Predictors of persistent methicillin-resistant Staphylococcus aureus bacteraemia in patients treated with vancomycin

Yoon, Young Kyung; Kim, Jeong Yeon; Park, Dae Won; Sohn, Jang Wook; Kim, Jong Hun

doi:10.1093/jac/dkq050

Cited by 84 publications

(69 citation statements)

References 9 publications

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“…While vancomycin remains a frequently used treatment for pneumonia caused by MRSA, clinical failures in this setting have been increasingly recognized (12,31,32). As such, additional treatment options appear necessary as MRSA isolates with reduced VAN susceptibilities (MIC, 2 g/ml) are becoming more prevalent and may contribute to poorer clinical outcomes (22,32,41). In addition to reductions in potency, the relatively low penetration (ϳ50%) of vancomycin into ELF has also been suggested as a reason for the compound's diminished clinical efficacy (6,22,30,35).…”

Section: Discussionmentioning

confidence: 99%

Comparative In Vivo Efficacies of Epithelial Lining Fluid Exposures of Tedizolid, Linezolid, and Vancomycin for Methicillin-Resistant Staphylococcus aureus in a Mouse Pneumonia Model

Tessier

Keel²,

Hagihara

et al. 2012

Antimicrob Agents Chemother

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The antibacterial efficacies of tedizolid phosphate (TZD), linezolid, and vancomycin regimens simulating human exposures at the infection site against methicillin-resistant Staphylococcus aureus (MRSA) were compared in an in vivo mouse pneumonia model. Immunocompetent BALB/c mice were orally inoculated with one of three strains of MRSA and subsequently administered 20 mg/kg TZD every 24 hours (q24h), 120 mg/kg linezolid q12h, or 25 mg/kg vancomycin q12h over 24 h. These regimens produced epithelial lining fluid exposures comparable to human exposures observed following intravenous regimens of 200 mg TZD q24h, 600 mg linezolid q12h, and 1 g vancomycin q12h. The differences in CFU after 24 h of treatment were compared between control and treatment groups. Vehicle-dosed control groups increased in bacterial density an average of 1.1 logs. All treatments reduced the bacterial density at 24 h with an average of 1.2, 1.6, and 0.1 logs for TZD, linezolid, and vancomycin, respectively. The efficacy of TZD versus linezolid regimens against the three MRSA isolates was not statistically different (P > 0.05), although both treatments were significantly different from controls. In contrast, the vancomycin regimen was significantly different from TZD against one MRSA isolate and from linezolid against all isolates. The vancomycin regimen was less protective than either the TZD or linezolid regimens, with overall survival of 61.1% versus 94.7% or 89.5%, respectively. At human simulated exposures to epithelial lining fluid, vancomycin resulted in minimal reductions in bacterial counts and higher mortality compared to those of either TZD or linezolid. TZD and linezolid showed similar efficacies in this MRSA pneumonia model. Methicillin-resistant Staphylococcus aureus (MRSA), including community-associated (CA) and health care-associated (HA) strains, continue to dominate the infectious disease landscape. MRSA strains USA100, USA300, and USA400 are increasingly more resistant to antimicrobials and are spread over the United States and globally (3,10,13,23,27). As this species continues to adapt, the treatment of both CA-MRSA and HA-MRSA pneumonia has become more difficult (27,33). Tedizolid phosphate (TZD; formerly torezolid phosphate) is a novel oxazolidinone antibiotic that is under investigation in phase III trials for acute bacterial skin and skin structure infections (ABSSSI) and has proven to be a powerful new agent against Gram-positive pathogens, including MRSA, Streptococcus pneumonia, and enterococci (2, 29). TZD is a prodrug antibiotic that is rapidly converted in vivo to the microbiologically active moiety tedizolid, also known as TR-700. Human pharmacokinetic studies of tedizolid showed improved pharmacokinetic results compared to those of linezolid and support a once-daily dose of 200 mg (25, 29). Additionally, tedizolid was shown to have in vivo efficacy in a pneumonia model of infection (26).In this current study, the epithelial lining fluid (ELF) profile observed after the administration of 200 mg tedizolid every...

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Section: Discussionmentioning

confidence: 99%

Comparative In Vivo Efficacies of Epithelial Lining Fluid Exposures of Tedizolid, Linezolid, and Vancomycin for Methicillin-Resistant Staphylococcus aureus in a Mouse Pneumonia Model

Tessier

Keel²,

Hagihara

et al. 2012

Antimicrob Agents Chemother

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“…These complicated infections in turn lead to poorer outcomes (170,171). Even in the absence of metastatic complications, persistence per se portends a worse outcome, with infection-related mortality rates being higher for patients with MRSA-B persistence (Ͼ3 days) than for nonpersistent episodes (45.2% and 9.4%, respectively; P ϭ 0.002) (323). Similar results were obtained by a larger case-controlled study, where mortality rates for persistent (Ͼ7 days) SAB were significantly higher than mortality rates for nonpersistent controls (54.8% and 31.4%, respectively; P Ͻ 0.01) (93).…”

Section: Persistent Bacteremiamentioning

confidence: 99%

Predictors of Mortality in Staphylococcus aureus Bacteremia

et al. 2012

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SUMMARY Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes.

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“…In many of the reported studies looking at in vitro susceptibility data, MIC testing was performed retrospectively on isolates retrieved from storage, not at the time of isolation of the organism, and often this is not made explicitly clear (1,7,8,10,12,13,15,16,18,19,25,27,28,30,31,32,34,35). It has been demonstrated that certain organisms can become more susceptible when stored (3,22), and it is possible that this phenomenon, together with differing methodologies, may explain some of the conflicting results in the literature (9).…”

mentioning

confidence: 99%

Is Vancomycin MIC “Creep” Method Dependent? Analysis of Methicillin-Resistant Staphylococcus aureus Susceptibility Trends in Blood Isolates from North East Scotland from 2006 to 2010

et al. 2012

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Predictors of persistent methicillin-resistant Staphylococcus aureus bacteraemia in patients treated with vancomycin

Abstract: To minimize the risk of PMRSAB, early removal of implicated devices and evaluation for metastatic infections should be encouraged. Alternative antibiotic therapy is warranted for infections due to isolates with elevated vancomycin MICs, as well as for the high rates of side effects.

Cited by 84 publications

References 9 publications

Comparative In Vivo Efficacies of Epithelial Lining Fluid Exposures of Tedizolid, Linezolid, and Vancomycin for Methicillin-Resistant Staphylococcus aureus in a Mouse Pneumonia Model

Comparative In Vivo Efficacies of Epithelial Lining Fluid Exposures of Tedizolid, Linezolid, and Vancomycin for Methicillin-Resistant Staphylococcus aureus in a Mouse Pneumonia Model

Predictors of Mortality in Staphylococcus aureus Bacteremia

Is Vancomycin MIC “Creep” Method Dependent? Analysis of Methicillin-Resistant Staphylococcus aureus Susceptibility Trends in Blood Isolates from North East Scotland from 2006 to 2010

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