Staphylococcus aureus: Resources

Challenges in the Prevention of Coagulase-Negative Staphylococcal Sepsis in Neonates (Doctoral Thesis)

Hira, V. — 2013-03-27T00:00:00Z

Coagulase-negative staphylococci (CoNS) are the leading cause of late-onset sepsis (LOS) worldwide. As antibiotic resistance is dramatically increasing in these organisms, prevention is becoming more and more important. CoNS that are isolated from blood cultures of neonates with LOS on neonatal intensive care units (NICU) are mostly clonally related. Furthermore, there is a correlation between antibiotic resistance and biofilm production in CoNS. NICU personnel play an important role in the transmission of virulent CoNS strains, as 90% of the strains isolated from blood cultures can be found on the hands of NICU personnel. Hand hygiene is therefore important in the prevention of CoNS LOS. During hospitalization, CoNS on the skin of neonates become increasingly antibiotic resistant. Over time the CoNS species also change. Neonates with multiresistant CoNS in the first 72 hours after birth have a higher risk for developing CoNS LOS. Analysis of surface-exposed proteins of Staphylococcus epidermidis shows a role for SesC in biofilm production. Antibodies against SesC inhibit biofilm production. SesC is therefore an interesting target for prevention and treatment of S. epidermidis biofilms. A review of literature shows that hand hygiene is the most important readily implementable prevention strategy against CoNS. Other strategies, for example administering antibiotics when removing intravascular catheters, may also add to a reduction of CoNS LOS.

Outbreak of severe sepsis due to contaminated propofol: Lessons to learn (Article)

Muller, A.E. — 2010-11-01T00:00:00Z

Nosocomial infections are a frequent concern in healthcare. Despite the available knowledge on nosocomial infections and preventive measures, outbreaks of infections continue to occur. An outbreak of severe sepsis in patients who underwent minor procedures in an operating theatre during two consecutive days is described and analysed in this study. We performed a retrospective cohort study using epidemiological data in order to investigate the source of infection together with microbiological and on-site investigations and interviews. Seven patients met the case definition of postoperative systemic inflammatory response syndrome (SIRS). All other patients operated on over the same period served as controls. Of the risk factors investigated, general anaesthesia and propofol were statistically significant (P=0.003). Klebsiella pneumoniae and Serratia marcescens were cultured from opened vials of propofol, propofol-related devices and from blood cultures from two of the patients. These strains were genotypically indistinguishable. Lapses in aseptic preparation, handling and storage of the propofol were observed, and were the most probable cause of the extrinsic contamination. The daily procedure of handling propofol was not performed according to the manufacturer's recommendations, the main departure being the use of a single-use vial for multiple patients. This study documents the risk of infection due to contaminated propofol and the importance of having written guidelines for its handling.

Genome analysis of Moraxella catarrhalis strain RH4, a human respiratory tract pathogen (Article)

Vries, S.P.W. de — 2010-07-01T00:00:00Z

Moraxella catarrhalis is an emerging human-restricted respiratory tract pathogen that is a common cause of childhood otitis media and exacerbations of chronic obstructive pulmonary disease in adults. Here, we report the first completely assembled and annotated genome sequence of an isolate of M. catarrhalis, strain RH4, which originally was isolated from blood of an infected patient. The RH4 genome consists of 1,863,286 nucleotides that form 1,886 protein-encoding genes. Comparison of the RH4 genome to the ATCC 43617 contigs demonstrated that the gene content of both strains is highly conserved. In silico phylogenetic analyses based on both 16S rRNA and multilocus sequence typing revealed that RH4 belongs to the seroresistant lineage. We were able to identify almost the entire repertoire of known M. catarrhalis virulence factors and mapped the members of the biosynthetic pathways for lipooligosaccharide, peptidoglycan, and type IV pili. Reconstruction of the central metabolic pathways suggested that RH4 relies on fatty acid and acetate metabolism, as the genes encoding the enzymes required for the glyoxylate pathway, the tricarboxylic acid cycle, the gluconeogenic pathway, the nonoxidative branch of the pentose phosphate pathway, the beta-oxidation pathway of fatty acids, and acetate metabolism were present. Moreover, pathways important for survival under challenging in vivo conditions, such as the iron-acquisition pathways, nitrogen metabolism, and oxidative stress responses, were identified. Finally, we showed by microarray expression profiling that ∼88% of the predicted coding sequences are transcribed under in vitro conditions. Overall, these results provide a foundation for future research into the mechanisms of M. catarrhalis pathogenesis and vaccine development.

