**1. Introduction**

Antibiotic resistance is a worldwide problem of major importance. Isolations in some countries of multi-drug-resistant (resistant to three or more classes of antimicrobials), extensively-drug-resistant (resistant to all but one or two classes) or even pan-drugresistant (resistant to all available classes) Gram-negative pathogens are causing therapeu‐ tic problems and- in the same time- are posing infection control issues in many hospitals. In fact, numerous studies highlight the link between multi-drug-resistance and increased morbidity and mortality, increased length of hospital stay and higher hospital costs [1-4].

*Pseudomonas aeruginosa* is a Gram-negative opportunistic nosocomial pathogen responsi‐ ble for a wide range of infections that may present high rates of antimicrobial resistance. The genome of this microorganism is among the largest in the bacterial world allowing for great genetic capacity and high adaptability to environmental changes. In fact, *P. aeruginosa* has 5567 genes encoded in 6.26 Mbp of DNA while *Escherichia coli* K12 for example has 4279 genes encoded in 4.46 Mbp and *Haemophilus influenzae* Rd has 1.83 Mbp encoding 1714 genes [5]. This large genetic armamentarium- that can be further enriched with the addition of genes acquired by transferable genetic elements via horizontal gene transfer- is a major contributing factor to its formidable ability to develop resistance against all known antibiotics.

Generally, antibiotic resistance mechanisms of *P. aeruginosa* can be divided in intrinsic and acquired. Intrinsic refers to resistance that is a consequence of a large selection of genetical‐ ly-encoded mechanisms and acquired refers to resistance that is achieved via the acquisi‐

© 2013 Meletis and Bagkeri; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

tion of additional mechanisms or is a consequence of mutational events under selective pressure.

**Efflux system Efflux pump family Substrates References**

Fluoroquinolones Aminoglycosides β-Lactams (preferably Meropenem, Ticarcillin)

*Pseudomonas aeruginosa*: Multi-Drug-Resistance Development and Treatment Options

[17]

http://dx.doi.org/10.5772/55616

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[17]

[17] [18]

[17]

Tetracycline Tigecycline Chloramphenicol

Tetracycline Tigecycline Chloramphenicol Erythromycin Roxythromycin

Fluoroquinolones β-Lactams (preferably Meropenem, Ticarcillin)

Fluoroquinolones β-Lactams (preferably Meropenem, Ticarcillin)

Fluoroquinolones Aminoglycosides β-Lactams (preferably Meropenem, Ticarcillin,

Aminoglycosides [19]

Fluoroquinolones [17]

Macrolides [20]

Aminoglycosides [21]

Tetracycline Tigecycline Chloramphenicol

Cefepime) Tetracycline Tigecycline Chloramphenicol

MexAB-OprM Resistance Nodulation

MexCD-OprJ Resistance Nodulation

MexEF-OprN Resistance Nodulation

MexXY-OprM Resistance Nodulation

AmrAB-OprA Resistance Nodulation

PmpM Multidrug And Toxic

Mef(A) Major Facilitator Superfamily (MFS)

ErmEPAF Small Multidrug Resistance (SMR)

**Table 1.** Efflux systems of *P. aeruginosa*.

Division (RND)

Division (RND)

Division (RND)

Division (RND)

Division (RND)

compound Extrusion (MATE)
