BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) infections are associated with significant mortality and health care costs. To improve treatment outcomes for MRSA, a better understanding of the pharmacokinetic/pharmacodynamic parameters of vancomycin is required to develop optimal dosing strategies, particularly in elderly patients (≥75 years of age) with limited renal function. The purpose of this study was to determine whether pharmacokinetic indices for vancomycin are associated with mortality from MRSA hospital-acquired pneumonia in elderly patients.MethodsWe conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 patients with MRSA hospital-acquired pneumonia who had been treated with vancomycin from January 2006 through December 2012. Our most recent sampling of MRSA isolates had a minimum inhibitory concentration (MIC) for vancomycin of 1 μg/mL (86%), indicating that the area under the curve (AUC) was equal to the AUC/MIC in these isolates. The primary data from 28-day survivors and nonsurvivors were compared.ResultsAmong 94 elderly patients, the mean age was 82 (75–99) years. Multivariate analyses revealed that, among the factors examined, only the nonoptimal AUC (<250, >450 μg*h/mL) was an independent predictor of 28-day mortality in elderly patients (odds ratio 23.156, 95% confidence interval 6.814–78.687, P < 0.001). We detected a significant difference for increasing nephrotoxicity in nonsurvivors (nine of 32 patients [28%]) compared with survivors (three of 62 patients [4.8%], P = 0.003).ConclusionThis finding indicates that patients with potentially poor renal function are likely to have increased AUC values and a poor prognosis. Consideration of the pharmacokinetics/pharmacodynamics of vancomycin and targeting an AUC/MIC value of 250–450 μg*h/mL may result in improved treatment outcomes for elderly patients with MRSA hospital-acquired pneumonia.
BackgroundVancomycin (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. However, the reason that severe hypoalbuminemia has an influence on the treatment outcome of VCM remains unknown.ObjectiveTo elucidate the association between severe hypoalbuminemia and VCM treatment outcomes, we examined pharmacokinetic/pharmacodynamic (PK/PD) parameters in elderly patients with severe hypoalbuminemia.MethodsWe conducted a retrospective observational study of 94 patients with methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired pneumonia who had been treated with VCM between January 2006 and December 2012. The 94 patients were divided into severe hypoalbuminemia and non-severe hypoalbuminemia groups. The PK/PD parameters and treatment outcomes of VCM were compared between the two groups.ResultsThe half-life of VCM in the severe hypoalbuminemia group was significantly longer than in the non-severe hypoalbuminemia group (33.2 + 5.4 vs 24.9 + 1.6; P = 0.049). Area under the concentration curve (AUC)/minimum inhibitory concentration (MIC) values of 250–450 and >450 μg × h/mL were significantly associated with 28-day mortality in the severe hypoalbuminemia group (P < 0.001), whereas AUC/MIC values of <250 μg × h/mL were not associated. We also detected a significant difference in the increased percentage of nephrotoxicity in the severe hypoalbuminemia group (6 of 23 patients [26%]) compared with the non-severe hypoalbuminemia group (6 of 71 patients [8%]; P < 0.001).ConclusionThese findings indicate that severe hypoalbuminemia influences the half-life of VCM and treatment outcomes in elderly patients (≥75 years of age). To establish a more effective and safer treatment protocol, the issue of malnutrition in elderly patients needs to be addressed and improved.
Firstly, it was reported that phytohemagglutinin P (PHA-P) can induce the immediate skin reaction besides the delayed one. 70 out of 80 cases (87.5%) gave positive immediate reactions with 1 μg of PHA-P. There was a close correlation between the radioallergosorbent test (RAST) counts against PHA-P and the total IgE value or erythematous diameter of the immediate skin reactions. Absorption with anti-IgE or PHA-P reduced the RAST counts against PHA-P to 79 and 56% of their initial values, respectively, but did not effect the RAST counts against streptokinase-streptodornase (SK-SD). These results suggest that the immediate skin reaction might be induced by specific IgE antibody against PHA-P. Secondly, using three fractions of PHA-P obtained by Sephadex G-200 gel filtration, skin test and RAST in humans, ACA in rats, and 3H-thymidine incorporation into human leukocytes, were carried out and data obtained that showed some discrepancy between them. That is, on skin testing, it was shown that all of the three fractions (fr.) had the ability to elicit the immediate and delayed skin reaction in humans and rats with the order of fr. 1, 2 and 3, and it was confirmed by RAST. On the other hand, the leukocyte-stimulating activity resided in fr. 1 and 2, while fr. 3, which seemed to be a group of subunits with a molecular weight of around 35,000, had almost no activity. These findings have been discussed in view of the earlier studies on the structure of PHA-P.
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