Preventing Surgical-Site Infections in Nasal Carriers of Staphylococcus aureus (Article)

Bode, L.G.M. — 2010-01-07T00:00:00Z

Background Nasal carriers of Staphylococcus aureus are at increased risk for health care–associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. Methods In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. Results From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin–chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin–chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin–chlorhexidine group (P=0.005). Conclusions The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788 [controlled-trials.com] .)

Short term micro-evolution and PCR-detection of methicillin-resistant and -susceptible Staphylococcus aureus sequence type 398 (Article)

Wamel, W.J.B. van — 2010-01-01T00:00:00Z

Micro-evolutionary analysis of 70 ST398 isolates by pulsed-field gel electrophoresis (PFGE) using Cfr9I revealed three sub-clones with abundant inter- and intra-sub-clone heterogeneity in spa- and SCC mec-types. In addition, we developed two specific PCRs for the detection of Staphylococcus aureus sequence type 398 (ST 398) isolates with 100% specificity and high sensitivity.

Immunogenicity of toxins during Staphylococcus aureus infection (Article)

Verkaik, N.J. — 2010-01-01T00:00:00Z

AB - BACKGROUND: Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated. METHODS: Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects were analyzed for immunoglobulin (Ig) G binding to 20 toxins, using flow-cytometry based technology. Antibody levels were associated with polymerase chain reaction-defined presence of toxin genes in homologous S. aureus isolates. RESULTS: IgG levels directed to exfoliative toxin (ET) A, ETB, gamma hemolysin B (HlgB), leukocidin (Luk) D, LukE, LukS, staphylococcal enterotoxin (SE) A, SEE, SEH, SEI, and SElM were higher in S. aureus-infected patients than in control subjects ([Formula: see text]). Furthermore, in the S. aureus-infected patient group, IgG levels were higher if genes encoding ETA, ETB, SEA, SEC, SEH, SElQ, toxic shock syndrome toxin-1 (TSST-1), or Panton-Valentine leukocidin (PVL) were present in the infectious isolate (P< .05). Levels of anti-SEA IgG increased during infections with sea-positive (median fluorescence intensity from 11,555 to 12,388; P<.05) but not sea-negative strains. In addition, anti-LukS IgG levels increased during skin and soft-tissue infections with luk-PV-positive (median fluorescence intensity from 15,231 to 15,911; P<.05) but not luk-PV-negative strains. Bacteremia was associated with sea (odds ratio, 3.4; 95% confidence interval, 1.2-10.0) and tst (odds ratio, 5.7; 95% confidence interval, 1.6-20.8). Skin and soft-tissue infections and bone and joint infections were associated with luk-PV (odds ratio, 2.5; 95% confidence interval, 1.2-5.2). CONCLUSIONS: Many toxins are expressed in vivo and recognized by the immune system during staphylococcal infections,

WNT proteins: Environmental factors regulating HSC fate in the niche (Article)

Luis, T.C. — 2009-10-15T00:00:00Z

The Wnt signaling pathway has been implicated in regulation of hematopoiesis through a plethora of studies from many different laboratories. However, different inducible gain- and loss-of-function approaches retrieved controversial and sometimes contradictory results. Different levels of activation of the pathway, dosages of Wnt signaling required, and the interference by other signals in the context of Wnt activation collectively explain these controversies. Gain-of-function or in vitro exposure to WNT proteins and more specifically WNT3a was shown to enhance hematopoietic stem cell (HSC) activity, but its exact role was still not completely understood. In a recent study we analyzed the hematopoietic system of mice deficient for this specific Wnt gene. Wnt3a deficiency results in early embryonic lethality around embryonic day 12.5 (E12.5), precluding analysis in adult mice, but allowing hematopoiesis to be studied in fetal liver (FL) and in the just colonized thymic rudiment. Notably, we showed that long-term HSCs and multipotent progenitors are reduced in FL and have severely reduced long-term reconstitution capacity as observed in serial transplantation assays. Of interest, deficiency in Wnt3a leads to complete abolition of canonical Wnt signaling in FL hematopoietic stem and progenitor cells. This HSC deficiency is not explained by altered cell cycle or survival and is irreversible, since it cannot be restored by transplantation into Wnt3a-competent mice. In addition, Wnt3a deficiency differentially affects myeloid and B-lymphoid lineages, with myeloid cells being affected at the progenitor level, while B lymphopoiesis is apparently unaffected. Immature thymocytes, however, were reduced in cell numbers due to lack of Wnt3a production by the thymic microenvironment. Our results show that while in the thymus Wnt3a provides cytokine-like, proliferative stimuli to developing thymocyte Wnt3a regulates cell fate decisions of FL HSC in a nonredundant way.

