Selection of Aminoglycoside-Resistant Variants of Pseudomonas aeruginosa in an in Vivo Model

1982 ◽  
Vol 146 (5) ◽  
pp. 691-697 ◽  
Author(s):  
A. U. Gerber ◽  
A. P. Vastola ◽  
J. Brandel ◽  
W. A. Craig
2019 ◽  
Vol 206 ◽  
pp. 41-56 ◽  
Author(s):  
Stephanie A. Fong ◽  
Amanda J. Drilling ◽  
Mian Li Ooi ◽  
Sathish Paramasivan ◽  
John W. Finnie ◽  
...  

1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 519-519
Author(s):  
Yiyu Dong ◽  
Brandon Manley ◽  
A. Ari Hakimi ◽  
Jonathan A. Coleman ◽  
Paul Russo ◽  
...  

519 Background: The use of xenograft tumor models is considered the ideal platform to investigate the effects and toxicities of novel drugs in primary human tumors. The establishment of a personalized xenograft model using preoperative or pretherapy biopsy for patients with metastatic or high risk disease could improve selection of targeted therapy. We report on our xenograft model using various tissue sources including biopsies and correlation with patient’s clinical features. Methods: 56 specimens from primary and metastatic ccRCC from 48 patients were collected. After surgery (n=35) or biopsy (n=21) the specimen was transplanted either subcutaneously or after cell culture to immunodeficient mice. Tumor engraftment was followed for up to 4 months. Successfully engrafted patient-derived tumors were passaged to further mice. Conformation of xenograft tumors with formalin-fixed, paraffin-embedded and Hematoxylin and eosin stained tumor sections was done to assure morphological concordance with the patients tumor. We used a two-tailed two proportion z-test to compare the number of successful xenografts harvested from surgical tissue or biopsy tissue. Results: Overall 25 of the 56 specimens were successful in growing tumor in our immunodeficient mice. The frequency of success based on the type and site of tissue harvest may be seen in Table 1. We found biopsy tissue to be significantly more successful compared to surgical tissue, 61.9% compared to 34.2% (p-value=0.044). Conclusions: We believe our xenograft model, using biopsy tissue, demonstrates the feasibility of a real time personalized in vivo model to aid in the selection of targeted treatments for systemic therapy in ccRCC patients. [Table: see text]


2001 ◽  
Vol 194 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Piotr Kraj ◽  
Rafal Pacholczyk ◽  
Hanna Ignatowicz ◽  
Pawel Kisielow ◽  
Peter Jensen ◽  
...  

The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.


Urology ◽  
2001 ◽  
Vol 58 (1) ◽  
pp. 125-128 ◽  
Author(s):  
Masahiro Nakano ◽  
Mitsuru Yasuda ◽  
Shigeaki Yokoi ◽  
Yoshihito Takahashi ◽  
Satoshi Ishihara ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Beatriz Alonso ◽  
Laia Fernández-Barat ◽  
Enea Gino Di Domenico ◽  
Mercedes Marín ◽  
Emilia Cercenado ◽  
...  

Abstract Background The objective of this study was to evaluate the virulence of P. aeruginosa ventilator-associated pneumonia (VAP) strains (cases) in terms of biofilm production and other phenotypic and genotypic virulence factors compared to P. aeruginosa strains isolated from other infections (controls). Methods Biofilm production was tested to assess biomass production and metabolic activity using crystal violet binding assay and XTT assay, respectively. Pigment production (pyocyanin and pyoverdine) was evaluated using cetrimide agar. Virulence genes were detected by conventional multiplex PCR and virulence was tested in an in vivo model in Galleria mellonella larvae. Results We did not find statistically significant differences between VAP and no-VAP strains (p > 0.05) regarding biofilm production. VAP strains had no production of pyocyanin after 24 h of incubation (p = 0.023). The distribution of virulence genes between both groups were similar (p > 0.05). VAP strains were less virulent than non-VAP strains in an in vivo model of G. mellonella (p < 0.001). Conclusion The virulence of VAP-Pseudomonas aeruginosa does not depend on biofilm formation, production of pyoverdine or the presence of some virulence genes compared to P. aeruginosa isolated from non-invasive locations. However, VAP strains showed attenuated virulence compared to non-VAP strains in an in vivo model of G. mellonella.


2006 ◽  
Vol 50 (7) ◽  
pp. 2374-2383 ◽  
Author(s):  
D. Andes ◽  
A. Forrest ◽  
A. Lepak ◽  
J. Nett ◽  
K. Marchillo ◽  
...  

ABSTRACT Numerous factors have been theorized to affect the development of antimicrobial resistance, including those specific to the host, the organism, the environment, the drug, and the drug prescriber. One variable under the control of the prescriber is the drug dosing regimen. Dosing regimens can vary in dose level, dosing interval, and treatment duration. The current studies examined the relationships between antimicrobial dosing regimens and resistance development by use of an in vivo model. A murine model of systemic Candida albicans infection was used to examine resistance emergence during exposure to the triazole antifungal fluconazole. Data from this experimental model demonstrated that the more frequently administered dosing prevented selection of the isogenic resistant cell populations. Conversely, dosing regimens producing prolonged sub-MIC effects appeared to contribute to the outgrowth of isogenic resistant strains. The association between dosing and resistance emergence observed in the current investigation is disparate from that described for antimicrobial compounds with cidal killing characteristics. The inhibitory or static antimicrobial activity of the triazole compounds may explain these differences.


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