Treatment of Mediastinitis due to Methicillin-resistant Staphylococcus aureus in a Renal Dysfunction Patient Undergoing Adjustments to the Linezolid Dose

Tsuji, Yasuhiro; Tashiro, Masato; Ashizawa, Naoto; Ota, Yukio; Obi, Hayato; Nagura, Saori; Narukawa, Munetoshi; Fukahara, Kazuaki; Yoshimura, Naoki; To, Hideto; Yamamoto, Yoshihiro

doi:10.2169/internalmedicine.54.2292

Cited by 16 publications

(14 citation statements)

References 19 publications

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“…In the four youngest hospitalized patients (aged 1, 5, 8 and 13 years), RF was assumed to be 0.5. RF was included in the model, using a linear independent combination of renal and non-renal CL parameters, as shown in Equation (6). CL OVERALL is the overall population value of parameter for CL.…”

Section: Covariate Modelmentioning

confidence: 99%

“…Linezolid is a member of the oxazolidinone class of synthetic antimicrobial agents with a unique mechanism action compared with other agents in this class . It has been used to treat critical infections, including pneumonia, sepsis, and wound, skin and soft tissue infections . It has strong antibacterial activity against aerobic Gram‐positive cocci (GPC), methicillin‐resistant coagulase‐negative staphylococci, vancomycin‐resistant enterococci and methicillin‐resistant Staphylococcus aureus (MRSA) , and has been approved for use in more than 60 countries.…”

Section: Introductionmentioning

confidence: 99%

“…Nukui et al demonstrated that thrombocytopenia developed more frequently in patients with a linezolid trough concentration of >7.5 μg ml –1 . It has been recommended that the dose of linezolid should be adjusted based on serum concentrations .…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics and pharmacodynamics of linezolid‐induced thrombocytopenia in hospitalized patients

Tsuji

Holford

Kasai

et al. 2017

Brit J Clinical Pharma

Self Cite

107

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We have described the influence of weight, renal function, age and plasma protein binding on the pharmacokinetics of linezolid. This combined pharmacokinetic, pharmacodynamic and turnover model identified that the most common mechanism of thrombocytopenia associated with linezolid is PDI. Impaired RF increases thrombocytopenia by a pharmacokinetic mechanism. The linezolid dose should be reduced in RF.

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Section: Covariate Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics and pharmacodynamics of linezolid‐induced thrombocytopenia in hospitalized patients

Tsuji

Holford

Kasai

et al. 2017

Brit J Clinical Pharma

Self Cite

107

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“…Brier et al showed approximately 30% -50% of the administered dose of the drug was removed by hemodialysis, but hemodialysis patients had the higher concentration of linezolid than that of non-hemodialysis patients [10]. Despite of the decreasing daily dose of linezolid from 1200 to 600 mg at the start of treatment to prevent thrombocytopenia in a renal dysfunction patient, the concentration of linezolid in the serum was 11.5 μg/mL on 21st day of linezolid therapy, which was sufficient to induce thrombocytopenia [11]. Additionally, they reported that linezolid concentration was similar between the wound exudate and serum [11].…”

Section: Discussionmentioning

confidence: 96%

“…Despite of the decreasing daily dose of linezolid from 1200 to 600 mg at the start of treatment to prevent thrombocytopenia in a renal dysfunction patient, the concentration of linezolid in the serum was 11.5 μg/mL on 21st day of linezolid therapy, which was sufficient to induce thrombocytopenia [11]. Additionally, they reported that linezolid concentration was similar between the wound exudate and serum [11]. Therefore, we thought that thrombocytopenia in hemodialysis patients was associated with the accumulation of linezolid.…”

Section: Discussionmentioning

confidence: 97%

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Kato¹,

Hagihara²,

Yamagishi³

et al. 2016

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Previous study suggested that low body weight was one of the risk factors of thrombocytopenia induced by linezolid in non-hemodialysis patients. However, there have been little investigations for the linezolid-induced thrombocytopenia in hemodialysis patients. This study was to evaluate the association between several factors of body size descriptors and thrombocytopenia in hemodialysis-patients. No factor of body size descriptors showed significant correlation with linezolid-induced thrombocytopenia (patients with thrombocytopenia vs patients without thrombocytopenia: body

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Rationale Antibiotikatherapie der Mediastinitis

Ambrosch

2016

Chirurg

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Mediastinitis occurs as a severe complication of thoracic and cardiac surgical interventions and is the result of traumatic esophageal perforation, conducted infections or as a result of lymphogenic and hematogenic spread of specific infective pathogens. Treatment must as a rule be accompanied by antibiotics, whereby knowledge of the spectrum of pathogens depending on the pathogenesis is indispensable for successful antibiotic therapy. Polymicrobial infections with a high proportion of anaerobes are found in conducted infections of the mediastinum and after esophageal perforation. After cardiac surgery Staphylococci are the dominant pathogens and a nasal colonization with Staphylococcus aureus seems to be a predisposing risk factor. Fungi are the predominant pathogens in immunocompromised patients with consumptive underlying illnesses and can cause acute or chronic forms with granulomatous inflammation. Resistant pathogens are increasingly being found in high-risk patient cohorts, which must be considered for a calculated therapy. For calculated antibiotic therapy the administration of broad spectrum antibiotics, mostly beta-lactams alone or combined with metronidazole is the therapy of choice for both Gram-positive and Gram-negative bacteria inclusive of anaerobes. For patients at risk, additional antibiotic classes with a spectrum against methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) can be administered. Increasing rates of multidrug-resistant Gram-negative bacteria (e.g. Enterobacteriaceae) and non-fermenting bacteria (e.g. Pseudomonas and Acinetobacter) in individual cases necessitates the use of polymyxins (e.g. colistin), new tetracyclines (e.g. glycylglycines) and newly developed combinations of beta-lactams and beta-lactam inhibitors. For treatment of fungal infections (e.g. Candida, Aspergillus and Histoplasma) established and novel azoles, amphotericin B and echinocandins seem to be successful; however, detection of Candida, particularly in mixed infections does not always necessitate treatment. Mediastinitis is still a severe infectious disease with a high mortality, which necessitates an early and broad spectrum antibiotic therapy; however, with respect to optimal duration of therapy and selection of antibiotics, data from good quality comparative studies are lacking.

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Treatment of Mediastinitis due to Methicillin-resistant Staphylococcus aureus in a Renal Dysfunction Patient Undergoing Adjustments to the Linezolid Dose

Cited by 16 publications

References 19 publications

Population pharmacokinetics and pharmacodynamics of linezolid‐induced thrombocytopenia in hospitalized patients

Population pharmacokinetics and pharmacodynamics of linezolid‐induced thrombocytopenia in hospitalized patients

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Rationale Antibiotikatherapie der Mediastinitis

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