eMedicine Specialties > Infectious Diseases > Bacterial Infections

Pseudomonas aeruginosa Infections: Treatment & Medication

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
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
Contributor Information and Disclosures

Updated: Mar 17, 2008

Treatment

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.

Medication

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.

Antibiotics

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

Gentamicin (Garamycin)

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.

Ticarcillin and clavulanate (Timentin)

Inhibits 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.

Piperacillin and tazobactam (Zosyn)

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

Imipenem and cilastatin (Primaxin)

Extremely 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.

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)

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. 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.

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)

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

Tobramycin (Nebcin)

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

Meropenem (Merrem)

Semisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis.

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