Pseudomonas aeruginosa Infections 

Updated: Dec 20, 2018
Author: Marcus Friedrich, MD, MBA, FACP; Chief Editor: Michael Stuart Bronze, MD 

Overview

Practice Essentials

Pseudomonas aeruginosa has become an important cause of gram-negative infection, especially in patients with compromised host defense mechanisms. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week, and it is a frequent cause of nosocomial infections. Pseudomonal infections are complicated and can be life-threatening.

Signs and symptoms

Pseudomonal infections can involve the following parts of the body, with corresponding symptoms and signs:

  • Respiratory tract (eg, pneumonia)

  • Bloodstream (bacteremia)

  • Heart (endocarditis)

  • CNS (eg, meningitis, brain abscess)

  • Ear (eg, otitis externa and media)

  • Eye (eg, bacterial keratitis, endophthalmitis)

  • Bones and joints (eg, osteomyelitis)

  • GI tract (eg, diarrhea, enteritis, enterocolitis)

  • Urinary tract

  • Skin (eg, ecthyma gangrenosum)

Physical findings depend on the site and nature of the infection, as follows:

  • Endocarditis: Fever, murmur, and positive blood culture findings; peripheral stigmata such as Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, and splenomegaly

  • Pneumonia: Rales, rhonchi, fever, cyanosis, retractions, and hypoxia; occasionally shock; with cystic fibrosis, clubbing, increased anteroposterior (AP) diameter, and malnutrition

  • GI tract: Fever, signs of dehydration, abdominal distention, and signs of peritonitis; physical findings of Shanghai fever

  • Skin and soft tissue infections: Hemorrhagic and necrotic lesions, with surrounding erythema; subcutaneous nodules, deep abscesses, cellulitis, and fasciitis; in burns, black or violaceous discoloration or eschar

  • Skeletal infections: Local tenderness and a decreased range of motion; neurologic deficits

  • Eye infections: Lid edema, conjunctival erythema and chemosis, and severe mucopurulent discharge

  • Malignant otitis externa: Erythematous, swollen, and inflamed external auditory canal; local lymphadenopathy

  • Bacteremia: Fever, tachypnea, and tachycardia; hypotension and shock; jaundice

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies that may be helpful include the following:

  • Complete blood count (CBC)

  • Blood cultures

  • In urinary tract infection (UTI), urinalysis

  • In pneumonia, culture of sputum and respiratory secretions, as well as blood gas analysis

  • Wound and burn cultures and cultures from other body fluids and secretions according to the clinical scenario

  • Gram stain and culture of CSF if meningitis is suspected

Imaging studies that may be warranted include the following:

  • Chest radiography

  • Triple-phase bone scanning in suspected skeletal infection (though many prefer MRI)

  • Brain CT or MRI of the brain for suspected pseudomonal brain abscess

  • Renal ultrasonography for suspected of perinephric abscess complicating UTI

  • Echocardiography for suspected endocarditis with positive blood culture findings

Other tests and procedures that may be helpful in specific scenarios include the following:

  • Fluorescein staining and slit-lamp examination of the cornea for keratitis

  • Flexible fiberoptic bronchoscopy with bronchoalveolar lavage or bronchial brushing

  • Thoracocentesis

  • Lumbar puncture with cell count and cultures

See Workup for more detail.

Management

Antimicrobials are the mainstay of therapy. It is important to consider antibiotic resistance when selecting the regimen. Combination therapy should be used in severe infection. Recommended pharmacologic approaches to specific infections are as follows:

  • Endocarditis: Give a high-dose aminoglycoside plus an extended-spectrum penicillin or antipseudomonal cephalosporin for 6 weeks; surgical evaluation is required
  • Pneumonia: Start with 2 antipseudomonal antibiotics, then deescalating to monotherapy (eg, according to American Thoracic Society-Infectious Diseases Society of America guidelines)
  • Bacteremia: Initiate intravenous antipseudomonal antibiotic therapy before a specific diagnosis is made; subsequent presumptive therapy includes an aminoglycoside plus a broad-spectrum antipseudomonal penicillin or cephalosporin; alternatives include fluoroquinolones and rifampin. In the setting of neutropenia, which carries a high mortality rate, two intravenous antipseudomonal antibiotics from different classes should be used.
  • Meningitis: Ceftazidime is the antibiotic of choice; initial therapy in the critically ill should include an IV aminoglycoside; therapy is ordinarily continued for 2 weeks
  • Ear infections: Treat external otitis with antibiotics and steroids; treat malignant otitis aggressively with 2 antibiotics (and surgery)
  • Eye infections: Treat small superficial ulcers with topical therapy (eg, ophthalmic aminoglycoside solution rather than an ointment) every 30-60 minutes; when perforation is imminent, subconjunctival (or subtenon) administration is preferred; management of endophthalmitis requires aggressive antibiotic therapy (parenteral, topical, subconjunctival [or subtenon], and, often, intraocular)
  • UTIs: Parenteral aminoglycosides are generally preferred, though quinolones are used; monotherapy is appropriate in most cases; alternatives include antipseudomonal penicillins and cephalosporins, carbapenems, and aztreonam; ciprofloxacin is the preferred oral agent
  • GI tract infections: Treatment includes antibiotics and hydration
  • Skin and soft tissue infections: Give double-antibiotic therapy in accordance with local susceptibility pattern. 

 Surgical debridement should be aggressive. Principles of surgical care are as follows:

  • As a rule, infected medical devices should be removed, although exceptions may occur

  • In wounds infected with Pseudomonas, surgical removal of eschars, debridement of necrotic tissue, or, in severe cases, amputation may be required

  • Diabetic foot ulcers may require surgical debridement of necrotic tissue

  • Malignant otitis requires surgery to debride granulation tissue and necrotic debris

  • Surgery may be required for bowel necrosis, perforation, obstruction, or abscess drainage

See Treatment and Medication for more detail.

