Infectious Diseases Society of America.

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

With improved obstetrical management and evidence-based use of intrapartum antimicrobial therapy, early-onset neonatal sepsis is becoming less frequent. However, early-onset sepsis remains one of the most common causes of neonatal morbidity and mortality in the preterm population. The identification of neonates at risk for early-onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis have a poor positive predictive accuracy. As a result, clinicians often treat well-appearing infants for extended periods of time, even when bacterial cultures are negative. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed). Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality. To reduce these risks, antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the management of infants with suspected or proven early-onset sepsis.

https://pediatrics.aappublications.org/content/pediatrics/early/2012/04/25/peds.2012-0541.full.pdf

Management of neonates with suspected or proven early-onset bacterial sepsis.

Background: Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Methods and Findings: Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients ,5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and $65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the $65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). Conclusions: Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors’ Summary.

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Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

Objective To evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza. Design Systematic review. Study selection Observational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes. Data sources Medline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011. Risk of bias assessment Newcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence. Results 63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for “any risk factor” (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81). Conclusion The level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.

https://www.bmj.com/content/bmj/347/bmj.f5061.full.pdf

Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis

To assess the value of serum procalcitonin (PCT) for the differentiation between patients with and without neonatal sepsis. We systematically searched PubMed, Scopus, and the Cochrane Library for studies evaluating PCT in neonatal sepsis. PCT had to be measured in neonatal blood samples, at the initial presentation of patients with suspected sepsis, before the administration of antibiotics. We performed a bivariate meta-analysis of sensitivity and specificity, and constructed a hierarchical summary receiver-operating characteristic (HSROC) curve. Overall, 29 studies eligible for inclusion were identified. We analyzed the 16 studies (involving 1,959 neonates) that evaluated PCT in neonates with culture-proven or clinically diagnosed sepsis in comparison with ill neonates with other conditions. The pooled (95% confidence interval) sensitivity and specificity were 81% (74–87%) and 79% (69–87%), respectively. The area under the HSROC curve (AUC) was 0.87. The diagnostic accuracy of PCT seemed higher for neonates with late-onset sepsis (>72 h of life) than for those with early onset sepsis; the AUC for these analyses was 0.95 and 0.78, respectively. However, fewer data were available for late-onset sepsis. High statistical heterogeneity was observed for all analyses. Our findings suggest that serum PCT at presentation has very good diagnostic accuracy (AUC = 0.87) for the diagnosis of neonatal sepsis. However, in view of the marked observed statistical heterogeneity, along with the lack of a uniform definition for neonatal sepsis, the interpretation of these findings should be done with appropriate caution.

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Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis.

Serum Procalcitonin for Prediction of Renal Parenchymal Involvement in Children with Urinary Tract Infections: A Meta-analysis of Prospective Clinical Studies

Objective. The authors aimed to describe the epidemiological characteristics, clinical features, risk factors for severe disease, and complications in children with laboratory-confirmed pandemic influenza A (H1N1). Methods. H1N1 was confirmed by performing reverse-transcriptase polymerase chain reaction (RT-PCR) assay on oropharyngeal swab specimens. The medical charts of a subset of the evaluated patients were reviewed retrospectively; another subset was enrolled prospectively. Results. A total of 51 patients (44 [86%] > 5 years) were identified to have laboratory-confirmed H1N1. Fever was the most common presenting symptom (92%). Of the 15 hospitalized patients, 4 had asthma, and 5 were overweight or obese. All but 1 of these 9 patients developed influenza-related complications. Overall, 10 of the 15 hospitalized patients (67%) developed an influenza-related complication (6 bronchitis and 4 pneumonia). Conclusion. In this cohort, most children with confirmed H1N1 infection experience an uncomplicated vi...

Clinical Features, Risk Factors, and Complications Among Pediatric Patients With Pandemic Influenza A (H1N1)

Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence.

BACKGROUNDSkin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues.OBJECTIVETo compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs.METHODSPubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus; (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance.RESULTSFour studi...

Eleni Plessa

Papers

Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis.

Serum Procalcitonin for Prediction of Renal Parenchymal Involvement in Children with Urinary Tract Infections: A Meta-analysis of Prospective Clinical Studies

Clinical Features, Risk Factors, and Complications Among Pediatric Patients With Pandemic Influenza A (H1N1)

Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence.

Daptomycin Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis