Pseudomonas aeruginosa is one of the most commonly considered gram-negative aerobic bacilli in the differential diagnosis of a number of probable gram-negative infections. Consideration of this organism is important because it causes severe hospital-acquired infections, especially in immunocompromised hosts, is often antibiotic resistant, complicating the choice of therapy, and is associated with a high mortality rate.
Bloodstream infection with P. aeruginosa is most commonly hospital-acquired. Risk factors for P. aeruginosa bacteremia include neutropenia or other immunodeficiency (eg, hematologic malignancy, solid organ or bone marrow transplantation, or HIV infection), advanced age, pancreatobiliary tract disease, severe burns, an indwelling central venous or urinary catheter, antimicrobial therapy within the last 30 days, and traumatic wounds that have been contaminated with fresh water.
Hospital-acquired P. aeruginosa bacteremia may result from primary infection in the lungs, biliary and gastrointestinal tract, urinary tract, skin and soft tissues or from infected intravascular catheters.
Bacteremic patients typically present with fever, tachycardia, and tachypnea. Disorientation, hypotension, and respiratory failure due to either pneumonia or acute respiratory distress syndrome are other common complications, especially in immunocompromised or debilitated patients. Although it is usually impossible to distinguish patients with P. aeruginosa bacteremia from patients with bacteremia due to other gram-negative rods on clinical grounds alone, patients with P. aeruginosa infection are more likely to have a fatal outcome and to develop ecthyma gangrenosum. The lesions of ecthyma gangrenosum involve the skin or mucous membranes, beginning as a small area of edema and quickly evolving into painless nodular lesions with central hemorrhage, ulceration, and necrosis.
Prompt empiric therapy with an active antimicrobial agent is critical in the management of known or suspected P. aeruginosa bacteremia, as delayed therapy correlates with increased mortality. In certain high risk patients (eg, patients with neutropenia or severe burns) and those with severe infections (eg, patients with sepsis/shock), we favor the use of combination antimicrobial therapy for empiric therapy. Otherwise, a single antipseudomonal agent is likely appropriate. In addition, infected catheters should be removed, and abscesses or obstructions should be drained or removed, whenever possible. The rationale for combination therapy in select settings is discussed elsewhere.
When the isolate and results of susceptibility testing are known, antimicrobial therapy should be adjusted accordingly. In general, there is no clinical evidence that using two active antipseudomonal agents offers a mortality benefit over a single active agent.
Thus, for most patients with P. aeruginosa bacteremia, we suggest treatment with a single intravenous antipseudomonal antibiotic to which the isolate is susceptible instead of a combination antimicrobial regimen (Grade 2B). Aminoglycosides should not be used as a single agent. However, because of the high associated mortality rate of P. aeruginosa bacteremia in the setting of neutropenia, it is reasonable to continue a second active antipseudomonal agent for the first three to five days of treatment of neutropenic patients pending clinical improvement.
Bacteremia due to P. aeruginosa is associated with a high mortality rate compared with bacteremia due to other gram-negative bacilli as well as gram-positive organisms.
Infective endocarditis (IE) due to P. aeruginosa is uncommon, but when it occurs, it is strongly associated with intravenous drug use (IVDU) and/or prosthetic heart valves and pacemakers.
Given the close association with IVDU, the most frequently involved valve is the tricuspid valve. Additionally, multiple valve involvement can occur. Since tricuspid infection is common, many patients present with pulmonary manifestations, including cough, chest pain, and hemoptysis. Patients with left-sided valvular infections often develop fulminant or rapidly progressive symptoms that are due to either congestive heart failure or embolism of large or medium-sized arteries. Ring and annular abscesses are also frequent complications.
In the setting of P. aeruginosa bacteremia, the diagnosis of endocarditis can be made with echocardiography and application of the Duke Criteria for endocarditis. The vast majority of patients with P. aeruginosa bacteremia do not have infective endocarditis.
For patients with P. aeruginosa infective endocarditis, we suggest combination antimicrobial therapy for the duration of the treatment course (Grade 2C). This regimen should include two antipseudomonal antibiotics from different classes to which the isolate is susceptible.
We routinely obtain early surgical consultation in all cases of P. aeruginosa endocarditis because of the association of improved prognosis with early valve replacement. Particularly in patients with left-sided disease, the prognosis for medical therapy is worse than for combined medical and surgical therapy.
Prompt active antimicrobial therapy is critical in the management of P. aeruginosa bacteremia, as delayed therapy correlates with increased mortality. In certain high risk patients (eg, patients with neutropenia or severe burns) and those with severe infections (eg, patients with sepsis/shock), we favor the use of combination antimicrobial therapy for empiric therapy of known or suspected P. aeruginosa bacteremia prior to determination of drug susceptibility. The rationale for the use of combination therapy in select situations is discussed elsewhere.
Discussion of empiric therapy for gram-negative rod bacteremia and when P. aeruginosa should be covered is also found elsewhere.
When the isolate and results of susceptibility testing are known, antimicrobial therapy should be adjusted accordingly. In general, there is no convincing clinical evidence that using two active antipseudomonal agents offers a mortality benefit over a single active agent. This is discussed in detail elsewhere.
Thus, for most patients with P. aeruginosa bacteremia, we suggest treatment with a single intravenous antipseudomonal antibiotic to which the isolate is susceptible; aminoglycosides should not be used as a single agent. Treatment duration is largely dictated by the primary site of infection. If bacteremia is secondary to a central venous or an indwelling urinary catheter infection in a nonneutropenic host, treatment can be stopped after 7 to 10 days if the catheter has been removed and the patient has responded promptly to therapy.
However, P. aeruginosa bacteremia in the setting of neutropenia has been associated with a particularly high mortality, although less than previously. In such settings, because of the high mortality, some experts, despite the absence of data to support the practice, continue to use two intravenous antipseudomonal antibiotics from different classes to which the isolate is susceptible for the first three to five days of treatment to ensure clinical improvement. A single active agent can then be used for the remainder of the course. Antimicrobial treatment should generally be continued at least 14 days or longer, until recovery of the neutrophil count.
Antipseudomonal agents and their dosing are discussed elsewhere.
In addition to antimicrobial therapy, the primary site of infection should also be addressed. All infected catheters should be removed, and abscesses or obstructions should be drained or removed whenever possible.
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