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Lincomycin-induced endotoxin release in Escherichia coli sepsis: evidence for release in vitro and in vivo
1Department of Internal Medicine, Tsushima Chuoh Hospital, Tsushima, Japan. horii@tsuru.med.nagoya-u.ac.jp
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.
Conclusion:
Results of this study suggest that the bacteriostatic antibiotics, lincomycin and clindamycin, induce endotoxin release in the treatment of E. coli infections.