Background

Pseudomonas is a gram-negative rod that belongs to the family Pseudomonadaceae. More than half of all clinical isolates produce the blue-green pigment pyocyanin. Pseudomonas often has a characteristic sweet odor.

These pathogens are widespread in nature, inhabiting soil, water, plants, and animals (including humans). Pseudomonas aeruginosa has become an important cause of infection, especially in patients with compromised host defense mechanisms. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week. It is a frequent cause of nosocomial infections such as pneumonia, urinary tract infections (UTIs), and bacteremia. Pseudomonal infections are complicated and can be life threatening.

Pathophysiology

P aeruginosa is an opportunistic pathogen. It rarely causes disease in healthy persons. In most cases of infection, the integrity of a physical barrier to infection (eg, skin, mucous membrane) is lost or an underlying immune deficiency (eg, neutropenia, immunosuppression) is present. Adding to its pathogenicity, this bacterium has minimal nutritional requirements and can tolerate a wide variety of physical conditions.

The pathogenesis of pseudomonal infections is multifactorial and complex. Pseudomonas species are both invasive and toxigenic. The 3 stages, according to Pollack (2000), are (1) bacterial attachment and colonization, (2) local infection, and (3) bloodstream dissemination and systemic disease.[1] The importance of colonization and adherence is most evident when studied in the context of respiratory tract infection in patients with cystic fibrosis and in those that complicate mechanical ventilation. Production of extracellular proteases adds to the organism's virulence by assisting in bacterial adherence and invasion.

Frequency

United States

According to the Centers for Disease Control and Prevention (CDC), an estimated 51,000 healthcare associated P aeruginosa infections in US hospitals  occur each year. More than 6,000 (13%) of these are multidrug-resistant, with about 440 deaths per year.[2, 3] Multidrug-resistant P aeruginosa was given a threat level serious by the CDC.

International

P aeruginosa is common in immunocompromised patients with diabetes.

Mortality/Morbidity

All infections caused by P aeruginosa are treatable and potentially curable. Acute fulminant infections, such as bacteremic pneumonia, sepsis, burn wound infections, and meningitis, are associated with extremely high mortality rates.

In patients with Charcot arthropathy of the foot, infections with P aeruginosa are associated with a greater number of surgical procedures (1.71 vs 1.28) and longer hospital stays (52 vs 35 days) than infections with methicillin-resistant Staphylococcus aureus (MRSA) or other bacteria, according to a study of 205 patients who underwent surgery for Charcot arthropathy of the feet. The authors propose an algorithm for isolation and surgical and pharmacologic treatment of P aeruginosa infections in this setting, similar to one for MRSA.[4]

Race

P aeruginosa endocarditis in individuals who abuse intravenous drugs is observed mainly among young black males.

Sex

Cases of endocarditis and vertebral osteomyelitis have been observed in young males who use intravenous drugs.

Age

Vertebral osteomyelitis due to pseudomonal infection mainly occurs in elderly patients and often involves the lumbosacral spine. Young people who use intravenous drugs may also be affected.

Involvement of the GI tract most commonly occurs in infants and patients with hematologic malignancies and neutropenia that has resulted from chemotherapy.

The incidence of pseudomonal pneumonia in patients with cystic fibrosis has shown a shift towards patients who are older than 26 years.

Epidemiology

P aeruginosa is the second most common cause of nosocomial pneumonia (17%), third most common cause of urinary tract infection (7%), fourth most common cause of surgical-site infection (8%), and fifth most common isolate (9%) overall from all sites.[5]  

Prognosis

Pseudomonas causes a wide spectrum of diseases; therefore, prognosis is varied.

Prognosis of malignant otitis is improving with earlier recognition of the disease and appropriate antibiotic therapy.

Pseudomonal bacteremia, septicemia, meningitis, burn wound sepsis, and eye infections carry a grave prognosis.

Patient Education

Patients should be educated about good hygiene in the care of their ears.

Patients should be educated about the potential adverse effects of medications and should be monitored for the same.

For excellent patient education resources, visit eMedicineHealth's Ear, Nose, and Throat Center. Also, see eMedicineHealth's patient education article Swimmer's Ear.

 

Presentation

History

Pseudomonal infections can involve any part of the body.

Respiratory tract

Pneumonia is observed in patients with immunosuppression and chronic lung disease. It can be acquired nosocomially in the intensive care unit (ICU) setting and is associated with positive-pressure ventilation and endotracheal tubes. The pneumonia may be primary, following 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. This is observed commonly in patients following chemotherapy-induced neutropenia.

Bacteremic pneumonia occurs in patients with neutropenia following chemotherapy and in patients with AIDS.

Chronic infection of the lower respiratory tract with P aeruginosa is prevalent among patients with cystic fibrosis. These patients may present with chronic productive cough, anorexia, weight loss, wheezing, and tachypnea.[6]

Symptoms of pneumonia include fever, chills, severe dyspnea, cyanosis, productive cough, confusion, and other signs of a systemic inflammatory response.

Bacteremia

Bacteremia may be acquired via medical devices in hospitals and nursing homes, and the mortality rate remains greater than 10%.

Signs and symptoms depend on the primary site of infection.

Endocarditis

P aeruginosa may infect native heart valves in individuals who abuse intravenous drugs and may infect prosthetic heart valves.

Right-sided and left-sided valve infections may occur.

Nonspecific symptoms include fever and malaise, with more specific symptoms depending on which cardiac valve is involved. Left-sided endocarditis typically presents with symptoms of congestive heart failure and those resulting from systemic spread of septic emboli.

Central nervous system

P aeruginosa infection can cause meningitis and brain abscess.

Most infections follow an extension from a contiguous parameningeal structure, such as an ear, a mastoid, paranasal sinus surgery, or diagnostic procedures. In some patients, the involvement of the CNS is due to hematogenous spread of the organism from infective endocarditis, pneumonia, or UTI.

