[Effects of isepamicin and beta-lactam antibiotics on the release of endotoxin from Pseudomonas aeruginosa].
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 beta-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/ml at 1MIC). PIPC and CAZ caused a gradual killing and a large amount of LPS release at 4 hrs (515 ng/ml and 493 ng/ml, respectively, at 1 MIC). At 1/4 x MIC, PIPC and CAZ did not reduce colony forming counts and induced 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 pharmacokinetic autosimulation system. ISP inhibited the bacterial regrowth and the following release of free LPS by 8 hrs. Great amounts of free LPS were released 4 hrs after the administration of PIPC and CAZ in the simulation system, associated with morphological changes; elongation, cell lysis or regrowth. IPM showed a strong bactericidal activity and less liberation 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 system were as follows; ISP < IPM < CAZ < PIPC.
Yamaguchi
S
S
Institute for Life Science Research, Asahi Chemical Industry.
Sato
S
S
Toriya
M
M
Tsuji
A
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D004731:Endotoxins / Q000378:metabolism*; D005839:Gentamicins / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism*; D013845:Thienamycins / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004731:Endotoxins; D005839:Gentamicins; D010406:Penicillins; D013845:Thienamycins; D015378:Imipenem; D002442:Ceftazidime; C016927:isepamicin; D010878:Piperacillin