Pretreatment of Pseudomonas aeruginosa with a sub-MIC of imipenem enhances bactericidal activity of neutrophils

Sasahara, Takeshi; Satoh, Yoshinori; Sekiguchi, Tomoko; Suzuki, Kaoruko; Irinoda, Kazuhiko; Takayama, Yoko; Sakamoto, Ayako; Kitasato, Hidero; Okamoto, Ryoichi; Inoue, Matsuhisa

doi:10.1007/s10156-003-0264-4

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…A similar mechanism may also be at play for doripenem. For instance, exposure of neutrophils to carbapenems has been associated with increased phagocytic killing of pathogenic bacteria (31,32), and hemocytes of G. mellonella share similar kinetics of phagocytosis and microbial killing with human neutrophils (33). Therefore, it is possible that certain immunologic effects are augmenting the antibacterial activity of these agents, leading to better efficacy than is observed in vitro.…”

Section: Resultsmentioning

confidence: 99%

Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

O’Hara

Ambe

Casella

et al. 2013

Antimicrob Agents Chemother

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Section: Resultsmentioning

confidence: 99%

Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

O’Hara

Ambe

Casella

et al. 2013

Antimicrob Agents Chemother

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“…The bacteriostatic activity of isolated neutrophils was determined by an in vitro killing assay as described in ref. 31. Briefly, purified neutrophils (5 ϫ 10 5 ) were resuspended in 1 ml of warmed PBS containing 10% fresh serum obtained from syngeneic mice and 0.1% gelatin.…”

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confidence: 99%

Lipocalin 2-deficient mice exhibit increased sensitivity toEscherichia coliinfection but not to ischemia-reperfusion injury

Berger

Togawa

Duncan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

418

402

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Diverse functions have been reported for lipocalin 2. To investigate these functions in vivo, we generated gene-targeted lipocalin 2-deficient mice (Lcn2 ؊/؊ mice). In vitro studies have suggested that lipocalin 2 is important for cellular apoptosis induced by IL-3 withdrawal, and for the induction of kidney differentiation during embryogenesis. Analysis of Lcn2 ؊/؊ mice showed normal cell death upon IL-3 withdrawal and normal kidney development. However, we found that Lcn2 ؊/؊ mice exhibited an increased susceptibility to bacterial infections, in keeping with the proposed function of lipocalin 2 in iron sequestration. Neutrophils isolated from Lcn2 ؊/؊ mice showed significantly less bacteriostatic activity compared with WT controls. The bacteriostatic property of the WT neutrophils was abolished by the addition of exogenous iron, indicating that the main function of lipocalin 2 in the antibacterial innate immune response is to limit this essential element. Another important function ascribed to lipocalin 2 has been its protective role against kidney ischemia-reperfusion injury. We analyzed Lcn2 ؊/؊ mice using a mouse model for severe renal failure and could not detect any significant differences compared with their WT littermates.24p3 ͉ bacteriostatic ͉ kidney ischemia-reperfusion injury ͉ NGAL

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“…Previous studies revealed that the synergistic activity among β-lactams and amikacin was not attributed to the level of the minimum inhibitory concentrations (MICs) of the antibiotics tested in combination but due to the post-antibiotic effect (PAE) of the tested amikacin and other antibiotics [ 20 , 21 ]. The synergistic effect of amikacin with other antimicrobials was studied by many researchers that explained the action of combinations tested based on post-antibiotic effects [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Effect of Amikacin and Imipenem Combinations against Multidrug-Resistant E. coli

et al. 2022

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Introduction: The emergence of multidrug-resistant (MDR) E. coli has developed worldwide; therefore, the use of antibiotic combinations may be an effective strategy to target resistant bacteria and fight life-threatening infections. The current study was performed to evaluate the in vitro and in vivo efficacy of amikacin and imipenem alone and in combination against multidrug-resistant E. coli. Methods: The combination treatment was assessed in vitro using a checkerboard technique and time-killing curve and in vivo using a peritonitis mouse model. In resistant isolates, conventional PCR and quantitative real-time PCR techniques were used to detect the resistant genes of Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib). Scanning electron microscopy was used to detect the morphological changes in the resistant isolates after treatment with each drug alone and in combination. In vitro and in vivo studies showed a synergistic effect using the tested antibiotic combinations, showing fractional inhibitory concentration indices (FICIs) of ≤0.5. Regarding the in vivo study, combination therapy indicated a bactericidal effect after 24 h. E. coli isolates harboring the resistant genes Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib) represented 80% and 66.7%, respectively, which were mainly isolated from wound infections. The lowest effect on Metallo-β-lactamase gene Imipenemase (bla-IMP) and aminoglycoside 6′-N-acetyltransferase (aac (6′)-Ib) gene expression was shown in the presence of 0.25 × MIC of imipenem and 0.5 × MIC of amikacin. The scanning electron microscopy showed cell shrinkage and disruption in the outer membrane of E. coli in the presence of the antibiotic combination. Amikacin and imipenem combination can be expected to be effective in the treatment and control of serious infections caused by multidrug-resistant (MDR) E. coli and the reduction in bacterial resistance emergence.

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Pretreatment of Pseudomonas aeruginosa with a sub-MIC of imipenem enhances bactericidal activity of neutrophils

Cited by 5 publications

References 24 publications

Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

Activities of Vancomycin-Containing Regimens against Colistin-Resistant Acinetobacter baumannii Clinical Strains

Lipocalin 2-deficient mice exhibit increased sensitivity toEscherichia coliinfection but not to ischemia-reperfusion injury

In Vitro and In Vivo Effect of Amikacin and Imipenem Combinations against Multidrug-Resistant E. coli

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