h of hospital admission (HCA <48 h), and CA SAB were compared with controls. Second, a cohort study including all patients with SAB was performed to identify factors associated with in-hospital mortality. SAB was diagnosed in 165 patients over the study period (January 2007 to December 2007). Five variables were independently associated with HCA ≥ 48 h SAB: presence of central venous catheter, solid tumour, chronic renal failure, previous hospitalization and previous antibiotic therapy. Significant risk factors for HCA <48 h SAB were: Charlson Comorbidity Index ≥ 3, previous hospitalization, living in long-term care facilities and corticosteroid therapy. Factors independently associated with CA SAB were: diabetes mellitus, HIV infection and chronic live disease. Patients with HCA <48 h SAB were significantly more likely to receive initial inadequate antimicrobial treatment than patients with CA or HCA ≥ 48 h SAB (44.8% versus 33.3% and 31.5%, respectively). Logistic-regression analysis identified three variables as independent predictors of mortality: presentation with septic shock, infection with methicillin-resistant S. aureus, and initial inadequate antimicrobial treatment. More than half of patients with SAB have MRSA strains and presentation with septic shock, and inappropriate empirical therapy was associated with increased mortality.     

Incidence of and risk factors for community-associated methicillin-resistant Staphylococcus aureus acquired infection or colonization in intensive-care-unit patients

The incidence of and risk factors for acquiring community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among patients staying in intensive care units (ICUs) remain unclear. We enrolled patients staying in two ICUs at the Far Eastern Memorial Hospital during the period of 1 September 2008 to 30 September 2009 to clarify this issue. Surveillance cultures for MRSA were taken from nostril, sputum or throat, axillae, and the inguinal area in all enrolled patients upon admission to the ICU, every 3 days thereafter, and on the day of discharge from the ICU. For each MRSA isolate, we performed multilocus sequence typing, identified the type of staphylococcal cassette chromosome mec, detected the presence of the Panton-Valentine leukocidin gene, and conducted drug susceptibility tests. Among the 1,906 patients who were screened, 203 patients were carriers of MRSA before their admission to the ICU; 81 patients acquired MRSA during their stay in the ICU, including 31 who acquired CA-MRSA. The incidence rates of newly acquired MRSA and CA-MRSA during the ICU stay were 7.9 and 3.0 per 1,000 patient-days, respectively. Prior usage of antipseudomonal penicillins and antifungals and the presence of a nasogastric tube were found to be independent risk factors for acquiring CA-MRSA during the ICU stay when data for CA-MRSA carriers and patients without carriage of MRSA were compared (P=0.0035, 0.0330, and 0.0262, respectively). Prior usage of carbapenems was found to be a protective factor against acquiring CA-MRSA when data for patients with CA-MRSA and those with health care-associated MRSA acquired during ICU stay were compared (P=0.0240).