eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Pseudomonas Infection: Treatment & Medication

Author: Selina SP Chen, MD, MPH, Assistant Professor of Pediatrics, Department of Internal Medicine, John A Burns School of Medicine, University of Hawaii; Internal Medicine and Pediatric Hospitalist, Kapiolani Medical Center for Women and Children; Internal Medicine Hospitalist, Straub Clinic and Hospital
Coauthor(s): Ralph Rudoy, MD, Chief, Division of Pediatric Infectious Disease, Acting Chair, Professor, Department of Pediatrics, John A Burns School of Medicine, University of Hawaii
Contributor Information and Disclosures

Updated: Oct 22, 2009

Treatment

Medical Care

Antimicrobial agents are needed to treat Pseudomonas infections. Two antipseudomonal drug combination therapy (eg, a beta-lactam antibiotic with an aminoglycoside) is usually recommended for the initial empiric treatment of a pseudomonal infection, especially for patients with neutropenia, bacteremia, sepsis, severe upper respiratory infections (URIs), or abscess formation. The choice of antibiotic also depends on the site and extent of infection and on local resistance patterns.⁵ Reports of more resistant strains of Pseudomonas organisms to the currently used antimicrobials are causing much concern.

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

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

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

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

• Bacteremia
  • Empiric antibiotics are often started before the organism is identified.
  • Whether single-drug or combination therapy is most effective in patients who have bacteremia and neutropenia is debated. The author is unaware of any prospective randomized comparison between monotherapy and combination drug therapy for patients with pseudomonal bacteremia. Duration of treatment is at least 2 weeks.
• Bone and skin infections
  • A 4-week course of aminoglycoside antibiotics is often successful for managing vertebral osteomyelitis.
  • Sternoarticular pyarthrosis has been managed effectively with aminoglycoside and antipseudomonal penicillin if administered for at least 6 weeks.
  • Patients with osteomyelitis of the pubic symphysis require treatment for at least 4 weeks with an antipseudomonal penicillin and aminoglycoside combination. Surgical intervention is not usually indicated.
  • Patients with osteochondritis require medical and surgical treatment. Parenteral administration of 1-2 antipseudomonal agents is recommended before surgical debridement. The recommended regimen continues postsurgical treatment for 1-2 additional weeks with oral (PO) ciprofloxacin.
  • Chronic contiguous pseudomonal osteomyelitis requires 4-6 weeks of combination therapy, in addition to surgical debridement.
  • Burn wound sepsis management requires early intervention with daily wound inspection and systemic antibiotic combination regimens. Monotherapy is not indicated.
  • Management of pseudomonal cellulitis includes the use of PO antibiotic for 7-10 days; this often resolves a localized infection.
  • Pseudomonal toe web infections require initial debridement with applications of silver nitrate or 5% acetic acid to the toe webs and the dorsal and planter areas. Following this initial treatment, apply a topical antibiotic, silver sulfadiazine cream, or Castellani paint until infection resolves. PO quinolone effectively reduces the duration of infection.
  • Pseudomonal folliculitis is often self-limited; treatment may require only application of silver sulfadiazine cream or 5% acetic acid wet compresses for 20 minutes 2-4 times daily with topical antibiotics.
• CNS infections
  • Ceftazidime, cefepime, or meropenem are the antibiotics of choice because of their high CNS penetration. Initially, consider double coverage with an aminoglycoside for patients with adequate renal function. Aztreonam, ciprofloxacin, or levofloxacin are indicated for patients with renal failure and those allergic to beta-lactam. Imipenem-cilastatin should be avoided because of the risk of seizures. Intrathecal treatment should also be considered. Treatment duration should be at least 2 weeks.
