Monotherapy or Combination Therapy?

The Pseudomonas aeruginosa Conundrum

Kristi A. Traugott, Pharm.D.; Kelly Echevarria, Pharm.D.; Pamela Maxwell, Pharm.D.; Kay Green, B.S.; James S. Lewis, II, Pharm.D.


Pharmacotherapy. 2011;31(6):598-608. 

In This Article


Pseudomonas aeruginosa bacteremia and VAP are severe illnesses with exceedingly high mortality rates. Numerous studies have demonstrated that appropriate empiric therapy leads to significantly lower mortalities in bacteremia, and one large trial has demonstrated similar results for VAP. In addition, several studies have linked combination therapy to significantly higher rates of adequate empiric therapy and lower mortality. Therefore, it may be reasonable to consider empiric combination therapy in seriously ill patients with suspected pseudomonal infections, especially in those with sepsis, septic shock, surgery, or pneumonia, to improve the likelihood of an active agent being included in the initial antibiotic regimen of these patients. When empiric combination therapy is used, the second agent chosen should be one likely to be active against an organism resistant to the primary agent.

The data for combination therapy are less clear with regard to definitive therapy. Most studies failed to show mortality benefits of combination therapy when examining only adequate empiric therapy or definitive therapy. Therefore, deescalation of antibiotics to monotherapy once susceptibility data are known appears reasonable. Finally, since combination regimens are not innocuous, one must keep in mind the rarity of these infections. Most combination therapy is empirically started before organism identification, and most patients empirically starting combination therapy will not have a pseudomonal infection; therefore, numerous patients receive all the risk of combination therapy with little benefit.

It is prudent to evaluate the clinical status of the patient and true likelihood of encountering an MDR organism before deciding on empiric combination therapy or monotherapy. Future research may be able to better identify which patient populations might receive the most benefit from combination therapy rather than using combination therapy on everyone at risk for these infections.