Pseudomonas Infection

In 1882, Gessard first discovered Pseudomonas, a strictly aerobic, gram-negative bacterium of relatively low virulence. The organism is ubiquitous, with a predilection to moist environments, primarily as waterborne and soilborne organisms. Pseudomonal species have been found in soil, water, plants, and animals; Pseudomonas aeruginosa colonization reportedly occurs in more than 50% of humans, and P aeruginosa is the most common pseudomonal species.

Pseudomonas is a clinically significant and opportunistic pathogen, often causing nosocomial infections. In addition to causing serious and often life-threatening diseases, these organisms exhibit innate resistance to many antibiotics and can develop new resistance after exposure to antimicrobial agents. Some pseudomonal species that previously were considered the causative agents of old diseases now are being reexamined for their potential use as biological warfare agents.

The current classification of the genus Pseudomonas is divided into 5 groups based on ribosomal RNA (rRNA)/DNA homology. Of the more than 20 pseudomonal species that have been found from human clinical specimens, the following 4 representative organisms are discussed in this article:

• P aeruginosa (homology group I)

• Burkholderia (Pseudomonas) cepacia (group II)

• Burkholderia (Pseudomonas) pseudomallei (group II)

• Burkholderia (Pseudomonas) mallei (group II)

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),[1] 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 3 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 new 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 3 stages: (1) bacterial attachment and colonization, followed by (2) local invasion and (3) dissemination and systemic disease.[2]

In healthy children, disease is primarily limited to the first 2 stages (as in diseases such as otitis externa, urinary tract infections (UTIs), dermatitis, cellulitis, and osteomyelitis), although recent case reports describe bacteremia, sepsis, and GI infections in previously healthy children.

In immunocompromised hosts, including neonates, infection can progress rapidly through the 3 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.[3] 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.

Frequency

United States

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 U.S. National Hospital Discharge Surveys from 1996-2010 found that Pseudomonas aeruginosa septicemia incidence 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.[4]

International

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 NICU surveillance data on more than 44,000 infants below 1500 g birth weight with the aim to quantify the pathogen-specific risk of a blood stream infection in preterm infants after an index case of the same pathogen in the NICU department. The relative risk was markedly elevated for Serratia and Pseudomonas aeruginosa.  With only 38 cases of Pseudomonas aeruginosa out of the 2004 culture-positive infections, the relative risk was still high at 64.5.[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.

Mortality/Morbidity

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. 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.

Race

Black men reportedly have an increased incidence of pseudomonal endocarditis.

Sex

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

Age

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 to 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. Endocarditis occurs most often in young (mean age 29 y) black men.

In patients with CF, 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 has increased 4-fold, from 8% in 1969 to 33% in 1990.

Pseudomonas aeruginosa is so ubiquitous in the hospital environment that distinguishing infection from colonization is often difficult. Furthermore, symptoms are often identical to those observed in other gram-negative infections. As a result, clinical evidence of infection should accompany any culture of the organism at a potential infection site. P aeruginosa reportedly emits a characteristic sweet odor. P aeruginosa is responsible for a broad spectrum of disease, including the following types of infections:

• AIDS-related infections

• Bacteremia and sepsis

  • Fever is often the initial symptom. Some patients may also present with tachypnea or tachycardia.

  • Hypotension and shock may develop.

  • Jaundice may occur.

  • Suspect pseudomonal bacteremia in individuals who are immunocompromised (including neonates), who have an extended hospitalization, who have received prolonged antibiotic administration or multiple antibiotics, or who have indwelling catheters.

• Febrile neutropenia

• Bone and joint infection (eg, osteochondritis, osteomyelitis, pyarthrosis)

  • Infections of the bones and joints typically result from hematogenous spread from another primary site. This may occur in individuals who have used intravenous (IV) drugs and who have associated urinary tract infections (UTIs) or pelvic infections, in those with penetrating trauma, in postsurgical patients, in those with primary soft tissue infection, and in patients with diabetes or rheumatoid disease.

  • Patients (especially children) may present with osteochondritis after a puncture of the foot through a sneaker or tennis shoe.

  • The sternoclavicular and sacroiliac joints, vertebra, and symphysis pubis are typically involved in individuals who have used IV drugs.

  • Postsurgical patients tend to develop infections in the long bones, especially patients who underwent internal fixation for open fractures. Vertebral osteomyelitis is occasionally observed as a complication of UTI and genitourinary (GU) surgery or instrumentation. Because of vascular insufficiency in the lower extremities of patients with diabetes, they may develop osteomyelitis of the foot. Patients with rheumatoid disease may develop infections in large synovial joints.

  • Children who present with osteochondritis typically experience pain and edema 3-4 days following a puncture wound, only to have symptoms recur or worsen later. Symptoms usually persist more than 1 week without any systemic signs or fever.

  • Sternoarticular pyarthrosis, often seen in individuals who abuse IV drugs, is usually associated with endocarditis, although the primary site is often indiscernible. Joint involvement is typically monoarticular. Complaints include fever, pain, and restricted movement of the shoulder, with limited-to-severe anterior chest pain over the affected joint.

  • Patients with vertebral osteomyelitis can present with pain that persists from weeks to months, especially in the neck or back region. Fever and constitutional symptoms are relatively rare.

  • Chronic contiguous osteomyelitis commonly occurs after a compound fracture or as a complication of surgery for closed fracture of the long bones. It occasionally occurs after a foot puncture wound, as an extension of infection of ischemic ulcers in patients with peripheral vascular disease, following cardiac surgery, and as a complication of peripheral neuropathy associated with pressure necrosis of skin and soft tissue.

• Skin and soft tissue infections (eg, burn wound sepsis, dermatitis, ecthyma gangrenosum [EG], pyoderma, cellulitis, hot tub folliculitis, necrotizing fasciitis, chronic paronychia)

  • Do not confuse EG with pyoderma gangrenosum or streptococcal ecthyma; EG is a rare but pathognomonic form of pseudomonal infection. Although EG is often due to Pseudomonas, case reports indicate that the same frequency is associated with non-Pseudomonas EG (ie, Fusarium, Klebsiella).

