In vitro and in vivo activities of piperacillin‐tazobactam and meropenem at different inoculum sizes of ESBL‐producing Klebsiella pneumoniae. (14th June 2014)

• Record Type: Journal Article
• Authors: Harada, Y.; Morinaga, Y.; Kaku, N.; Nakamura, S.; Uno, N.; Hasegawa, H.; Izumikawa, K.; Kohno, S.; Yanagihara, K.; Rolain, J.‐M.
• Is Part Of: Clinical microbiology and infection. Volume 20:Number 11(2014:Nov.)
• Page Start: O831
• Page End: O839
• Publication Date: 2014-06-14
• Subjects: Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1111/1469-0691.12677
• Languages: English
• ISSNs: 1198-743X

Abstract

<abstract abstract-type="main" id="clm12677-abs-0001"> <title>Abstract</title> <p>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 <italic>β</italic>‐lactamase‐producing <italic>Klebsiella pneumoniae</italic> (ESBL‐Kpn) infections, the inoculum effect of ESBL‐Kpn on <italic>β</italic>‐lactams was studied <italic>in vitro</italic> and <italic>in vivo</italic> using an experimental model of pneumonia. The <italic>in vitro</italic> inoculum effect of 45 clinical ESBL‐Kpn isolates on β‐lactams was evaluated at standard (10<sup>5</sup> CFU/mL) and high (10<sup>7</sup> CFU/mL) organism concentrations. The MIC<sub>50</sub> of piperacillin‐tazobactam, cefotaxime and cefepime was increased eight‐fold or more and that of meropenem was increased two‐fold. The <italic>in vivo</italic> inoculum effect was evaluated in an ESBL‐Kpn pneumonia mouse model treated with bacteriostatic effect‐adjusted doses of piperacillin‐tazobactam (1000 mg/kg four times daily, %T > MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T > MIC; 28.65%) at low/standard (10<sup>4</sup> CFU/mouse) and high (10<sup>6</sup> 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 <italic>in vitro</italic> and <italic>in vivo</italic>. In the management of severe pneumonia caused by ESBL‐Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.</p> </abstract>