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1.  Methicillin-Susceptible Staphylococcus aureus Endocarditis Isolates Are Associated With Clonal Complex 30 Genotype and a Distinct Repertoire of Enterotoxins and Adhesins 
The Journal of Infectious Diseases  2011;204(5):704-713.
Background. Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity.
Methods. IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes.
Results. 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all).
Conclusions. MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.
doi:10.1093/infdis/jir389
PMCID: PMC3156104  PMID: 21844296
2.  Discriminative Value of Inflammatory Biomarkers for Suspected Sepsis 
Background
Circulating biomarkers can facilitate sepsis diagnosis enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.
Methods
Adults with suspected sepsis in the Emergency Department were enrolled. PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.
Results
Of 336 enrolled subjects, 60% had definite infection, 13% possible infection and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were significantly higher in septicemia (median PCT 2.3 vs. 0.2ng/mL; IL-6 178 vs. 72pg/mL; CRP 106 vs. 62mg/dL, p<0.001). Biomarker concentrations increased with greater likelihood of infection and sepsis severity. Using ROC analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67) but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cut-off of 0.5ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length-of-stay (p=0.015), but no biomarker independently predicted discharge to a higher level of care.
Conclusions
In adult Emergency Department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but do not meaningfully predict length-of-stay or need for discharge to a higher level of care.
doi:10.1016/j.jemermed.2011.05.072
PMCID: PMC3740117  PMID: 22056545
Sepsis; Procalcitonin; Interleukin-6; C-Reactive Protein; Sensitivity and Specificity
3.  Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?1 
Seminars in Immunopathology  2011;34(2):185-200.
Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility and therapeutics.
Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use.
Humans and S. aureus co-exist and the dynamic interface between host, pathogen and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA.
doi:10.1007/s00281-011-0300-x
PMCID: PMC3272122  PMID: 22160374
Staphylococcus aureus; methicillin-resistant; MRSA; epidemiology; pathogenesis; treatment
4.  Identifying and Aligning Expectations in a Mentoring Relationship 
The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar’s research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities.
doi:10.1111/j.1752-8062.2011.00356.x
PMCID: PMC3476480  PMID: 22212226
mentors; mentoring; career development; faculty development; staff development
5.  Use of a Simple Criteria Set for Guiding Echocardiography in Nosocomial Staphylococcus aureus Bacteremia 
A set of simple clinical prediction criteria for patients with nosocomial Staphylococcus aureus bacteremia was developed to identify patients at low risk of infective endocarditis in whom transesophageal echocardiography might be dispensable and was validated with two independent cohorts.
(see the editorial commentary and Soriano and Mensa, on pages 10–12.)
Background. Infective endocarditis (IE) is a severe complication in patients with nosocomial Staphylococcus aureus bacteremia (SAB). We sought to develop and validate criteria to identify patients at low risk for the development of IE in whom transesophageal echocardiography (TEE) might be dispensable.
Methods. Consecutive patients with nosocomial SAB from independent cohorts in Europe (Invasive S. aureus Infection Cohort [INSTINCT]) and North America (S. aureus Bacteremia Group [SABG]) were evaluated for the presence of clinical criteria predicting an increased risk for the development of IE (ie, prolonged bacteremia of >4 days' duration, presence of a permanent intracardiac device, hemodialysis dependency, spinal infection, and nonvertebral osteomyelitis). Patients were observed closely for clinical signs and symptoms of IE during hospitalization and a 3-month follow-up period.
Results. IE was present in 13 (4.3%) of 304 patients in the INSTINCT cohort and in 40 (9.3%) of 432 patients in the SABG cohort. Within 14 days after the first positive blood culture result, echocardiography was performed in 39.8% and 57.4% of patients in the INSTINCT and SABG cohorts, respectively. In patients with IE, the most common clinical prediction criteria present were prolonged bacteremia (69.2% vs 90% for INSTINCT vs SABG, respectively) and presence of a permanent intracardiac device (53.8% vs 32.5%). In total, 13 of 13 patients in the INSTINCT cohort and 39 of 40 patients in the SABG cohort with documented IE fulfilled at least 1 criterion (sensitivity, 100% vs. 97.5%; negative predictive value, 100% vs 99.2%).
Conclusions. A simple criteria set for patients with nosocomial SAB can identify patients at low risk of IE. Patients who meet these criteria may not routinely require TEE.
doi:10.1093/cid/cir320
PMCID: PMC3149212  PMID: 21653295
6.  Coagulase-negative Staphylococcal Infections in the Neonatal Intensive Care Unit 
Background
Coagulase-negative staphylococci (CoNS) are the most commonly isolated pathogens in the neonatal intensive care unit (NICU). CoNS infections are associated with increased morbidity including neurodevelopmental impairment.
Objective
Describe the epidemiology of CoNS infections in the NICU. Determine mortality among infants with definite, probable, or possible CoNS infections.
Methods
We performed a retrospective cohort study of all blood, urine, and cerebrospinal fluid cultures from infants <121 postnatal days.
