Rationale for use of antimicrobial combinations in treatment of gram-negative infections. A review of recent reviews.

All investigators apparently agree that the most common and compelling reason for using more than one antibiotic to treat a single organism is to achieve a bactericidal effect. Most studies, both retrospective and prospective, have demonstrated that two effective antibiotics yield better results than one in neutropenic patients and/or those with rapidly fatal underlying disease, despite the absence of consistent in vitro synergy. Bacteremias caused by Pseudomona aeruginosa or Klebsiella pneumoniae may be benefited most by synergistic combinations. This may not be true for patients with non-neoplastic disease and normal granulocyte counts, or for patients infected with other species of gram-negative bacilli. Synergistic bactericidal activity is necessary for the successful therapy of endocarditis due to P. aeruginosa, but it may not assure success. The systemic immunodeficiency of neutropenic patients may parallel a localized immunodeficiency in endocarditis, since leukocytes are not effectively mobilized to the site of infection in endocarditis. Antagonistic antibiotic combinations are likely to be particularly harmful in neutropenic patients.