Pseudomonas aeruginosa is resistant to which antibiotics

Pseudomonas (page 2) © Kenneth Todar, PhD

Resistance to Antibiotics

Pseudomonas aeruginosa is notorious for its resistance to antibiotics and is, therefore, a particularly dangerous and dreaded pathogen. The bacterium is naturally resistant to many antibiotics due to the permeabiliity barrier afforded by its Gram-negative outer membrane. Also, its tendency to colonize surfaces in a biofilm form makes the cells impervious to therapeutic concentrations antibiotics. Since its natural habitat is the soil, living in association with the bacilli, actinomycetes and molds, it has developed resistance to a variety of their naturally-occuring antibiotics. Moreover, Pseudomonas maintains antibiotic resistance plasmids, both R-factors and RTFs, and it is able to transfer these genes by means of the bacterial mechanisms of horizontal gene transfer (HGT), mainly transduction and conjugation.

Only a few antibiotics are effective against Pseudomonas aeruginosa, including fluoroquinolones, gentamicin and imipenem, and even these antibiotics are not effective against all strains. The futility of treating Pseudomonas infections with antibiotics is most dramatically illustrated in cystic fibrosis patients, virtually all of whom eventually become infected with a strain that is so resistant that it cannot be treated.

Diagnosis

Diagnosis of P.aeruginosa infection depends upon isolation and laboratory identification of the bacterium. It grows well on most laboratory media and commonly is isolated on blood agar or eosin-methylthionine blue agar. It is identified on the basis of its Gram morphology, inability to ferment lactose, a positive oxidase reaction, its fruity odor, and its ability to grow at 42°C. Fluorescence under ultraviolet light is helpful in early identification of P. aeruginosa colonies. Fluorescence is also used to suggest the presence of P. aeruginosa in wounds.

Pathogenesis

For an opportunistic pathogen such as Pseudomonas aeruginosa, the disease process begins with some alteration or circumvention of normal host defenses. The pathogenesis of Pseudomonas infections is multifactorial, as suggested by the number and wide array of virulence determinants possessed by the bacterium. Multiple and diverse determinants of virulence are expected in the wide range of diseases caused, which include septicemia, urinary tract infections, pneumonia, chronic lung infections, endocarditis, dermatitis, and osteochondritis.

Most Pseudomonas infections are both invasive and toxinogenic. The ultimate Pseudomonas infection may be seen as composed of three distinct stages: (1) bacterial attachment and colonization; (2) local invasion; (3) disseminated systemic disease. However, the disease process may stop at any stage. Particular bacterial determinants of virulence mediate each of these stages and are ultimately responsible for the characteristic syndromes that accompany the disease.

Colonization

Although colonization usually precedes infections by Pseudomonas aeruginosa, the exact source and mode of transmission of the pathogen are often unclear because of its ubiquitous presence in the environment. It is sometimes present as part of the normal flora of humans, although the prevalence of colonization of healthy individuals outside the hospital is relatively low (estimates range from 0 to 24 percent depending on the anatomical locale).

The pili of Pseudomonas aeruginosa will adhere to the epithelial cells of the upper respiratory tract and, by inference, to other epithelial cells as well. These adhesins appear to bind to specific galactose or mannose or sialic acid receptors on epithelial cells. Colonization of the respiratory tract by Pseudomonas requires pili adherence and may be aided by production of a protease enzyme that degrades fibronectin in order to expose the underlying pilus receptors on the epithelial cell surface. Tissue injury may also play a role in colonization of the respiratory tract, since P. aeruginosa will adhere to tracheal epithelial cells of mice infected with influenza virus but not to normal tracheal epithelium. This has been called opportunistic adherence, and it may be an important step in Pseudomonas keratitis and urinary tract infections, as well as infections of the respiratory tract.

The receptor on tracheal epithelial cells for Pseudomonas pili is probably sialic acid (N-acetylneuraminic acid). Mucoid strains, which produce an exopolysaccharide (alginate), have an additional or alternative adhesin which attaches to the tracheobronchial mucin (N-acetylglucosamine). Besides pili and the mucoid polysaccharide, there are possibly other cell surface adhesins utilized by Pseudomonas to colonize the respiratory epithelium or mucin. Also, it is possible that surface-bound exoenzyme S could serve as an adhesin for glycolipids on respiratory cells.

The mucoid exopolysaccharide produced by P. aeruginosa is a repeating polymer of mannuronic and glucuronic acid referred to as alginate. Alginate slime forms the matrix of the Pseudomonas biofilm which anchors the cells to their environment and in medical situations, it protects the bacteria from the host defenses such as lymphocytes, phagocytes, the ciliary action of the respiratory tract, antibodies and complement. Biofilm mucoid strains of Pseudomonas are also less susceptible to antibiotics than their planktonic counterparts. Mucoid strains of P. aeruginosa are most often isolated from patients with cystic fibrosis and they are usually found in lung tissues from such individuals.

Invasion

The ability of Pseudomonas aeruginosa to invade tissues depends upon production of extracellular enzymes and toxins that break down physical barriers and damage host cells, as well as resistance to phagocytosis and the host immune defenses. As mentioned above, the bacterial capsule or slime layer effectively protects cells from opsonization by antibodies, complement deposition, and phagocyte engulfment.

Two extracellular proteases have been associated with virulence that exert their activity at the invasive stage: elastase and alkaline protease. Elastase has several activities that relate to virulence. The enzyme cleaves collagen, IgG, IgA, and complement. It also lyses fibronectin to expose receptors for bacterial attachment on the mucosa of the lung. Elastase disrupts the respiratory epithelium and interferes with ciliary function. Alkaline protease interferes with fibrin formation and will lyse fibrin. Together, elastase and alkaline protease destroy the ground substance of the cornea and other supporting structures composed of fibrin and elastin. Elastase and alkaline protease together are also reported to cause the inactivation of gamma interferon (IFN) and tumor necrosis factor (TNF).

Pseudomonas aeruginosa produces three other soluble proteins involved in invasion: a cytotoxin (mw 25 kDa) and two hemolysins. The cytotoxin is a pore-forming protein. It was originally named leukocidin because of its effect on neutrophils, but it appears to be cytotoxic for most eucaryotic cells. Of the two hemolysins, one is a phospholipase and the other is a lecithinase. They appear to act synergistically to break down lipids and lecithin. The cytotoxin and hemolysins contribute to invasion through their cytotoxic effects on neutrophils, lymphocytes and other eucaryotic cells.

One Pseudomonas pigment is probably a determinant of virulence for the pathogen. The blue pigment, pyocyanin, impairs the normal function of human nasal cilia, disrupts the respiratory epithelium, and exerts a proinflammatory effect on phagocytes. A derivative of pyocyanin, pyochelin, is a siderophore that is produced under low-iron conditions to sequester iron from the environment for growth of the pathogen. It could play a role in invasion if it extracts iron from the host to permit bacterial growth in a relatively iron-limited environment. No role in virulence is known for the fluorescent pigments.

Is Pseudomonas aeruginosa resistant to amoxicillin?

How did Pseudomonas aeruginosa become resistant to antibiotics?