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Author: Samer Qarah, MD, Pulmonary Critical Care Consultant, Department of Internal Medicine, Division of Pulmonary and Critical Care, The Brooklyn Hospital Center and Cornell University

Samer Qarah is a member of the following medical societies: American College of Critical Care Medicine

Coauthor(s): Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital; Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center; Klaus-Dieter Lessnau, MD, FCCP, Clinical Assistant Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital; Tarun Madappa, MD, MPH, Pulmonary Fellow, Section of Pulmonary Medicine, Lenox Hill Hospital

Editors: Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Author and Editor Disclosure

Synonyms and related keywords: Pseudomonas aeruginosa, P aeruginosa, Pseudomonas aeruginosa infection, P aeruginosa infection, swimmer's ear, Shanghai fever, tropical immersion foot syndrome, green nail syndrome, green foot, Pseudomonas hot-foot syndrome, nosocomial infections, nosocomial pneumonia, urinary tract infection, UTI, bacteremia, Pseudomonas aeruginosa pneumonia, Pseudomonas aeruginosa endocarditis, vertebral osteomyelitis, pseudomonal infection, pseudomonal pneumonia, pseudomonal endocarditis, cystic fibrosis, pseudomonal bacteremia, chronic otitis media, ecthyma gangrenosum, burn wound infection, neutropenia



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), the overall prevalence of P aeruginosa infections in US hospitals is approximately 4 per 1000 discharges (0.4%).2 P aeruginosa is also the fourth most commonly isolated nosocomial pathogen, accounting for 10.1% of all hospital-acquired infections. It is found on the skin of some healthy persons and has been isolated from the throat and stool of 5% and 3% of nonhospitalized patients, respectively. The gastrointestinal carriage rates among hospitalized patients increases to 20% within 72 hours of admission.

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.

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.



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.
    • 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.
  • 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



Acute Respiratory Distress Syndrome
Pneumococcal Infections
Pneumocystis Carinii Pneumonia
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Community-Acquired
Pneumonia, Fungal
Pneumonia, Viral
Sepsis, Bacterial
Septic Shock
Stenotrophomonas Maltophilia

Other Problems to be Considered

AIDS
Malignant otitis media
Infectious complications of diabetes
Jacuzzi (hot tub) itch



Lab Studies

  • 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.
  • In UTI, urinalysis is helpful in determining a diagnosis.
  • 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.
  • 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.
  • 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 allows for evaluation of patients suspected of having a pseudomonal brain abscess.
  • Renal ultrasonography is useful in evaluating patients suspected of having a perinephric abscess complicating UTI.
  • 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

  • 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.



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 (eg, ticarcillin 18 g/d) 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.
  • 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.
    • 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.
  • GI tract infection treatment includes administration of antibiotics and hydration.
  • 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.

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.



Pseudomonal infections are 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.

Drug Category: Antibiotics

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

Drug NameGentamicin (Garamycin)
DescriptionAminoglycoside 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.
Adult DoseSerious infections and normal renal function: 3 mg/kg/d IV q8h
Loading dose: 1-2.5 mg/kg IV q8h
Maintenance dose: 1-1.5 mg/kg IV q8h
Extended-dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion
Pediatric Dose<5 years: 2.5 mg/kg/dose IV/IM q8h
>5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
ContraindicationsDocumented hypersensitivity; non–dialysis-dependent renal insufficiency
InteractionsCoadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents; thus, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNarrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug NameTicarcillin and clavulanate (Timentin)
DescriptionInhibits biosynthesis of cell wall and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.
Adult Dose3.1 g IV q4-6h
Pediatric Dose75 mg/kg IV q6h
ContraindicationsDocumented hypersensitivity; severe pneumonia; bacteremia; pericarditis; emphysema; meningitis; purulent or septic arthritis should not be treated with oral penicillin during the acute stage
InteractionsTetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects are synergistic when administered concurrently with aminoglycosides; probenecid may increase penicillin levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsPerform CBC count prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiency; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Drug NamePiperacillin and tazobactam (Zosyn)
DescriptionAntipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall and is effective during stage of active multiplication.
Adult Dose3.375 g IV q6h
Pediatric Dose75 mg/kg IV q6h
ContraindicationsDocumented hypersensitivity; severe pneumonia; bacteremia; pericarditis; emphysema; meningitis; purulent or septic arthritis should not be treated with an oral penicillin during the acute stage
InteractionsTetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects are synergistic when administered concurrently with aminoglycosides; probenecid may increase penicillin levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsPerform CBC count prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Drug NameImipenem and cilastatin (Primaxin)
DescriptionExtremely potent broad-spectrum beta-lactam antibiotic. Rapidly hydrolyzed by enzyme dehydropeptidase I located on brush border of renal tubular cells, hence its combination with cilastatin (a reversible inhibitor of dehydropeptidase I). For treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated due to potential for toxicity.
Adult DoseBase initial dose on severity of infection and administer in equally divided doses
250-500 mg IV q6h; not to exceed 3-4 g/d
500-750 mg IM or intra-abdominally q12h
Pediatric Dose<12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for > 3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Moderately susceptible organisms: Not to exceed 4 g/d
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with cyclosporine may increase adverse CNS effects of both agents; coadministration with ganciclovir may result in generalized seizures; chloramphenicol decreases effect; probenecid increases half-life
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAdjust dose in renal insufficiency; avoid use in children <12 y

