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. However, a lack of clinical evidence in terms of mortality benefit limits its use. [11]
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 usually is 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. [12]
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. [13] In February 2018, the FDA extended its indication to include hospitalized adults with nosocomial and ventilator-associated pneumonia [14] and, in March 2019, to hospitalized pediatric patients aged 3 months to 18 years with complicated intra-abdominal infections with metronidazole and complicated UTIs. [15]
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. [16] 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. [17, 18]
For multidrug-resistant isolates, aminoglycosides, fosfomycin, [19, 20, 21] and polymyxins (colistin or polymyxin B) are used as alternatives, either singly or in combinations, with limited success, limiting their use because of severe adverse effects, including nephrotoxicity and ototoxicity. [22, 23, 24] An expert should always be asked to help in these circumstances.
Pseudomonas Aeruginosa with Difficult-to-Treat Resistance
In 2018, the concept of “difficult-to-treat” resistance was proposed. [25] In this guidance document, DTR is defined as P aeruginosa exhibiting non-susceptibility to all of the following: piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin. IDSA is actively updating its treatment recommendations for Gram-Negative resistant infections. [26]
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 healthcare 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.
