Pseudomonas aeruginosa: Well-qualified for the New Age

February 1, 2001

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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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