Pseudomonas aeruginosa: Well-qualified for the New Age

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Pseudomonas aeruginosa: Well-qualified for the New Age

By Judy Gassett, MT, CIC, MPH, CRCST

Pseudomonas aeruginosa is a gram-negative, aerobic rod, belonging to the bacterial family Pseudomonadaceae. The family includes Xanthomonas, which together with Pseudomonas, comprise a group of bacteria colloquially known as Pseudomonads. These bacteria are common inhabitants of soil and water. They occur regularly on the surfaces of plants and occasionally on the surfaces of animals. The group is more commonly known as plant pathogens. Relatives can cause very serious diseases in herding animals and occasionally in man. Pseudomonas mallei causes a disease in horses known as glanders and Pseudomonas pseudomallei is the agent of melioidosis, a rapidly fatal tropical disease of humans and other mammals. Although colonization usually precedes infections by Pseudomonas aeruginosa, the exact source and mode of transmission are often unclear because of the organism's wide-spread presence in the environment.

The very fact that Pseudomonas aerginosa causes diseases in both plant and animal tissues suggests a remarkable metabolic diversity. It can use many substances as food sources and has been isolated from distilled water. The microbial patriarch of the organisms first bioengineered to clean up toxic waste spills was a Pseudomonas species. If NO3 (nitrates) are present, Pseudomonas does fine without O2 (oxygen) but it is not an anaerobe. It also tolerates a variety of temperatures, preferring 37°C, but also grows at 42°C.1Hot tub folliculitis is common and results from the organism's ability to prosper at temperature extremes.

Why Nosocomial Environments Are Accommodating

Pseudomonas aeruginosa has a deserved reputation as a relentless nosocomial pathogen due to its natural resistance to many chemicals and ability to tolerate sparse conditions. It has a preference for moist environments that accommodate nosocomial-type interactions such as water-based therapies and treatments, especially respiratory support. Besides the wide availability of water in hospitals, clinics, and nursing homes, intense antibiotic pressures and ability to use a wide variety of compounds as energy sources (disinfectants, handwash creams, distilled water), nosocomial environments are quite attractive when most other organisms would be eliminated quickly.

Pseudomonas is motile by means of a single polar (attached at one end) flagellum and is considered the greyhound of the bacterial world, from which the speed of other bacteria are often bench-marked. The flagella does not gently wave back and forth. Rather, it spins like a propeller on a shaft. Pseudomonas plies its trade as either a permanently attached "sessile" form embedded in a slimy matrix ("biofilm") with other bacteria, or as a "plaktonic" form (an independent, free-swimming cell). Most clinical isolates produce a characteristic green or blue-green pigment, pyocyanin, having a distinctive fruity odor and considered toxic to human tissue. Sources from highly colonized clinical specimens often have a green-blue discoloration and can fluoresce.2

Always Found in Cystic Fibrosis (CF)

Initially, young CF patients are colonized with Pseudomonas aeruginosa strains typically found in the environment. These bacteria produce a green pigment when grown on agar plates in the laboratory. Once established within the lungs, the colonies take on a mucoid appearance3. The growth of the organisms in a biofilm allows the production of a unique slime (alginate) coating. The biofilm coating makes the organism resistant to opsonization (antibody attachment) and phagocytosis. The mechanism is purely mechanical as antibody particles--leukocytes--cannot penetrate the slime.

During chronic infection in the CF patient, bacteria undergo phenotypic (visible) changes. P. aeruginosa loses its flagella and pili (attachment organelles). Although the infection is never cleared, Pseudomonas sepsis is very rare in cystic fibrosis. Victims usually survive to the third decade of life.

The organism does not adhere to intact epithelium but has specific receptors for damaged respiratory epithelium (present in cystic fibrosis), which is uncovered by a bacterial enzyme. 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.4 This is also thought to be an important step in Pseudomonas keratitis (eye infections) and urinary tract infections. As if it were not sticky enough, P. aeruginosa virulence has recently been shown to be controlled by a complex regulatory circuit involving multiple bacterial cell-to-cell signaling systems that allow the bacteria to produce virulence factors in a coordinated, cell-density dependent manner.5

Natural Resistance Explained

Pseudomonas aeruginosa's high resistance to many antibiotics makes it a particularly dreaded pathogen. Several features of its niche coupled to its own plentiful natural endowments contribute to this: 1) A sturdy outer lipid coating which repels antibiotics; and 2) life as a dirt-dweller with continual exposure to chemical-spewing actinomycetes, molds, and other microbes (which are used to make antibiotics). This equates to abundant natural resistance before the organism even enters the hospital.

Pseudomonas causes disease mainly in patients who have impaired body defenses. Occasionally it can overcome the defenses of healthy persons but this is likely only if the inoculum is huge. A detailed discussion of pathogenic qualities is shortened and summarized in Table 1.

Normally, Pseudomonas cannot survive in the blood stream and only causes septicemia in those with severe white cell depression.6 Other Pseudomonas diseases, such as endopthalmitis or osteomyelitis, are also states where there is low leukocyte count due to penetration difficulties or normal absence of leukocytes--a situation Pseudomonas will then exploit. The growth of Pseudomonas in tissue depends greatly upon the ability of the organism to resist phagocytosis. The most important risk factor for septicemia is low white cell count (neutropenia). Pseudomonas aeruginosa blood stream infection carries a very high mortality in neutropenic patients.