  • EG in patients without neutropenia is very rare, as is nonbacteremic EG cases. However, nonsepticemic cases occur in patients without immunosuppression or neutropenia or following antibiotic therapy.

  • Pseudomonal burn wound infections occur with systemic involvement (eg, bacteremia, fever, hypothermia, disorientation, obtundation, hypotension, oliguria, ileus, leukopenia).

  • Chronic paronychia slowly evolves and initially presents with tenderness and mild swelling about the proximal and lateral nail folds.

  • Pseudomonal toe web infections are distinctive clinical entities often misdiagnosed as tinea pedis. Dried exudate or a green stain (caused by pyoverdin) may be found on socks or toenails.

  • Pseudomonal folliculitis presents as cutaneous lesions any time from 8 hours to 5 days or more (mean incubation period is 48 h) after using a contaminated whirlpool, home hot tub, water slide, physiotherapy pool, or contaminated loofah sponge. Malaise and fatigue may occur during initial days of the eruption. Fever (uncommon) is low grade when present.

  • Localized cellulitis can occur as a secondary infection of tinea of the toe webs or groin; from bedsores, stasis ulcers, or burns; in grafted areas; or under the foreskin of the penis. Maceration or occlusion of these skin lesions leads to secondary infection. Deep erosions and tissue necrosis may occur before the condition is diagnosed correctly. Severe pain is highly characteristic of an evolving infection.

• CNS infection (eg, brain abscess, meningitis)

  • CNS infections are more common among patients who are immunocompromised or in patients who recently have undergone a neurosurgical procedure.

  • P aeruginosa has been isolated with increasing frequency in older patients with meningitis, but pseudomonal infections rarely cause neonatal meningitis.

  • Clinical symptoms are indistinguishable from other forms of bacterial meningitis. Symptoms can be nonspecific (eg, headache, fever, nausea, vomiting, disorientation, lethargy, stiff neck).

  • Often, CNS involvement is due to a complication from another site (eg, malignant external otitis). Although CNS complications are rare, they are often fatal. These include meningitis, brain abscess, and dural sinus thrombophlebitis.

• Ear infections (eg, otitis media, chronic suppurative otitis media, otitis externa, malignant external otitis)

  • Involvement of the ear can present as a mild, superficial, and often self-limited infection (eg, swimmer ear) or as malignant otitis externa. Early stages of swimmer's ear are characterized by erythema, edema, accumulation of debris in the canal, and, sometimes, pain. As the disease progresses, the erythema radiates into the pinna, and purulent material partly obstructs the ear, exuding from the canal.

  • More than 95% of cases of malignant external otitis are caused by P aeruginosa. Clinical presentation starts with a history of nonresolving otitis externa, especially in patients who have diabetes or AIDS. Patients present with severe ear pain (otalgia) that worsens at night and a purulent discharge (otorrhea). The pinna may be involved. As the disease progresses, osteomyelitis of the base of the skull and temporomandibular joint osteomyelitis can occur.

  • Children with malignant external otitis have a higher incidence of facial palsy because of underdevelopment of their mastoid process and because of the more medial location of the fissures of Santorini, placing the facial nerve closer to the ear canal. The glossopharyngeal, vagal, spinal accessory, and hypoglossal nerves can be involved. The trigeminal and abducens nerves are rarely affected, and optic nerve involvement has been reported. Involvement of the olfactory, oculomotor, and trochlear nerves has not been reported.

• Eye infections (eg, endophthalmitis, keratitis, ophthalmia neonatorum, blepharoconjunctivitis, scleral abscess, orbital cellulitis)

  • Although pseudomonal eye infections are often associated with hydrophilic contact lens wear, infections have also been reported in patients who do not wear contact lenses.

  • Pseudomonal keratitis can present as a rapidly developing, necrotic, grayish stromal infiltrate in a bed of epithelial injury and surrounding edema. Disease progression varies but can rapidly progress and involve the entire cornea within 48 hours, leading to perforation. Fever and systemic symptoms are usually absent.

  • Pseudomonal corneal ulcers may lead to rapid loss of visual function and are considered a medical emergency.

  • Pseudomonal endophthalmitis progresses more rapidly than other bacterial infections. Clinical features may include pain, conjunctival hyperemia, chemosis, lid edema, decreased visual acuity, hypopyon, or severe anterior uveitis with involvement of the vitreous and panophthalmitis.

• GI infections (eg, epidemic diarrhea, necrotizing enterocolitis (NEC), typhlitis, rectal abscess, Shanghai fever)

  • Presentation is indistinguishable from other bacteremic GI infections.

  • Neonates may present with NEC.

  • Those with hematological malignancies may develop typhlitis or a rectal abscess.

  • Epidemics of pseudomonal diarrheal diseases occur in children.

• GU infections (eg, epididymitis, prostatitis, urethritis, UTIs): The clinical presentation of pseudomonal UTIs is indistinguishable from other bacterial UTIs.

• Cardiovascular (CV) infections (eg, endocarditis, pericarditis, cardiac tamponade)

  • Pseudomonal infectious endocarditis (IE) affects normal and abnormal valves on both sides of the heart, resulting in valve destruction and heart failure. Biventricular and multiple valve infections are common in pseudomonal IE.

  • This organism has been isolated in patients with IE who abuse IV drugs, specifically pentazocine and tripelennamine (ie, "Ts" and "blues"). Individuals who abuse pentazocine and tripelennamine have a propensity for right-sided IE.

  • Fever is the most common symptom

• Respiratory infections (eg, primary or nonbacteremic, bacteremic, colonization, and nosocomial pneumonia, lower respiratory tract infections of cystic fibrosis [CF], ventilator-associated pneumonia [VAP])

  • Symptoms in patients with CF vary from frequent upper respiratory tract infections (URTIs) and a persistent cough after each bout to recurrent episodes of pneumonia, with or without a lingering cough between exacerbations.

  • Initial age of initiation of Pseudomonas is affected by genotype functional class but not in lifestyle changes (eg, breastfeeding, cigarette smoke).[6] Most patients eventually develop a chronic and increasingly severe productive cough, decreased appetite, weight loss, and diminished activity, particularly during exacerbation.