Patients present with fever, headache, and confusion. The onset may be fulminant or subacute, often depending on the immune status of the patient.

Ear

In otitis externa (swimmer's ear), patients present with pain, pruritus, and ear discharge. The pain is worsened by traction on the pinna.

Pseudomonas infection is a common cause of chronic otitis media. Malignant otitis externa is a manifestation of invasive infection predominantly observed in patients with uncontrolled diabetes. It begins as ordinary otitis externa that fails to respond to antibiotic therapy. Presenting symptoms are persistent pain, edema, and tenderness of the soft tissues of the ear, with a purulent discharge. Fever is uncommon, and some patients present with a facial nerve palsy. Extension of the infection to the temporal bone can result in osteomyelitis, and further extension can create cranial nerve palsies and possibly a CNS infection.

Eye

The cornea, aqueous humor, and vitreous humor comprise an immunocompromised environment, and Pseudomonas, when introduced, produces extracellular enzymes that cause a rapidly progressive and destructive lesion. P aeruginosa is a common cause of bacterial keratitis, scleral abscess, and endophthalmitis in adults and ophthalmia neonatorum in children.

Predisposing conditions for corneal involvement are trauma, contact lens use, predisposing ocular conditions, exposure to an ICU environment, and AIDS. Corneal lesions can progress to endophthalmitis and orbital cellulitis. Symptoms are pain, redness, swelling, and impaired vision.

Bones and joints

The most common sites of involvement are the vertebral column, the pelvis, and the sternoclavicular joint.

Infection may be blood-borne, as in individuals who abuse intravenous drugs or in patients with pelvic infections or UTI. Alternatively, the infection may be contiguous, related to penetrating trauma, surgery, or overlying soft tissue infections. Patients at risk for pseudomonal bone and joint infections include those with puncture wounds to the foot, peripheral vascular disease, intravenous drug abuse, or diabetes mellitus.

Vertebral osteomyelitis may involve the cervical spine, and patients present with neck or back pain lasting weeks to months. Occasionally, patients with complicated UTI may develop lumbosacral vertebral osteomyelitis.

Patients with pyoarthrosis present with swelling and pain in the affected joint. Patients are persistently febrile.

Gastrointestinal

Pseudomonal infections can affect every portion of the GI tract. The disease is often underestimated but usually affects very young children and adults 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 necrotizing enterocolitis with significant morbidity and mortality.

Epidemics of pseudomonal diarrhea can occur in nurseries. Young infants may present with irritability, vomiting, diarrhea, and dehydration.

The infection can cause enteritis, with patients presenting with prostration, headache, fever, and diarrhea (Shanghai fever).

Pseudomonas typhlitis typically presents in patients with neutropenia resulting from acute leukemia, with a sudden onset of fever, abdominal distension, and worsening abdominal pain.

Urinary tract infections

Pseudomonal UTIs are usually hospital-acquired and are associated with catheterization, instrumentation, and surgery.

These infections can involve the urinary tract through an ascending infection or through bacteremic spread. In addition, these infections are a frequent source of bacteremia.

No specific characteristics distinguish this type of infection from other forms of UTI.

Skin

Pseudomonas does not grow on dry skin, but it flourishes on moist skin.

Green nail syndrome is a paronychial infection that can develop in individuals whose hands are frequently submerged in water.

Secondary wound infections occur in patients with decubiti, eczema, and tinea pedis. These infections may have a characteristic blue-green exudate with a fruity odor.

Pseudomonas is a common cause of hot tub or swimming pool folliculitis. Patients present with pruritic follicular, maculopapular, vesicular, or pustular lesions on any part of the body that was immersed in water.

Pseudomonal bacteremia produces distinctive skin lesions known as ecthyma gangrenosum.

Pseudomonas also has emerged as an important source of burn wound sepsis. Invasive burn wound sepsis is defined as the bacterial proliferation of 100,000 organisms per gram of tissue, with subjacent involvement of subjacent unburned tissue.

Physical

Endocarditis

Cardinal features of bacterial endocarditis include fever, murmur, and positive blood culture findings.

A new onset of cardiac murmur or a change in character of a preexisting murmur may develop, although these may be absent on presentation.

Peripheral stigmata of endocarditis include Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages, and splenomegaly.

Pneumonia

Patients have rales, rhonchi, fever, cyanosis, retractions, and hypoxia.

Shock may develop in patients with bacteremic pneumonia.

Patients with cystic fibrosis may develop clubbing, increased anteroposterior (AP) diameter, and malnutrition.

Gastrointestinal tract

Young infants with diarrhea may have fever, signs of dehydration, abdominal distension, and signs of peritonitis.

Physical findings of Shanghai fever may include fever, splenomegaly, and rose spots. Depending on the severity of the illness, prostration, dehydration, and vascular collapse may be observed.

Skin and soft tissue infections

Ecthyma gangrenosum lesions are hemorrhagic and necrotic, with surrounding erythema. These characteristic lesions are almost always caused by Pseudomonas infection and usually are found in the axilla, groin, or perianal area but may involve any part of body.

Subcutaneous nodules, deep abscesses, cellulitis, and fasciitis may also occur.

Pseudomonal burn wound infections appear black or as a violaceous discoloration or eschar. Systemic manifestations of burn wound sepsis may include fever or hypothermia, disorientation, hypotension, oliguria, ileus, and leukopenia.

Skeletal infections

Vertebral osteomyelitis manifests as local tenderness and a decreased range of motion.

Osteomyelitis may complicate puncture wounds.

Neurological deficits, when present, suggest spinal cord involvement.

Eye infections

With eye infections, the physical examination reveals lid edema, conjunctival erythema and chemosis, and severe mucopurulent discharge adherent to an underlying corneal ulcer.

Malignant otitis externa

The external auditory canal is erythematous, swollen, and inflamed, and a discharge may be observed.

