Lincomycin-induced endotoxin release in Escherichia coli sepsis: evidence for release in vitro and in vivo.
OBJECTIVE
To evaluate the propensity of lincomycin and clindamycin to induce release of endotoxin, the authors investigated endotoxin release in Escherichia coli isolated from a patient who developed septic shock following lincomycin treatment.


METHODS
Endotoxin release from the E. coli isolate exposed to lincomycin, clindamycin, and ceftazidime were determined in vitro and in vivo.


RESULTS
In vitro, this E. coli released significantly larger amounts of endotoxin after exposure for 6 hours to lincomycin or clindamycin versus no antibiotic; however, endotoxin release with these antibiotics was significantly less than with ceftazidime. There was no significant difference in in vitro endotoxin release between small (8 mg/L) and large (0.5 minimum inhibitory concentration [MIC]) doses of these antibiotics, and 0.5 MICs of lincomycin and clindamycin were 1024 and 256 mg/L, respectively. These results were supported by scanning electron microscopic observations, which demonstrated that lincomycin, clindamycin, and ceftazidime induced formation of filamentous cells. In addition, plasma endotoxin concentrations after treatment for 4 hours with lincomycin, clindamycin, and ceftazidime (5 mg/kg) were at least 20-fold higher than with no antibiotic in an E. coli sepsis rat model.


CONCLUSIONS
Results of this study suggest that the bacteriostatic antibiotics, lincomycin and clindamycin, induce endotoxin release in the treatment of E. coli infections.
Horii
T
T
Department of Internal Medicine, Tsushima Chuoh Hospital, Tsushima, Japan. horii@tsuru.med.nagoya-u.ac.jp
Kimura
T
T
Nadai
M
M
Kobayashi
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002442:Ceftazidime / Q000009:adverse effects; D002981:Clindamycin / Q000009:adverse effects; D004731:Endotoxins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008034:Lincomycin / Q000009:adverse effects*; D008297:Male; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D002981:Clindamycin; C044101:endotoxin, Escherichia coli; D002442:Ceftazidime; D008034:Lincomycin