5 years of experience implementing a methicillin-resistant Staphylococcus aureus search and destroy policy at the largest university medical center in the Netherlands (Article)

Vos, M.C. — 2009-10-01T00:00:00Z

OBJECTIVE: To evaluate the effectiveness of a rigorous search and destroy policy for controlling methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization. DESIGN: Hospital-based observational follow-up study. SETTING: Erasmus University Medical Center Rotterdam, a 1,200-bed tertiary care center in Rotterdam, the Netherlands. METHODS: Outbreak control was accomplished by the use of active surveillance cultures for persons at risk, by the preemptive isolation of patients at risk, and by the strict isolation of known MRSA carriers and the eradication of MRSA carriage. For unexpected cases of MRSA colonization or infection, patients placed in strict isolation or contact isolation and healthcare workers (HCWs) were screened. We collected data from 2000-2004. RESULTS: During the 5-year study period, 51,907 MRSA screening cultures were performed for 21,598 persons at risk (8,403 patients and 13,195 HCWs). By screening, it was determined that 123 (1.5%) of 8,403 patients and 31 (0.2%) of 13,195 HCWs were MRSA carriers. From the performance of clinical cultures, it was determined that 54 additional patients were MRSA carriers, resulting in a total of 177 patients carrying MRSA. Of the 177 patients carrying MRSA, 144 (81%) were primary patients, and 33 (19%) secondary patients. The average number of nosocomial transmissions was 6.7 per year. The cumulative incidence of MRSA colonization among this group of patients was 0.10 cases per 100 admissions. Of 156 cases of MRSA colonization, 44 (28%) were acquired in a foreign healthcare institution, and 45 (29%) were acquired in other Dutch hospitals, 22 (47%) of which were acquired in a single hospital in our region. There were 16 cases (10%) that occurred in a nursing home and another 16 cases (10%) that fulfilled our definition of community-acquired MRSA colonization; there were 4 cases (3%) categorized as "other" and 31 cases (20%) for which the source of MRSA acquisition remained unknown. The basic reproduction rate was 10-fold less for patients isolated on admission, compared with those who were not. During the 5-year study period, 5 episodes of MRSA bacteremia occurred in which 4 patients died, an incidence rate of 0.28 cases of infection per 100,000 patient-days per year. CONCLUSION: Our results show that, during a rigorous search and destroy policy, a low incidence of MRSA in our medical center was continuously observed and that this policy most likely contributed to a very low nosocomial transmission rate.

Inhibition of Staphylococcus epidermidis biofilm formation by rabbit polyclonal antibodies against the SesC protein (Article)

Shahrooei, M. — 2009-09-01T00:00:00Z

Several well-studied proteins with defined roles in Staphylococcus epidermidis biofilm formation are LPXTG motif-containing proteins. Here, we investigate the possible use of the LPXTG motif-containing protein SesC (S. epidermidis surface protein C; accession no. NP-765787) as a target for antibodies to prevent biofilm formation. In vitro and in a in vivo rat model of catheter infection, gene and protein expression analysis showed that SesC is expressed more strongly in biofilm-associated cells than in planktonic cells and is expressed particularly during the late phase of in vivo biofilm formation. Polyclonal rabbit antibodies raised against SesC reduced the fibrinogen-binding ability of S. epidermidis RP62A and Staphylococcus aureus RN4220 transformants expressing SesC, inhibited in vitro biofilm formation by S. epidermidis strains 10b and 1457, and significantly reduced the numbers of bacteria in a 1-day-old in vivo biofilm (P < 0.001, one-way analysis of variance). Our findings revealed that SesC is a promising target for prevention and treatment of S. epidermidis biofilms because it affects both the primary attachment and biofilm accumulation phases. The precise role of SesC in biofilm formation remains to be identified. Copyright