The tympanic membrane is hidden from view because of edema and may be ruptured.

Local lymphadenopathy may be present.

Bacteremia

Patients have fever, tachypnea, and tachycardia.

Hypotension and shock may develop.

Jaundice may occur.

Skin shows characteristic skin lesions called ecthyma gangrenosum.

Causes

Pseudomonal bacteremia occurs in association with malignancy, chemotherapy, AIDS, burn wound sepsis, and diabetes.

Certain populations of patients are especially susceptible to pseudomonal infections. Predisposing conditions include placement of intravenous lines, severe burns, urinary tract catheterization, surgery, trauma, and premature birth (infants).

Conditions predisposing to pseudomonal infections and major manifestations include the following:

  • Diabetes - Malignant otitis externa
  • Drug addiction - Endocarditis, osteomyelitis
  • Leukemia - Sepsis, typhlitis
  • Cancer - Pneumonia, sepsis
  • Burn wound - Cellulitis, sepsis
  • Cystic fibrosis - Pneumonia
  • Surgery involving CNS - Meningitis
  • Tracheostomy - Pneumonia
  • Neonatal period - Diarrhea
  • Corneal ulcer - Panophthalmitis
  • Vascular catheterization - Bacteremia, suppurative thrombophlebitis
  • Urinary catheterization - UTI

Risk factors for infection with resistant P aeruginosa include the following:

  • Intensive care unit (ICU) stay
  • Bedridden status
  • Prior use of certain antibiotics, including broad­-spectrum cephalosporins, aminoglycosides, carbapenems, and fluoroquinolones
  • Presence of invasive devices
  • Diabetes mellitus
  • Undergoing surgery [7]  
 

DDx

 

Workup

Laboratory Studies

CBC count

A CBC count may reveal leukocytosis with a left shift and bandemia. In patients with hematologic malignancy or status postchemotherapy, leukopenia with neutropenia is expected. Leukopenia is a poor prognostic indicator.

Blood cultures

Obtain at least 2 sets of blood cultures (2 aerobic, 2 anaerobic bottles) from different sites.

Positive results on blood culture in the absence of extracardiac sites of infection may indicate pseudomonal endocarditis. However, bacteremia may complicate intravenous catheter infections, urinary tract instrumentation, trauma, and surgery in the absence of endocarditis.

Other cultures

In UTI, urinalysis is helpful in determining a diagnosis. Culture confirms the diagnosis and provides information concerning antibiotic susceptibility.

In pneumonia, sputum and respiratory secretions should be cultured. However, the isolation of Pseudomonas from sputum and tracheal secretions might indicate airway colonization. The poor sensitivity and specificity of sputum in determining the bacterial cause of pneumonia in patients who are mechanically ventilated has led to greater use of quantitative cultures obtained from protected bronchoalveolar lavage and protected specimen brushings. Blood gas analysis to evaluate for hypoxia or hypercarbia should also be performed in patients with pneumonia.

Obtain wound and burn cultures and cultures from other body fluids and secretions according to the clinical scenario. To aid in diagnosis, obtaining burn wound biopsies with quantitative bacterial cultures is recommended. A bacterial count of greater than 105 organisms per gram of tissue is diagnostic of a burn wound infection.

Gram stain

Obtain Gram stain and culture of cerebrospinal fluid if meningitis is suspected.

Imaging Studies

Chest radiography

Abnormalities observed in pseudomonal pneumonia depend on the pathogenesis of the infections. In primary pseudomonal pneumonia, in which aspiration of infected secretions results in pneumonia, the chest radiograph often reveals bilateral bronchopneumonia consisting of nodular infiltrates with or without pleural effusion. Lobar pneumonia is uncommon.

Early pulmonary vascular congestion is found in patients with bacteremic pseudomonal pneumonia and rapidly progresses to pulmonary edema and necrotizing bronchopneumonia. Within 48-72 hours, the radiograph demonstrates a mixture of alveolar and interstitial infiltrates, and cavitation may be present.

Bone scan

Triple-phase bone scan may be useful in patients with suspected skeletal infection, although many would preferentially rely on MRI.

Brain CT scan or MRI

Brain CT scan or MRI allows for evaluation of patients suspected of having a pseudomonal brain abscess.

Renal ultrasonography

Renal ultrasonography is useful in evaluating patients suspected of having a perinephric abscess complicating UTI.

Echocardiography

Echocardiography should be considered in patients with positive blood culture findings in whom endocarditis is suspected. Normal transthoracic echocardiography findings do not rule out endocarditis in patients in whom clinical suspicion is high. Transesophageal echocardiography should then be considered.

Other Tests

See the list below:

  • Gram stain of respiratory secretions and cerebrospinal fluid

  • Fluorescein staining and slit-lamp examination of the cornea for keratitis

Procedures

Procedures indicated for pseudomonal infections depend on the clinical picture and the site of infection.

Flexible fiberoptic bronchoscopy with bronchoalveolar lavage or bronchial brushing may be useful in pneumonia. Pleural effusions may require thoracocentesis.

Lumbar puncture with cell count and cultures is indicated in suspected pseudomonal meningitis.

Histologic Findings

Pseudomonas infection causes necrotizing inflammation. Histologically, gram-negative rods are observed in the walls of blood vessels, causing coagulation necrosis, along with thrombosis and hemorrhage.

 

Treatment

Approach Considerations

P aeruginosa is intrinsically resistant to certain antibiotics and can potentially acquire resistance during treatment (see Presentation/Causes for risk factors).

Medical Care

Antimicrobials are the mainstay of therapy. Two-drug combination therapy, such as an antipseudomonal beta-lactam with an aminoglycoside, can be used.