Manufactured Virulence Properties7,8

Pseudomonas must deploy several compounds including elastase and an alkaline protease to obtain scarce nutrients during infection, damaging host tissue in the process. One such essential metabolite is phosphate. The organism's phospholipase digests host cell membranes for whatever it needs. Pseudomonal elastase is elaborated to get molecular iron, which is very tightly bound, in the body. Elastase is crucial to invasion because strains without it remain local colonizers. This elastase also wrecks specific anti-pseudomonal antibodies, collagen, fibrin and lyses fibronectin to expose receptors for bacterial attachment on the respiratory epithelium. Pseudomonal infection in the eye can be disastrous. Remember, there are no white cells to oppose infection. Together with bacterial alkaline protease, the ground substance of the cornea and other supporting structures composed of fibrin and elastin are destroyed quickly. Endophthalmitis due to Pseudomonas is a medical emergency. The most common risk is direct invasion after cataract surgery. Not only are systemic antibiotics required but also, injections into the eyeball (anterior chamber) are necessary. This is very tricky, as only certain antibiotics can be used and those that are must be carefully titered or the retina is irreversibly burned.

The latest aggregated National Nosocomial Infections Surveillance (NNIS) data from 1992-97 show that P. aeruginosa continues to be the agent responsible for most gram negative nosocomial pneumonia and one of the primary agents responsible for hospital-acquired urinary tract infections, second only to E. coli.9

As a leading cause of nosocomial pneumonias, risk factors include mechanical ventilation, setting in the ICU, cancer with neutropenia, and depleted immune resources. Urinary tract infections are usually related to instrumentation, or kidney stones. These infections have a tendency to persist and the organism may be impossible to eradicate until the predisposition leading to the infection (i.e., catheter, anatomic defect) is removed.

Antimicrobial Therapy

Each Pseudomonas strain tends to be unique to the particular hospital environment. Thus, chemoprophylaxis must be guided by the local susceptibility patterns. Generally, however, piperacillin and ceftazidime are the most active penicillin and cephalosporin. Monotherapy with these antibiotics is not recommended because when used alone the organism produces huge amounts of beta lactamase.10 Beta lactamase inhibitors such as sulbactam, clavulanate, or tazobactam are worthless against Pseudomonas and should not be used. Currently, alteration of penicillin-binding proteins is a rare cause of resistance in Pseudomonas.

The most consistently active aminoglycosides are tobramycin and Amikacin.

While we are in the fourth generation of quinolones now, Ciprofloxacin, a second generation drug, is the still most active. Cipro has wonderful kinetics and tissue penetration properties. Prior to Cipro, osteomyelitis could not be treated orally regardless of the agent. In many cases now, osteomyelitis can be treated on an outpatient basis on oral therapy.

Carbapenems are highly active against Pseudomonas. Both imipenem and meropenem work and are not inactivated by the beta lactamases. However, some nosocomial super strains are resistant to these as well. In these cases, the infection is not treatable. P

Judy Gassett has been an ICP for 10 years. She is certified in infection control, is a medical technologist in microbiology, and a certified central service technician (CRCST). She is in a private infection control practice and acts as a consultant, lecturer and writer. She lives in Vista, Calif.

Table 1
Summary of Some Pseudomonas aeruginosa Pathogenic Properties

Adhering attributes
Fimbriae (pili), polysaccharide capsule (glycocalyx), alginate slime (biofilm).

Invasion properties (Pseudomonal infections are usually both invasive and toxigenic)
Elastase, alkaline protease, various hemolysins (phospholipase and lecithinase acting synergistically to break down lipids and lecithin), various cytotoxins, such as leukocidin, which destroys WBCs.
Presence of potent elastases or siderophores (iron-grabbing enzymes).

Toxins
Exotoxin A, a pore-drilling protein.
Lipopolysaccharide (LPS), causes shock and hypotension. Is located in the bacterial cell membrane.
Pyocyanin diffusible pigment (harmful to human cells).

Anti-phagocytic properties
Capsules, slime layers.
Both act to prevent engulfment.
Protease enzymes (which destroy specific antibody).

Natural/ Ecological
Minimum nutritional requirements.
Metabolic diversity.
Ability to tolerate sparse conditions.
Widespread in a variety of habitats.

Table 2
Summary of Agents Approved for Use as the Principal Active Ingredient in Preoperative-Preparation Formula

Antimicrobial Agent Spectrum of Activity Rapidity Safety Development of Resistance Debris Removal Persistence
Alcohol Broad Fast Long history, safe Non-existent Generally poor detergency Short, in minutes
CHG Broad Moderate Requires data to demonstrate safety Low Good when formulated with surfactants Relatively long, in hours
Iodophors Broad, can be neutralized by blood or other organic materials Fast Generally safe. Skin irritation and sensitization can occur. Low to negligible Good in povidone- iodine formulations Intermediate to short, in minutes


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