notes by dr. Claudio Italiano
A patient comes to us with intense dyspnea, fever and cyanosis We make the
first investigations of the case, including a hemogas because the patient
ventilates badly a thoracic rx, after having set a broad-spectrum antibiotic
therapy for ventilator pneumonia (in fact the patient was recently intubated due
to severe respiratory failure), we proceed to an "induced sputum" culture
examination (see pneumonia_2). With apprehension, the culture examination report
diagnoses a serious infection with pseudomonas aeruginosa, fortunately still
sensitive, to the antibiogram, to various antibiotics, including quinolones,
aminoglycosides, ampicillin-tazobactam. Another very serious case presented to
us was that of a 65-year-old woman with a neurogenic bladder carrying a
permanent bladder catheter with an antibiotic-resistant pseudomonas aeruginosa
infection. The patient, despite intensive care and repeated admissions over the
course of three years, finally went into sepsis and from there the exitus was
inevitable after a short time.
Pseudomonas are gram-negative aerobic rods that prefer moist environments and
are relatively non-invasive, yet they can cause serious and often fatal
infections when the host's defense mechanisms are damaged or deficient. Each
species is different in its pathogenic properties, each causes quite different
types of infection and expresses its invasiveness as a result of different
defects in defense of the host; but with every pseudomonas the environmental
source is usually water, moist soil or a contaminated medical device, an
infusion or an injection. Pseudomonas are divided into five main groups based on
RNA homology.
Group RNA I Fluorescent group: P. aeruginosa P.fluerescens P. putida
Non-fluorescent group: P.stutzeri, P. alcaligenes, P. pseudoalcaligenes
Group II RNA: P. (Burkholderia) mallei, P. (Burkholderia) pseudomallei P. (Barkolderia)
cepacia, P. pickettii
Group III RNA: P. acidovorans, P. testosterones
Group IV RNA: P. diminuta, P. vesicularis
RNA of group V: Xanthomonas
Most human infections are caused by members of groups I, II and V. To be
highlighted for their pathogenic characteristics we have:
Pseudomonas pseudomallei (etiologic agent of melioidosis), Pseudomonas malici (etiologic
agent of morva), Pseudomonas aeruginosa (mainly causing bacteremia, endocarditis,
pneumonia, keratitis and urinary tract infections), Pseudomonas cepacia,
Pseudomonas pickettii and Xanthomonas (Pseudomonas) maltophilia ( which causes
bacteraemia, pseudobacteremia, endocarditis and urinary tract infections). Many
pseudomonas have been reclassified according to genetic characteristics.
Pseudomonas maltophėlia (group RNA 1) has become Xanthomonas maltophilia over a
decade ago and is now known as Stenotrophomonas maltophėlia; and recently,
organisms with group II RNA have become malicum Burkholderia, pseudomallei,
cepacia and pickettii respectively.
The term aeruginosa derives from piocianina, a blue-green fluorescent pigment produced by many, but not all, strains. Like other pseudomonas, P. aeruginosa grows well in many moist environments with limited nutrients. Found in soil, water and plants, it can also be a normal commensal of humans and animals. Man's colonization usually takes place in humid areas, such as the perineum, the ear canal, the armpits and the distal alimentary canal. It is commonly found in the aerators of faucets, siphons, ice machines and hospital kitchens; it can become a particular problem when it contaminates drugs or medical instruments kept in a wet environment, such as fans, endoscopes, pressure monitoring tools. It can withstand many disinfectants and is resistant to a wide range of antimicrobial agents. In the non-hospital environment, infections have been related to growth in swimming pools, contact lens solutions and radiator tubes. P. aeruginosa infection has become, by far, a result of advances in medical technology. In recent years, P. aeruginosa was the fourth leading cause of gram-negative nosocomial bacteraemia and the fourth most frequently isolated nosocomial pathogen, having caused around 10% of all hospital acquired infections worldwide.
 Chest x-ray of a patient suffering from pseudomonas aeruginosa pneumonia. Note the cottony aspect of multiple thickenings |
The most frequent infections caused by P. aeruginosa include:
a) nosocomial bacteraemia
b) nosocomial pneumonia,
c) nosocomial infections of the urinary tract
d) infection of the surgical wound
e) endocarditis related to intravenous drug abuse or the placement of artificial
heart valves,
f) respiratory infection associated with cystic fibrosis,
g) external otitis (including "malignant" external otitis),
h) corneal keratitis
i) spinal osteomyelitis in heroin addicts
j) cases of meningitis or cerebral abscess.
A frequent source of bacteraemia in the granulocytopenic patient is infection of
the alimentary canal, especially perianal cellulitis, colon lesions and rarely
pharyngitis or esophagitis. Finally, extensive burns are frequently colonized by
P. aeruginosa with progression to sepsis and death.
P. aeruginosa almost never causes infections in the absence of:
1) damage to a normal defense mechanism of the host (eg, mucous damage of the
alimentary duct induced by chemotherapy, granulocytopenia or extended third
degree burns),
2) deficiency or alteration of a defensive mechanism (eg, progressive changes in
the respiratory tract in cystic fibrosis) or
3) the by-pass of a normal defensive mechanism (eg, assisted breathing devices
directly inoculate the organisms in the bronchial tree while simultaneously
limiting or damaging the mucociliary mechanism, or the insertion of a permanent
urinary catheter that bypasses the normal bladder clearance mechanisms).