Role of Staphylococcus aureus nasal colonization in atopic dermatitis in infants: The generation R study (Article)

Lebon, A. — 2009-08-01T00:00:00Z

Objective: To study the association between Staphylococcus aureus nasal colonization and atopic dermatitis (AD) in infancy. Design: Population-based prospective cohort study of pregnant women and their children. Setting: This project was embedded in the Generation R Study. Participants: A total of 1079 postnatal Dutch infants/ children participated in the focus cohort. Main Exposures: Nasal swabs for S aureus cultivation were taken at ages 1.5, 6, and 14 months. Main Outcome Measure: Questionnaires that pertain to AD and confounders (birth weight, gestational age, sex, and parental eczema) were completed prenatally and postnatally. The outcome was AD in the first and second years of life. Results: A first positive culture for S aureus at age 6 months was associated with AD prevalence in the first and second years of life (adjusted odds ratio [aOR], 2.13; 95% confidence interval [CI], 1.17-3.87; and aOR, 2.88; 95% CI, 1.60-5.19, respectively) and also with severity (aOR, 3.27; 95% CI, 1.30-8.03). Moreover, frequent colonization in the first year of life (≥2 times) held a 4.29-fold (95% CI, 1.03- to 17.88-fold) risk of moderate to severe AD in the second year of life. Conclusion: Colonization with S aureus at age 6 months and frequent colonization in the first year of life are associated with AD and its severity in young children.

Induction of Staphylococcus aureus-specific IgA and agglutination potency in milk of cows by mucosal immunization (Article)

Tempelmans Plat-Sinnige, M.J. — 2009-06-19T00:00:00Z

Lactating cows were immunized with inactivated Staphylococcus aureus strains and concentrated culture supernatants. Application of a repeated mucosal immunization scheme resulted in significant levels of S. aureus-specific IgA in milk of dairy cows. Average IgA titers against whole cell S. aureus increased during the first 10 weeks of immunization after which a plateau level was reached and maintained during lactation. Immune whey agglutinated both bovine and human S. aureus strains including methicillin-resistant S. aureus (MRSA) strains and recognized extracted S. aureus proteins on Western blot. ELISAs to quantify milk IgA reactive with a number of S. aureus virulence proteins (e.g. enterotoxins, microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and immune modulating proteins) and cell wall components, demonstrated the polyclonality of the IgA. Correlations observed between agglutination and specific IgA titers for whey and for purified IgA suggested functionality of the induced antibodies. Milk from immunized cows may provide a way of producing potentially therapeutic polyclonal antibodies against S. aureus colonization and infection.

Reclassification of Staphylococcus aureus nasal carriage types (Article)

Belkum, A.F. van — 2009-06-05T00:00:00Z

BACKGROUND: Persistent nasal carriers have an increased risk of Staphylococcus aureus infection, whereas intermittent carriers and noncarriers share the same low risk. This study was performed to provide additional insight into staphylococcal carriage types. METHODS: Fifty-one volunteers who had been decolonized with mupirocin treatment and whose carriage state was known were colonized artificially with a mixture of S. aureus strains, and intranasal survival of S. aureus was compared between carriage groups. Antistaphylococcal antibody levels were also compared among 83 carriage-classified volunteers. RESULTS: Persistent carriers preferentially reselected their autologous strain from the inoculum mixture (P=.02). They could be distinguished from intermittent carriers and noncarriers on the basis of the duration of postinoculation carriage (154 vs. 14 and 4 days, respectively; P=.017, by log-rank test). Cultures of swab samples from persistent carriers contained significantly more colony-forming units per sample than did cultures of swab samples from intermittent carriers and noncarriers (P=.004). Analysis of serum samples showed that levels of immunoglobulin G and immunoglobulin A to 17 S. aureus antigens were equal in intermittent carriers and noncarriers but not in persistent carriers. CONCLUSIONS: Along with the previously described low risk of infection, intermittent carriers and noncarriers share similar S. aureus nasal elimination kinetics and antistaphylococcal antibody profiles. This implies a paradigm shift; apparently, there are only 2 types of nasal carriers: persistent carriers and others. This knowledge may increase our understanding of susceptibility to S. aureus infection.

