Vancomycin Bactericidal Activity as a Predictor of 30-Day Mortality in Patients with Methicillin-Resistant
            <i>Staphylococcus aureus</i>
            Bacteremia

Miyazaki, Motonobu; Takata, Tohru; Yoshimura, Hisae; Matsunaga, Akira; Ohta, Daisuke; Ishikura, Hiroyasu; Futo, Maki; Hara, Shuuji; Kamimura, Hidetoshi; Tamura, Kazuo; Ngo, Dung; Tsuji, Brian T.

doi:10.1128/aac.01536-10

Cited by 18 publications

(13 citation statements)

References 7 publications

(2 reference statements)

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“…It is important to achive the therapeutic trough concentration range of VCM more rapidly and consistently because VCM needs to contact bacteria for a long time to have effects [ 20 ]. Miyazaki et al demonstrated that the bactericidal activity of VCM was closely associated with 30-day mortality in patients with MRSA bacteremia initially administered VCM [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of pharmacist intervention in Vancomycin treatment for patients with bacteremia due to Methicillin-resistant Staphylococcus aureus

et al. 2018

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ObjectiveWe conducted a retrospective study based on composite endpoints for treatment failure to evaluate the effect of pharmacist-led VCM initial dose planning for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia patients.MethodsA retrospective cohort study was performed between pharmacist intervention and non-intervention groups. In this study, four types of failure were defined as the composite endpoint. When any one of the following failures occurred: 1) Death within 30 days from the start of VCM therapy, 2) Positive blood culture 7 days after the start of VCM therapy, 3) Change of VCM to another anti-MRSA agent, and 4) Development of nephrotoxicity, we considered that VCM treatment had failed. Survival time analysis was conducted with the Kaplan-Meier method and Cox’s proportional hazard model that included seven predefined parameters: pharmacist intervention, age, sex, weight, baseline VCM trough concentration, Charlson Comorbidity Index (CCI), and Pitt Bacteremia score (PBS). The effect of pharmacist intervention was studied as the survival probability estimated from the period of time from the start of VCM administration to the earliest failure.ResultsThe survival rate at 30 days after starting VCM therapy, at the end of follow-up, was 53.1 and 82.1% in the non-intervention and intervention groups, respectively. A significant survival time prolongation was noted in the intervention group (p = 0.011, log rank test). Among the seven parameters, only pharmacist intervention was significantly different and its hazard ratio was 0.26 (p = 0.014). The survival probability of the intervention group was higher than that of the non-intervention group for the time to each failure. In subgroup analyses, a significant difference was noted in male patients between the intervention and non-intervention groups (p = 0.005). Age was categorized into those under and over 65 years old. For those over 65 years old, a significant difference was shown between the groups (p = 0.018).ConclusionTo our knowledge, this is the first study to evaluate the failure of VCM treatment based on the composite endpoint. Pharmacist intervention through the initial VCM dose planning could maintain a balance between the efficacy and safety of VCM treatment and might avoid treatment failure for patients with MRSA bacteremia. Further investigations with large sample sizes are required to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Effects of pharmacist intervention in Vancomycin treatment for patients with bacteremia due to Methicillin-resistant Staphylococcus aureus

et al. 2018

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“…The association between VAN MIC and clinical outcomes has been evaluated exhaustively in the literature, while little attention has been paid to the potential importance of bactericidal activity (3,5). Studies that have evaluated VAN bactericidal activity have noted an apparent association between reduced bactericidal activity and worse clinical outcomes (7,8). Although VAN MIC and MBC values are correlated, it is not uncommon for these values to be either slightly or greatly dissociated (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

Britt

Patel

Horvat

et al. 2016

Antimicrob Agents Chemother

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T he incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in health care and community settings has increased in recent years (1). Vancomycin (VAN) has been a mainstay in the armamentarium against MRSA for nearly half a century, but changes in susceptibility patterns have presented new treatment challenges (2). The gradual reduction in susceptibility of MRSA isolates to VAN occurring over the last 2 decades has been associated with increased treatment failure and mortality (3, 4). While the relationship between VAN MIC and clinical outcomes in MRSA bacteremia (MRSA-B) is well established, the importance of VAN minimum bactericidal concentration (MBC) is less clear (5).Multiple studies have highlighted the importance of bactericidal therapy in treating S. aureus bacteremia (SAB). Previous research has demonstrated that in vitro 24-h bactericidal activity by VAN is associated with a decrease in the duration of MRSA-B clinically compared to in vitro bacteriostatic activity (6). Additionally, decreased in vitro VAN killing activity over 72 h also has been associated with an increase in 30-day mortality in patients with MRSA-B treated with VAN (7). Sakoulas et al. reported an association between elevated VAN MIC and treatment failure but also noted that reduced bactericidal activity had a similar effect (8).Lastly, multiple studies have demonstrated improved clinical outcomes with ␤-lactam therapy compared to those with VAN for methicillin-susceptible SAB, which may be partially attributed to the superior killing activity of ␤-lactams compared to that of VAN (9,10). Thus, there is evidence to suggest that VAN bactericidal activity plays an influential role in clinical outcomes of SAB, including MRSA-B.Consensus recommendations support a VAN area under the curve (AUC)/MIC ratio of Ն400 as a pharmacodynamic predictor of therapeutic effectiveness for MRSA infections (11). An AUC/ MIC ratio of Ն421 also has been associated with clinical success in MRSA-B (12). Due to the trend toward improved outcomes with increased bactericidal activity of VAN, we hypothesized that VAN exposure as a function of MBC rather than MIC may be a more important predictor of VAN effectiveness in the treatment of MRSA-B. Therefore, the objectives of this study were to (i) evaluate the association between pharmacodynamic parameters (VAN AUC 24 /MIC ratio determined by broth microdilution [MIC BMD ], VAN AUC 24 /MIC ratio determined by Etest [MIC Etest ], and VAN AUC 24 /MBC ratio) and 30-day mortality and (ii) quantify the VAN AUC 24 /MBC threshold associated with an increased probability of mortality in a cohort of hospitalized patients with MRSA-B.

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“…We then tested the eradicating potential of the ADEP4/rifampicin combination against a variety of S. aureus strains. These included laboratory strain SA113, as well as clinical isolates USA300, UAMS-1 and strain 37, a S. aureus strain isolated from a patient undergoing vancomycin therapy who succumbed to infection 20 (Extended Data Fig. 2).…”

mentioning

confidence: 99%

Activated ClpP kills persisters and eradicates a chronic biofilm infection

Conlon

Nakayasu

Fleck

et al. 2013

Nature

593

567

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Vancomycin Bactericidal Activity as a Predictor of 30-Day Mortality in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia

Cited by 18 publications

References 7 publications

Effects of pharmacist intervention in Vancomycin treatment for patients with bacteremia due to Methicillin-resistant Staphylococcus aureus

Effects of pharmacist intervention in Vancomycin treatment for patients with bacteremia due to Methicillin-resistant Staphylococcus aureus

Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

Activated ClpP kills persisters and eradicates a chronic biofilm infection

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