  • Antibiotics can be used in the initial treatment of brain abscesses that are multiple, small (ie, <2 cm), poorly distributed, or relatively difficult to access. Antibiotic therapy duration depends on the speed of abscess shrinkage, but therapy usually lasts 2-6 weeks.
• Ear and eye infections
  • Otitis media in at-risk populations should be treated with antipseudomonal agents for at least 10 days.
  • Chronic suppurative otitis media requires daily aural toilet and treatment with antibiotics (eg, ceftazidime, mezlocillin, ciprofloxacin), and often surgical treatment.
  • Otitis externa can be treated with local care using an acetic acid compress and daily aural cleaning.
  • Management of malignant externa otitis should be aggressive and involve both medical and surgical therapies. The conventional therapy (ie, an aminoglycoside and a beta-lactam agent with antipseudomonal activity) is needed for at least 4 weeks to treat localized infections and 6-8 weeks or longer to treat extensive disease. Monotherapy using ceftazidime intravenously (IV), cefepime IV, or ciprofloxacin PO for 6 weeks has been reported effective.
  • If gram-negative rods are isolated from the Gram stain of an eye infection, immediately start a combined topical and subconjunctival (or subtenon) therapy of aminoglycoside antibiotics. Aminoglycoside solution (not ointment) must be applied to the affected eye every 30-60 minutes. Subconjunctival therapy is needed for the first 3 days of treatment. Total duration of therapy is at least 1 week. An alternative therapy uses a quinolone antibiotic solution. The addition of parental or PO antipseudomonal antibiotics also has been beneficial.
  • Pseudomonal endophthalmitis requires immediate antibiotic therapy, using aminoglycoside and antipseudomonal penicillin administered via a parenteral and subconjunctival, topical, or intraocular route. Therapy duration depends on the clinical improvement.
• GI and GU infections
  • Treat GI manifestations of pseudomonal infection with antibiotic therapy for patients with severe localized or systemic infections.
  • The treatment modality for urinary tract infection (UTI) depends on the presence of sepsis, degree of chronicity, potential sites of persistent infection, and local antibiotic susceptibility. Ideally, indwelling urinary catheters should be removed. If the catheter cannot be removed, consider treating only symptomatic episodes or exacerbations because it is not feasible to totally eradicate the organism. Aminoglycosides and quinolones remain the agents of choice.
• Cardiovascular (CV) and respiratory infections
  • To treat endocarditis, administer an antipseudomonal beta-lactam with high-dose aminoglycoside for approximately 6 weeks.
  • According to the criteria used in France to select antibiotics to treat VAP, the following 2 risk factors must be considered: (1) administration of broad-spectrum antibiotics in the previous 15 days and (2) mechanical ventilation for fewer than 7 days or for 7 or more days. The extended factors predict the involvement of multiresistant nosocomial P aeruginosa, suggesting administration of carbapenems to those who have undergone mechanical ventilation of 7 or more days and who have been exposed to antibiotics in the prior 15 days.
  • The role of antibiotic prophylaxis or chronic suppression of respiratory pseudomonal infections in patients with CF is controversial. Among the promising treatment plans are intermittent aerosolization of antibiotics to patients with CF who have established pseudomonal lung infections.
  • Choices for empiric antibiotic treatment in patients with a history of Pseudomonas infection requires review of previous culture sensitivity.
  • More widely accepted is the treatment of children with pseudomonal infections by using fluoroquinolone, especially children with previous therapeutic failure or resistance to multiple other antibiotics. Treatment often continues until symptoms resolve (ie, 1-2 wk).
  • Inhalation of mucolytic and hydrating agents, postural drainage, and chest physiotherapy often are therapies used together. Bronchial lavage also has been used to remove respiratory secretions.