Endocarditis

A high-dose aminoglycoside (eg, tobramycin 8 mg/kg/d) and an extended-spectrum penicillin in combination with a beta-lactamase inhibitor (eg, ticarcillin-clavulanate or piperacillin-tazobactam) or antipseudomonal cephalosporin (eg, cefepime) are used for 6 weeks.

Renal function and aminoglycoside level should be monitored.

Surgical evaluation is required because many patients with right-sided endocarditis require valvulectomy, especially if the bacteremia is not cleared after 2-6 weeks of antibiotics. For left-sided disease, early surgery is usually required for those with refractory bacteremia or hemodynamic instability.

Pneumonia

Most experts recommend starting with 2 antipseudomonal antibiotics and then de-escalating to monotherapy.

Except in patients with cystic fibrosis, the role of an aerosolized aminoglycoside or ceftazidime is controversial. Efficacy appears to be greater in patients with cystic fibrosis, in whom aerosolized aminoglycosides have been shown to assist clinical improvement and symptom abatement.

Deciding when to switch from combination therapy to monotherapy: According to the American Thoracic Society-Infectious Diseases Society of America guidelines for ventilator-assisted pneumonia, start with combination therapy that includes a beta-lactam and aminoglycoside for 5 days and de-escalate to monotherapy based on organism culture sensitivity.

See also Complicated P aeruginosa infections (below).

Bacteremia

Antibiotic therapy is instituted before a specific diagnosis is made.

Once pseudomonal sepsis is suspected in patients with neutropenia, presumptive therapy is a combination of an aminoglycoside and a broad-spectrum antipseudomonal penicillin or cephalosporin. The use of monotherapy ceftazidime, a carbapenem (eg, imipenem-cilastatin, meropenem), or double beta-lactams in patients who are febrile and neutropenic is still controversial. Fluoroquinolones provide an alternative for the beta-lactam–sensitive patient, and the addition of rifampin to the beta-lactam and aminoglycoside combination may improve bacteriologic cure.

Early appropriate antibiotics and aggressive volume replacement have been shown to improve outcome in septic shock. Positive-pressure ventilation may be required.

Meningitis

Ceftazidime is the antibiotic of choice because of its high penetration into the subarachnoid space and the high susceptibility of Pseudomonas to this drug.

Initial therapy in critically ill patients should include an intravenous aminoglycoside. The use of an intrathecal aminoglycoside should be considered, especially in the setting of treatment failure or relapse.

In renal failure or in the setting of beta-lactam allergy, aztreonam may be an effective second-line drug. However, clinical experience is limited, and careful observation is suggested.

Clinical experience with ciprofloxacin and meningitis is limited. Animal models suggest equivalent efficacy to that of ceftazidime and tobramycin, but, for now, combination therapy is suggested.

Therapy is ordinarily continued for 2 weeks. Duration of therapy is determined by the severity of disease. Monitoring serial CSF cultures and cell counts may be useful in evaluating response to treatment.

Undertreatment increases the relapse rate and probably the likelihood of acquired resistance, while overtreatment increases costs and adverse medication effects. In meningitis, overtreatment is obviously preferred.

Ear infections

External otitis is treated locally with antibiotics and steroids.

Malignant otitis requires aggressive treatment with 2 antibiotics and surgery.

Duration of treatment is 4-8 weeks, depending on the extent of involvement.

Eye infections

In cases of small superficial ulcers, topical therapy, consisting of an ophthalmic aminoglycoside solution rather than an ointment, is applied to the affected eye every 30-60 minutes.

An ophthalmic quinolone antibiotic is an alternative. When perforation is imminent, subconjunctival (or subtenon) administration of antibiotics is preferred.

Management of endophthalmitis is quite complex, requiring aggressive antibiotic therapy (parenteral, topical, subconjunctival [or subtenon], and, often, intraocular). Vitrectomy may be required to assist in eyesight preservation.

Urinary tract infections

Parenteral aminoglycosides may remain the antibiotics of choice, although quinolones are often used.[8]

Tobramycin is preferred to gentamicin in patients with renal dysfunction.

UTI can be treated with a single agent, except in cases of bacteremia and upper tract infections with abscess formation.

Alternative antibiotics include antipseudomonal penicillins and cephalosporins, carbapenems (eg, imipenem, meropenem), and aztreonam. Ciprofloxacin continues to be the preferred oral agent.

Duration of therapy is 3-5 days for uncomplicated infections limited to the bladder; 7-10 days for complicated infections, especially with indwelling catheters; 10 days for urosepsis; and 2-3 weeks for pyelonephritis. Longer duration of treatment is necessary for those patients with perinephric or intrarenal abscesses.

See also Complicated P aeruginosa infections (below).

GI tract infection

GI tract infection treatment includes administration of antibiotics and hydration. 

See also Complicated P aeruginosa infections (below).

Skin and soft tissue infections

Double antibiotic therapy should be instituted in accordance with the local susceptibility patterns because burn centers may harbor Pseudomonas strains that are resistant to multiple drugs.

Silver sulfadiazine and sodium piperacillin have been shown to be effective in experimental models of burn sepsis.

Aggressive surgical debridement is necessary, and avoidance of whirlpool treatments is suggested.

Complicated P aeruginosa infections

Ceftazidime/avibactam (Avycaz) is a combination cephalosporin and beta-lactamase inhibitor that was FDA-approved in February 2015. The ceftazidime component has activity against gram-negative bacteria, including P aeruginosa. The addition of avibactam increases the spectrum of activity to organisms that produce beta-lactamase enzymes. Unlike other beta-lactam/beta-lactamase inhibitors, however, this drug has no activity against anaerobic organisms.

Ceftazidime/avibactam is indicated for the treatment of patients aged 18 years or older with complicated intra-abdominal infections and complicated UTIs. Phase II clinical trials for ceftazidime/avibactam have shown an 85.7% favorable clinical response rate for complicated UTIs and 92.7% favorable clinical response rate for complicated intra-abdominal infections when combined with metronidazole.[9] Full results from the Phase III trials and future studies are likely to expand the use of ceftazidime/avibactam to include hospitalized adults with nosocomial and ventilator-associated pneumonia, hospitalized pediatric patients aged 3 months to 18 years with complicated intra-abdominal infections, and patients with cystic fibrosis who have resistant respiratory P aeruginosa infections.

