Pseudomonas aeruginosa Disease: Clinical Aspects

P . aeruginosa DISEASE:CLINICAL ASPECTS

MANIFESTATIONS

P. aeruginosa can produce any of the opportunistic extraintestinal infections caused by members of the Enterobacteriaceae. Burn, wound, urinary tract, skin, eye, ear, and respiratory infections all occur and may progress to bacteremia. P. aeruginosa is also one of the most common causes of infection in environmentally contaminated wounds (eg, osteomyelitis after compound fractures or nail puncture wounds of the foot).

P. aeruginosa pneumonia is a rapid, destructive, infection particularly in patients withgranulocytopenia. It is associated with alveolar necrosis, vascular invasion, infarcts, and bacteremia. Pulmonary infection in CF patients is quite different; it is a chronic infection that alternates between a state of colonization and more overt bronchitis or pneumonia. Although the more aggressive features of Pseudomonas infection in the immunocompro-mised are not common, the infection is still serious enough to be a leading cause of death in CF patients.

P. aeruginosa is also a common cause of otitis externa, including “swimmer’s ear”and a rare but life-threatening “malignant” otitis externa seen in patients with diabetes. Folliculitis of the skin may follow soaking in inadequately decontaminated hot tubs that can become heavily contaminated with the organism. The organism can cause conjunctivitis, keratitis, or endophthalmitis when introduced into the eye by trauma or contaminated medication or contact lens solution. Keratitis can progress rapidly and destroy the cornea within 24 to 48 hours. In some cases of P. aeruginosa bacteremia, cutaneous papules develop that progress to black, necrotic ulcers. It is calledecthymagangrenosum and is the result of direct invasion and destruction of blood vessel wallsby the organism.

DIAGNOSIS

P. aeruginosa is readily grown in culture. The combination of characteristic oxidase posi-tive colonies, pyocyanin production and the ability to grow at 42°C is sufficient to distin-guish P. aeruginosa from other Pseudomonas species. No other diagnostic modalities are in routine use.

TREATMENT

Of the pathogenic bacteria, P. aeruginosa is the organism most consistently resistant to many antimicrobics. This is primarily due to the porins that restrict their entry to the periplasmic space. P. aeruginosa strains are regularly resistant to penicillin, ampi-cillin, cephalothin, tetracycline, chloramphenicol, sulfonamides, and the earlier aminoglycosides (streptomycin, kanamycin). Much effort has been directed toward the development of antimicrobics with anti-Pseudomonas activity. The newer aminoglyco-sides — gentamicin, tobramycin, and amikacin — are all active against most strains despite the presence of mutational and plasmid-mediated resistance. Carbenicillin and ticarcillin are active and can be given in high doses, but plasmid-mediated resistance and permeability mutations occur more frequently than with the aminoglycosides. The most prized feature of some of the third-generation cephalosporins (ceftazidime, cefepime, cefoperazone), carbapenems (imipenem, meropenem), and monobactams (aztreonam) is their activity against Pseudomonas. In general, urinary infections may be treated with a single drug, but more serious systemic P. aeruginosa infections are usually treated with a combination of an anti-Pseudomonas -lactam antimicrobic and an aminoglycoside, particularly in neutropenic patients. Ciprofloxacin is also used in treatment of such cases. In all instances, susceptibility must be confirmed by in vitro tests.

The treatment of P. aeruginosa in CF presents special problems because most of the effective antimicrobics are only given intravenously. There is a reluctance to hospitalize in many patients, and oral agents are used instead. There is less experience with their effi-cacy under these conditions, and the chronic nature of CF is a set-up for development of resistance during therapy. This has already been seen with ciprofloxacin and aztreonam. Aerosolized tobramycin has also been used in some CF patients, with some evidence of clinical improvement.

PREVENTION

Vaccines incorporating somatic antigens from multiple P. aeruginosa serotypes have been developed and proved immunogenic in humans. The primary candidates for such preparations are patients with burn injuries, CF, or immunosuppression. Although some protection has been demonstrated, these preparations are still experimental.