Surgical Care

• Brain abscesses usually require surgical drainage, followed by a prolonged course of antibiotic therapy.
• Sternoarticular pyarthrosis often requires surgical debridement.
• Patients with osteochondritis or chronic contiguous osteomyelitis require surgical debridement of necrotic bone, foreign bodies, or possible prosthetic materials.
• Tympanomastoid surgery is no longer considered standard management for chronic suppurative otitis media, unless a cholesteatoma is present.
• Patients with malignant externa otitis usually require surgical treatment (eg, ear canal debridement, bone or cartilage debridement, mastoidectomy, facial nerve decompression).
• Surgical intervention is indicated for bowel necrosis, perforation, obstruction, or undrained pus, although intervention for anorectal infections of patients with malignancies and neutropenia is controversial.
• Patients with endocarditis require aggressive antibiotic therapy and surgery. If bacteremia persists 2 weeks after antimicrobial therapy, a valvulectomy is indicated. Patients with left-sided endocarditis that is refractory to antibiotic treatment and is hemodynamically unstable require early valve replacement.
• Bilateral lung and heart-lung transplants are options offering moderate success rates for children and young adults in whom end-stage CF lung disease is associated with chronic pseudomonal lower respiratory tract infections.

Consultations

• Consultation with an infectious disease specialist is suggested for complicated cases, such as persistent or resistant infections.
• Consultation with an orthopedic surgeon may be needed for possible open biopsy or surgical intervention for patients whose infections involve the joint.
• A podiatrist can assist in foot care by performing debridement and nail care.
• A neurologist and neurosurgeon are needed for patients with neurological infections (eg, a brain abscess).
• Consult an otolaryngologist for cases of malignant otitis media that may require surgery.
• Consult an ophthalmologist for pseudomonal eye infections.
• A cardiologist or cardiac surgeon often becomes involved in the care of patients with pseudomonal endocarditis (especially left-sided endocarditis).
• Pulmonologists are often involved with patients who have CF. Pulmonologists may also be consulted for patients who require bronchoscopy.
• Critical care specialists are often involved in the treatment of patients who require intensive care, such as those in septic shock or with severe burns.

Diet

• The main goal regarding diet, as it relates to patients with pseudomonal infections, is to provide adequate nutrition, prevent malnutrition, and avoid complications related to dietary delivery.
• Patients with CF who require increased energy intake should receive a higher proportion of fat to nonprotein energy value. Avoid diets with increased amounts of carbohydrates because the increased carbon dioxide production causes difficulty in breathing and ventilation support.

Activity

• Restrictions depend on the area of infection.
• Localized infections rarely require activity limitations.

Medication

Pseudomonas should be considered in the differential diagnoses in any probable gram-negative infections. Often, the effect of this organism causes concern because it can cause severe hospital-acquired infection, especially in immunocompromised hosts. Furthermore, a concomitant antibiotic resistance is often present, which makes the choice of treatment difficult. Therefore, Pseudomonas organisms should always be treated with two antipseudomonal antibiotics, each with different mechanisms of action. Often, treatment is achieved with a combination of an aminoglycoside or quinolone with another antipseudomonal antibiotic.

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

Previous animal studies had brought concern of the use of quinolone in children. However, the use of quinolone is now being revisited.⁶ Discussion of these previous animal studies with parents may be warranted.

Exceptions to double-coverage antibiotics include the treatment of simple urinary infection (eg, cystitis) or local skin infection or empiric antibiotic coverage in the febrile patient with neutropenia.

Antibiotics

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

Ceftazidime (Ceptaz, Fortaz, Tazidime, Tazicef)

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

Cefepime (Maxipime)

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

Meropenem (Merrem IV)

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

Imipenem and cilastatin (Primaxin)

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

Piperacillin and tazobactam (Zosyn)

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

Ticarcillin and clavulanate (Timentin)

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

Tobramycin (Nebcin)

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

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage, used in combination with agents against gram-positive organisms and anaerobes.
Often not DOC, yet consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, or in mixed infections caused by susceptible staphylococcal and gram-negative organisms. Base choice between tobramycin and gentamicin on the susceptibility of the area.
DOC for pediatric pseudomonal UTI.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM; once-a-day dosing is more effective.
Follow each regimen by at least a trough level drawn before the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after completion of 30-min infusion.

Ciprofloxacin (Cipro)

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

Aztreonam (Azactam)

Monobactam, not beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. Is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.
Duration of therapy depends on the severity of the infection; therapy is continued for at least 48 h after the patient is asymptomatic or evidence of bacterial eradication has been obtained. Doses smaller than indicated should not be used. Transient or persistent renal insufficiency may prolong serum levels. After initial loading dose of 1 or 2 g, reduce dose by one half for estimated ClCr of 10-30 mL/min/1.73 m². When only serum creatinine concentration available, the following formula (based on sex, weight, age) can approximate ClCr. Serum creatinine should represent a steady state of renal function.
Males: ClCr = [(weight in kg)(140 - age)] / (72 X serum creatinine in mg/dL).
Females: 0.85 X above value. In patients with severe renal failure (ClCr <10 mL/min/1.73 m²) and those supported by hemodialysis, the usual dose of 500 mg, 1 g, or 2 g is given initially.
Maintenance dose is one fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 h.
For serious or life-threatening infections, supplement maintenance doses with one eighth of the initial dose after each hemodialysis session.
Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of ClCr and make appropriate dosage modifications. Insufficient data are available in regard to IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.

Streptomycin sulfate

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

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

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

Tetracycline (Sumycin)

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

Acetic acid (VoSoL Otic)

Effectively treats superficial bacterial infections of otitis externa.

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