Although in vitro data suggest that tigecycline is active against
Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-Kp),
experimental and clinical data are limited. We studied the effect of
tigecycline alone or in combination for experimental infections by
KPC-Kp. A total of 540 male C57BL/6 mice were infected with three
genetically diverse KPC-Kp isolates susceptible to tigecycline with
meropenem minimum inhibitory concentrations (MICs) of 4, 16 and 256 mu
g/mL, respectively. Mice were randomly treated with water for injection,
tigecycline, meropenem and colistin alone, and double or triple
combinations of tigecycline, colistin and meropenem. Mouse survival was
recorded for 14 days. In separate experiments, mice were sacrificed 6 h
and 24 h after bacterial challenge for quantitative culture of tissues
and serological analysis. Time-kill curves were performed. Tigecycline,
colistin and meropenem concentrations were measured in tissues and serum
by high-performance liquid chromatography (HPLC). Survival was
significantly prolonged when mice were treated with tigecycline alone
and tigecycline-containing regimens compared with control mice and mice
treated with tigecycline-sparing regimens. Tigecycline-sparing regimens
were active only against the isolate with a meropenem MIC of 4 mu g/mL.
Mortality was associated with progression to multiple organ failure.
Tigecycline and tigecyclinecontaining regimens achieved a rapid decrease
of bacterial loads both in tissues and in vitro. Tigecycline
concentrations in tissues were negatively correlated with tissue
bacterial load. Tigecycline alone or in combination with meropenem
and/or colistin achieves effective treatment of experimental KPC-Kp
infections irrespective of the meropenem MIC. (c) 2021 Elsevier Ltd and
International Society of Antimicrobial Chemotherapy. All rights
reserved
