Pseudomonas Infection

Pseudomonas aeruginosa

Although P aeruginosa is a common human saprophyte, it rarely causes disease in healthy persons. Most infections with this organism occur in compromised hosts. Examples of compromising conditions include disrupted physical barriers to bacterial invasion (eg, burn injuries, intravenous [IV] lines, urinary catheters, dialysis catheters, endotracheal tubes) and dysfunctional immune mechanisms, such as those that occur in neonates and in individuals with cystic fibrosis (CF), acquired immunodeficiency syndrome (AIDS), neutropenia, complement deficiency, hypogammaglobulinemia, and iatrogenic immunosuppression.

The complete sequence of the genome of P aeruginosa strain, PAO1, is noted for its large size and diverse metabolic capacity. The pathogenesis of this organism is multifactorial and involves various toxins and proteases (eg, exotoxin A, lecithinase) and the glycocalyx "slime." P aeruginosa is both invasive and toxigenic. The three stages of Pseudomonas infections are (1) bacterial attachment and colonization, (2) local infection, and (3) bloodstream dissemination and systemic disease.

Efflux systems are thought to contribute to antimicrobial resistance in P aeruginosa; thus, efflux pump inhibitors are thought to be useful in reducing the invasiveness and antimicrobial resistance of P aeruginosa and may be promising as anti-infectious agents. The genome annotation is continually updated, and the database functionality is being expanded to facilitate accelerated discovery of P aeruginosa drug targets and vaccine candidates.

Pseudomonal infection, as described by Pollack, occurs in three stages: (1) bacterial attachment and colonization, followed by (2) local invasion and (3) dissemination and systemic disease.

In healthy children, disease is primarily limited to the first two stages (as in diseases such as otitis externa, urinary tract infections (UTIs), dermatitis, cellulitis, and osteomyelitis), although case reports describe bacteremia, sepsis, and gastrointestinal (GI) infections in previously healthy children.

In immunocompromised hosts, including neonates, infection can progress rapidly through the three stages and cause pneumonia, endocarditis, peritonitis, meningitis, ecthyma gangrenosum (EG), bacteremia, and overwhelming septicemia.

Pseudomonas cepacia

In 1949, Walter Burkholder of Cornell University first described P cepacia (now known as Burkholderia cepacia) as the phytopathogen responsible for the bacterial rot of onions. In the 1950s, B cepacia was first reported as a human pathogen that causes endocarditis. Subsequently, the organism has been found in numerous catheter-associated UTIs, wound infections, and IV catheter–associated bacteremias.

In 1971, this species was reported as the causative organism of foot rot in US troops on swamp training exercises in northern Florida; it also was isolated from troops serving in Vietnam's Mekong Delta. In 1972, B cepacia was discovered as an opportunistic human pathogen in a patient with CF. Since then, B cepacia has emerged with increasing frequency as the cause of pneumonia and septicemia in children with CF.

Pseudomonas mallei

P mallei (now known as Burkholderia mallei) causes glanders, a serious infectious disease of animals (primarily horses, although it has also been isolated in donkeys, mules, goats, dogs, and cats). Transmission is believed to occur through direct contact. Glanders transmission to humans is rare and presumably occurs through inoculation of broken skin or the nasal mucosa with contaminated discharges. Manifestation of the disease in humans varies, ranging from an acute localized suppurative infection, acute pulmonary infection, or acute septicemic infection to chronic suppurative infection. Fulminant disease with multiple organ system involvement occurs with septicemic infection.

Pseudomonas pseudomallei

P pseudomallei (now known as Burkholderia pseudomallei) causes melioidosis (from the Greek, "resemblance to distemper of asses"). Melioidosis, also called Whitmore disease, clinically and pathologically resembles glanders but has an entirely different epidemiologic profile from B mallei. It occurs in many animals (eg, sheep, goats, horses, swine, cattle, dogs, cats). Transmission is believed to occur through direct contact, although inhalation reportedly is a possible route of acquisition. Since the first description of the disease from North Queensland, Australia, in 1962, melioidosis has spread to Southeast Asia.

B pseudomallei is found in contaminated water and soil. The pathogen spreads to humans and animals through direct contact with a contaminated source. In otherwise healthy hosts, disease manifestations range from acute to chronic local suppurative infections to septicemia with multiple abscesses in all organs of the body.

Individuals who are immunocompromised tend to be vulnerable to pseudomonal infections. People who work with animals or who are exposed to contaminated soil and water in certain endemic areas are at risk for glanders and melioidosis.

