Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia

Objectives: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. Methods: An observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture. Results: Among 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score–weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511–0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480–0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score–weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567–2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245–2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs. Conclusions: Rates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB

Variation in Target Attainment of Beta-Lactam Antibiotic Dosing Between International Pediatric Formularies.

As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. Beta-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dosing recommendations from the major pediatric reference sources and tries to answer the questions: Does beta-lactam dose heterogeneity matter? Does it impact pharmacodynamic target attainment? For three important severe clinical infections-pneumonia, sepsis, and meningitis-pharmacokinetic models were identified for common for beta-lactam antibiotics. Real-world demographics were derived from three multicenter point prevalence surveys. Simulation results were compared with minimum inhibitory concentration distributions to inform appropriateness of recommended doses in targeted and empiric treatment. While cephalosporin dosing regimens are largely adequate for target attainment, they also pose the most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin, and meropenem doses as potentially requiring review/optimization in order to preserve the use of these agents in future

The risk of cardiac device-related infection in bacteremic patients is species specific: Results of a 12-year prospective cohort

Background. The species-specific risk of cardiac device-related infection (CDRI) among bacteremic patients is incompletely understood. Methods. We conducted a prospective cohort study of hospitalized patients from October 2002 to December 2014 with a cardiac device (CD) and either Staphylococcus aureus bacteremia (SAB) or Gram-negative bacteremia (GNB). Cardiac devices were defined as either prosthetic heart valves (PHVs), including valvular support rings, permanent pacemakers (PPMs)/automatic implantable cardioverter defibrillators (AICDs), or left ventricular assist devices (LVADs). Results. During the study period, a total of 284 patients with ≥1 CD developed either SAB (n = 152 patients) or GNB (n = 132 patients). Among the 284 patients, 150 (52.8%) had PPMs/AICDs, 72 (25.4%) had PHVs, 4 (1.4%) had LVADs, and 58 (20.4%) had &gt;1 device present. Overall, 54.6% of patients with SAB and 16.7% of patients with GNB met criteria for definite CDRI (P &lt; .0001). Multivariable logistic regression analysis revealed that 3 bacterial species were associated with an increased risk for CDRI: Staphylococcus aureus (odds ratio [OR] = 5.57; 95% confidence interval [CI], 2.16-14.36), Pseudomonas aeruginosa (OR = 50.28; 95% CI, 4.16-606.93), and Serratia marcescens (OR = 7.75; 95% CI, 1.48-40.48). Conclusions. Risk of CDRI among patients with bacteremia varies by species. Cardiac device-related infection risk is highest in patients with bacteremia due to S aureus, P aeruginosa, or S marcescens. By contrast, it is lower in patients with bacteremia due to other species of Gram-negative bacilli. Patients with a CD who develop bacteremia due to either P aeruginosa or S marcescens should be considered for diagnostic imaging to evaluate for the presence of CDRI. © The Author 2017

L’apport de l’approche juridique pour l’étude des Acta Alexandrinorum : l’exemple des Acta Pauli et Antonini. Akten der Gesellschaft für Griechische und Hellenistische Rechtsgeschichte|Symposion 2017 Akten der Gesellschaft für griechische und hellenistische Rechtsgeschichte Band 27|

Les Acta Pauli et Antonini ont été la plupart du temps mal compris. Une analyse plus fine révèle pourtant que les Alexandrins, avec Antonin à leur tête, contrevinrent à la lex Iulia de vi, et furent condamnés au terme d’un processus respectant le droit. Ces événements s’inscrivent par ailleurs dans une situation d’instabilité plus générale en Égypte qui aboutirait à la réorganisation de la juridiction préfectorale et à une restriction des appels auprès du tribunal impérial afin de répondre plus rapidement à une situation d’État d’urgence

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping

The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ 2 (1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P&lt;5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P&lt;9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB. © 2017 Macmillan Publishers Limited. All rights reserved

Changing Characteristics of Staphylococcus aureus Bacteremia: Results from a 21-Year, Prospective, Longitudinal Study

Background: We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) in an academic, US medical center. Methods: Consecutive patients with monomicrobial SAB were enrolled from January 1995 to December 2015. Each person&apos;s initial bloodstream S. aureus isolate was genotyped using spa typing. Clonal complexes (CCs) were assigned using Ridom StaphType software. Changes over time in both the patient and bacterial characteristics were estimated with linear regression. Associations between genotypes or clinical characteristics and complications were estimated using multivariable regression models. Results: Among the 2348 eligible participants, 54.2% had an implantable, foreign body of some type. This proportion increased significantly during the 21-year study period, by 0.96% annually (P =. 002), as did comorbid conditions and acquisition outside of the hospital. Rates of any metastatic complication also significantly increased, by 0.94% annually (P =. 019). Among the corresponding bloodstream S. aureus isolates, spa-CC012 (multi-locus sequence type [MLST] CC30), -CC004 (MLST CC45), -CC189 (MLST CC1), and -CC084 (MLST CC15) all significantly declined during the study period, while spa-CC008 (MLST CC8) significantly increased. Patients with SAB due to spa-CC008 were significantly more likely to develop metastatic complications in general, and abscesses, septic emboli, and persistent bacteremia in particular. After adjusting for demographic, racial, and clinical variables, the USA300 variant of spa-CC008 was independently associated with metastatic complications (odds ratio 1.42; 95% confidence interval 1.02-1.99). Conclusions: Systematic approaches for monitoring complications of SAB and genotyping the corresponding bloodstream isolates will help identify the emergence of hypervirulent clones and likely improve clinical management of this syndrome. © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]

The Diversity of Lipopolysaccharide (O) and Capsular Polysaccharide (K) Antigens of Invasive Klebsiella pneumoniae in a Multi-Country Collection

10.3389/fmicb.2020.01249Frontiers in Microbiology11124