Improved Genomic Prediction of Staphylococcus epidermidis Isolation Sources with a Novel Polygenic Score.

Staphylococcus epidermidis infections can be challenging to diagnose due to the species frequent contamination of clinical specimens and indolent course of infection. Nevertheless, S. epidermidis is the major cause of late-onset sepsis among premature infants and of intravascular infection in all age groups. Prior work has shown that bacterial virulence factors, antimicrobial resistances, and strains have up to 80% in-sample accuracy to distinguish hospital from community sources, but are unable to distinguish true bacteremia from blood culture contamination. Here, a phylogeny-informed genome-wide association study of 88 isolates was used to estimate effect sizes of particular genomic variants for isolation sources. A "polygenic score" was calculated for each isolate as the summed effect sizes of its repertoire of genomic variants. Predictive models of isolation sources based on polygenic scores were tested with in-samples and out-samples from prior studies of different patient populations. Polygenic scores from accessory genes (AGs) distinguished hospital from community sources with the highest accuracy to date, up to 98% for in-samples and 65% to 91% for various out-samples, whereas scores from single nucleotide polymorphisms (SNPs) had lower accuracy. Scores from AGs and SNPs achieved the highest in-sample accuracy to date, up to 76%, in distinguishing infection from contaminant sources within a hospital. Model training and testing data sets with more similar population structures resulted in more accurate predictions. This study reports the first use of a polygenic score for predicting a complex bacterial phenotype and shows the potential of this approach for enhancing S. epidermidis diagnosis.

Understanding Policy Decisions and Their Implications Regarding Preventive Interventions for Respiratory Syncytial Virus (RSV) Infection in Canadian Infants: A Primer for Nurses.

Respiratory syncytial virus (RSV) is a leading cause of morbidity and hospitalization in young children, and prevention is the primary management strategy. At present, palivizumab, a monoclonal antibody providing immediate passive immunity, rather than a vaccine that induces active immunity, is the only preventive intervention used in routine practice internationally. In Canada, access varies across the country. Prophylaxis policies are mainly driven by cost-effectiveness analyses, and it is crucial that the full costs and benefits of any intervention are captured. Positive results from a new Canadian cost-effectiveness analysis of palivizumab will help address the current inequality in use while providing a framework for future models of RSV preventives. Nurses are the principal educators for parents about the risks of childhood RSV and optimal prevention via basic hygiene, behavioral and environmental measures, and seasonal prophylaxis. Nurses should be provided not only with regular, up-to-date, and accurate information on RSV and the clinical aspects of emerging interventions but be informed on the decision-making governing the use of preventive strategies.

Introduction of biosimilar pegfilgrastim in France: Economic analysis of switching from originator.

OBJECTIVES: To assess the economic impact of introducing biosimilar pegfilgrastim compared to the current standard granulocyte colony-stimulating factor (G-CSF) practice in France. METHODS: A budget impact model was developed to investigate the impact of introducing pegfilgrastim biosimilar over 5 years. The model analysed drug acquisition costs, ambulatory costs, as well as costs associated with poor outcomes, and compared the current standard practice of long-acting and short-acting G-CSF to a revised practice including pegfilgrastim biosimilar in addition to standard practice treatments. The cost of switching to pegfilgrastim biosimilar, within a pharmacy setting, was analysed within the model using data from a survey of French pharmacists. RESULTS: The budget impact model calculated a cost saving of €51,007,531 over 5 years switching from the current standard practice to pegfilgrastim biosimilar. A sensitivity analysis accounting for variation in pegfilgrastim biosimilar uptake of 1) 15% in year 1 and 1% in years 2-5 and 2) 15% in years 1-5, estimated savings ranging between €29,377,784 and €79,847,194, respectively. A further analysis predicted cost savings of €287,344,835 over 5 years with the extension of pegfilgrastim biosimilar, at an uptake of 15% in year 1 and 7% in years 2-4, to both long-acting and short-acting G-CSF groups compared to unchanged current practice. CONCLUSIONS: The introduction of pegfilgrastim biosimilar will help to reduce cost and alleviate some of the financial pressure on the French healthcare system.

