Teicoplanin Dosing Strategy for Treatment of Staphylococcus aureus in Korean Patients with Neutropenic Fever

PURPOSE: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever. MATERIALS AND METHODS: One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis. RESULTS: The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively. CONCLUSION: The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.

Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis

This study tested the hypothesis that the use of corticosteroids prior to antibiotics can lower the mortality rate in severe infections by S. aureus or Gram-negative bacilli, using an animal model. This study was a prospective and controlled study, placed in a university laboratory. Seven hundred and sixty mice distributed into three groups (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae infected). The interventions in each group were: I) infection control (intra-peritoneal); II) treatment solely with antibiotics (teicoplanin or amikacin); III) antibiotics administered prior to the corticosteroid (methylprednisolone); IV) antibiotics administered after the corticosteroid. Mortality in the E. coli group, subgroup I: 100 percent; subgroup II: 55 percent (p<0.001); subgroup III: 62.5 percent (p=0.2488, compared to subgroup II); subgroup IV: 20 percent (p<0.01 compared to subgroups II and III). Mortality in the K. pneumoniae group: subgroup I: 100 percent; subgroup II: 72.5 percent (p<0.01); subgroup III: 80 percent (p=0.215 compared to subgroup II); subgroup IV: 45 percent (p<0.01 compared to subgroups II and III). Mortality in the S. aureus group: subgroup I: 82.5 percent; II: 42.5 percent (p<0.001); subgroup III: 77.5 percent (p=0.2877 compared to subgroup I); subgroup IV: 32.5 percent (p=0.1792 compared to subgroup II). The use of corticosteroids prior to antibiotics lowered the mortality rate caused by Gram-negative bacteria and did not affect the mortality caused by S. aureus. When used after starting treatment with antibiotics, the corticosteroid was not superior to the use of antibiotics alone in the case of the Gram-negative bacteria, and was not significantly different from non-treatment of the infection, in the case of S. aureus.

Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

Glicopéptidos en el tratamiento de infecciones por microorganismo gram positivos / Glycopeptides in the treatment of gram positive infections

Glycopeptides have become a very important class of antibiotics because its widespread usage, the emergence of resistance to this antibiotics and need for new antibiotics to treat serious resistant gram positive infections. We discuss the general characteristics of this class of antibiotics, resistance to glycopeptides in gram positive organisms, the recommendations for the appropriate usage of glycopeptides, and the development of new antibiotics as alternatives to treat serious gram positive infections. Because it is important to limit the indiscriminate usage of glycopeptides, in order to avoid the emergence of resistance, recommendations for the appropriate and inappropriate usage of vancomycin are highlighted

Eficacia y seguridad de teicoplanina en el tratamiento de infecciones severas causadas por Staphylococcus / Efficacy and security of teicoplasnin in the treatment of severe infections caused by staphylococcus

Se realizó un estudio abierto no comparativo para evaluar la eficacia y seguridad de la administración de teicoplanina en pacientes con infecciones bacterianas causadas por gérmenes grampositivos, principalmente Staphylococus y Enterococcus. Fueron tratados 20 enfermos con infecciones de tejidos blandos, osteoarticulares y del aparato respiratorio inferior, causado por Staphylococcus aureus. Se les administró teicoplanina por vía intravenosa en infusión durante 30 minutos o por inyección intramuscular; la dosis inicial fue de 6 mg/kg, seguida de 3 mg/kg administrada una vez al día. Los resultados clínicos obtenidos fueron 65 por ciento de curación y 35 por ciento mejoría, con una erradicación bacteriológica del 100 por ciento. La tolerancia fue buena; sólo un enfermo fue retirado del estudio debido a que presentó rash, probablemente relacionado al fármaco en estudio. Podemos concluir que la administración de teicoplanina en dosis de 400 mg iniciales y 200 mg subsecuentes, una sola vez al día, por vía intravenosa o intramuscular, fue eficaz y segura en este estudio