Risk factors and predisposing conditions include the following.

Bacteremia

Conditions that predispose disease progress to bacteremia include hematologic malignancies, immunoglobulin deficiency states, neutropenia, diabetes mellitus (DM), organ transplantation, severe burns, diffuse dermatitis, and AIDS. Other predisposing factors include cancer chemotherapy that causes neutropenia or ulceration of the respiratory and gastrointestinal (GI) tracts, steroid administration, antibiotic therapy, placement of intravenous (IV) lines, urinary tract instrumentation or catheterization, surgery, trauma, and premature birth. IV lines should be inserted under sterile conditions and should be changed per hospital protocol.

Bone infections

Individuals at risk include persons who abuse IV drugs; postsurgical patients; patients with penetrating trauma, diabetes, peripheral vascular disease, or rheumatoid arthritis; older persons; and patients with chronic debilitation.

Skin infections

Pseudomonas species do not grow on dry skin. Patients who are exposed to moisture have an increased risk for skin infections. Separation of the cuticle from the nail plate (ie, onycholysis) leaves the space between the proximal nail fold and nail plate exposed to bacteria, which results in chronic paronychia and pseudomonal toe web.

The contamination of healthcare workers' protective gear has been linked to transmission of multidrug-resistant P aeruginosa (17.4%; 95% confidence interval, 9.4-25.4%). People who wear heavy wet boots also are more likely to develop pseudomonal toe web infections. Children have a higher risk than adults of developing folliculitis from exposure to Pseudomonas organisms in a contaminated whirlpool, home hot tub, water slide, physiotherapy pool, or contaminated loofah sponge.

CNS infections

Pseudomonal meningitis occurs in patients who have had recent neurosurgical procedures or who are immunocompromised. A brain abscess, however, rarely occurs in an immunocompromised host; the risk of brain abscess is higher is patients with otitis media or paranasal sinusitis, and it is a common etiology in older patients.

Predisposing factors for neonatal meningitis include maternal infections (especially urinary tract and uterine infections) and the following obstetrical risk factors:

• Prolonged and premature rupture of membranes

• Birth trauma

• Prematurity

• Low birth weight (ie, < 2500 g)

• Congenital anomalies

• Perinatal hypoxia or asphyxia

Neonates whose treatment included cardiopulmonary resuscitation and monitoring, prolonged ventilatory support, and/or multiple IV line insertions are also at risk.

Ear infections

Malignant otitis externa occurs in patients who are older and in patients who have diabetes or AIDS.

Eye infections

Contact lens wearers have an increased risk of developing gram-negative infections, including pseudomonal infections. Pseudomonal endophthalmitis may result from penetrating trauma, intraocular surgery, posterior perforation of a corneal ulcer, or hematogenous spread from another primary site.

GI infections

Pseudomonal infections can affect every portion of the gastrointestinal (GI) tract. The disease is often underestimated; the highest risk is among young infants, children, and persons with hematologic malignancies and chemotherapy-induced neutropenia. Additionally, colonization of the GI tract is an important portal of entry for pseudomonal bacteremia in patients who are neutropenic. The spectrum of disease can range from very mild symptoms to severe NEC with significant morbidity and mortality.

Genitourinary infections

The greatest risk is among patients who are hospitalized and patients who had urinary tract catheterization, instrumentation, or surgery. These infections can involve the urinary tract through an ascending infection or through bacteremic spread and are a frequent source of bacteremia.

An obvious preventive measure is to avoid catheterization. If this is not possible, the catheter should be removed as soon as possible. Catheters should be inserted aseptically under sterile conditions. The most important hygienic measure is handwashing by healthcare personnel. If a urinary catheter is required for long periods, it should be replaced per hospital protocol. Catheters and the area around the urethra should be cleaned with soap and water daily and after each bowel movement. Prophylactic use of antibiotics is not recommended because it leads to the emergence of resistant strains of bacteria.

Cardiovascular infections

The risk of endocarditis among individuals who abuse IV drugs (ie, 2-5% per person-year) is much greater than the risk for patients with rheumatic heart disease or prosthetic valves. A case report describes an infant with human immunodeficiency virus (HIV) who developed pseudomonal pericarditis and tamponade, which suggests pericardial effusions are more common in patients with HIV infection than previously recognized.