Ceftolozane/tazobactam is a novel cephalosporin developed with a beta-lactamase inhibitor for the treatment of complicated UTIs, complicated intra-abdominal infections, and ventilator-associated bacterial pneumonia. Ceftolozane has similar activity to that of ceftazidime, piperacillin/tazobactam, and the carbapenemase family of antibiotics.[10] The tazobactam component allows for the drug to act against extended-spectrum beta-lactamase (ESBL) bacteria, as well as some anaerobic species, although data from previous Phase III trials show that, for anaerobic coverage, combining ceftolozane/tazobactam with metronidazole is recommended.

Ceftolozane/tazobactam is a promising carbapenem-sparing alternative agent for the treatment of complicated UTIs and complicated intra-abdominal infections, including those caused by ESBL-producing Enterobacteriaceae and multidrug-resistant P aeruginosa.[11]

Surgical Care

As a rule, infected medical devices should be removed, although exceptions may occur.

In wounds infected with Pseudomonas, surgical removal of eschars, debridement of necrotic tissue, or, in severe cases, amputation may be required.

Diabetic foot ulcers may require surgical debridement of necrotic tissue.

Malignant otitis requires surgery to debride granulation tissue and necrotic debris.

Surgery may be required for bowel necrosis, perforation, obstruction, or abscess drainage.

Consultations

Pulmonary and critical care medicine consultations are requested in pseudomonal pneumonia that requires bronchoalveolar lavage, thoracocentesis, or ventilatory support.

Refractoriness to antibiotic therapy and hemodynamic instability in pseudomonal endocarditis directs toward valve replacement. A cardiothoracic consultation is required.

If drainage of brain abscesses is required, neurosurgical consultation is requested.

Ophthalmology consultation should be requested without delay in cases of pseudomonal eye infection. Vitrectomy may be needed in cases of endophthalmitis.

Diet

Always prevent malnutrition, and treat it when present.

General goals of nutritional support

Provide nutritional support consistent with the patient's medical condition, nutritional status, and available route of nutrient administration.

Prevent or treat macronutrient and micronutrient deficiencies.

Provide doses of nutrients compatible with existing metabolism.

Avoid complications related to the technique of dietary delivery.

Improve patient outcomes, such as those related to disease morbidity (eg, body composition, tissue repair, organ function), resource utilization, medical morbidities and mortalities, and subsequent patient performance.

Patients with cystic fibrosis

In patients with cystic fibrosis, when increased caloric support is needed, carbohydrates in large quantities can result in increased carbon dioxide production and increased effort for breathing. Instead, an increased proportion of fat calories to nonprotein calories should be provided. Medium-chain fatty acids can be very useful in these cases.

When enteral feeding is chosen, take special care to avoid aspiration and other mechanical complications.

Electrolytes, trace elements, and vitamins are provided as needed.

Remember that hypophosphatemia and, in particular, hypomagnesemia impair diaphragmatic function. Commercial products, such as Pulmocare, that are targeted to meet these needs are available. Specific data demonstrating efficacy, however, are not readily available.

Activity

Patients require no specific limitations on activity.

Complications

Pseudomonal endocarditis may cause brain abscess, cerebritis, and mycotic aneurysms. Septic emboli to the lungs and spleen are not uncommon, and cardiac complications may include conduction blocks and congestive heart failure.

Pseudomonal bacteremia can cause septic shock and death.

Pseudomonal pneumonia may be severe enough to require respiratory support.

Ear infections can cause perichondritis; sinusitis; mastoiditis; osteomyelitis of the temporal bones; cranial nerve involvement of seventh, ninth, eleventh, and twelfth nerves; and thrombosis of the lateral and sigmoid sinuses. Meningitis and brain abscesses are relatively rare.

Eye infections can result in corneal perforations, endophthalmitis, and orbital cellulitis.

GI involvement by Pseudomonas can cause typhlitis, cecal perforation, and peritonitis.

A severe bout of diarrhea can result in vascular collapse and death.

Pseudomonas skin and soft tissue infections can be destructive and can cause massive necrosis and gangrene.

Prevention

Catheter-induced UTIs are very common, and preventive measures are extremely important. 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 hand washing by health care personnel. If a urinary catheter is required for long periods, it should be replaced often. Patients should drink plenty of fluids every day. 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 antibiotic-resistant strains of bacteria.

Intravenous catheters should be inserted under sterile conditions and with aseptic precautions. Palpate the catheter site for tenderness daily through an intact dressing. Record the date and time of catheter insertion in an obvious location near the insertion site.

To prevent cross-contamination, strict isolation is required for patients with severe burns.

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

Failure to cover bacteremic pneumonia with double antibiotics may lead to a potential lawsuit.

Obtain ophthalmology consultation without delay in cases of suspected pseudomonal eye infections.

Further Outpatient Care

Carefully monitor patients for adverse effects of medications.

Relapses are common in meningitis, and re-treatment may be necessary. Intrathecal antibiotics may be required.

Treatment failures can occur after terminating antibiotic therapy for malignant otitis, thereby requiring careful outpatient follow-up care.

Further Inpatient Care

Patients receiving intravenous therapy are usually admitted, although home antibiotic programs exist.

Admission is required for surgical management, if necessary.

Critically ill patients require ICU care.

Inpatient & Outpatient Medications

Aminoglycosides in combination with beta-lactam agents with good antipseudomonal activity may be prescribed on an inpatient or outpatient basis.

Transfer

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

Patients with endocarditis refractory to antibiotics may need transfer to a facility with arrangements for cardiothoracic surgery for valve replacement.

