Abstract
Antibiotic-induced release of endotoxin (lipopolysaccharide, LPS) from
Pseudomonas aeruginosa was investigated in
in vitro with different antibiotic concentrations and in the pharmacokinetic autosimulation system.We compared the effect of isepamicin (ISP) with those of 3 β-lactam antibiotics, piperacillin (PIPC), ceftazidime (CAZ) and imipenem (IPM).
ISP showed a strong bactericidal activity, but the amount of free LPS did not increase by 6 hrs (28±2 ng/mlat 1MIC). PIPC and CAZ caused a gradual killing and a large amount of LPS release at 4 hrs (515 ng/ml and493 ng/ml, respectively, at 1 MIC). At 1/4×MIC, PIPC and CAZ did not reduce colony forming counts andinduced more release of free LPS. The organism treated with IPM released less LPS, while it was killed rapidly.
The viable cell counts decreased dramatically after administration of ISP in the pharmacokineticautosimulation system.
ISP inhibited the bacterial regrowth and the following release of free LPS by 8 hrs. Great amounts of freeLPS were released 4 hrs after the administration of PIPC and CAZ in the simulation system, associated withmorphological changes; elongation, cell lysis or regrowth. IPM showed a strong bactericidal activity and lessliberation of free LPS, but the free LPS level increased at 8 hrs, accompanied by the regrowth of the organism.The total amounts of LPS released by P. aeruginosa PAO1 in 8 hours of the pharmacokinetic simulation systemwere as follows;
ISP<IPM<CAZ<PIPC.