  • Evidence suggests that chronic P aeruginosa lung infection plays a role in bronchiectasis development. Other symptoms include wheezing, tachypnea, and irritability. Low-grade fever often accompanies exacerbations; high-grade fever is uncommon.

• Bacteremic pseudomonal pneumonia usually occurs in patients with malignancies (especially malignancies involving the hematopoietic system), in patients who are neutropenic as a result of chemotherapy, and in children and adults with AIDS.

• Primary or nonbacteremic pneumonia results from aspiration of Pseudomonas species from upper respiratory structures that have been colonized. The disease process is fulminant, usually fatal, and characterized clinically by fever, chills, severe dyspnea, copious and purulent-productive cough, cyanosis, apprehension, mental confusion, and systemic toxicity.

• Glanders

  • Glanders also occurs in stages, with symptoms depending on the organism's route of infection. Generalized symptoms include fever, muscle aches, chest pain, muscle tightness, and headache. Additional symptoms may include excessive eye tearing, light sensitivity, and diarrhea.

  • Types of infections associated with glanders include the following:

    • Localized infections: From a cut or scratch in the skin, a localized infection with ulceration develops within 1-5 days at the site where the bacteria penetrated the body. Lymph nodes may also be swollen. Infections involving the mucous membranes in the eyes, nose, and respiratory tract cause increased mucus production from the respective sites.

    • Pulmonary infections: These may cause pneumonia, pulmonary abscesses, and pleural effusion. Radiography reveals localized infection in the lobes of the lungs.

    • Bloodstream infections: A bloodstream infection associated with glanders is usually fatal within 7-10 days without any treatment.

    • Chronic infections: The chronic form of glanders involves multiple abscesses within the muscles of the arms and legs or in the spleen or liver.

• Melioidosis

  • Melioidosis stages include acute, localized, and chronic infections. The incubation period is not clearly defined but may range from 2 days to years.

  • Stages of melioidosis include the following:

    • Acute: Characterized by a localized nodule, caused by inoculation of the bacteria through a break in the skin, which can lead to secondary lymphangitis, regional lymphadenitis, fever, and myalgia. Acute melioidosis may rapidly progress to infect the bloodstream.

    • Pulmonary infection: The clinical picture ranges from mild bronchitis to severe pneumonia. Onset of pulmonary melioidosis is usually associated with high fever, headache, anorexia, and general myalgia. Chest pain is also common. The hallmark is a nonproductive or productive cough with normal sputum.

    • Acute bloodstream infection: Patients with underlying illness (eg, HIV, renal failure, diabetes) are predisposed to this form of the disease, which usually results in septic shock. Symptoms of bloodstream infection vary, depending on the original infection site, but generally include respiratory distress, severe headache, fever, diarrhea, development of pus-filled lesions on the skin, myalgia, and disorientation. The infection typically has short duration, although abscesses form throughout the body.

    • Chronic suppurative infection: Chronic melioidosis is an infection involving several organs, typically including the joints, viscera, lymph nodes, skin, brain, liver, lung, bones, and spleen. Chronic apical lung disease often resembles tuberculosis (TB).

The clinical presentation of pseudomonal infections depends on the site of infection and is often indistinguishable from other gram-negative organisms.

Glanders and melioidosis infections have different stages with varied clinical presentations.

• Bacteremia and sepsis

  • Clinical presentation is often identical to other gram-negative organisms.

  • Fever is usually present, except in very young or premature infants. Fever is often accompanied by tachycardia and tachypnea.

  • Patients appear toxic and may present with apprehension, disorientation, or obtundation.

  • Signs of shock, including hypotension, azotemia, or acute renal failure, may be observed.

  • Respiratory failure occurs in the presence of bacteremic pseudomonal pneumonia or in conjunction with airway restrictive disease syndrome.

  • Jaundice appears to occur more often than in other forms of gram-negative sepsis, but disseminated intravascular coagulation (DIC) is relatively uncommon.

  • Skin lesions may be an important distinguishing feature of pseudomonal bacteremia, especially typical EG lesions.

  • A diffuse maculopapular eruption, primarily on the trunk, has also been reported in early stages of pseudomonal sepsis. Metastatic abscesses of the extremities and fingertips occasionally manifest later in the course of the disease.

• Bone infections

  • Because pseudomonal infections have a predilection for fibrocartilaginous joints of the axial skeleton, determining whether arthritis preceded or resulted from the infection is difficult. The disease process is usually indolent, and it is not as destructive and does not progress as rapidly as other infections.

  • Pseudomonal osteochondritis presents with a superficial area of cellulitis on the plantar surface of the foot; deep palpation reveals slight tenderness.

  • Physical signs of sternoarticular pyarthrosis include erythema, edema, and tenderness over the affected joint, and restricted range of motion of the ipsilateral shoulder.

  • Physical signs in patients with vertebral osteomyelitis include local tenderness and decreased range of motion of the spine. Neurologic deficits, which tend to be mild, occur in approximately 15% of cases.

  • Differentiate between patients with infection of the pubic symphysis and those with osteitis pubis.

• Skin infections

  • The hallmark lesions resulting from pseudomonal wound infections are multifocal, with dark-brown to black or violaceous discoloration of the burn eschar, and are accompanied by edema and hemorrhagic necrosis.

  • EG lesions are multiple noncontiguous ulcers or solitary ulcers. These lesions begin as isolated, red, purpuric macules that become vesicular, indurated, and, eventually, bullous or pustular. The bullae may be hemorrhagic but contain little if any pus. Lesions can remain localized or, more often, can extend over several centimeters. The central area of these lesions becomes hemorrhagic and necrotic, and then the lesion denudes to form a gangrenous ulcer with a gray-black eschar and erythematous halo. Although lesions can occur anywhere, they occur mainly in the gluteal and perineal regions (57%), the extremities (30%), the trunk (6%), and the face (6%). These skin lesions slowly heal. Patients with septicemia have associated signs that include elevated temperatures, chills, hypotension, tachycardia, and tachypnea.