Patients with malignant otitis may need to be transferred to a facility where surgery can be performed.

 

Medication

Medication Summary

Pseudomonal infections are increasingly resistant to certain antibiotics, and the organism may acquire resistance during therapy. Two agents from different classes should be used when the risk of antibiotic resistance is high (eg, in severe sepsis, septicemia, and inpatient neutropenia).

Pseudomonas infection can be treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Carbapenems (eg, imipenem, meropenem) with antipseudomonal quinolones may be used in conjunction with an aminoglycoside. With the exception of cases involving febrile patients with neutropenia, in whom monotherapy with ceftazidime or a carbapenem (eg, imipenem, meropenem) is used, a 2-drug regimen is recommended.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Gentamicin

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.

Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Dosing regimens are numerous. Adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.

Piperacillin and tazobactam (Zosyn)

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

Aztreonam (Azactam)

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

Ciprofloxacin (Cipro, Cipro XR)

Exerts bactericidal effect against both actively dividing and dormant bacteria. Fluoroquinolone effective against pseudomonads, streptococci, some MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms disappear.

Cefepime (Maxipime)

For the treatment of Pseudomonas infections. Fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has better gram-positive coverage. Cefepime is a zwitterion that rapidly penetrates gram-negative cells. Best beta-lactam for IM administration. Poor capacity to cross blood-brain barrier precludes use for treatment of meningitis.

Ceftazidime (Fortaz, Tazicef)

Third-generation cephalosporin with high activity against Pseudomonas. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Tobramycin

Obtained from Streptomyces tenebrarius. Two to 4 times more active against pseudomonal organisms as compared to gentamicin.

Meropenem (Merrem)

Ultra–broad-spectrum beta-lactam semisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis.

Doripenem (Doribax)

Binds to several of penicillin-binding proteins, which in turn inhibit bacterial cell wall synthesis. Bacteria eventually lyse due to ongoing cell wall autolytic enzymes.

Ceftazidime/avibactam (Avycaz)

Ceftazidime/avibactam (Avycaz) is a combination cephalosporin and beta-lactamase inhibitor that was FDA-approved in February 2015. The ceftazidime component has activity against gram-negative bacteria, including P aeruginosa. The addition of avibactam increases the spectrum of activity to organisms that produce beta-lactamase enzymes. Unlike other beta-lactam/beta-lactamase inhibitors, however, this drug has no activity against anaerobic organisms.

Ceftazidime/avibactam is indicated for the treatment of patients aged 18 years or older with complicated intra-abdominal infections and complicated UTIs. Phase II clinical trials for ceftazidime/avibactam have shown an 85.7% favorable clinical response rate for complicated UTIs and 92.7% favorable clinical response rate for complicated intra-abdominal infections when combined with metronidazole. Full results from the phase III trials and future studies are likely to expand the use of ceftazidime/avibactam to include hospitalized adults with nosocomial and ventilator-associated pneumonia, hospitalized pediatric patients aged 3 months to 18 years with complicated intra-abdominal infections, and patients with cystic fibrosis who have resistant respiratory P aeruginosa infections.

Ceftolozane/tazobactam (Zerbaxa)

Ceftolozane/tazobactam is a novel cephalosporin developed with a beta-lactamase inhibitor for the treatment of complicated UTIs, complicated intra-abdominal infections, and ventilator-associated bacterial pneumonia. Ceftolozane has similar activity to that of ceftazidime, piperacillin/tazobactam, and the carbapenemase family of antibiotics. The tazobactam component allows for the drug to act against extended-spectrum beta-lactamase (ESBL) bacteria, as well as some anaerobic species, although data from previous Phase III trials show that, for anaerobic coverage, combining ceftolozane/tazobactam with metronidazole is recommended.

Ceftolozane/tazobactam is a promising carbapenem-sparing alternative agent for the treatment of complicated UTIs and complicated intra-abdominal infections, including those caused by ESBL-producing Enterobacteriaceae and multidrug-resistant P aeruginosa.

 

Questions & Answers

Overview

What is Pseudomonas (P) aeruginosa?

How do Pseudomonas (P) aeruginosa infections manifest?

What are the physical findings in Pseudomonas (P) aeruginosa infections?

Which lab studies are used in the workup of Pseudomonas (P) aeruginosa infections?

Which imaging studies are used in the workup of Pseudomonas (P) aeruginosa infections?

What are the secondary tests and procedures used in the workup of Pseudomonas (P) aeruginosa infections?

Which medications are used to treat Pseudomonas (P) aeruginosa infections?

What is the role of surgical care in the treatment of Pseudomonas (P) aeruginosa infections?

What is Pseudomonas aeruginosa?

What type of pathogen is Pseudomonas (P) aeruginosa?

What is the pathogenesis of Pseudomonas (P) aeruginosa infections?

What is the prevalence of Pseudomonas (P) aeruginosa infections in the US?

What is the worldwide prevalence of Pseudomonas (P) aeruginosa infections?

What is the mortality/morbidity of Pseudomonas (P) aeruginosa infections?

Who is at greatest risk of Pseudomonas (P) aeruginosa endocarditis?

What are the age-related demographics of Pseudomonas (P) aeruginosa infections?

What is the epidemiology of Pseudomonas (P) aeruginosa infections?

What is the prognosis of Pseudomonas (P) aeruginosa infections?

What is included in the patient education information for Pseudomonas (P) aeruginosa infections?

Presentation

Where in the body do Pseudomonas (P) aeruginosa infections occur?

How does Pseudomonas (P) aeruginosa infections affect the respiratory tract?

What are symptoms of Pseudomonas (P) aeruginosa pneumonia?

How is Pseudomonas (P) aeruginosa bacteremia acquired?

What are the signs and symptoms of Pseudomonas (P) aeruginosa infection?

How does Pseudomonas (P) aeruginosa endocarditis manifest?

