Friday, February 22, 2008
Pseudomonas aeruginosa Serious Infections: Mono or Combination Antimicrobial Therapy?
Curr Med Chem. 2008
Bassetti M, Righi E, Viscoli C.
Infectious Diseases Division, San Martino University Hospital, Genoa, Italy. email@example.com.
P. aeruginosa is a serious cause of infection with reported rates of mortality being up to 61%. Several studies evidenced a correlation between hospital mortality due to P. aeruginosa bloodstream infections and an inappropriate antimicrobial treatment. Increasing resistance in P. aeruginosa isolates complicates the selection of adequate empirical therapy in severe infections and P. aeruginosa is often indistinguishable from other gram-negative bacterial infections. For these reasons, present guidelines for the treatment of suspected P. aeruginosa bacteraemia recommend the rapid introduction of empirical antimicrobial therapy that includes at least one antipseudomonal agent until having microbiological results. Current consensus favours the use of empirical combination, balancing the potential for greater toxicity against the lower emergence of antimicrobial resistance and the greater killing that might be achieved by combination therapies acting synergistically. Advantages and disadvantages of combination therapy towards monotherapy for P. aeruginosa severe infections, current antibiotics used for P. aeruginosa severe infections and main studies published on this issue are reviewed.
PMID: 18289007 [PubMed - in process]
Pseudomonas aeruginosa: combined treatment vs. monotherapy
Med Intensiva. 2007 Mar
Bodí M, Garnacho J.
Hospital Universitario Joan XXIII de Tarragona, Tarragona, España. firstname.lastname@example.org
Keywords: Pseudomonas aeruginosa, combination therapy, microbiological results.
Pseudomonas aeruginosa is a pathogen commonly encountered in clinical practice in critically ill patients. It is a serious cause of infection, associated with a high rate of morbidity and mortality. Inappropriate antimicrobial therapy and delay in starting effective antimicrobial therapy is associated with worse prognostic. This microorganism is clinically indistinguishable from others forms of gram-negative bacterial infection. The rate of multidrug-resistant P. aeruginosa has increased in the last years. For these reasons, patients with Pseudomonas infection might receive empirical antibiotics that are inactive against Pseudomonas, especially before antibiotic susceptibility results become available. It remains controversial whether combination therapy, given empirically or as definitive treatment, for suspected Pseudomonas aeruginosa infections is justifiable. In the present article, we aimed to review recent studies that have evaluated the impact of combination therapy on Pseudomonas infections outcome and we exhibit our point of view in this subject. It seems justifiable to start combination therapy with two antipseudomonal agents in patients with risk for Pseudomonas infection during the first 3-5 days, until having microbiological results. This combination therapy must be changed to monotherapy on the basis on the specific susceptibility pattern of the initial isolate. In cases without microbiological diagnosis and poor outcome, combination therapy will be maintained and other causes of infection will be studied. Multicentre prospective randomized trials in critically ill patients are needed to determine which antimicrobials combinations improve outcome in Pseudomonas infections.
Pseudomonas aeruginosa bloodstream infections: how should we treat them?
Int J Antimicrob Agents. 2007 N
Pseudomonas aeruginosa remains a major cause of bloodstream infections associated with high mortality. Adequacy of empirical therapy seems to influence outcome. Because of its high intrinsic resistance and its capacity to develop resistance during therapy, exposure to antimicrobial therapies frequently leads to subsequent P. aeruginosa bacteraemia with resistant isolates, increasing the risk of inadequate empirical therapy. Therefore empirical therapy should not include antimicrobial agents used in the last few months. Definitive combination therapy does not influence the prognosis of P. aeruginosa bacteraemia. Similarly, empirical combination therapy does not improve survival until receipt of the antibiogram. In contrast, empirical combination therapy does improve survival from the day of receipt of antibiogram to day 30. We therefore suggest that patients suspected of P. aeruginosa bacteraemia should receive empirical combination therapy until receipt of the antibiogram, followed by downgrading to an adequate monotherapy. This strategy might reduce mortality in P. aeruginosa bloodstream infections without exposing the patient to an excessive risk of adverse events. Antimicrobial therapies might select P. aeruginosa isolates with particular virulence phenotypes. The influence of specific virulence determinants on the prognosis of P. aeruginosa bacteraemia, as well as the potential benefit of virulence inhibition, deserves further investigation.