Setting
248 NICUs managed by the Pediatrix Medical Group from 1997 to 2009.
Results
We identified 16,629 infants with 17,624 episodes of CoNS infection: 1734 (10%) definite, 3093 (17%) probable, and 12,797 (73%) possible infections. Infants with lower gestational age and birth weight had a higher incidence of CoNS infection. Controlling for gestational age, birth weight, and 5-minute Apgar score, infants with definite, probable, or possible CoNS infection had lower mortality—OR=0.74 (95% confidence interval; 0.61, 0.89), OR= 0.68 (0.59, 0.79), and OR=0.69 (0.63, 0.76)—compared to infants with negative cultures (P<0.001). No significant difference in overall mortality was found in infants with definite CoNS infection compared to those with probable or possible CoNS infection—OR=0.93 (0.75, 1.16) and OR=0.85 (0.70, 1.03), respectively.
Conclusions
CoNS infection was strongly related to lower gestational age and birth weight. Infants with clinical sepsis and culture-positive CoNS infection had lower mortality rates than infants with clinical sepsis and negative blood culture results. No difference in mortality between infants diagnosed with definite, probable, or possible CoNS infection was observed.
doi:10.1086/660361
PMCID: PMC3238054  PMID: 21666399
nosocomial infection; infant; prematurity; Staphylococcus
7.  Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography 
Aims
Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population.
Methods and results
From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17–27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14–25%) compared with 38% (95% CI: 20–55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05).
Conclusion
SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.
doi:10.1093/ejechocard/jer023
PMCID: PMC3117467  PMID: 21685200
Infective endocarditis; Echocardiography; Staphylococcus aureus; Screening
8.  Future challenges and treatment of Staphylococcus aureus bacteremia with emphasis on MRSA 
Future microbiology  2011;6(1):43-56.
Summary
Staphylococcus aureus bacteremia (SAB) is an urgent medical problem due to its growing frequency and its poor associated outcome. As healthcare delivery increasingly involves invasive procedures and implantable devices, the number of patients at risk for SAB and its complications is likely to grow. Compounding this problem is the growing prevalence of methicillin resistant S. aureus (MRSA) and the dwindling efficacy of vancomycin, long the treatment of choice for this pathogen. Despite the recent availability of several new antibiotics for S. aureus, new strategies for treatment and prevention are required for this serious, common cause of human infection.
doi:10.2217/fmb.10.155
PMCID: PMC3031962  PMID: 21162635
Staphylococcus aureus; bacteremia; MRSA; epidemiology; infective endocarditis; treatment
9.  Transmission of MRSA between Companion Animals and Infected Human Patients Presenting to Outpatient Medical Care Facilities 
PLoS ONE  2011;6(11):e26978.
Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both human and veterinary medicine. The importance of companion animals as reservoirs of human infections is currently unknown. The companion animals of 49 MRSA-infected outpatients (cases) were screened for MRSA carriage, and their bacterial isolates were compared with those of the infected patients using Pulsed-Field Gel Electrophoresis (PFGE). Rates of MRSA among the companion animals of MRSA-infected patients were compared to rates of MRSA among companion animals of pet guardians attending a “veterinary wellness clinic” (controls). MRSA was isolated from at least one companion animal in 4/49 (8.2%) households of MRSA-infected outpatients vs. none of the pets of the 50 uninfected human controls. Using PFGE, patient-pets MRSA isolates were identical for three pairs and discordant for one pair (suggested MRSA inter-specie transmission p-value = 0.1175). These results suggest that companion animals of MRSA-infected patients can be culture-positive for MRSA, representing a potential source of infection or re-infection for humans. Further studies are required to better understand the epidemiology of MRSA human-animal inter-specie transmission.
doi:10.1371/journal.pone.0026978
PMCID: PMC3213111  PMID: 22102871
10.  Transmission of Methicillin-Resistant Staphylococcus aureus between Human and Hamster▿ 
Journal of Clinical Microbiology  2011;49(4):1679-1680.
Transmission of methicillin-resistant Staphylococcus aureus (MRSA) between humans and animals is increasingly recognized. We newly document that the transmission of MRSA between human and hamster is possible.
doi:10.1128/JCM.02469-10
PMCID: PMC3122837  PMID: 21325561
11.  Potential Associations between Severity of Infection and the Presence of Virulence-Associated Genes in Clinical Strains of Staphylococcus aureus 
PLoS ONE  2011;6(4):e18673.
Background
The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome.
Methodology/Principal Findings
Two hundred thirty-nine S. aureus isolates (121 methicillin-resistant S. aureus [MRSA] and 118 methicillin-susceptible S. aureus [MSSA]) were screened by array comparative genomic hybridization (aCGH) to identify genes implicated in complicated infections. After adjustment for multiple tests, 226 genes were significantly associated with severity of infection. Of these 226 genes, 185 were not in the SCCmec element. Within the 185 non-SCCmec genes, 171 were less common and 14 more common in the complicated infection group. Among the 41 genes in the SCCmec element, 37 were more common and 4 were less common in the complicated group. A total of 51 of the 2014 sequences evaluated, 14 non-SCCmec and 37 SCCmec, were identified as genes of interest.
Conclusions/Significance
Of the 171 genes less common in complicated infections, 152 are of unknown function and may contribute to attenuation of virulence. The 14 non-SCCmec genes more common in complicated infections include bacteriophage-encoded genes such as regulatory factors and autolysins with potential roles in tissue adhesion or biofilm formation.
doi:10.1371/journal.pone.0018673
PMCID: PMC3082525  PMID: 21541311

Results 1-11 (11)