Comparison of the DiversiLab system, Pulsed-Field Gel Electrophoresis and Multi-Locus Sequence Typing for the characterization of epidemic reference MRSA strains (Article)

Witt, R. te — 2009-04-01T00:00:00Z

We have analyzed a representative selection of the HARMONY meticillin-resistant Staphylococcus aureus strain collection originating from 11 European countries (Cookson, B.D. et al., 2007, J. Clin. Microbiol. 45: 1830-1837) with the DiversiLab System, Pulsed-Field Gel Electrophoresis (PFGE) and Multi-Locus Sequence Typing (MLST). Simpson's diversity indices were 0.905, 0.877 and 0.860 for PFGE, MLST and DiversiLab, respectively. All methods displayed concordant classification of the MRSA strains, although with divergent resolution and reproducibility.

Anti-staphylococcal humoral immune response in persistent nasal carriers and noncarriers of Staphylococcus aureus (Article)

Verkaik, N.J. — 2009-03-01T00:00:00Z

BACKGROUND. Persistent carriers have a higher risk of Staphylococcus aureus infections than noncarriers but a lower risk of bacteremia-related death. Here, the role played by anti-staphylococcal antibodies was studied. METHODS. Serum samples from 15 persistent carriers and 19 noncarriers were analyzed for immunoglobulin (Ig) G, IgA, and IgM binding to 19 S. aureus antigens, by means of Luminex technology. Nasal secretions and serum samples obtained after 6 months were also analyzed. RESULTS. Median serum IgG levels were significantly higher in persistent carriers than in noncarriers for toxic shock syndrome toxin (TSST)-1 (median fluorescence intensity [MFI] value, 11,554 vs. 4291; P < .001) and staphylococcal enterotoxin (SE) A (742 vs. 218; P < .05); median IgA levels were higher for TSST-1 (P < .01), SEA, and clumping factor (Clf) A and B (P < .05). The in vitro neutralizing capacity of anti-TSST-1 antibodies was correlated with the MFI value (R(2) = 0.93) and was higher in persistent carriers (90.6% vs. 70.6%; P < .05). Antibody levels were stable over time and correlated with levels in nasal secretions (for IgG, R(2) = 0.87; for IgA, R(2) = 0.77). CONCLUSIONS. Antibodies to TSST-1 have a neutralizing capacity, and median levels of antibodies to TSST-1, SEA, ClfA, and ClfB are higher in persistent carriers than in noncarriers. These antibodies might be associated with the differences in the risk and outcome of S. aureus infections between nasal carriers and noncarriers.

Optical fingerprinting in bacterial epidemiology: Raman spectroscopy as a real-time typing method (Article)

Willemse-Erix, H.F.M — 2009-03-01T00:00:00Z

Hospital-acquired infections (HAI) increase morbidity and mortality and constitute a high financial burden on health care systems. An effective weapon against HAI is early detection of potential outbreaks and sources of contamination. Such monitoring requires microbial typing with sufficient reproducibility and discriminatory power. Here, a microbial-typing method is presented, based on Raman spectroscopy. This technique provides strain-specific optical fingerprints in a few minutes instead of several hours to days, as is the case with genotyping methods. Although the method is generally applicable, we used 118 Staphylococcus aureus isolates to illustrate that the discriminatory power matches that of established genotyping techniques (numerical index of diversity [D]=0.989) and that concordance with the gold standard (pulsed-field gel electrophoresis) is high (95%). The Raman clustering of isolates was reproducible to the strain level for five independent cultures, despite the various culture times from 18 h to 24 h. Furthermore, this technique was able to classify stored (-80 degrees C) and recent isolates of a methicillin-resistant Staphylococcus aureus-colonized individual during surveillance studies and did so days earlier than established genotyping techniques did. Its high throughput and ease of use make it suitable for use in routine diagnostic laboratory settings. This will set the stage for continuous, automated, real-time epidemiological monitoring of bacterial infections in a hospital, which can then be followed by timely corrective action by infection prevention teams.

Induction of antibodies by Staphylococcus aureus nasal colonization in young children (Article)

Verkaik, N.J. — 2009-01-01T00:00:00Z

Abstract In order to develop novel anti-staphylococcal 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 of fifty-seven (non) colonized children serially collected at birth, 6, 14 and 24 months, were analyzed 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 anti-staphylococcal IgA and IgM increased from birth until the age of two 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 to a number of proteins were higher than in non-colonized children. At both 14 and 24 months, IgG levels to Chemotaxis Inhibitory Protein of S. aureus (at 24 months, Median fluorescence intensity; 4928 vs. 13, P<0.01), Extracellular fibrinogen-binding protein (987 vs. 440, P<0.01), Clumping factor B (63 vs. 2, P<0.05) and Iron-surface determinant H (100 vs. 3, P<0.01) were significantly higher in colonized children. Therefore, these proteins seem to play a role in nasal colonization of young children.

