The following general principles apply to the management of serious Pseudomonas aeruginosa infections
Antibiotic resistance, both intrinsic and acquired, is important to consider when selecting empiric or directed therapy.
Combination therapy is indicated in certain high risk patients and in severe infections.
Antimicrobial therapy should be prompt, as delayed therapy correlates with increased mortality.
All infected catheters should be removed, and abscesses or obstructions should be drained or removed, whenever possible.
P. aeruginosa is intrinsically resistant to a number of antibiotics and can acquire resistance during therapy. These features limit the choices of antibiotics for P. aeruginosa.
A limited number of antimicrobial agents have reliable activity against P. aeruginosa isolates that have not acquired additional resistance mechanisms. Additionally, certain agents require higher dosing when used for presumptive or known P. aeruginosa infections.
Fluoroquinolones are the only class of antibiotics which has an oral formulation that is reliably active against P. aeruginosa.
Aminoglycosides (gentamicin, tobramycin, amikacin) are active against P. aeruginosa but are generally not used as single agents because of inadequate clinical efficacy at most sites.
The use of combination antimicrobial therapy in patients with serious P. aeruginosa infections remains controversial, largely because of the paucity of well controlled comparison trials using clinically important end points. There is no convincing clinical evidence that using two active agents instead of one leads to improved outcomes despite theoretical synergistic activity or decreases the risk of emergent resistance. However, using two agents for empiric therapy may increase the likelihood that an active agent will be used for a potentially resistant organism, and this, in turn, is associated with better outcomes for serious infections.
We typically reserve combination therapy for empiric treatment of serious infections known or suspected to be caused by P. aeruginosa that are associated with high mortality or when the risk of resistance is high.
Thus, for patients who have sepsis or septic shock, have neutropenia and bacteremia, have severe burns, or are in a setting where the incidence of resistance to the chosen antibiotic class is high (eg, >10 to 15 percent), we suggest empiric therapy with a combination of two antipseudomonal agents (Grade 2C). The two agents should be from different antibiotic classes, eg, a beta-lactam with an aminoglycoside.
For patients without any of these additional risk factors for mortality or resistant organisms, we recommend empiric treatment with a single antipseudomonal agent (Grade 2B).
Once antimicrobial susceptibility data are available, we typically use a single active antipseudomonal agent. The rare exceptions when a combination regimen may be warranted include neutropenia and bacteremia, endocarditis, failure to improve on therapy, and multidrug resistance.
Multidrug resistance in many organisms, including P. aeruginosa, is a growing clinical problem, and often treatment with alternative antibiotics, such as colistin, is necessary.
Certain strategies for treatment of resistant P. aeruginosa include the use of alternative drug combinations, and, for pneumonia, inhaled antibiotics as adjunctive therapy. However, the clinical data for some of these strategies are limited. Multidrug resistant P. aeruginosa should be managed with the assistance of an expert in the treatment of such infections.
The general principles of antipseudomonal therapy in children are similar to those in adults with the main exception that antimicrobial dosing is weight-based. Use of a fluoroquinolone is a consideration for gram-negative infections caused by isolates susceptible to these agents, including infections caused by P. aeruginosa. No compelling published evidence supports the occurrence of sustained injury to developing bones or joints in children treated with available fluoroquinolone agents.
Combination therapy for highly resistant infections
- Ticarcillin plus tobramycin plus rifampin
- Polymyxin B plus rifampin
- A fluoroquinolone plus either ceftazidime or cefepime
- Ceftazidime plus colistin
- Clarithromycin plus tobramycin
- Azithromycin plus one of the following: tobramycin, doxycycline, trimethoprim, or rifampin
- Colistin plus rifampin
- Fosfomycin plus a carbapenem
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