Decreased neutrophil response in a model of chronic intraperitoneal Klebsiella infection.
BACKGROUND
Previously, we developed an infection model by intraperitoneal (IP) injection of Klebsiella pneumoniae. The high early mortality rate prompted a study of the effect of gentamicin on the disease course.


METHODS
Infection was induced in Balb/c mice by IP inoculation of 10(3) colony-forming units (cfu) of K. pneumoniae serotype 2. Mice then received either saline or gentamicin twice daily at 5 mg/kg/day. Survival and weight loss were determined daily over 14 days. Leukocyte counts (WBC) were performed on peritoneal lavage fluid (PL) and peripheral blood. Bacterial counts in blood, lung homogenate, and PL were determined by culture.


RESULTS
A significant survival benefit was seen in the gentamicin group by 48 h (p < 0.05), which persisted at 14 days. Weight loss of 2 g (p < 0.05) occurred in all mice by day three, with recovery seen only in the gentamicin-treated mice. Mice that did not regain their weight by day seven or lost more than 4 g (20%) died. All animals had peritoneal bacteria recovered at all time points. The gentamicin group showed fewer bacteria at one day in lung, blood, and PL, the difference being significant for the PL. Gentamicin did not clear peritoneal bacteria, and counts remained at inoculum concentration (10(3) cfu), but elicited no significant neutrophil influx. Whereas there was a progressive increase in total lavage WBC over time, the gentamicin group showed no significant neutrophil influx in PL or lung until bacterial counts exceeded 10(5) cfu.


CONCLUSIONS
Despite persistent intra-abdominal infection, gentamicin treatment significantly prolonged survival in this uniformly lethal model. Although antibiotic treatment did not suppress bacteremia, it did diminish bacterial spread from the blood to the lung. This procedure produced a clinically relevant, novel model of antibiotic-treated chronic intraperitoneal infection, which will allow future study of specific host defense mechanisms.
Woods
Dustin R
DR
Veterans Affairs Medical Center and Department of Surgery, University of Louisville, Louisville, Kentucky, USA.
Peyton
James C
JC
Franklin
Glen A
GA
Turina
Mathias
M
Cheadle
William G
WG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D005839:Gentamicins / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007710:Klebsiella Infections / Q000188:drug therapy / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000472:pathogenicity*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000382:microbiology; D010533:Peritoneal Lavage; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D005839:Gentamicins