  • In chronic paronychia, the skin around the nail becomes pale, red, painful, and swollen. A small amount of pus may occasionally be expressed from beneath the proximal nail fold. The nail plate turns green-black, which is characteristic of pseudomonal infections. The conditions cause little discomfort or inflammation. This presentation is often confused with subungual hematoma.

  • A Pseudomonas -infected toe web presents as a thick, white, macerated scale with a green discoloration in the toe webs. The most consistent clinical feature is soggy wet toe webs and adjacent skin. In the mildest form of pseudomonal infection in the toe web, the affected tissue is damp, softened, boggy, and white. The second, third, and fourth toe webs are the most common sites of initial involvement. Severe forms may progress to denuded skin and profuse, serous, or purulent material.

  • Pseudomonal folliculitis presents with a few to more than 50 urticarial plaques that measure 0.5-3 cm in diameter, with a central papule or pustule on all skin surfaces other than the head. The rash can be a polymorphous eruption or a mixture of follicular, maculopapular, vesicular, or pustular lesions. These lesions often are pruritic; most clear in 7-10 days, leaving round spots of red-brown postinflammatory hyperpigmentation. However, some patients may have recurrent crops of lesions over an extended period of 3 months (see the image below).

    Erythematous papulopustules of pseudomonas folliculitis. Courtesy of Mark Welch, MD.

  • Pseudomonal cellulitis presents with a dusky red–to–bluish green skin discoloration and purulent discharge. The typical fruity or mouselike odor has been linked to pseudomonal infection. Vesicles and pustules may occur as satellite lesions. The eruption may spread to cover wide areas and cause systemic manifestations.

• CNS infections

  • Clinical signs of pseudomonal meningitis are indistinguishable from bacterial meningitis, except for the hallmark EG skin lesions.

  • Signs of CNS infections in neonates are often nonspecific and subtle (eg, fever, hypothermia, lethargy, seizures, irritability, bulging fontanel, respiratory distress, feeding intolerance, vomiting).

  • In children and adults, physical presentations of bacterial meningitis can include fever, photophobia, nuchal rigidity, lethargy, disorientation, coma, and ataxia.

• Ear infections

  • Involvement of the ear can be mild to severe.

  • Pain can be elicited by traction of the tragus or pinna, although pain becomes persistent as the disease progresses.

  • Typical presentations include erythema, edema, pain, and warmth; however, many individuals who are immunocompromised may manifest no signs.

• Eye infections

  • Ring ulcers can reportedly develop.

  • The corneal epithelium peripheral to the primary ulcer typically develops a diffuse, gray, ground-glass appearance. The ulcer is also associated with marked anterior chamber reaction and hypopyon formation.

  • Extensive keratitis can extend to the limbus and produce an infectious scleritis.

  • Diffuse epithelial disease is usually associated with hydrophilic contact lens wear.

• GI infections

  • Pseudomonal infections can affect the entire alimentary canal, from the oropharynx to the rectum. The clinical presentation is often indolent, except for occasional NEC (in premature infants), typhlitis, hemorrhagic and necrotic ulcers, and abscesses in infants, older children, and adults. Skin manifestations can occur.

  • NEC presents with irritability, signs of dehydration, vomiting, diarrhea, dehydration, abdominal distension, and signs of peritonitis.

  • Diarrheal epidemics can present with mild-to-severe diarrhea, signs of dehydration, and vascular collapse. Pseudomonal infections have also been causally associated with Shanghai fever, a syndrome associated with diarrhea or constipation, rash, and fever persisting as long as 1-2 weeks.

  • The pathological changes observed in patients with typhlitis range from localized lesions in the cecum to necrosis and gangrene with perforation and peritonitis.

  • Although rare, rectal abscesses can spread to the scrotum and penis, leading to Fournier gangrene.

• GU infections

  • Presentations of pseudomonal UTIs are generally indistinguishable from other bacterial UTIs.

  • One rare exception is development of ulcerative lesions of the bladder mucosa, ureters, and renal pelvis, resulting in sloughing of vesical membrane in the urine.

  • Another rare sequela is the development of multiple renal infarcts.

• CV infections

  • Endocarditis can present with a cardiac murmur, depending on the valve affected.

  • Skin and soft tissue manifestations (eg, Osler nodes, Janeway lesions) are rare in both right-sided and left-sided diseases.

• Respiratory infections

  • Physical signs in patients with CF include evidence of undernutrition, increased anteroposterior diameter, retractions, cyanosis, inspiratory and expiratory wheezing, rhonchi, localized or generalized moist rales, abdominal distention, and clubbing of fingers and toes.

  • A rapid progression from pulmonary vascular congestion to pulmonary edema to necrotizing bronchopneumonia occurs in patients with bacteremic pseudomonal infections. Physical signs that can be expected include retraction, crackles, rhonchi, dulled reflexes, fever, and cyanosis.

  • Primary nonbacteremic pseudomonal infections can present as a diffuse bronchopneumonia, which is typically bilateral. Small pleural effusions are common, empyema is rare, and a pattern of lobar consolidation is sometimes noted. Correlating physical signs include crackles, rhonchi, and dulled reflexes at bases.

  • 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.[7]

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 hematological 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 GI tracts, steroid administration, antibiotic therapy, placement of 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%).[8] People who wear heavy wet boots also are more likely to develop pseudomonal toe web infections. Children have 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 of neonatal meningitis include maternal infections (especially UTI and uterine infections) and the following obstetrical risk factors:

  • Prolonged and premature rupture of membranes

  • Birth trauma

  • Prematurity

  • Low birth weight (ie, < 2500 g)

 

See the list below:

• Congenital anomalies

• Perinatal hypoxia or asphyxia

• Neonates whose treatment included cardiopulmonary resuscitation and monitoring, prolonged ventilatory support, and/or multiple IV line insertions

• 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 GI tract. The disease is often underestimated; the highest risk is among young infants, children, and persons with hematological 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.

• GU 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 health care 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.

• CV 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 than previously recognized.[9]

• Respiratory 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.

  • 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.

