outcomes for elderly patients with MRSA infections will therefore increase survival and quality of life, and reduce health care expenditure burdens.2
MRSA HAP is primarily treated via the intravenous administration of vancomycin (VCM), and the dosage is determined by pharmacokinetic/pharmacodynamic (PK/PD) parameters. However, a previous study involving adult patients with MRSA pneumonia or sepsis failed to show an association between the PK/PD parameters for VCM and treatment outcome.3 Martin et al4 recommend a target area under the concentration curve (AUC)/minimum inhibitory concentration (MIC) for VCM of .400 μg × h/mL, while we previously reported that AUC/MIC values of 250–450 μg × h/mL were acceptable for elderly patients.5 The reason for this discrepancy is currently unclear.
VCM treatment outcomes depend on the characteristics of the patient, and it is well known that hypoalbuminemia is a risk factor for poor treatment outcomes, as reported in a previous study.6 Hayashi et al7 reported that hypoalbuminemia was a risk factor with the long-term administration of VCM. However, the reason that hypoalbuminemia has an influence on the treatment outcome of VCM remains unknown.
Since the potency of VCM is dependent on the free unbound form, albumin levels may have an influence on VCM treatment outcomes. In addition, body fluid volume and renal function are frequently decreased in elderly patients, and such patients show large individual differences in PK/PD parameters. Nevertheless, these parameters in elderly patients with hypoalbuminemia have not been clarified. To elucidate the association between severe hypoalbuminemia and VCM treatment outcomes, we examined PK/PD parameters in elderly patients with severe hypoalbuminemia.
Methods
Study location and patients
The study was conducted at the National Center for Geriatrics and Gerontology Hospital, Obu, Japan. This 320-bed hospital oversees general (including emergency) services, except pediatrics, and admits approximately 5,000 patients per year (more than 50% of whom are aged over 75 years). The average number of HAP-MRSA patients is 10–20 per year. MRSA is endemic in this hospital, and the ratio of MRSA isolates per total S. aureus isolates is approximately 70%.
Over a 7-year period (from January 2006 through December 2012), all hospitalized patients aged 75 years or older with MRSA pneumonia that had been microbiologically confirmed by sputum or blood cultures, and who had been treated with VCM therapy, were identified using the Clinical Pharmacokinetics Department computer database.
Study design and data collection
We conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 elderly patients with MRSA pneumonia who had been treated with VCM during the 7-year study period. The secondary outcomes were nephrotoxicity and liver dysfunction. The baseline characteristics of the study patients were age, gender, body weight, serum creatinine level, Charlson Comorbidity Index, albumin level, combination antibiotic therapy, diagnosis of pneumonia, and infection severity. In addition, we assessed the relationship between the effect of VCM PK indices, including serum peak and trough concentrations, AUC/MIC values, volume of distribution, half-life, clearance of VCM, single and daily dose of VCM, and dose interval of VCM. The clinical characteristics of the study patients were retrieved from the hospital medical records. For patients with multiple episodes, only the first episode was counted. This study was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology Hospital.
Definitions
The definition of HAP was based on American Thoracic Society guidelines for the management of adults with hospital-acquired, ventilator-associated, and health care-associated pneumonia.2 For the purposes of this study, HAP was defined as pneumonia that occurred 48 hours or more after hospitalization for an acute lung infection characterized by a cough, fever, purulent sputum, and an abnormal chest X-ray that was not deemed to be incubating at the time of admission. Among the HAP cases, those with MRSA isolated from blood cultures or sputum that showed no signs of improvement after treatment with broad-spectrum antibiotics, such as carbapenem, for more than 3 days were defined as MRSA HAP.
