**3. Antipseudomonal treatment**

Despite the intrinsic resistance of *P. aeruginosa* to many antimicrobials, some antibiotics are active against this microorganism [14]. Those used more frequently belong to three antibiotic classes: (1) Beta-lactams, (2) Quinolones and (3) Aminoglycosides (Table 2).

**3.3. Aminoglycosides**

infections due to *P. aeruginosa* [14].

**4. Acquired resistance of** *Pseudomonas aeruginosa*

mases and aminoglycoside-modifying enzymes (Table 3).

**Resistance to Resistance mechanism** Beta-lactams Endogenous beta-lactamases

Fluoroquinolones Target site mutations

Polymyxins LPS modification

**Table 3.** Resistance mechanisms of *P. aeruginosa* to anti-pseudomonal drugs.

**4.1. Resistance to beta-lactams**

[26] classification.

Aminoglycosides Aminoglycoside-modifying enzymes

Aminoglycosides inhibit protein synthesis by binding to the 30S or 50S ribosomal subunit [22]. Drugs of this antibiotic class that can be used against *P. aeruginosa* are tobramycin, amikacin and gentamicin. Aminoglycosides are associated with ototoxicity and nefrotoxicity [23]. Because of these adverse effects and because of their narrow therapeutic range, aminoglyco‐ sides are used in combination with agents belonging to other antibiotic classes. The only treatment in which aminoglycosides are recommended as monotherapy is that of urinary tract

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

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

37

Apart from being resistant to a variety of antimicrobial agents, *P. aeruginosa* develops resistance to anti-pseudomonal drugs as well. This acquired resistance is a consequence of mutational changes or the acquisition of resistance mechanisms via horizontal gene transfer and can occur during chemotherapy [24]. Mutational events may lead to over-expression of endogenous beta-lactamases or efflux pumps, diminished expression of specific porins and target site modifications while acquisition of resistance genes mainly refers to transferable beta-lacta‐

Acquired beta-lactamases

Diminished permeability

16S rRNA methylases

Efflux

Efflux

Efflux

Resistance to beta-lactam antibiotics is multi-factorial but is mediated mainly by inactivating enzymes called beta-lactamases. These enzymes cleave the amide bond of the beta-lactam ring causing antibiotic inactivation and are classified according to a structural [25] and a functional

#### **3.1. Beta-lactams**

Beta-lactams bind to and inactivate penicillin-binding proteins (PBPs) that are transpeptidases involved in bacterial cell wall synthesis [15]. The group of beta-lactam antibiotics includes penicillins, cepholosporins, monobactams and carbapenems. The beta-lactams that are most active against *P. aeruginosa* are: Piperacillin and ticarcillin (penicillins), ceftazidime (3rd generation cephalosporin), cefepime (4th generation cephalosporin), aztreonam (monobac‐ tam), imipenem, meropenem and doripenem (carbapenems).

#### **3.2. Quinolones**

Quinolones are synthetic antimicrobials that block DNA replication by inhibiting the activity of DNA gyrase and topoisomerase IV [16]. The fluorquinolones with anti-pseudomonal activity are ciprofloxacin, levofloxacin and ofloxacin.


**Table 2.** Commonly used anti-pseudomonal drugs.

### **3.3. Aminoglycosides**

**3. Antipseudomonal treatment**

**3.1. Beta-lactams**

36 Infection Control

**3.2. Quinolones**

Despite the intrinsic resistance of *P. aeruginosa* to many antimicrobials, some antibiotics are active against this microorganism [14]. Those used more frequently belong to three antibiotic

Beta-lactams bind to and inactivate penicillin-binding proteins (PBPs) that are transpeptidases involved in bacterial cell wall synthesis [15]. The group of beta-lactam antibiotics includes penicillins, cepholosporins, monobactams and carbapenems. The beta-lactams that are most active against *P. aeruginosa* are: Piperacillin and ticarcillin (penicillins), ceftazidime (3rd generation cephalosporin), cefepime (4th generation cephalosporin), aztreonam (monobac‐

Quinolones are synthetic antimicrobials that block DNA replication by inhibiting the activity of DNA gyrase and topoisomerase IV [16]. The fluorquinolones with anti-pseudomonal

Penicillin / Beta-lactamase inhibitor Bacterial cell wall synthesis inhibition Ticarcillin/Clavulanic acid

Piperacillin/Tazobactam

Cefepime

Meropenem Doripenem

Levofloxacin Ofloxacin

Tobramycin Amikacin

classes: (1) Beta-lactams, (2) Quinolones and (3) Aminoglycosides (Table 2).

tam), imipenem, meropenem and doripenem (carbapenems).

**Antibiotic Class Mechanism of action Drug** Penicillins Bacterial cell wall synthesis inhibition Ticarcillin

Cefalosporins Bacterial cell wall synthesis inhibition Ceftazidime

Monobactams Bacterial cell wall synthesis inhibition Aztreonam Carbapenems Bacterial cell wall synthesis inhibition Imipenem

Fluoroquinolones Block of DNA synthesis Ciprofloxacin

Aminoglycosides Protein synthesis inhibition Gentamycin

**Table 2.** Commonly used anti-pseudomonal drugs.

activity are ciprofloxacin, levofloxacin and ofloxacin.

Aminoglycosides inhibit protein synthesis by binding to the 30S or 50S ribosomal subunit [22]. Drugs of this antibiotic class that can be used against *P. aeruginosa* are tobramycin, amikacin and gentamicin. Aminoglycosides are associated with ototoxicity and nefrotoxicity [23]. Because of these adverse effects and because of their narrow therapeutic range, aminoglyco‐ sides are used in combination with agents belonging to other antibiotic classes. The only treatment in which aminoglycosides are recommended as monotherapy is that of urinary tract infections due to *P. aeruginosa* [14].