Clinical burden of severe respiratory syncytial virus infection during the first 2 years of life in children born between 2000 and 2011 in Scotland.

National data from Scotland (all births from 2000 to 2011) were used to estimate the burden associated with respiratory syncytial virus hospitalisation (RSVH) during the first 2 years of life. RSVHs were identified using the International Classification of Diseases 10th Revision codes. Of 623,770 children, 13,362 (2.1%) had ≥ 1 RSVH by 2 years, with the overall rate being 27.2/1000 (16,946 total RSVHs). Median age at first RSVH was 137 days (interquartile range [IQR] 62-264), with 84.3% of admissions occurring by 1 year. Median length of stay was 2 (IQR 1-4) days and intensive care unit (ICU) admission was required by 4.3% (727) for a median 5 (IQR 2-8) days. RSVHs accounted for 6.9% (5089/73,525) of ICU bed days and 6.2% (64,395/1,033,121) of overall bed days (5370/year). RSVHs represented 8.5% (14,243/168,205) of all admissions between October and March and 14.2% (8470/59,535) between December and January. RSVH incidence ranged from 1.7 to 2.5%/year over the study period. Preterms (RSVH incidence 5.2%), and those with congenital heart disease (10.5%), congenital lung disease (11.2%), Down syndrome (14.8%), cerebral palsy (15.5%), cystic fibrosis (12.6%), and neuromuscular disorders (17.0%) were at increased risk of RSVH.Conclusions: RSV causes a substantial burden on Scottish paediatric services during the winter months.What is known:• Respiratory syncytial virus (RSV) is a leading cause of childhood hospitalisation.What is new:• This 12-year study is the first to estimate the burden of RSV hospitalisation (RSVH) in Scotland and included all live births from 2000 to 2011 and followed > 600,000 children until 2 years old.• The overall RSVH rate was 27.2/1000 children, with 2.1% being hospitalised ≥ 1 times.• RSVHs accounted for 6.2% of all inpatient bed days, which rose to 14.2% during the peak months of the RSV season (December-January), equating to over 1400 hospitalisations and nearly 5500 bed days each year.

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).

AIM: We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This survey-based, observational study was conducted during 2014-2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important). RESULTS: The five most important factors for parents were: healthcare professionals' awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support. CONCLUSION: The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.

Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?

Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital.

Maternal Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Otherwise Healthy Preterm and Term Infants: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVE: To date, there is no published, formal assessment of all maternal risk factors for respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) in infants. A systematic literature review and meta-analysis were undertaken to ascertain: What maternal risk factors are associated with an increased risk of RSV-LRTI in infants? METHODS: The systematic literature review used explicit methods to identify, select and analyze relevant data. PubMed, Embase and the Cochrane Library were searched (November 2022) using terms regarding: (1) RSV/LRTI; (2) risk factors; (3) pregnant/postpartum population. Bayesian meta-analysis compared RSV hospitalization (RSVH) risk in infants born to mothers with or without certain risk factors. RESULTS: A total of 2353 citations were assessed and 20 were included in the final review (10 individual studies; 10 pooled analyses). In 10 studies examining infants (<1 year) without comorbidities (primary outcome), 10 maternal risk factors were associated with RSV-LRTI/RSVH in multivariate analyses. Meta-analysis revealed smoking while pregnant increased infant RSVH risk by 2.01 (95% credible interval: 1.52-2.64) times, while breast-feeding was protective (0.73, 95% credible interval: 0.58-0.90). Risk scoring tools have reported that maternal risk factors contribute between 9% and 21% of an infant's total risk score for RSVH. CONCLUSIONS: A greater understanding of maternal risk factors and their relative contribution to infant RSV-LRTI will enable more accurate assessments of the impact of preventive strategies.

An unusual case of cervical diverticulum identified by presence of 3 cavities at diagnostic hysteroscopy.

Herein is presented the case report of a patient who had severe dysmenorrhea since menarche, known right unicornuate uterus with a left rudimentary horn, and recurrent hematometra. Previous hysteroscopic drainage of the hematometra temporarily alleviated the symptoms. At subsequent hysteroscopy, 3 cavities were identified, 2 corresponding to the uterine horns and the other to a cervical diverticulum. Hysteroscopic metroplasty with drainage of the rudimentary horn hematometra provided long-term relief of the symptoms. The diagnosis was verified at diagnostic laparoscopy.

Perspective: the potential of wastewater-based surveillance as an economically feasible game changer in reducing the global burden of pediatric respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading viral cause of childhood bronchiolitis and pneumonia causing over 3 million hospitalizations and 100,000 deaths in children under 5 years of age annually. Wastewater-based surveillance (WBS) has proven an effective early warning system for high-consequence pathogens, including SARS-CoV-2, polio, mpox, and influenza, but has yet to be fully leveraged for RSV surveillance. A model predicated on the Canadian province of Ontario demonstrates that implementation of a WBS system can potentially result in significant cost savings and clinical benefits when guiding an RSV preventive program with a long-acting monoclonal antibody. A network of integrated WBS initiatives offers the opportunity to help minimize the devastating global burden of RSV in children by optimizing the timing of preventive measures and we strongly advocate that its benefits continue to be explored.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

Thoracic vertebral osteomyelitis with paraspinous mass and intraspinal extension: an atypical presentation of cat-scratch disease.

Children with cat-scratch disease (CSD) commonly present with fever and tender lymphadenopathy. The disease is mild and manifestations of infection resolve spontaneously within several weeks. However, some children with CSD have unusual features that present diagnostic challenges. Children with atypical CSD may present with prolonged fever, hepatosplenic disease or ocular disease. We performed an MRI on a child who presented with persistent back pain. The MRI demonstrated a paravertebral mass with intraspinous extension and the collapse of T7 vertebral body. A biopsy was reported to show a small round blue cell tumor. An evaluation for malignancy was negative, but Bartonella henselae DNA was detected by polymerase chain reaction on the biopsy specimen. We present this case because it is a rare but important radiological presentation of CSD.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Exposure of Thomsen-Friedenreich antigen in Streptococcus pneumoniae infection is dependent on pneumococcal neuraminidase A.

Pneumococcal hemolytic uremic syndrome is recognized in a small portion of otherwise healthy children who have or have recently had Streptococcus pneumoniae infections, including severe pneumonia, meningitis, and bacteremia. As in other types of hemolytic uremic syndrome (HUS), pneumococcal HUS is characterized by microangiopathic hemolytic anemia, and thrombocytopenia, usually with extensive kidney damage. Although not demonstrated in vivo, the pathogenesis of pneumococcal HUS has been attributed to the action pneumococcal neuraminidase exposing the usually cryptic Thomsen-Friedenreich antigen (T-antigen) on red blood cells (RBC), and kidney glomeruli. We evaluated the effect of pneumococcal infection on desialylation of RBC and glomeruli during pneumococcal infections in mice. Following intravenous infection with capsular type 19F pneumococci, CFU levels exceeding 1000 CFU/mL blood by the third day were significantly more likely to result in exposed T-antigen on RBC than lower levels of bacteremia. In a pneumonia model, significantly more T-antigen was exposed on RBC in mice treated with penicillin than in those receiving mock treatment. Utilizing mutant pneumococci, we demonstrated that neuraminidase A but not neuraminidase B was necessary for exposure of T-antigen on RBC in vivo. Thus, pneumococcal neuraminidase A is necessary for the exposure of T-antigen in vivo and treatment with penicillin increases this effect. Interestingly, NanA(-) pneumococci were found in the blood in higher numbers and caused more deaths than wild type, NanB(-), or the NanA(-)/NanB(-) pneumococci.

Challenges in the prevention or treatment of RSV with emerging new agents in children from low- and middle-income countries.

INTRODUCTION: Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs). AREAS COVERED: There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs. EXPERT OPINION: We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.

Adoption in Canada of an international risk scoring tool to predict respiratory syncytial virus hospitalization in moderate-to-late preterm infants.