Therefore, P. aeruginosa infections are seen more frequently in patients with a
permanently inserted urinary catheter; in neutropenic ones for pathology,
chemotherapy or both; in those suffering from cystic fibrosis; in those with
extended thermal injuries; in those admitted to intensive care units who are
subject to a series of invasive procedures; in those with head injuries, which
allow direct entry or through a pressure monitoring device; in those with
artificial heart valves or endocardium damaged by contaminants present in
illicit drugs; and in those that have undergone extensive surgery, particularly
when there is a consequent need for open drainage. Pulmonary infection can occur
in the advanced stages of AIDS as an acute or torpid, often recurrent infection
that mimics those seen in cystic fibrosis.
There are three distinct stages of Pseudomonas infection:
a) stage I - bacterial adhesion and colonization;
b) stage II - local invasion;
c) stage III - blood dissemination and systemic disease.
Stage I is a prerequisite of stage II which, in turn, is a prerequisite of stage III, although obviously not all colonized individuals present with a local invasion and not all those with local invasion progress towards systemic dissemination or disease. The three stages are related to the fact that this organism is both invasive and toxic. Colonization in a normal person is relatively infrequent in most locations, although, over time, a fair portion of the population will exhibit transient colonization of the colon. However, hospitalized patients have a much higher rate of colonization, related in part to host defense changes, as discussed above, and in part to the frequency of hospital reservoirs of this organism. Furthermore, broad-spectrum antimicrobial therapy suppresses the rest of normal microbial flora, especially along the alimentary canal. This suppression reduces the normal bodily mechanisms of colonization resistance so that an organism such as P. aeruginosa or other antibiotic-resistant species used can rapidly colonize multiple sites in high concentrations. Additional specific factors further predispose to colonization by P. aeruginosa. These include the presence of pili for adhesion, scourges for motility and exogenous products, especially proteinases. The loss of fibronectin induced by secretory proteases by epithelial cells is also involved during serious illness (between hospitalized or non-hospitalized patients), which in turn allows pili or fimbriae to adhere to the oral, pharyngeal or respiratory epithelium. Therefore, the pathologies that determine a protease production are the main modulators of the oral flora. This colonization can in turn be accentuated by local damage caused by an endotracheal tube, viral infection (such as influenza), thermal damage or antitumor chemotherapy and is exacerbated by antibiotics. P. aeruginosa, in some paintings, can defend itself from defense mechanisms by producing a glycocalyx, a carbohydrate-based structure produced by many bacteria, which, surrounding the cell and anchoring it to epithelial cells or invasive devices such as an intravascular or urinary catheter, protects the bacterium from antibodies, from the complement, from polymorphonuclear leukocytes or from macrophages. After colonization, P. aeruginosa can proceed to invasion, in appropriate situations, through the effect of extracellular enzymes (toxins). These include elastase, alkaline protease, cytotoxins and hemolysins. Elastase and protease have been shown to cause necrotising lesions in the skin, lungs and cornea, together with small necrotic lesions of the vessels, which cause the characteristic skin finding known as "ectima gangrenoso". It is this combination of local necrosis and destruction of blood vessels the essence of the initial invasive characteristic of P. aeruginosa.
Cytotoxin damages granulocytes and has a role in the early stages of adult respiratory distress syndrome. Hemolysins are also cytotoxic, therefore capable of amplifying tissue invasion. The third stage of Pseudomonas infection, dissemination and systemic disease, is due, in the first case, to the same extracellular enzymes and, in the second case, to the liposaccharide of Pseudomonas (endotoxin) and to exotoxin A. As in other septicemia caused by gram-negative bacilli, endotoxin is thought to be a critical factor in the activation of coagulation and fibrinolytic systems, kinins and complement, along with the production of prostaglandins and leukotrienes, the release of beta-endorphins and the release cytokines, including tumor necrosis factor. For some interaction of many or all of these factors there is fever, shock, disseminated intravascular coagulation (which is relatively rare in Pseudomonas bacteremia) and adult respiratory distress syndrome. The other factor, exotoxin A, is similar to diphtheria toxin as it inhibits protein synthesis. It causes local necrosis and encourages bacterial dissemination in the systemic circulation and its ability to provoke, in itself, shock in animal models has been demonstrated. Pseudomonas bacteremia occurs more frequently in cancer patients who are receiving intensive chemotherapy capable of causing granulocytopenia, in patients with extensive third-degree burns and, occasionally, in patients with hypocomplementemia or immuno-globulin deficiency. It is also a frequent cause of bacteremia in patients with urinary catheterization. Sepsis in burn patients originates from the skin damaged by heat. Bacteremia in neutropenic patients originates primarily from the distal intestinal tract and occasionally from primary pneumonia. Granulocytopenic patients become frequently colonized and almost all colonized patients will develop bacteraemia if a deep granulocytopenia (<100 cell / microl) persists for more than a few days. The ectima gangrenoso, usually a sign of fairly advanced systemic infection, is not pathognomonic but very frequently associated with P. aeruginosa bacteraemia. These skin lesions are first small and hardened and then rapidly enlarge, become necrotic and can ulcerate. It has been seen in histological sections that bacteria invade small arteries and veins, with a minimal characteristic of inflammation. Histologically similar injuries can be seen in the lungs as a secondary consequence of bacteraemia. The mortality of sepsis from Pseudomonas is high, as the two critical factors affecting survival are the underlying state of host defenses and the speed of empirical antibiotic therapy. The presence of septic shock and / or evidence of septic metastasis when antibiotic initiation is usually considered to be unfavorable prognostic signs, but in reality represents another measure of late institution of therapy. These procedures are performed for the most part under antibiotic coverage which is mandatory in those patients in whom an incomplete drainage is performed. Patients are normally sedated with diazepam or midazolam, sometimes combined with either fentanyl or pethidine, and should be monitored by oximetry. The supervision of an anesthesiologist can sometimes be necessary