Etiology

Pseudomonas aeruginosa is a gram-negative rod and is a strict aerobe. It can multiply in a great variety of environments that contain minimal amounts of organic compounds. Strains from clinical specimens do not ferment lactose, are oxidase positive, and may produce β-hemolysis on blood agar. Many produce pigments including pyocyanin, pyoverdin, and pyorubrin that diffuse into and color the surrounding medium. Strains of Pseudomonas can be differentiated for epidemiologic purposes by serologic, phage, and pyocin typing and by genome restriction fragment length polymorphisms using pulsed-field gel electrophoresis.

Epidemiology

P. aeruginosa is a classic opportunist. It rarely causes disease in people who do not have a predisposing risk factor. Compromised host defense mechanisms owing to trauma, neutropenia, mucositis, immunosuppression, or impaired mucociliary transport explain the predominant role of this organism in producing opportunistic infections. The rate of P. aeruginosa bacteremia in children is 3.8/1,000 patients over 10 yr, with a 20% mortality rate; rates vary according to the prevalent underlying diseases. P. aeruginosa and other pseudomonads frequently enter the hospital environment on the clothes, skin, or shoes of patients or hospital personnel, with plants or vegetables brought into the hospital, and in the gastrointestinal tracts of patients. Colonization of any moist or liquid substance may ensue; the organisms may be found growing in any water reservoir, including distilled water, and in hospital kitchens and laundries, some antiseptic solutions, and equipment used for respiratory therapy. Colonization of skin, throat, stool, and nasal mucosa of patients is low at admission to the hospital but increases to as high as 50-70% with prolonged hospitalization and with the use of broad-spectrum antibiotics, chemotherapy, mechanical ventilation, and urinary catheters. Patients’ intestinal microbial flora may be altered by the use of broad-spectrum antibiotics, which reduces resistance to colonization and permits P. aeruginosa in the environment to populate the gastrointestinal tract. Intestinal mucosal breakdown associated with medications, especially cytotoxic agents, and nosocomial enteritis may provide a pathway by which P. aeruginosa spreads to the lymphatics or bloodstream.

Pathology

The pathologic manifestations of Pseudomonas infections depend on the site and type of infection. Due to its elaboration of toxins and invasive factors, the organism can often be seen invading blood vessels and causing vascular necrosis. In some infections there is spread through tissues with necrosis and microabscess formation. In patients with cystic fibrosis, focal and diffuse bronchitis/bronchiolitis leading to bronchiolitis obliterans has been reported.

Pathogenesis

Invasiveness of P. aeruginosa is mediated by a host of virulence factors. Bacterial attachment is facilitated by pili that adhere to epithelium damaged by prior injury or infection. Extracellular proteins, proteases, elastases, and cytotoxin disrupt cell membranes, and in response, host-produced cytokines cause capillary vascular permeability and induce an inflammatory response. Dissemination and bloodstream invasion follow extension of local tissue damage and are facilitated by the antiphagocytic properties of endotoxin, the exopolysaccharide, and protease cleavage of immunoglobulin G. P. aeruginosa also produces numerous exotoxins, including exotoxin A, which causes local necrosis and facilitates systemic bacterial invasion. P. aeruginosa possesses a type III secretion system (TTSS) that is important for virulence in multiple animal models. This needle structure inserts into host cell membranes and allows secretion of exotoxins directly into host cells. P. aeruginosa strains with the gene encoding the TTSS dependent phospholipase ExoU have been associated with increased mortality compared with ExoU-negative strains in retrospective studies of patients with P. aeruginosa ventilator-associated pneumonia. The host responds to infection by producing antibodies to Pseudomonas exotoxin A and endotoxin.

In addition to acute infection, P. aeruginosa is also capable of chronic persistence thought to be due in part to the formation of biofilms, organized communities of bacteria encased in an extracellular matrix that protects the organisms from the host immune response and the effects of antibiotics. Biofilm formation requires pilus-mediated attachment to a surface, proliferation of the organism, and production of exopolysaccharide as the main component of the extracellular matrix. A mature biofilm is resistant to many antimicrobials and difficult to eradicate with current therapies.

Clinical Manifestations

Most clinical patterns (Table 197-1) are related to opportunistic infections (Chapter 171) or are associated with shunts and indwelling catheters (Chapter 172). P. aeruginosa may be introduced into a minor wound of a healthy person as a secondary invader, and cellulitis and a localized abscess that exudes green or blue pus may follow. The characteristic skin lesions of Pseudomonas, ecthyma gangrenosum, whether caused by direct inoculation or metastatic secondary to septicemia, begin as pink macules and progress to hemorrhagic nodules and eventually to ulcers with ecchymotic and gangrenous centers with eschar formation, surrounded by an intense red areola.

Table 197-1 PSEUDOMONAS AERUGINOSA INFECTIONS

Outbreaks of dermatitis and urinary tract infections caused by P. aeruginosa have been reported in healthy persons after use of pools or hot tubs. Skin lesions of folliculitis develop several hours to 2 days after contact with these water sources. Skin lesions may be erythematous, macular, papular, or pustular. Illness may vary from a few scattered lesions to extensive truncal involvement. In some children, malaise, fever, vomiting, sore throat, conjunctivitis, rhinitis, and swollen breasts may be associated with dermal lesions.

Pseudomonads other than P. aeruginosa rarely cause disease in healthy children, but pneumonia and abscesses due to Burkholderia cepacia, otitis media due to P. putrefaciens or P. stutzeri, abscesses due to P. fluorescens, and cellulitis and septicemia and osteomyelitis due to S. maltophilia have been reported. Septicemia and endocarditis due to S. maltophilia have also been associated with abuse of intravenous drugs.