Drug NameAztreonam (Azactam)
DescriptionMonobactam 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.
Adult Dose500-2000 mg IV/IM q8-12h
Pediatric Dose90-120 mg/kg/d IV/IM divided q6-8h
ContraindicationsDocumented hypersensitivity
InteractionsTetracyclines may reduce effects
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal insufficiency

Drug NameCiprofloxacin (Cipro)
DescriptionExerts 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. Trovafloxacin (Trovan) overcomes many of these limitations but has been removed from general use. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms disappear.
Adult Dose250-750 mg PO q12h
400 mg IV q8h
Pediatric Dose<18 years: Not recommended
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsAntacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIn prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; can damage juvenile weight-bearing joints, not to be used in children unless strong medical indications exist

Drug NameCefepime (Maxipime)
DescriptionFor 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.
Adult Dose1-2 g IV q12h; pseudomonal infections require higher or more frequent doses
Dosage adjustments (adult adjustments)
CrCl (mL/min) 80-50: 0.5-2 g IV q12-24h
CrCl 50-10: 0.5-2 g/d IV
CrCl <10: 0.25-0.5 g/d IV
HD: as for CrCl <10, with an extra 0.25 g after HD
During peritoneal dialysis: 1-2 g IV q48h
Pediatric Dose50 mg/kg IV q8h; not to exceed 2 g/dose
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may increase effects of cefepime; aminoglycosides increase the nephrotoxic potential of cefepime
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsHigh doses may cause CNS toxicity; prolonged use of cefepime may predispose patients to superinfection

Drug NameCeftazidime (Fortaz)
DescriptionThird-generation cephalosporin with high activity against Pseudomonas. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult Dose1-2 g IV/IM q8-12h; not to exceed 6 g/d
Pediatric DoseNeonates: 30 mg/kg IV q12h
Infants and children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d
Adolescents: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels; decreases efficacy of OCPs
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal impairment

Drug NameTobramycin (Nebcin)
DescriptionObtained from Streptomyces tenebrarius. Two to 4 times more active against pseudomonal organisms as compared to gentamicin.
Adult DoseEndocarditis: 8 mg/kg/d IV divided q8h; alternatively, 1 mg/kg IV q8h
Pediatric Dose6-7.5 mg/kg/d IV divided tid/qid (2-2.5 mg/kg q8h or 1.5-1.9 mg/kg q6h)
ContraindicationsDocumented hypersensitivity
InteractionsIncreases effects of neuromuscular blockers and potentiates effect of extended-spectrum penicillins; concurrent administration with amphotericin B, cephalosporins, and loop diuretics increases risk of nephrotoxicity
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAvoid use in renal impairment, preexisting auditory or vestibular impairment, and in patients with neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity

Drug NameMeropenem (Merrem)
DescriptionSemisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis.
Adult Dose1 g IV q8h
Pediatric Dose<10 years: Not established
>10 years: Administer as in adults
ContraindicationsDocumented hypersensitivity to carbapenem or beta-lactams; first trimester of pregnancy
InteractionsProbenecid increases serum levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal impairment; pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication



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.

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.

In/Out Patient Meds

  • 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.

Deterrence/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.

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.

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 eMedicine's Ear, Nose, and Throat Center. Also, see eMedicine's patient education article Swimmer's Ear.



Medical/Legal Pitfalls

  • Failure to monitor for the adverse effects of medications
  • Failure to cover bacteremic pneumonia with double antibiotics

Special Concerns

  • Infections of the lower respiratory tract in patients with cystic fibrosis are a special concern because they represent long-standing conditions complicated by acute exacerbations, signaling a downhill course.



For additional information, see Medscape’s Pneumonia Resource Center, Sepsis Resource Center, and Cystic Fibrosis Resource Center.



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Pseudomonas aeruginosa Infections excerpt

Article Last Updated: Mar 17, 2008