Respiratory tract infections

Lower respiratory tract infections with P aeruginosa occur almost exclusively in persons with compromised respiratory systems, especially patients with CF. Most bacteremic pseudomonal pneumonia occurs in patients with malignancies and immunodeficiencies.

A randomized controlled trial by Eklöf et al found that recurrent P aeruginosa infection was common in patients with chronic obstructive pulmonary disease. Throughout a 1-year period, P aeruginosa was identified in the airways of 83% of patients in the study.

Primary nonbacteremic pseudomonal pneumonia occurs in patients who have colonization of Pseudomonas organisms. It can be hospital-associated in the ICU setting and is associated with positive-pressure ventilation and endotracheal tubes. The pneumonia may be primary or may follow aspiration of the organism from the upper respiratory tract, especially in patients on mechanical ventilation. Alternatively, it may occur as a result of bacteremic spread to the lungs.

Because Pseudomonas species can multiply in nebulizer fluid, proper cleaning, sterilization, and disinfection of reusable equipment are required.

United States statistics

According to data from the Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance System, P aeruginosa can be rated as follows:

• Number 1 cause of intensive care unit (ICU)–related pneumonia

• Number 1 cause of osteochondritis

• Number 2-ranked gram-negative organism, responsible for 9% of all nosocomial bacterial and fungal isolates

• Number 2 cause of nosocomial pneumonia

• Number 3-ranked isolate in hospital-acquired UTIs

• Number 4 cause of surgical site infections and of hospital-acquired gram-negative rod bacteremia

• Number 5 hospital pathogen

• Number 8-ranked bloodstream isolate

• Causes 10% of nosocomial infections

• Most common bacteria isolated from mild-to-severe form of external otitis and chronic suppurative otitis media

• Most common gram-negative organism isolated from corneal ulcers and endocarditis

• Frequent cause of contact lens–associated keratitis

• Second most frequent cause of brain abscess and meningitis in patients with cancer

• Third most common cause of recurrent UTIs complicated by obstruction, catheters, or stones

• Fifth most common cause of recurrent UTIs in schoolchildren

B cepacia is associated with increased illness and death in patients with CF. In several small focal hospital outbreaks that involved patients who did not have CF, the typical cause was a contaminated common source (eg, IV solutions, disinfectant preparations). In the early 1980s, the organism emerged as a major threat, causing superinfection in as many as 40% of patients in some CF centers. Approximately 35% of patients infected with B cepacia develop accelerated pulmonary deterioration or fulminant necrotizing pneumonia with rapidly fatal bacteremia, a condition also referred to as cepacia syndrome.

A retrospective analysis of the US National Hospital Discharge Surveys from 1996-2010 found that the incidence of P aeruginosa septicemia declined from 6.5 per 10,000 in 1996 to 3.1 per 10,000 in 2001 and then increased to 6.5 per 10,000 in 2010.

In the United States, infection with an extensively drug-resistant strain of P aeruginosa was linked to contaminated bottles of artificial tears. The 2023 outbreak led to loss of vision in 14 patients, surgical removal of the eyeball in 4 patients, and 4 deaths.

International statistics

Numerous B cepacia epidemics associated with CF have been reported. A particular highly transmissible strain, which spread epidemically within and between CF centers in Western Europe and the United States, carries the cblA gene. This cblA strain has spread across Canada and now has been isolated in 50% of CF centers in the United Kingdom. Another strain of B cepacia has been found in CF centers in 4 regions of France. The propensity for transmission evidently varies among strains; most strains are not involved in epidemics but appear to be acquired independently without evidence of epidemic transmission.

A study reviewed German neonatal intensive care unit (NICU) surveillance data  to quantify the pathogen-specific risk of a bloodstream infection in preterm infants after an index case of the same pathogen in the NICU. The relative risk was markedly elevated for Serratia and P aeruginosa. With only 38 cases of P aeruginosa out of the 2004 culture-positive infections, the relative risk was still high at 64.5.

Glanders caused by B mallei has not occurred in the United States since the 1940s, although it remains common in domestic animals in Africa, Asia, the Middle East, Central America, and South America.

Melioidosis caused by B pseudomallei is endemic in Southeast Asia. The highest concentrations of cases occur in Vietnam, Cambodia, Laos, Thailand, Malaysia, Myanmar (formerly Burma), and northern Australia. Melioidosis also occurs in the South Pacific, Africa, India, and the Middle East. The B pseudomallei organism is so prevalent that it is often found as a contaminant.