  • Pseudomonas risk should be considered and appropriate empiric antibiotics should be started in accordance to Core Measure for Pneumonia.

Pseudomonas aeruginosa and other Pseudomonas organisms are aerobic, nonfermentative, nonenterobacterial gram-negative bacilli. Obtain 2 sets of blood cultures (ie, aerobic and anaerobic bottles) from different sites before starting empiric antibiotics. The following laboratory results are helpful to confirm a pseudomonal infection:

• CBC counts revealing leukocytosis with a left shift and bandemia, which indicates possible presence of toxic granulations or vacuoles

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, which may be elevated in infection

• Metabolic profile revealing any electrolyte abnormalities, degree of dehydration, and worsening renal function

The following additional studies may be indicated, depending on the site of infection:

• Culture of the purulent discharge helps diagnose suppurative otitis media or malignant otitis externa.

• Corneal scrapings and culture may reveal pseudomonal involvement.

• Culture of vegetations from patients with pseudomonal infectious endocarditis (IE) reveals high quantities of the organisms, although diagnosis is usually confirmed by a repeated blood culture.

• Sputum Gram stain and culture may be indicated to evaluate for respiratory infection. This is especially recommended in children who may be predisposed to such infections.

• Blood gas levels may reveal hypoxemia, with or without hypercarbia.

• Wound and burn cultures can be helpful to identify pseudomonal infections.

• Urinalysis with culture and sensitivity is helpful when evaluating for urinary tract infection (UTI). Although rare, sloughing of vesical membrane in the urine can indicate complications of pseudomonal infections.

• Obtain stool cultures in patients with diarrhea. Note, however, that pseudomonal organisms produce no toxins.

Diagnosis of glanders can be confirmed by isolating B mallei from blood, sputum, urine, or skin lesions. No serologic tests are available. Diagnosis of melioidosis can be confirmed by isolating B pseudomallei from the blood, urine, sputum, or skin lesions. Detecting antibodies to the bacteria in the blood is another method.

See the list below:

• Chest radiography

  • Patients with cystic fibrosis (CF) may have a small heart, depressed diaphragm, and increased anteroposterior chest diameter. Chest radiography may also reveal cyst formation, mucus plugging of dilated bronchi, generalized bronchiectasis, patchy atelectasis, peribronchial thickening, overaeration, or extensive peribronchial infiltration.

  • The classic presentation of bacteremic pseudomonal pneumonia includes rapid progression of radiographic findings. Chest radiography performed within 48-72 hours after initial fever onset reveals parenchymal involvement with interstitial and alveolar infiltrates. Cavitation appears after 48 hours.

  • Typical findings include (1) poorly-defined, hemorrhagic, often subpleural, nodular areas with a small central area of necrosis and (2) multiple, 2-mm to 15-mm, necrotic, umbilicated nodules with hemorrhagic parenchyma, representing the pulmonary component of an ecthyma gangrenosum (EG) skin lesion.

  • The typical progression of disease is from pulmonary vascular congestion to pulmonary edema to necrotizing bronchopneumonia.

  • Radiographs of patients with primary nonbacteremic pneumonia are similar to those from patients whose pneumonia is caused by Staphylococcus aureus. Among the common features are a diffuse bronchopneumonia (usually bilateral with distinctive nodular infiltrates with small areas of radiolucency) and pleural effusions; empyema or lobar consolidation is occasionally observed.

• CT scanning

  • A CT scan of the head may reveal a brain abscess. A CT scan of the surrounding soft tissue and osseous lesions is recommended in patients with malignant otitis externa to help define the intracranial and extracranial extent of disease.

  • Perform a CT scan of the abdomen as part of the workup for endocarditis, especially left-sided disease. Complications such as splenic abscesses require splenectomy before valvular replacement.

  • A CT scan of the chest is not usually indicated, except when respiratory failure requires better definition of chest involvement. With left-sided endocarditis, a CT scan of the chest also can reveal septic pulmonary emboli as a complication.

  • A CT scan of soft tissue and bone of skin infections may be required to exclude an abscess formation or osteomyelitis.

• MRI

  • Consider MRI of the head to evaluate a patient with a brain abscess. MRI of the head in a patient with left-sided endocarditis may show cerebritis and mycotic aneurysm.

  • A CT scan or MRI of the surrounding tissue of the site of infection may be needed to delineate abscess formation.

• Other studies

  • Echocardiography (ECHO) may reveal vegetations in endocarditis. However, because the yield is low, consider a transesophageal ECHO or repeat ECHO for highly suspicious cases.

  • Bone radiography or a nuclear study is helpful in diagnosing patients with suspected osteomyelitis.

  • Renal ultrasound may be helpful to evaluate patients with a suspected obstruction or abscess formation complicating a UTI.

  • A gallium WBC scan may help determine the extent of infection.

See the list below:

• To evaluate eye infections to determine the degree of corneal involvement, perform fluorescein staining and slit-lamp examination of the cornea.

• Patients who develop septic pulmonary emboli as a complication may require a ventilation-perfusion scan.

• A Wood light examination of a pseudomonal toe web reveals a green-white fluorescence from the elaboration of pyoverdin.

See the list below:

• Needle biopsy or aspiration of the joint, possibly with fluoroscopic guidance, can be helpful in identifying the infectious organism. An open biopsy may be necessary, depending on disease extent.

• Lumbar puncture is indicated when CNS involvement is suspected. Workup of neonatal sepsis should include lumbar puncture, if indicated.

• Cardiac catheterization may reveal valvular involvement or vegetations.

• Quantitative cultures from bronchoalveolar lavage obtained by bronchoscopy helps distinguish infection from colonization.

• Thoracentesis may be indicated for patients who have pleural effusion.

See the list below:

• Histological findings of EG include edema, epidermal necrosis, and gram-negative rods on tissue gram stain.

• Few neutrophils in the sparse inflammatory infiltrate can also be seen.

