Chest
Original ResearchPneumoniaEffect of Linezolid Compared With Glycopeptides in Methicillin-Resistant Staphylococcus aureus Severe Pneumonia in Piglets
Section snippets
Materials and Methods
Forty-eight healthy 3-month-old Largewhite-Landrace piglets with a mean (± SD) weight of 20.2 ± 1.9 kg were intubated and mechanically ventilated with a volume-cycled ventilator (Luft 1; Leistung Ingeniería SRL; Córdoba, Argentina); death during the first 24 h related to early complications was considered a cause of exclusion for further analysis. The model of bacterial pneumonia on mechanical ventilation (MV) was elsewhere described for Gram-negative bacteria.8, 9 Anesthesia, analgesia, and
Results
Piglets were divided in five groups. One group (6 piglets) received neither MV nor AMT; the remaining groups (10 piglets in each group) continued to receive MV, and treatment with VAN, TEI, LZD, or no AMT. Ten piglets were dismissed from the study, 8 because of early death and 2 because of protocol deviation (ie, received a wrong AMT at least once), and periodically the planed inclusion of new piglets had to be corrected to maintain equilibrium among the different AMT groups. A higher number of
Discussion
Inoculation produced MRSA severe pneumonia in mechanically ventilated piglets. S aureus occasionally had produced spontaneous pneumonia in a model of mechanically ventilated piglets.8 Pneumonia has been induced inoculating Gram-negative rods in pigs in the past,8, 9, 21 but there exists very limited experience with MRSA in this model.22 The high early death rate observed suggests that the model is akin to a community-acquired MRSA model and could also be applicable to human VAP associated with
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European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid
2014, Clinical Microbiology and InfectionCitation Excerpt :These data were recently confirmed in the ZEPHyR study (a phase IV, prospective, randomized, double-blind, multicentre, non-inferiority trial published in 2012), which assessed the efficacy, safety and tolerability of linezolid versus vancomycin in adult patients with culture-confirmed MRSA NP [110]. The results showed that for the primary endpoint, linezolid was statistically significantly superior to vancomycin, with a significantly higher clinical response at the end of study in the per-protocol (PP) population (57.6% versus 46.6%; p 0.042) [110]. Linezolid led to a significantly higher microbiological response than vancomycin at the end of the study (58.1% versus 47.1%, 95% CI 4–21.5) [110].
Linezolid Effects on Bacterial Toxin Production and Host Immune Response: Review of the Evidence
2012, Current Therapeutic Research - Clinical and ExperimentalCitation Excerpt :Furthermore, no differences were found in various measures of inflammation that included histologic damage, numbers of leukocytes in bronchoalveolar lavage (BAL) fluid, concentrations of cytokines (IL-6 and monocyte chemotactic protein-5), matrix metalloproteinase-9 and myeloperoxidase activity (inflammatory mediators) in BAL fluid, and the rate of apoptosis in neutrophils isolated from BAL fluid. Luna et al37 compared the effects of linezolid (300 mg q8h), vancomycin (500 mg q6h), and teicoplanin (200 mg q12h for 3 doses, then once daily) in mechanically ventilated piglets infected with MRSA. Treatment with linezolid resulted in significantly enhanced survival when compared with no treatment; however, no difference was noted when compared with treatment with vancomycin or teicoplanin.
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This study was funded by an independent research grant from Pfizer, which was administered by the Asociación Cooperadora del Hospital de Clínicas.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).
- 1
Dr. Luna has served on the advisory boards for Bayer, Wyeth, and Pfizer, and has been a speaker for AstraZeneca (for which he received $2,000).
- 2
Drs. Bruno, García-Morato, Mann, Risso Patrón, Sagardía, Absi, García Bottino, Marchetti, Famiglietti, Baleztena, and Biancolini have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.