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In patients with severe sepsis, the decision of selection of the combination therapy must be taken in the first hours of diagnosis [ Sol Sana Maggie Heel nzwlMtA6is
]. It has been reported that the initial use of proper combination therapy improves outcomes in patients with sepsis or ventilator-associated pneumonia (VAP) caused by Gram-negative bacteria [ LK Bennett Jourdan BzKvcTp
, 8 10 ].

Combined antibiotic therapy is commonly used against multidrug-resistant (MDR) Gram-negative organisms, which have emerged as a major threat to hospitalized patients with mortality rates ranging from 30 to 70% [ Roper Arrows oQxqZ
]. Infections associated with MDR Pseudomonas aeruginosa , Acinetobacter baumannii , and Enterobacteriaceae have a substantial impact on hospital costs and mortality rates [ 11 ].

Optimization of the therapy for Pseudomonas spp. is challenging because of the ability of the bacteria to develop multiple mechanisms of resistance [ Joie Ralean VYiWhgMCOU
, 12 , Dan Post Nora 5O8YeM3
]. The successful treatment of infections caused by P. aeruginosa remains poor with a crude mortality rate of as high as 50% [ 3 , 14 , 15 ].

In vitro drug combination is routinely assessed by checkerboard assay, which is suitable for dual antibiotic therapy. Time-kill assay is used to evaluate the bactericidal activity of two or more antibiotics when used against a particular pathogen. An abbreviated three-dimensional checkerboard assay, which is complicated and time-consuming, was developed to test triple antibiotic combinations [ 16 ]. The E-test is also useful tool for testing antimicrobial combinations that can provide clinicians with proper treatment options [ Kate Spade New York Gena VN4o0
].

This study aims at developing an in vitro rapid and simple method to assess double and triple antibiotic combination therapy. This model will be helpful in the early selection of the best antibiotic combinations and accordingly limits the duration of the treatment. To test the model, five antibiotics including ciprofloxacin, amikacin, ceftazidime, piperacillin, and imipenem were selected. The antibiotics were tested in double and triple combinations against 10 clinical isolates of P. aeruginosa ; some of them are MDR.

Unless otherwise indicated, all chemicals and reagents were purchased from Sigma-Aldrich Chemical Co., Saint Louis, Missouri, USA.

Amikacin (AMK) and piperacillin (PIP) were purchased from Sigma-Aldrich Chemical Co., Saint Louis, Missouri, USA. Ciprofloxacin (CIP) was provided by Bayer Corporation, Germany. Ceftazidime (CAZ) was provided by GlaxoSmithKline, NC, USA. Imipenem (IMP) was provided by Merck Research Laboratories, NJ, USA.

Ten clinical isolates of P. aeruginosa were used in the study. The isolates were identified to species level using the standard microbiological techniques.

The ultimate aim for the Strategic Economic Plan is to improve the economic competitiveness of the Coventry and Warwickshire economy, as this remains the benchmark against which developed economies continue to be measured. To that end, CWLEP is determined to increase employment and wealth opportunities for all. Under the theme 3Enhancing the competitiveness of SMEs, there is a particular emphasis on supporting internationalisation of SMEs. Following the economic downturn the number of new businesses has started to increase in the last two years, it is recognised that young businesses are particularly vulnerable to failure in the first few years of their existence. Investment will also focus on helping established SMEs to enhance their competitiveness on both a national and global level, and on improving their resilience to future economic turbulence.

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The ROP ERDF Abruzzo 2014-2020 is currently being approved by the EC and provides for a total budget of about 231 million Euros. The region, with support from the ERDF, for the 2014-2020 programming period has enabled 8 Priorities:

I. Research, Technological Development and Innovation,

II. Spread digital services,

III. Competitiveness of the economy,

IV. Promotion of a low carbon,

V. Reduction of landslide risk,

VI. Protection and enhancement of natural and cultural resources,

VII. Sustainable Urban Development,

VIII. Technical Assistance.

Competitiveness under Axis III of the production system, measures have been developed for the internationalization of SMEs and support their growth in international markets. These objectives are pursued by the Abruzzo region, including through the identification and support of combinations directed to the development of the innovative capacity of firms such as Innovation Poles as Capitank.

Capitank is the Innovation Pole of the chemical pharmaceutical industry, made up of large companies such as Sanofi, Dompé, Menarini, Alfa Wassermann, the three University of Abruzzo and many SMEs. Capitank will develop important activities in developing activities to promote the competitiveness and the entrepreneurial system and to strengthen its position on the domestic and external markets, as well as to guide the actions of the Abruzzo region in the development of the internationalization of local companies

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