Antimicrobial agents are needed to treat Pseudomonas infections. Two antipseudomonal drug combination therapy (eg, a beta-lactam antibiotic with an aminoglycoside) is usually recommended for the initial empiric treatment of a pseudomonal infection, especially for patients with neutropenia, bacteremia, sepsis, severe upper respiratory infections (URIs), or abscess formation. The choice of antibiotic also depends on the site and extent of infection and on local resistance patterns.[10] Reports of more resistant strains of Pseudomonas organisms to the currently used antimicrobials are causing much concern.

B cepacia has grown resistant to aminoglycosides, antipseudomonal penicillins, and most beta-lactam agents. Some strains are variably susceptible to third-generation cephalosporins, ciprofloxacin, trimethoprim-sulfamethoxazole, ampicillin-sulbactam, chloramphenicol, or meropenem.

Because human cases of glanders are rare, limited information is available about antibiotic treatment of the organism in humans. Sulfadiazine has been effective in experimental treatments of animals and humans. B mallei organisms are usually sensitive to tetracyclines, ciprofloxacin, streptomycin, novobiocin, gentamicin, imipenem, ceftazidime, and sulfonamides. Resistance to chloramphenicol has been reported. Treatment duration is often prolonged, from 1-2 months, often combined with surgical drainage.

Ceftazidime alone or in combination with either trimethoprim-sulfamethoxazole or amoxicillin clavulanate is the therapy of choice for B pseudomallei. The organism is usually sensitive to imipenem, penicillin, doxycycline, azlocillin, ceftazidime, ticarcillin-clavulanic acid, and ceftriaxone. Initiate treatment early in the course of the disease. The organism is resistant to ciprofloxacin and aztreonam. Treatment is often prolonged, from 3-12 months, with the longest duration of therapy used for chronic extrapulmonary disease.

Pseudomonas vaccines are also currently used to reduce infection risks in patients with cystic fibrosis (CF) and are still under investigation. Pseudomonas aeruginosa infections include the following:

• Bacteremia

  • Empiric antibiotics are often started before the organism is identified.

  • Whether single-drug or combination therapy is most effective in patients who have bacteremia and neutropenia is debated. The author is unaware of any prospective randomized comparison between monotherapy and combination drug therapy for patients with pseudomonal bacteremia. Duration of treatment is at least 2 weeks.

• Bone and skin infections

  • A 4-week course of aminoglycoside antibiotics is often successful for managing vertebral osteomyelitis.

  • Sternoarticular pyarthrosis has been managed effectively with aminoglycoside and antipseudomonal penicillin if administered for at least 6 weeks.

  • Patients with osteomyelitis of the pubic symphysis require treatment for at least 4 weeks with an antipseudomonal penicillin and aminoglycoside combination. Surgical intervention is not usually indicated.

  • Patients with osteochondritis require medical and surgical treatment. Parenteral administration of 1-2 antipseudomonal agents is recommended before surgical debridement. The recommended regimen continues postsurgical treatment for 1-2 additional weeks with oral (PO) ciprofloxacin.

  • Chronic contiguous pseudomonal osteomyelitis requires 4-6 weeks of combination therapy, in addition to surgical debridement.

  • Burn wound sepsis management requires early intervention with daily wound inspection and systemic antibiotic combination regimens. Monotherapy is not indicated.

  • Management of pseudomonal cellulitis includes the use of PO antibiotic for 7-10 days; this often resolves a localized infection.

  • Pseudomonal toe web infections require initial debridement with applications of silver nitrate or 5% acetic acid to the toe webs and the dorsal and planter areas. Following this initial treatment, apply a topical antibiotic, silver sulfadiazine cream, or Castellani paint until infection resolves. PO quinolone effectively reduces the duration of infection.

  • Pseudomonal folliculitis is often self-limited; treatment may require only application of silver sulfadiazine cream or 5% acetic acid wet compresses for 20 minutes 2-4 times daily with topical antibiotics.

• CNS infections

  • Ceftazidime, cefepime, or meropenem are the antibiotics of choice because of their high CNS penetration. Initially, consider double coverage with an aminoglycoside for patients with adequate renal function. Aztreonam, ciprofloxacin, or levofloxacin are indicated for patients with renal failure and those allergic to beta-lactam. Imipenem-cilastatin should be avoided because of the risk of seizures. Intrathecal treatment should also be considered. Treatment duration should be at least 2 weeks.

  • Antibiotics can be used in the initial treatment of brain abscesses that are multiple, small (ie, < 2 cm), poorly distributed, or relatively difficult to access. Antibiotic therapy duration depends on the speed of abscess shrinkage, but therapy usually lasts 2-6 weeks.

• Ear and eye infections

  • Otitis media in at-risk populations should be treated with antipseudomonal agents for at least 10 days.

  • Chronic suppurative otitis media requires daily aural toilet and treatment with antibiotics (eg, ceftazidime, mezlocillin, ciprofloxacin), and often surgical treatment.

  • Otitis externa can be treated with local care using an acetic acid compress and daily aural cleaning.

  • Management of malignant externa otitis should be aggressive and involve both medical and surgical therapies. The conventional therapy (ie, an aminoglycoside and a beta-lactam agent with antipseudomonal activity) is needed for at least 4 weeks to treat localized infections and 6-8 weeks or longer to treat extensive disease. Monotherapy using ceftazidime intravenously (IV), cefepime IV, or ciprofloxacin PO for 6 weeks has been reported effective.

  • If gram-negative rods are isolated from the Gram stain of an eye infection, immediately start a combined topical and subconjunctival (or subtenon) therapy of aminoglycoside antibiotics. Aminoglycoside solution (not ointment) must be applied to the affected eye every 30-60 minutes. Subconjunctival therapy is needed for the first 3 days of treatment. Total duration of therapy is at least 1 week. An alternative therapy uses a quinolone antibiotic solution. The addition of parental or PO antipseudomonal antibiotics also has been beneficial.

  • Pseudomonal endophthalmitis requires immediate antibiotic therapy, using aminoglycoside and antipseudomonal penicillin administered via a parenteral and subconjunctival, topical, or intraocular route. Therapy duration depends on the clinical improvement.

• GI and GU infections

  • Treat GI manifestations of pseudomonal infection with antibiotic therapy for patients with severe localized or systemic infections.

