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 circ*mstances.
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 asP aeruginosaexhibiting 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]
