Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates

Holmes, Natasha E; Turnidge, John; Munckhof, Wendy; Robinson, James O.; Korman, Tony M.; O’Sullivan, Matthew; Anderson, Tara; Roberts, Sally; Warren, Sanchia; Coombs, Geoffrey W.; Tan, Hui-Leen; Gao, Wei; Johnson, Paul; Howden, Benjamin P

doi:10.1128/jcm.01320-14

Cited by 37 publications

(23 citation statements)

References 41 publications

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“…Others have noted that high vancomycin MICs are associated with specific strains of MSSA, in particular agr -II as well as those with agr -dysfunction. 26,27 In contrast, we were unable to show a relationship with vancomycin MIC and agr -group; there was, however, a trend for higher vancomycin MICs among USA300 isolates. One could hypothesize that the increase in MSSA isolates with higher vancomycin MICs are related to an increase in the USA300 background among MSSA isolates, as has been previously demonstrated.…”

Section: Discussioncontrasting

confidence: 79%

Healthcare-associated Staphylococcus aureus Bacteremia in Children

McNeil

Kok

Forbes

et al. 2016

Pediatric Infectious Disease Journal

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Introduction Elevated vancomycin MICs in S. aureus have been associated with worse clinical outcomes in adults. For invasive MRSA infections in adults, the IDSA recommends targeting vancomycin serum trough concentrations between 15–20 μg/ml. We evaluated trends in vancomycin MICs from healthcare-associated S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Methods Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). Healthcare-associated S. aureus bacteremia isolates from 2003–2013 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. Results 341 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 μg/ml (from 32.7% to 5.6%, p<0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/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 μg/ml vs. < 15 μg/ml. A vancomycin trough > 15 μg/ml was, however, an independent risk factor for AKI. Conclusions Vancomycin MICs are shifting among healthcare-associated S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric healthcare-associated S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

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Section: Discussioncontrasting

confidence: 79%

Healthcare-associated Staphylococcus aureus Bacteremia in Children

McNeil

Kok

Forbes

et al. 2016

Pediatric Infectious Disease Journal

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“…We expected to find an association between a HVM and agrII polymorphism, relying on previous studies performed in MSSA bacteraemia [3,12]. In our study, agrII was two times more frequent in the HVM than in the LVM group (38% vs. 19%), but this did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 54%

Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis

Pericàs

Messina

García-de-la-Mària

et al. 2017

Clinical Microbiology and Infection

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Objectives Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.

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“…The increase in vancomycin MICs in MSSA isolates may be related to fit MSSA clones. Elevated vancomycin MICs have previously been associated with certain agr groups and/or agr dysfunction (26)(27)(28). Among isolates obtained in a multicenter cohort study in Australia and New Zealand, an elevated vancomycin MIC was associated with agr group 2 (28).…”

Section: Discussionmentioning

confidence: 88%

Association of Vancomycin MIC and Molecular Characteristics with Clinical Outcomes in Methicillin-Susceptible Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children

Kok

Vallejo

Sommer

et al. 2018

Antimicrob Agents Chemother

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Strains of methicillin-resistant (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections (OAIs). A vancomycin MIC of ≥1.5 μg/ml has been demonstrated to contribute to disease severity in adults with MRSA and even methicillin-susceptible (MSSA) bacteremia. Little data exist describing the outcomes of MSSA OAIs in terms of molecular characteristics and vancomycin MIC. All patients/isolates were chosen from a surveillance study at Texas Children's Hospital (TCH). OAI isolates were identified from 2011 to 2016 and subjected to vancomycin Etests, pulsed-field gel electrophoresis (PFGE), and PCR to determine Panton-Valentine leucocidin (PVL) production and group. Two hundred fifty-two cases of OAI were identified; 183 cases were MSSA (72.6%). During the study period, a decrease in the proportion of cases secondary to MRSA was observed, declining from 37.8% to 15.9% ( = 0.02). Of the MSSA isolates, 26.2% and 23.5% were USA300 and PVL positive, respectively. An increase in the proportion of MSSA isolates with a vancomycin MIC of ≥1.5 μg/ml occurred in the study period ( = 0.004). In MSSA, an elevated vancomycin MIC was associated with multiple surgical procedures and venous thromboses, even when adjusting for empirical β-lactam use. An increase in vancomycin MIC was noted among isolates belonging to group 4 during the study period. Methicillin resistance is declining among OAI isolates at TCH. Simultaneously, vancomycin Etest MICs are increasing among MSSA isolates. Vancomycin MICs of ≥2 μg/ml are associated with adverse clinical outcomes in MSSA irrespective of antibiotic choice, suggesting that this may be a surrogate for organism virulence.

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Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates

Cited by 37 publications

References 41 publications

Healthcare-associated Staphylococcus aureus Bacteremia in Children

Healthcare-associated Staphylococcus aureus Bacteremia in Children

Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis

Association of Vancomycin MIC and Molecular Characteristics with Clinical Outcomes in Methicillin-Susceptible Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children

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