  • The treatment modality for urinary tract infection (UTI) depends on the presence of sepsis, degree of chronicity, potential sites of persistent infection, and local antibiotic susceptibility. Ideally, indwelling urinary catheters should be removed. If the catheter cannot be removed, consider treating only symptomatic episodes or exacerbations because it is not feasible to totally eradicate the organism. Aminoglycosides and quinolones remain the agents of choice.

• Cardiovascular (CV) and respiratory infections

  • To treat endocarditis, administer an antipseudomonal beta-lactam with high-dose aminoglycoside for approximately 6 weeks.

  • According to the criteria used in France to select antibiotics to treat VAP, the following 2 risk factors must be considered: (1) administration of broad-spectrum antibiotics in the previous 15 days and (2) mechanical ventilation for fewer than 7 days or for 7 or more days. The extended factors predict the involvement of multiresistant nosocomial P aeruginosa, suggesting administration of carbapenems to those who have undergone mechanical ventilation of 7 or more days and who have been exposed to antibiotics in the prior 15 days.

  • The role of antibiotic prophylaxis or chronic suppression of respiratory pseudomonal infections in patients with CF is controversial. Among the promising treatment plans are intermittent aerosolization of antibiotics to patients with CF who have established pseudomonal lung infections.

  • Choices for empiric antibiotic treatment in patients with a history of Pseudomonas infection requires review of previous culture sensitivity.

  • More widely accepted is the treatment of children with pseudomonal infections by using fluoroquinolone, especially children with previous therapeutic failure or resistance to multiple other antibiotics.[11] Treatment often continues until symptoms resolve (ie, 1-2 wk).

  • Inhalation of mucolytic and hydrating agents, postural drainage, and chest physiotherapy often are therapies used together. Bronchial lavage also has been used to remove respiratory secretions.

  • A Cochrane review looked at 60 clinical trials to examine the effectiveness of antibiotic treatment in cystic fibrosis patients with early Pseudomonas aeruginosa infection. The study concluded that nebulized antibiotics by themselves or along with oral antibiotics were better than no treatment at all and that infection may be eradicated for up to two years. However, there is insufficient evidence that antibiotic treatment decreases mortality and morbidity or improves quality of life.[12]

See the list below:

• Brain abscesses usually require surgical drainage, followed by a prolonged course of antibiotic therapy.

• Sternoarticular pyarthrosis often requires surgical debridement.

• Patients with osteochondritis or chronic contiguous osteomyelitis require surgical debridement of necrotic bone, foreign bodies, or possible prosthetic materials.

• Tympanomastoid surgery is no longer considered standard management for chronic suppurative otitis media, unless a cholesteatoma is present.

• Patients with malignant externa otitis usually require surgical treatment (eg, ear canal debridement, bone or cartilage debridement, mastoidectomy, facial nerve decompression).

• Surgical intervention is indicated for bowel necrosis, perforation, obstruction, or undrained pus, although intervention for anorectal infections of patients with malignancies and neutropenia is controversial.

• Patients with endocarditis require aggressive antibiotic therapy and surgery. If bacteremia persists 2 weeks after antimicrobial therapy, a valvulectomy is indicated. Patients with left-sided endocarditis that is refractory to antibiotic treatment and is hemodynamically unstable require early valve replacement.

• Bilateral lung and heart-lung transplants are options offering moderate success rates for children and young adults in whom end-stage CF lung disease is associated with chronic pseudomonal lower respiratory tract infections.

• Over-the-counter topical antiseptic drugs for use prior to surgery or injections have reported outcomes that range from localized infections at injection sites to systemic infections that resulted in death. Organisms implicated in the outbreaks included P aeruginosa. The FDA recommends single-use packaging and to follow label instructions to reduce the number of bacteria on the skin.

See the list below:

• Consultation with an infectious disease specialist is suggested for complicated cases, such as persistent or resistant infections.

• Consultation with an orthopedic surgeon may be needed for possible open biopsy or surgical intervention for patients whose infections involve the joint.

• A podiatrist can assist in foot care by performing debridement and nail care.

• A neurologist and neurosurgeon are needed for patients with neurological infections (eg, a brain abscess).

• Consult an otolaryngologist for cases of malignant otitis media that may require surgery.

• Consult an ophthalmologist for pseudomonal eye infections.

• A cardiologist or cardiac surgeon often becomes involved in the care of patients with pseudomonal endocarditis (especially left-sided endocarditis).

• Pulmonologists are often involved with patients who have CF. Pulmonologists may also be consulted for patients who require bronchoscopy.

• Critical care specialists are often involved in the treatment of patients who require intensive care, such as those in septic shock or with severe burns.

See the list below:

• The main goal regarding diet, as it relates to patients with pseudomonal infections, is to provide adequate nutrition, prevent malnutrition, and avoid complications related to dietary delivery.

• Patients with CF who require increased energy intake should receive a higher proportion of fat to nonprotein energy value. Avoid diets with increased amounts of carbohydrates because the increased carbon dioxide production causes difficulty in breathing and ventilation support.

See the list below:

• Restrictions depend on the area of infection.

• Localized infections rarely require activity limitations.

Pseudomonas should be considered in the differential diagnoses in any probable Gram-negative infections. Often, the effect of this organism causes concern because it can cause severe hospital-acquired infection, especially in immunocompromised hosts. Furthermore, a concomitant antibiotic resistance is often present, which makes the choice of treatment difficult.

Often, treatment initially consists of empiric antibiotics. Therefore, when treating Pseudomonas organisms, one must consider some basic concepts. Indwelling catheters associated with any infections should be promptly removed. Delays in treatment are associated with high mortality. Combination therapy needs to be initiated in patients with severe infections and high-risk patients. Combination therapy requires 2 antipseudomonal antibiotics, each with different mechanisms of action. Often, treatment is achieved with a combination of an aminoglycoside or quinolone with another antipseudomonal antibiotic.