Genotypes, superantigen gene profiles, and presence of exfoliative toxin genes in clinical methicillin-susceptible Staphylococcus aureus isolates (Article)

Trijp, M.J.C.A. van — 2009-01-01T00:00:00Z

We compared genotype and virulence gene profiles for strains from carriers with autologous invasive infection (n = 56), nasal isolates from matched carriers (n = 108), and invasive strains from noncarriers (n = 34). Superantigen gene profiles and presence of exfoliative toxin genes A and D were associated with clonal complex rather than with invasive disease.

Co-evolutionary aspects of human colonisation and infection by Staphylococcus aureus (Article)

Belkum, A.F. van — 2009-01-01T00:00:00Z

Although Staphylococcus aureus is a bacterial species of medical significance, only approximately 30% of all humans carry staphylococcal cells persistently but asymptomatically in their nasopharynx and/or other body sites. This goes largely unnoticed by the host, which shows that in the natural situation the human ecosystem is hospitable or at least receptive to the bacteria and that by a process of co-evolution this has lead to a state of mutual acceptance or tolerance. However, upon disturbance of this balanced, neutral state, localized or disseminated invasive infection can occur. Unfortunately, the events leading to infection are still largely unknown and especially the causal events leading to the transition from colonization to infection are ill-defined in vivo. Whether certain genotypes of S. aureus are more prone to colonise and/or infect humans is still quite heavily debated. The genetic population structure of S. aureus has been largely solved by using a number of different DNA polymorphism-interrogating laboratory methods. However, even this major effort has not (yet) revealed major clues with respect to colonisation and infection potency of the clonal lineages that were thus identified, except for the fact that certain lineages are highly epidemic. The overall picture is that in principle all S. aureus strains can become invasive given the proper circumstances. What these, primarily host-defined circumstances are is still enigmatic. However, a large variety of staphylococcal virulence and colonization factors have been identified as well as a number of host' colonisation and infection susceptibility traits. How these are specifically involved in colonisation and infection has been experimentally substantiated in only a limited number of cases. The present review paper will explore the relevance of these and other, for instance environmental factors that define the colonisation or infection state in humans. When the nature of these states would be known in more detail, this knowledge could be used to design novel and empirical, knowledge-driven means of preventing colonisation from proceeding into S. aureus infection.

Dynamics and determinants of Staphylococcus aureus carriage in infancy: the Generation R Study (Article)

Lebon, A. — 2008-10-01T00:00:00Z

Serial nasal swabs were collected at the ages of 1.5, 6, and 14 months from 443 infants in the Generation R Study. The objective was to study the dynamics and determinants of Staphylococcus aureus nasal carriage in the first year of life. The prevalence of S. aureus carriage decreased in the first year of life, from 52.1% at the age of 1.5 months to 12.9% at 14 months. Persistent carriage, defined as continuous carriage of the same S. aureus strain at the three sampling moments, was rarely detected in early infancy.

Detection of methicillin-resistant Staphylococcus aureus in a low-prevalence setting by polymerase chain reaction with a selective enrichment broth. (Article)

Kerremans, J.J. — 2008-08-01T00:00:00Z

The objective of this study was to evaluate the test characteristics of a modified BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) assay on individual and pooled samples in a setting of low MRSA prevalence. The results of the polymerase chain reaction (PCR) assay were compared with culture results from a selective phenol red mannitol broth subcultured after 48 h. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were calculated. For individual testing, 581 samples from 201 persons were collected; 18 (3.2%) were MRSA culture positive. Five hundred ten broths from 174 persons were combined in 106 pools after overnight incubation; 8 pools (7.5%) contained 1 or more MRSA culture-positive specimens. There were no inhibited PCR tests. The combined sensitivity of individual and pooled specimens was 92% (95% confidence interval [CI], 73-99%), the specificity was 98% (95% CI, 96-99%), and the PPV and NPV were 63% and 99.7%, respectively. Our modified procedure gives satisfactory results, and the pooling of broths may reduce costs.