Severe hypoalbuminemia was defined as a serum albumin level of ,2.5 g/dL. The severity rating of pneumonia was defined according to the Japanese Respiratory Society guidelines for the management of HAP8 and was used to allocate the patients into severe, moderate, and mild groups. The severe group was defined as patients with three or more of the following risk factors or conditions: malignancy or immunocompromized status, impaired consciousness, requiring a fraction of inspired oxygen (FiO2) .35% to maintain a saturated oxygen (SaO2) level .90%, men aged 70 years or older, or women aged 75 years or older, and oliguria or dehydration. The moderate group was defined as patients with
outcomes for elderly patients with MRSA infections will therefore increase survival and quality of life, and reduce health care expenditure burdens.2MRSA HAP is primarily treated via the intravenous administration of vancomycin (VCM), and the dosage is determined by pharmacokinetic/pharmacodynamic (PK/PD) parameters. However, a previous study involving adult patients with MRSA pneumonia or sepsis failed to show an association between the PK/PD parameters for VCM and treatment outcome.3 Martin et al4 recommend a target area under the concentration curve (AUC)/minimum inhibitory concentration (MIC) for VCM of .400 μg × h/mL, while we previously reported that AUC/MIC values of 250–450 μg × h/mL were acceptable for elderly patients.5 The reason for this discrepancy is currently unclear.VCM treatment outcomes depend on the characteristics of the patient, and it is well known that hypoalbuminemia is a risk factor for poor treatment outcomes, as reported in a previous study.6 Hayashi et al7 reported that hypoalbuminemia was a risk factor with the long-term administration of VCM. However, the reason that hypoalbuminemia has an influence on the treatment outcome of VCM remains unknown.Since the potency of VCM is dependent on the free unbound form, albumin levels may have an influence on VCM treatment outcomes. In addition, body fluid volume and renal function are frequently decreased in elderly patients, and such patients show large individual differences in PK/PD parameters. Nevertheless, these parameters in elderly patients with hypoalbuminemia have not been clarified. To elucidate the association between severe hypoalbuminemia and VCM treatment outcomes, we examined PK/PD parameters in elderly patients with severe hypoalbuminemia.MethodsStudy location and patientsThe study was conducted at the National Center for Geriatrics and Gerontology Hospital, Obu, Japan. This 320-bed hospital oversees general (including emergency) services, except pediatrics, and admits approximately 5,000 patients per year (more than 50% of whom are aged over 75 years). The average number of HAP-MRSA patients is 10–20 per year. MRSA is endemic in this hospital, and the ratio of MRSA isolates per total S. aureus isolates is approximately 70%.Over a 7-year period (from January 2006 through December 2012), all hospitalized patients aged 75 years or older with MRSA pneumonia that had been microbiologically confirmed by sputum or blood cultures, and who had been treated with VCM therapy, were identified using the Clinical Pharmacokinetics Department computer database.Study design and data collectionWe conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 elderly patients with MRSA pneumonia who had been treated with VCM during the 7-year study period. The secondary outcomes were nephrotoxicity and liver dysfunction. The baseline characteristics of the study patients were age, gender, body weight, serum creatinine level, Charlson Comorbidity Index, albumin level, combination antibiotic therapy, diagnosis of pneumonia, and infection severity. In addition, we assessed the relationship between the effect of VCM PK indices, including serum peak and trough concentrations, AUC/MIC values, volume of distribution, half-life, clearance of VCM, single and daily dose of VCM, and dose interval of VCM. The clinical characteristics of the study patients were retrieved from the hospital medical records. For patients with multiple episodes, only the first episode was counted. This study was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology Hospital.
Definitions
The definition of HAP was based on American Thoracic Society guidelines for the management of adults with hospital-acquired, ventilator-associated, and health care-associated pneumonia.2 For the purposes of this study, HAP was defined as pneumonia that occurred 48 hours or more after hospitalization for an acute lung infection characterized by a cough, fever, purulent sputum, and an abnormal chest X-ray that was not deemed to be incubating at the time of admission. Among the HAP cases, those with MRSA isolated from blood cultures or sputum that showed no signs of improvement after treatment with broad-spectrum antibiotics, such as carbapenem, for more than 3 days were defined as MRSA HAP.
Severe hypoalbuminemia was defined as a serum albumin level of ,2.5 g/dL. The severity rating of pneumonia was defined according to the Japanese Respiratory Society guidelines for the management of HAP8 and was used to allocate the patients into severe, moderate, and mild groups. The severe group was defined as patients with three or more of the following risk factors or conditions: malignancy or immunocompromized status, impaired consciousness, requiring a fraction of inspired oxygen (FiO2) .35% to maintain a saturated oxygen (SaO2) level .90%, men aged 70 years or older, or women aged 75 years or older, and oliguria or dehydration. The moderate group was defined as patients with
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