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

Abstract

tion of additional mechanisms or is a consequence of mutational events under selective pressure. 2. Intrinsic resistance of Pseudomonas aeruginosa P. aeruginosa shows inherent resistance to antimicrobial agents through a variety of mechanisms: (1) decreased permeability of the outer membrane, (2) efflux systems which actively pump antibiotics out of the cell, and (3) production of antibiotic-inactivating enzymes [6]. 2.1. Outer membrane permeability The outer membrane of Gram-negative bacteria is a barrier which prevents large hydrophilic molecules to pass through it. Aminoglycosides and colistin interact with lipopolysaccharides changing the permeability of the membrane in order to pass whereas beta-lactams and quinolones need to diffuse through certain porin channels. Bacteria produce two major classes of porins: general; which allow almost any hydrophilic molecule to pass [7] and specific; which have binding sites for certain molecules, allowing them to be oriented and pass in the most energy-efficient way [8]. Most bacteria posses lots of general porins and relatively few specific ones. However, the exact opposite occurs for P. aeruginosa that expresses mainly specific porins [7]. 2.2. Efflux systems P. aeruginosa expresses several efflux pumps that expel drugs together with other substances out of the bacterial cell. These pumps consist of three proteins: (1) a protein transporter of the cytoplasmatic membrane that uses energy in the form of proton motive force, (2) a periplasmic connective protein, and (3) an outer membrane porin [5]. Most antibiotics-except polymyxins-are pumped out [9,10] by these efflux systems (Table 1) therefore their first two components are named multidrug efflux (Mex) along with a letter (e.g. MexA and MexB). The outer membrane porin is called Opr along with a letter (e.g. OprM) [11]. 2.3. Antibiotic-inactivating enzymes P. aeruginosa belongs to the SPICE group of bacteria (Serratia spp., P. aeruginosa, Indole positive Proteus, Citrobacter spp., Enterobacter spp.). These microorganisms share a common characteristic: the ability to produce chromosomal-encoded and inducible AmpC beta-lactamases. These are cephalosporinases that hydrolyze most beta-lactams and are not inhibited by the beta lactamase inhibitors. Another endogenous beta-lactamase produced by P. aeruginosa is the class D oxacillinase PoxB [12,13]. This enzyme however has only been found in laboratory mutants and is not clinically significant.

IDENTIFICATION OF BACTERIA CAUSING NECROTIC PULP WITH 16S rRNA GENE POLYMERASE CHAIN REACTION AND ANTIBIOTIC RESISTANCE TESTING AT THE DENTAL HOSPITAL IN SEKELOA, BANDUNG, INDONESIA

“…P. aeruginosa is intrinsically resistant to various antibiotics due to a low permeability of its the outer membrane, which acts as a selective barrier [23]. Resistance mechanisms of P. aeruginosa include producing the enzyme that inactive antibiotics, an antibiotics efflux system, and decreased the permeability of the outer membrane bacteria [24]. For A. schindleri, it is said to have resistance if it has a diameter of 1.8 cm below the inhibitory zone [8].…”

Prevalence of Oxacillinase Groups I, II and III in Pseudomonas aeruginosa Isolates by Polymerase Chain Reaction and Genotyping by ERIC-PCR Methods

“…The most potent combination is clearly that of a carbapenemase-producing isolate commonly enriched by resistance to quinolones and aminoglycosides, leaving very limited options for antimicrobial treatment (16). Carbapenem-resistant P. aeruginosa is mainly an ICU pathogen, and one of the frequent causes of VAP.…”

A Self‐Immobilizing and Fluorogenic Probe for β‐Lactamase Detection

“…To combat the increasing prevalence of antibiotic resistance, rapid detection of β‐lactamases is highly important. As a result, a wide variety of methods have been developed . Among these, the most widely used tests are the phenotypic tests, which investigate bacterial susceptibility in antibiotic‐containing culture media.…”