Pseudomonas aeruginosa: Well-qualified for the New Age

Pseudomonas aeruginosa: Well-qualified for the New Age

By Judy Gassett, MT, CIC, MPH, CRCST

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

The very fact that Pseudomonas aerginosa causes diseases in both plantand animal tissues suggests a remarkable metabolic diversity. It can use manysubstances as food sources and has been isolated from distilled water. Themicrobial patriarch of the organisms first bioengineered to clean up toxic wastespills was a Pseudomonas species. If NO_³ (nitrates)are present, Pseudomonas does fine without O_²(oxygen) but it is not an anaerobe. It also tolerates a variety of temperatures,preferring 37°C, but also grows at 42°C.¹Hot tubfolliculitis is common and results from the organism's ability to prosper attemperature extremes.

Why Nosocomial Environments Are Accommodating

Pseudomonas aeruginosa has a deserved reputation as a relentlessnosocomial pathogen due to its natural resistance to many chemicals and abilityto tolerate sparse conditions. It has a preference for moist environments thataccommodate nosocomial-type interactions such as water-based therapies andtreatments, especially respiratory support. Besides the wide availability ofwater in hospitals, clinics, and nursing homes, intense antibiotic pressures andability to use a wide variety of compounds as energy sources (disinfectants,handwash creams, distilled water), nosocomial environments are quite attractivewhen 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 thespeed of other bacteria are often bench-marked. The flagella does not gentlywave back and forth. Rather, it spins like a propeller on a shaft. Pseudomonasplies its trade as either a permanently attached "sessile" formembedded in a slimy matrix ("biofilm") with other bacteria, or as a"plaktonic" form (an independent, free-swimming cell). Most clinicalisolates produce a characteristic green or blue-green pigment, pyocyanin, havinga distinctive fruity odor and considered toxic to human tissue. Sources fromhighly colonized clinical specimens often have a green-blue discoloration andcan fluoresce.²

Always Found in Cystic Fibrosis (CF)

Initially, young CF patients are colonized with Pseudomonas aeruginosastrains typically found in the environment. These bacteria produce a greenpigment when grown on agar plates in the laboratory. Once established within thelungs, the colonies take on a mucoid appearance_³. Thegrowth of the organisms in a biofilm allows the production of a unique slime(alginate) coating. The biofilm coating makes the organism resistant toopsonization (antibody attachment) and phagocytosis. The mechanism is purelymechanical 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 (attachmentorganelles). Although the infection is never cleared, Pseudomonas sepsisis very rare in cystic fibrosis. Victims usually survive to the third decade oflife.

The organism does not adhere to intact epithelium but has specific receptorsfor damaged respiratory epithelium (present in cystic fibrosis), which isuncovered by a bacterial enzyme. Tissue injury may also play a role incolonization of the respiratory tract, since P. aeruginosa will adhere totracheal epithelial cells of mice infected with influenza virus but not tonormal tracheal epithelium.⁴ This is also thought to be an importantstep in Pseudomonas keratitis (eye infections) and urinary tractinfections. As if it were not sticky enough, P. aeruginosa virulence hasrecently been shown to be controlled by a complex regulatory circuit involvingmultiple bacterial cell-to-cell signaling systems that allow the bacteria toproduce virulence factors in a coordinated, cell-density dependent manner.⁵

Natural Resistance Explained

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

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

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

Manufactured Virulence Properties^7,8

Pseudomonas must deploy several compounds including elastase and analkaline protease to obtain scarce nutrients during infection, damaging hosttissue in the process. One such essential metabolite is phosphate. Theorganism's phospholipase digests host cell membranes for whatever it needs.Pseudomonal elastase is elaborated to get molecular iron, which is very tightlybound, in the body. Elastase is crucial to invasion because strains without itremain local colonizers. This elastase also wrecks specific anti-pseudomonalantibodies, collagen, fibrin and lyses fibronectin to expose receptors forbacterial attachment on the respiratory epithelium. Pseudomonal infection in theeye can be disastrous. Remember, there are no white cells to oppose infection.Together with bacterial alkaline protease, the ground substance of the corneaand other supporting structures composed of fibrin and elastin are destroyedquickly. Endophthalmitis due to Pseudomonas is a medical emergency. Themost common risk is direct invasion after cataract surgery. Not only aresystemic antibiotics required but also, injections into the eyeball (anteriorchamber) are necessary. This is very tricky, as only certain antibiotics can beused and those that are must be carefully titered or the retina is irreversiblyburned.

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

As a leading cause of nosocomial pneumonias, risk factors include mechanicalventilation, setting in the ICU, cancer with neutropenia, and depleted immuneresources. Urinary tract infections are usually related to instrumentation, orkidney stones. These infections have a tendency to persist and the organism maybe 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 hospitalenvironment. Thus, chemoprophylaxis must be guided by the localsusceptibility patterns. Generally, however, piperacillin and ceftazidime arethe most active penicillin and cephalosporin. Monotherapy with these antibioticsis not recommended because when used alone the organism produces huge amounts ofbeta lactamase.¹⁰ Beta lactamase inhibitors such as sulbactam,clavulanate, or tazobactam are worthless against Pseudomonas and shouldnot be used. Currently, alteration of penicillin-binding proteins is a rarecause of resistance in Pseudomonas.

The most consistently active aminoglycosides are tobramycin and Amikacin.

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

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

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

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 inPreoperative-Preparation Formula

For a complete list of references click here