Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE).The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC 24 )/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC 24 /MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC 24 /MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC 24 was determined using a maximum a posteriori probability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC 24 /MIC ratio and AM was <211. Patients with an AUC 24 /MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC 24 /MIC ratio of >211 (38 and 8%, respectively; P ؍ 0.02). In bivariate analysis the APACHE-II score and an AUC 24 /MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24; P ؍ 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4; P ؍ 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC 24 /MIC ratio of <211. We believe further investigations are warranted.
Peptoniphilus spp. are Gram-positive anaerobic cocci (GPAC) that were formerly classified in the genus Peptostreptococcus. This study describes 15 cases of Peptoniphilus spp. bloodstream infection (BSI) diagnosed from 2007 to 2011 using 16S rDNA sequencing in patients with pneumonia, pre-term delivery, soft tissue infection or colon or bladder disease. Seven out of 15 (47%) of these cases had polymicrobial BSIs. One of the isolates was closely related to P. duerdenii (EU526290), while the other 14 isolates were most closely related to a Peptoniphilus sp. reference strain (ATCC 29743) and P. hareii (Y07839). Peptoniphilus is a rare but important cause of BSI.
Despite emerging evidence that dysfunction in the accessory gene regulator (agr) locus is associated with deleterious outcomes among patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infections, factors predictive of agr dysfunction have not been evaluated. This study describes the epidemiology of agr dysfunction, identifies predictors of agr dysfunction in MRSA isolates among those with MRSA bloodstream infections, and describes the relationship between agr dysfunction and other microbiologic phenotypes. A cross-sectional study of patients with MRSA bloodstream infections at two institutions in upstate New York was performed. Clinical data on demographics, comorbidities, disease severity, hospitalization history, and antibiotic history were collected. Microbiologic phenotypes, including agr dysfunction, MIC values by broth microdilution (BMD) and Etest, and vancomycin heteroresistance (hVISA) were tested. Multivariable analyses were performed to identify factors predictive of agr dysfunction. Among 200 patients with an MRSA bloodstream infection, the proportion of strains with agr dysfunction was 31.5%. The distribution of MICs determined by both BMD and Etest were equivalent across agr groups, and there was no association between agr dysfunction and the presence of hVISA. Severity of illness, comorbidities, and hospitalization history were comparable between agr groups. In the multivariate analysis, prior antibiotic exposure was the only factor of variables studied found to be predictive of agr dysfunction. This relationship was predominantly driven by prior beta-lactam and fluoroquinolone administration in the bivariate analysis. Identifying these institution-specific risk factors can be used to develop a process to assess the risk of agr dysfunction and guide empirical antibiotic therapy decisions.The accessory gene regulator (agr) is a quorum-sensing operon which coordinates the expression of secreted and cellassociated virulence factors, and it controls several metabolic pathways in Staphylococcus aureus in a growth phase-related fashion (7,30). In vitro studies show that alterations in agr function result in several phenotypic changes in S. aureus, including diminished autolysis (21), attenuated vancomycin activity (20,22,29), vancomycin heteroresistance (22), and an increased proclivity for the development of intermediate resistance to vancomycin (7,22,29,30). There is also increasing clinical evidence showing that alterations in agr in S. aureus are a key risk factor for poor outcomes in patients with S. aureus bacteremia (7,25).Despite the poor outcomes associated with agr dysfunction, factors predictive of agr dysfunction have not been well described, and scant literature exists describing the relationship between agr dysfunction and other reduced vancomycin susceptibility phenotypes. This study describes the epidemiology of agr dysfunction, determines predictors of agr dysfunction in methicillin-resistant Staphylococcus aureus (MRSA) isolates among those with MRS...
Children presenting with chest pain require further investigation if electrocardiographs show any abnormalities. Children presenting with pericarditis require follow-up and caution about recurrence.
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