Survival after intramuscular or inhalation administration of gentamicin in neutropenic guinea pigs infected by Klebsiella pneumoniae

Guinea pigs were infected by intranasal administration of Klebsiella pneumoniae on day 7 after irradiation with a dose of 4 Gy and treated on days 8-10 by gentamicin 4 mg/kg bd im or by inhalation leading to estimated systemically absorbed doses of 5.9 mg/kg/day. All animals died; however, gentamicin treatment significantly (P less than 0.05, Fisher's exact test) delayed death in the specific time intervals: 7-13 days (with the exception of day 11) and 12-26 days after im and inhalation administration respectively. Comparison of the two treatments by Fisher's exact test showed a significant advantage (P less than 0.05) for im vs inhalation treatment on days 9 and 10 only. The log rank test gave somewhat different results in that the delay of death after im administration was highly significantly (P less than 0.002) different from control whereas results after inhalation were not significantly different from control (P = 0.06). Moreover, according to the log rank test, im administration delayed death significantly (P = 0.04) better than inhalation. In conclusion these data do not show any advantage of inhalation over im administration for treatment of experimental pneumonia, indeed they are compatible with im administration being marginally more effective.