Dataset Information

Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

ABSTRACT: Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 ?g/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes.Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine.Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ? 2 ?g/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ? 2 ?g/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 ?g/mL. A vancomycin trough >15 ?g/mL was, however, an independent risk factor for AKI.Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

SUBMITTER: McNeil JC

PROVIDER: S-EPMC4752422 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

McNeil J Chase JC Kok Eric Y EY Forbes Andrea R AR Lamberth Linda L Hulten Kristina G KG Vallejo Jesus G JG Mason Edward O EO Kaplan Sheldon L SL

The Pediatric infectious disease journal 20160301 3

<h4>Introduction</h4>Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to co ...[more]

PMID: 26646549

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Project description:The genomic evolution in vivo in persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) was adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates with incremental non-susceptibility to vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days of bacteremia. Whole genome sequencing (WGS) for all consecutive isolates were conducted to characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship with antimicrobial treatment. The WGS-based phylogeny categorized the isogenic strains into three major clades, I (22 isolates), II (7 isolates), and III (3 isolates), respectively, harboring a median (range) of 7 (1-30), 62 (53-65), and 118 (100-130) non-synonymous mutations when compared to the very first isolate. Clade I strains were further grouped into early and late subclades, which, respectively, shared the most recent common ancestor with Clade III strains at day 393.7 and Clade II strain at day 662.5. Clade I and Clade III strains were characterized, respectively, with high rates of VISA (9/22, 40.9%) and VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA phenotype was exclusively identified in Clade II strains after eight courses of linezolid treatment. The LRSA displayed a small colony variant phenotype and were associated with G2576T mutations in domain V region of 23S rRNA. Substantial loss of mobile elements or alleles mediating resistance or virulence were identified during the evolution of multi-resistance. However, the gene loss might not be correlated to the development of VISA, DRSA, or LRSA phenotype. In conclusion, MRSA in persistent bacteremia was adapted to harsh host environment through multiple pathways involving both resistance-associated mutations and extensive gene loss.

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Dataset Information

Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

Publications

Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

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