OBJECTIVE: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST. METHODS: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed. RESULTS: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores (p < .001) and risk categories (p < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%). CONCLUSIONS: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Association between respiratory syncytial virus hospitalization in infancy and childhood asthma.

INTRODUCTION: Respiratory syncytial virus infection in early childhood has been linked to longer-term respiratory morbidity; however, debate persists around its impact on asthma. The objective was to assess the association between respiratory syncytial virus hospitalization and childhood asthma. METHODS: Asthma hospital admissions and medication use through 18 years were compared in children with (cases) and without (controls) respiratory syncytial virus hospitalization in the first 2 years of life. All children born in National Health Service Scotland between 1996 and 2011 were included. RESULTS: Of 740 418 children (median follow-up: 10.6 years), 15 795 (2.1%) had a respiratory syncytial virus hospitalization at ≤2 years (median age: 143 days). Asthma hospitalizations were three-fold higher in cases than controls (8.4% vs 2.4%; relative risk: 3.3, 95% confidence interval [CI]: 3.1-3.5; P < .0001) and admission rates were four-fold higher (193.2 vs 46.0/1000). Cases had two-fold higher asthma medication usage (25.5% vs 14.7%; relative risk: 1.7, 95% CI: 1.7-1.8; P < .0001) and a three-fold higher rate of having both an asthma admission and medication (4.8% vs 1.5%; relative risk 3.1, 95% CI: 2.9-3.3; P < .0001). Admission rates and medication use remained significantly (P < .001) higher for cases than controls throughout childhood (admissions: ≥2-fold higher; medication: ≥1.5-fold higher). Respiratory syncytial virus hospitalization was the most significant risk factor for asthma hospitalizations±medication use (odds ratio: 1.9-2.8; P < .001). CONCLUSIONS: Respiratory syncytial virus hospitalization was associated with significantly increased rates and severity of asthma throughout childhood, which has important implications for preventive strategies.

Acquisition of high-level mupirocin resistance and its fitness cost among methicillin-resistant Staphylococcus aureus strains with low-level mupirocin resistance.

We investigated whether methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates with low-level mupirocin resistance can serve as recipients of a pSK41-like plasmid conferring high-level mupirocin resistance without substantial fitness cost. Our results suggest that acquisition of the plasmid conferring high-level mupirocin resistance was not necessarily associated with fitness cost in some MRSA recipients with low-level mupirocin resistance.

Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a Children's Hospital in central Illinois.

BACKGROUND: The nation-wide concern over methicillin-resistant Staphylococcus aureus (MRSA) has prompted many clinicians to use vancomycin when approaching patients with suspected staphylococcal infections. We sought to characterize the epidemiology of community-onset S. aureus infections in hospitalized children to assist local clinicians in providing appropriate empiric antimicrobial therapy. METHODS: From January 2005-June 2008, children (0-18 years old) admitted to the Children's Hospital of Illinois with community-onset S. aureus infections were identified by a computer-assisted laboratory-based surveillance and medical record review. RESULTS: Of 199 patients, 67 (34%) had invasive infections, and 132 (66%) had skin and soft tissue infections (SSTIs). Among patients with invasive infections, S. aureus isolates were more likely to be susceptible to methicillin (MSSA 63% vs. MRSA 37%), whereas patients with SSTIs, S. aureus isolates were more likely to be resistant to methicillin (MRSA 64% vs. MSSA 36%). Bacteremia and musculoskeletal infections were the most common invasive infections in both groups of S. aureus. Pneumonia with empyema was more likely to be caused by MRSA (P = 0.02). The majority (approximately 90%) of MRSA isolates were non-multidrug resistant, even in the presence of healthcare-associated risk factors. CONCLUSION: Epidemiological data at the local level is important for antimicrobial decision-making. MSSA remains an important pathogen causing invasive community-onset S. aureus infections among hospitalized children. In our hospital, nafcillin in combination with vancomycin is recommended empiric therapy in critically ill patients with suspected invasive staphylococcal infections. Because up to 25% of MSSA circulating in our area are clindamycin-resistant, clindamycin should be used cautiously as empiric monotherapy in patients with suspected invasive staphylococcal infections.