How is the CNS affected by Pseudomonas (P) aeruginosa infection?

How is the ear affected by Pseudomonas (P) aeruginosa infection?

How is the eye affected by Pseudomonas (P) aeruginosa infection?

What are the most common sites of Pseudomonas (P) aeruginosa infection?

How do Pseudomonas (P) aeruginosa infections manifest in the bones and joints?

How is the GI tract affected by Pseudomonas (P) aeruginosa infection?

How is the urinary tract affected by Pseudomonas (P) aeruginosa infection?

Does Pseudomonas (P) aeruginosa grow on skin?

How does green nail syndrome manifest from Pseudomonas (P) aeruginosa?

How are secondary wound infections associated with Pseudomonas (P) aeruginosa characterized?

What are the symptoms of swimming pool folliculitis caused by Pseudomonas (P) aeruginosa?

How is the skin affected by pseudomonal bacteremia?

How is burn wound sepsis caused by Pseudomonas (P) aeruginosa characterized?

What are the characteristics of bacterial endocarditis associated with Pseudomonas (P) aeruginosa?

What are the respiratory features of Pseudomonas (P) aeruginosa infections?

What are the GI findings in infants with Pseudomonas (P) aeruginosa infection?

What are the cutaneous characteristics of Pseudomonas (P) aeruginosa infections?

What are the characteristics of skeletal infections caused by Pseudomonas (P) aeruginosa?

What are the characteristics of eye infections caused by Pseudomonas (P) aeruginosa?

What are the characteristics of malignant otitis externa caused by Pseudomonas (P) aeruginosa?

What are the characteristics of bacteremia caused by Pseudomonas (P) aeruginosa?

What causes pseudomonal bacteremia?

What are the predisposing conditions of Pseudomonas (P) aeruginosa infections?

Which conditions are predisposing to Pseudomonas (P) aeruginosa infections and how do they manifest?

What are the risk factors for infection with resistant Pseudomonas aeruginosa?

DDX

What are the differential diagnoses for Pseudomonas aeruginosa Infections?

Workup

What is the role of a CBC in the workup of Pseudomonas (P) aeruginosa infection?

How are blood cultures used in the workup of Pseudomonas (P) aeruginosa infection?

Which cultures other than blood cultures are used in the workup of Pseudomonas (P) aeruginosa infection?

How is Gram stain used in the diagnosis of Pseudomonas (P) aeruginosa infection?

What is the role of chest radiography in the workup of Pseudomonas (P) aeruginosa?

What is the role of bone scanning in the workup of Pseudomonas (P) aeruginosa infection?

What is the role of brain CT scanning or MRI in the workup of Pseudomonas (P) aeruginosa infection?

What is the role of renal ultrasonography in the workup of Pseudomonas (P) aeruginosa infection?

What is the role of echocardiography in the workup of Pseudomonas (P) aeruginosa infection?

Which other tests are used in the workup of Pseudomonas (P) aeruginosa infection?

Which procedures are indicated in the workup of Pseudomonas (P) aeruginosa infection?

What are the histologic findings in Pseudomonas (P) aeruginosa infection?

Treatment

What are the approach considerations on the treatment of Pseudomonas (P) aeruginosa infection?

How are GI tract infections due to Pseudomonas (P) aeruginosa treated?

What is the mainstay therapy for Pseudomonas (P) aeruginosa infection?

What are the treatment options for Pseudomonas (P) aeruginosa endocarditis?

What are the treatment options for Pseudomonas (P) aeruginosa pneumonia?

What are the treatment options for bacteremia due to Pseudomonas (P) aeruginosa?

What are the treatment options for meningitis due to Pseudomonas (P) aeruginosa?

How are ear infections caused by Pseudomonas (P) aeruginosa treated?

How are eye infections caused by Pseudomonas (P) aeruginosa treated?

How are urinary tract infections (UTIs) due to Pseudomonas (P) aeruginosa treated?

What are the treatment options for skin and soft tissue infections due to Pseudomonas (P) aeruginosa?

What is the efficacy of ceftazidime/avibactam (Avycaz) combination therapy for Pseudomonas (P) aeruginosa infections?

What is the efficacy of ceftolozane/tazobactam combination therapy for Pseudomonas (P) aeruginosa infections?

What are the surgical options for the treatment of Pseudomonas (P) aeruginosa infections?

What are the consultations indicated in the treatment of Pseudomonas (P) aeruginosa infections?

How is nutritional support addressed in the treatment of Pseudomonas (P) aeruginosa infections?

How is nutritional support addressed in the treatment of cystic fibrosis and Pseudomonas (P) aeruginosa infection?

Are activity restrictions indicated for patients with Pseudomonas (P) aeruginosa infection?

What are the complications of pseudomonal endocarditis?

What are the complications of pseudomonal bacteremia?

What are the complications of pseudomonal pneumonia?

What are the complications of ear infections caused by Pseudomonas (P) aeruginosa?

What are complications of eye infections caused by Pseudomonas (P) aeruginosa?

What are the complications of GI infections caused by Pseudomonas (P) aeruginosa?

What are the complications of skin and soft tissue infections caused by Pseudomonas (P) aeruginosa?

How are Pseudomonas (P) aeruginosa infections prevented when catheters are necessary?

How can Pseudomonas (P) aeruginosa infections be prevented?

How are patients with Pseudomonas (P) aeruginosa infections monitored in an outpatient setting?

When is inpatient care indicated for patients with Pseudomonas (P) aeruginosa infections?

When are aminoglycosides indicated for the treatment of Pseudomonas (P) aeruginosa infections?

When is transfer indicated for patients with Pseudomonas (P) aeruginosa infection?

Medications

What medications are used in the treatment of Pseudomonas (P) aeruginosa infections?

Which medications in the drug class Antibiotics are used in the treatment of Pseudomonas aeruginosa Infections?