期刊
CLINICAL MICROBIOLOGY AND INFECTION
卷 20, 期 11, 页码 O831-O839出版社
ELSEVIER SCI LTD
DOI: 10.1111/1469-0691.12677
关键词
Extended-spectrum -lactamase; inoculum effect; Klebsiella pneumoniae; meropenem; piperacillin-tazobactam; pneumonia
资金
- Dainippon Sumitomo Pharma Co. Ltd.
- Taisho Toyama Pharmaceutical
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [21591294]
- Japan Society for the Promotion of Science [23791137, 25860830]
- Global Centers of Excellence Program, Nagasaki University
- Grants-in-Aid for Scientific Research [25860830, 23791137] Funding Source: KAKEN
The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum -lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on -lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on -lactams was evaluated at standard (10(5)CFU/mL) and high (10(7)CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000mg/kg four times daily, %T > MIC; 32.60%) or meropenem (100mg/kg twice daily, %T > MIC; 28.65%) at low/standard (10(4)CFU/mouse) and high (10(6)CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.
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