Combination therapy with antipseudomonal antibiotics is used to ensure treatment of resistant strains and to prevent selection of resistant mutants. Carbapenems (eg, imipenem, meropenem) and the monobactam antibiotic aztreonam are generally reserved for serious infections caused by organisms resistant to other beta-lactam antibiotics or in those with renal disease who are at risk for aminoglycoside-related nephrotoxicity.

Previous animal studies had brought concern of the use of quinolone in children. However, the use of quinolone is now being revisited.[13] Discussion of these previous animal studies with

parents may be warranted.

Some exceptions to double-coverage antibiotics include the treatment of simple urinary infection (eg, cystitis) or local skin infection or empiric antibiotic coverage in the febrile patient with neutropenia. However, one of the most controversial topics in management involves combination versus monotherapy treatment. Well-designed studies are still needed to settle this controversy. If monotherapy is chosen, certain antibiotics (eg, aminoglycosides, aztreonam) should not be used as empiric monotherapy.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the clinical setting. Whenever feasible, select antibiotics based on culture sensitivity. Review of the institution's resistance is essential.

Ceftazidime (Ceptaz, Fortaz, Tazidime, Tazicef)

DOC for pseudomonal CNS infections and melioidosis. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Cefepime (Maxipime)

Along with ceftazidime, DOC for CNS infections. Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.

Meropenem (Merrem IV)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococcal and streptococcal organisms compared to imipenem.

Imipenem and cilastatin (Primaxin)

Treats multiple organism infections when other agents do not have wide spectrum coverage or are contraindicated because of potential for toxicity.

Piperacillin and tazobactam (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.

Ticarcillin and clavulanate (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during active growth stage. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive, gram-negative, and anaerobic organisms.

Tobramycin (Nebcin)

Used in skin, bone, and skin structure infections, caused by S aureus, P aeruginosa, Proteus species, Escherichia coli, and Klebsiella and Enterobacter species.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage, used in combination with agents against gram-positive organisms and anaerobes.

Often not DOC, yet consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, or in mixed infections caused by susceptible staphylococcal and gram-negative organisms. Base choice between tobramycin and gentamicin on the susceptibility of the area.

DOC for pediatric pseudomonal UTI.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM; once-a-day dosing is more effective.

Follow each regimen by at least a trough level drawn before the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after completion of 30-min infusion.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against pseudomonads, streptococcal, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. DOC for adult pseudomonal UTI and some skin infections.

Aztreonam (Azactam)

Monobactam, not beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. Is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.

Duration of therapy depends on the severity of the infection; therapy is continued for at least 48 h after the patient is asymptomatic or evidence of bacterial eradication has been obtained. Doses smaller than indicated should not be used. Transient or persistent renal insufficiency may prolong serum levels. After initial loading dose of 1 or 2 g, reduce dose by one half for estimated ClCr of 10-30 mL/min/1.73 m2. When only serum creatinine concentration available, the following formula (based on sex, weight, age) can approximate ClCr. Serum creatinine should represent a steady state of renal function.

Males: ClCr = [(weight in kg)(140 - age)] / (72 X serum creatinine in mg/dL).

Females: 0.85 X above value. In patients with severe renal failure (ClCr < 10 mL/min/1.73 m2) and those supported by hemodialysis, the usual dose of 500 mg, 1 g, or 2 g is given initially.

Maintenance dose is one fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 h.

For serious or life-threatening infections, supplement maintenance doses with one eighth of the initial dose after each hemodialysis session.

Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of ClCr and make appropriate dosage modifications. Insufficient data are available in regard to IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.

Streptomycin

Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated. For treatment of susceptible infections and glanders infection.

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

DOC for B cepacia. Dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. Active in vitro against a broad range of gram-positive and gram-negative bacteria. Resistance is usually mediated by decreased cell permeability or alterations in amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production. Trimethoprim provides a synergistic effect when combined with sulfas.

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits; DOC in combination with streptomycin for glanders infection.

Acetic acid otic (VoSoL Otic)

Effectively treats superficial bacterial infections of otitis externa.

See the list below:

• Closely monitor patients for adverse effects of medications.

• Antibiotics (eg, aminoglycosides) may require drug level monitoring.

• Relapses are common in malignant otitis externa, CNS infections, and endocarditis; patients may require repeated treatment.

See the list below:

• Admission is required for acute Pseudomonas infections that require intravenous (IV) antibiotic administration or possible surgical treatment.

• Critically ill patients should be monitored in an ICU.

• Most pseudomonal infections are nosocomial; thus, any hardware (eg, central lines, Foley catheters, endotracheal tubes) is a possible source of infection.

See the list below:

• Double-coverage antibiotics may be prescribed on an inpatient or outpatient basis.

• Otitis externa may require acidification with 2% acetic acid, with or without 1% hydrocortisone.

See the list below:

• Neonates who require workup for sepsis should be transferred to a neonatal intensive or intermediate care unit.

• Patients may require transfer to a facility where ICU care is available.

See the list below:

• No vaccine is available to prevent infection by Pseudomonas organisms.

• Hospital personnel should enforce universal precautions to prevent spread of infections.

• Iatrogenic causes of nosocomial infections from central lines, Foley catheters, or endotracheal tubes can be prevented by avoiding such instrumentation, by limiting the time they are used, and by following CDC recommendations for inserting catheters. Prophylactic antibiotic administration is not recommended because of the emergence of resistant organisms;[14] however, the effectiveness of antibiotic-treated catheters is under study.

• To prevent folliculitis, CDC Health and Safety Guidelines for Public Spas and Hot Tubs recommend a free chlorine concentration of 1-3 mg/L and a pH of 7.2-7.8. Drain private hot tubs every 4-8 weeks, depending on the amount of use. Completely drain public hot tubs and whirlpools on a daily basis and clean interiors with an acidic solution. Bromine can be used as an alternative to chlorine.

• If possible, avoid contact with animals infected by B mallei and B pseudomallei.

See the list below:

• 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.

  • Septicemia may lead to septic shock and death.

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

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

• 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.

• Prognosis varies based on the site of infection.

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

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/mcL.

• 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.

See the list below:

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

• Inform at-risk populations about areas in which glanders or melioidosis are endemic.

• Inform patients about possible adverse effects of prescribed medications.