Race-, sex-, and age-related demographics

Black men reportedly have an increased incidence of pseudomonal endocarditis.

Sternoarticular pyarthrosis caused by pseudomonal infections occurs in young men, particularly those who engage in intravenous (IV) drug abuse. Some studies cite a 5.4:1 male-to-female ratio of P aeruginosa endocarditis.

Infants younger than 1 year have direct vascular communication with the epiphysis across the growth plate, allowing direct spread of pseudomonal osteomyelitis from the metaphysis to the epiphysis and, eventually, the joint. In older children, the growth plate provides a barrier; thus, the epiphysis and the joints seldom are involved.

Children have a higher predilection than adults for pseudomonal osteochondritis infections following puncture wounds of the foot. Older patients are more susceptible to pseudomonal bone and joint infections. Children have a higher likelihood of developing pseudomonal folliculitis than adults.

In patients with CF, the prevalence of pseudomonal pneumonia ranges from 21% in those younger than 1 year to more than 80% in those older than 19 years. The increasing longevity of patients with CF has created a significant shift in the proportion of adult patients with CF; their proportion increased 4-fold, from 8% in 1969 to 33% in 1990.

The site of infection determines the patient's prognosis.

For patients with septicemia or bacteremia, the following factors are associated with an unfavorable outcome:

• Persistent neutropenia

• Presence of septic shock

• Inappropriate antibiotic therapy

• Persistent infection in lung, skin, or soft tissue

• Unidentified source of infection

• Renal failure

• Metastatic foci

• Rapidly progressing underlying disease

• An absolute granulocyte count less than 100 cells/μL

For patients with cardiovascular (CV) infections, the following factors are associated with poor prognosis:

• Delayed initiation of antibiotic therapy

• Age older than 30 years

• Presence of left-sided disease with persistent fever, despite 2 weeks' therapy

• Mural vegetations

• Systemic embolization

• Mixed infections involving both P aeruginosa and S aureus

Morbidity/mortality

Pseudomonal infections (eg, bacteremic pneumonia, sepsis, burn wound infections, meningitis) are associated with an extremely high mortality rate.

Monocular blindness is primarily due to bacterial keratitis, the causes of which include pseudomonal infection. Colonization with B cepacia has been associated with increased morbidity and mortality in patients who are immunocompromised, especially those with CF.

Untreated glanders and melioidosis bloodstream infections are usually fatal within 7-10 days. P aeruginosa bacteremia has an estimated mortality rate exceeding 50% and is associated with fatality rates higher than those associated with other gram-negative bacteremic infections.

According to the CDC, multidrug-resistant P aeruginosa infections resulted in approximately 2700 deaths in the United States in 2017.

Pseudomonal pneumonia, especially the bacteremic type, is associated with mortality that typically occurs 3-4 days after the first signs or symptoms of pulmonary or extrapulmonary infection. Ventilator-associated pneumonia (VAP) caused by P aeruginosa is associated with higher mortality rates (estimated to be as high as 68%) than VAPs caused by other infectious organisms. The mortality rate is high for the septicemic form of EG and is approximately 15% for the nonsepticemic form of the disease.

Complications

Complications depend on the site of infection. Chronic glanders may lead to multiple abscesses within the muscles of the arms and legs or in the spleen or liver. Chronic melioidosis can involve several organs (eg, joints, viscera, lymph nodes, skin, brain, liver, lung, bones, spleen).

Pseudomonal skin infections can be destructive and lead to necrotizing fasciitis, compartment syndrome, necrosis, gangrene, and loss of an extremity.

Pseudomonal ear infections may lead to sinusitis, mastoiditis, perichondritis, osteomyelitis of the temporal bones, and thrombosis. Cases of central nervous system (CNS) involvement (especially seventh-cranial-nerve palsy) have been reported, although these cases are rare.

CNS infections may lead to seizures, increased intracranial pressure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Pseudomonal eye infections can lead to corneal perforations and ulcerations, endophthalmitis, and orbital cellulitis.

GI infections may lead to cecal perforation, peritonitis, typhlitis, and severe electrolyte and fluid disturbances.

Untreated endocarditis may lead to congestive heart failure, conduction heart block, cerebritis, mycotic aneurysms, or brain abscess. Septic emboli to the lung and spleen also have been reported. Pneumonia may require endotracheal intubation for respiratory support.

Septicemia may lead to septic shock and death.

Always emphasize good hygiene, universal precautions, and safe sexual practices.