Therapy of pulmonary nocardiosis in immunocompromised mice

Antimicrob Agents Chemother. 1990 Sep;34(9):1766-8. doi: 10.1128/AAC.34.9.1766.

Abstract

We compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced Nocardia asteroides pneumonia in immunocompromised mice. Cortisone acetate treatment, which produced impaired cell-mediated immune function, was followed by nasal inoculation of 5 x 10(4) CFU of N. asteroides into each mouse. Therapy was begun 24 h after inoculation and continued for the next 96 h. Dosages of antimicrobial agents resulted in concentrations approximating levels in human serum. Animals from each of nine treatment groups were sacrificed every 24 h. The pulmonary tissue obtained was homogenized and quantitatively cultured. Results were calculated to indicate the number of CFU per gram of lung tissue. Amikacin and imipenem were the two most effective single agents studied. Sulfadiazine and ciprofloxacin were ineffective, and ceftriaxone reduced bacterial counts modestly. Combination therapy did not enhance the bactericidal activities of the agents tested. We conclude that amikacin and imipenem, as well as select broad-spectrum cephalosporins, represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents (e.g., human immunodeficiency virus-infected patients) or who fail primary treatment.

Publication types

  • Comparative Study

MeSH terms

  • Amikacin / pharmacokinetics
  • Amikacin / therapeutic use
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Ceftriaxone / pharmacokinetics
  • Ceftriaxone / therapeutic use
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / therapeutic use
  • Cortisone / adverse effects
  • Cortisone / pharmacology
  • Female
  • Humans
  • Imipenem / pharmacokinetics
  • Imipenem / therapeutic use
  • Immunity, Cellular / drug effects
  • Immunologic Deficiency Syndromes / chemically induced
  • Immunologic Deficiency Syndromes / complications
  • Immunologic Deficiency Syndromes / drug therapy*
  • Lung Diseases / drug therapy*
  • Mice
  • Nocardia Infections / complications
  • Nocardia Infections / drug therapy*
  • Nocardia Infections / immunology
  • Nocardia asteroides
  • Sulfadiazine / pharmacokinetics
  • Sulfadiazine / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Sulfadiazine
  • Ciprofloxacin
  • Imipenem
  • Ceftriaxone
  • Amikacin
  • Cortisone