Effect of treatment with methicillin and gentamicin in a new experimental mouse model of foreign body infection.
A new mouse model of foreign body infection has been developed. Intraperitoneal placement of a silicone catheter followed by injection of 10(8) Staphylococcus aureus organisms resulted in a reproducible, localized foreign body infection. The infection persisted as an intra-abdominal abscess surrounding the catheter for at least 30 days. Treatment with up to nine doses of methicillin or gentamicin or both was started 3 days after infection. The treatment showed a significant effect (P < 0.05), measured as reduction of bacteria on the foreign body, for all three regimens with a reduction of up to 2 log units, but no synergism was observed. The result of the treatment was poor, despite the facts that the local concentrations of methicillin were greater than the MIC for at least 72 h and that nine peak concentrations of gentamicin of > 13 micrograms/ml were obtained. The poor result of the treatment was not caused by development of antibiotic resistance or influenced by protein concentration, pH, or local presence in the pus of inhibitors of antibiotics. Both antibiotics showed good effects in time-kill studies in vitro on bacteria on catheters taken out of infected mice and catheters infected in vitro. During treatment, the proportion of intracellular bacteria increased in all treated mice to 60 to 75% compared with 20 to 30% in nontreated mice (P < 0.05). This indicates that intracellular survival of staphylococci may influence the outcome of the treatment in foreign body infections.
Espersen
F
F
Division of Preventive Microbiology, Statens Seruminstitut, Rigshospitalet, Copenhagen, Denmark.
Frimodt-Møller
N
N
Corneliussen
L
L
Riber
U
U
Rosdahl
V T
VT
Skinhøj
P
P
D000818:Animals; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005122:Exudates and Transudates / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005549:Foreign-Body Reaction / Q000188:drug therapy* / Q000382:microbiology; D005839:Gentamicins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007700:Kinetics; D008712:Methicillin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016106:Methicillin Resistance; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects
D005839:Gentamicins; D008712:Methicillin