Antimicrobial therapy of septicemia due to Klebsiella pneumoniae in neutropenic rats.

Three different isolates of Klebsiella pneumoniae, highly sensitive to amikacin but varying in susceptibility to cefazolin, were injected intraperitoneally into neutropenic rats. Animals were treated every 8 hr for 72 hr with saline (controls), cefzolin (full dose, 40 mg/kg; one-fourth dose, 10 mg/kg), amikacin (full dose, 8 mg/kg; one-fourth dose, 2 mg/kg), or a combination of both drugs at either full dose or one-fourth dose. All drugs were given intramuscularly. Combination therapy with full doses produced higher mean bactericidal titers in serum and more rapid clearance of bacteria from blood and peritoneal washings. However, cumulative mortality at 72 hr in rats treated with amikacin plus cefazolin in full doses (24%, 23%, and 44%) was not significantly different from mortality in rats treated with amikacin alone (34%, 17%, and 62%). Results with cefazolin alone were not significantly different from the mortality in control animals for two of the three challenge organisms. When the minimal inhibitory concentration of cefazolin was less than or equal to 8 micrograms/ml, in vivo synergy was suggested by the similar survival rate obtained with a combination of a one-fourth dose of each agent and with amikacin alone in a full dose. These results demonstrate the relative ineffectiveness of cefazolin for therapy of klebsiella septicemia and suggest that in vivo antimicrobial synergy occurs in combination therapy against strains of bacteria relatively sensitive to cephalosporins.