Broad-spectrum  -lactams for treating experimental peritonitis in mice due to Escherichia coli producing plasmid-encoded cephalosporinases

Vimont, Sophie; Aubert, Daniel; Mazoit, Jean‐Xavier; Poirel, Laurent; Nordmann, Patrice

doi:10.1093/jac/dkm317

Cited by 14 publications

(11 citation statements)

References 30 publications

(13 reference statements)

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“…This lack of efficacy was also observed by Vimont et al in an experimental model of peritonitis caused by E. coli producing plasmid-mediated AmpC-type betalactamases, where the 50% effective doses (ED 50 ) of piperacillintazobactam ranged from 8.53 to 624 mg/kg, underscoring the lack of efficacy of this combination in this mouse model of infection (23). Whether the inoculum effect translates into clinical failure is controversial; even though failure of piperacillin-tazobactam in patients with intra-abdominal infections caused by susceptible isolates seems to be rare, the impact of the inoculum effect might be underestimated since surgery rapidly and drastically reduces the bacterial burden in such infections.…”

Section: Discussionsupporting

confidence: 73%

Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model

Docobo-Pérez

López-Cerero

López-Rojas

et al. 2013

Antimicrob Agents Chemother

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Escherichia coli is a common etiologic agent of intra-abdominal infections (IAI) (1) associated with a heavy bacterial burden (2) and of urinary tract infections and bacteremia (3-5), among others. The recommendations for empirical antimicrobial therapy for high-risk, severe, community-acquired, extrabiliary complicated IAI and health care-associated complicated IAI include piperacillin-tazobactam or carbapenems (6). Recently, data from an observational study suggested that amoxicillin-clavulanate and piperacillin-tazobactam are as effective as carbapenems in patients with bacteremia due to extended-spectrum ␤-lactamase (ESBL)-producing E. coli; however, most of the patients in that study had urinary or biliary tract infections and the number of patients with heavy bacterial loads was probably low (7). In this context, it is important to note that, in some areas, many ESBLproducing and non-ESBL-producing isolates of Klebsiella pneumoniae and E. coli are susceptible in vitro to piperacillin-tazobactam and imipenem, but the MICs may increase substantially if the susceptibility tests are performed with an inoculum concentration higher than the standard one (8-11). Recently, we have demonstrated, using a microdilution method and time-kill assays, that the reduction of in vitro activity at a high inoculum concentration does not occur with the amoxicillin-clavulanate combination against clinical non-ESBL-producing and ESBL-producing E. coli strains (9). Previously, when several Enterobacteriaceae species produced complex beta-lactamase patterns or ESBL (12, 13), both piperacillin-tazobactam and carbapenem compounds showed increased MICs when inoculum concentrations higher than the standard one are used. On the other hand, some authors have raised doubts about the existence of an inoculum effect (14), but in fact, little is known about the real in vivo impact of this effect. Thus, the objective of this study was to compare the in vivo efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against different tissue bacterial concentrations of two clinical E. coli strains in an experimental murine sepsis model.

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Section: Discussionsupporting

confidence: 73%

Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model

Docobo-Pérez

López-Cerero

López-Rojas

et al. 2013

Antimicrob Agents Chemother

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“…Talcum was added to the bacterial inoculum to enhance infection. The lack of a lethal effect of talcum alone has been shown previously (15). All experiments were done in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication 85-23, revised 1985).…”

mentioning

confidence: 81%

“…Taking into account the paucity of therapeutic options for the treatment of infections due to OXA-48 producers, we have tested the efficacy of five broad-spectrum ␤-lactam antibiotics against an OXA-48 producer (that did not coproduce an ESBL) using an experimental model of peritonitis in mice (15). The OXA-48 producer was a clinically significant Klebsiella pneumoniae isolate that was resistant to penicillins, including amoxicillin, ticarcillin, amoxicillin-clavulanate, piperacillin, and piperacillin-tazobactam, as described elsewhere (8).…”

mentioning

confidence: 99%

Broad-Spectrum β-Lactam Antibiotics for Treating Experimental Peritonitis in Mice Due to Klebsiella pneumoniae Producing the Carbapenemase OXA-48

Mimoz

Grégoire

Poirel

et al. 2012

Antimicrob Agents Chemother

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A lethal peritonitis model was induced in mice with a Klebsiella pneumoniae isolate producing the carbapenemase OXA-48. Administration of a single dose (up to 100 mg/kg) of the antibiotic piperacillin-tazobactam, imipenem-cilastatin, ertapenem, or cefotaxime had little or no impact on lethality. Ceftazidime had the highest efficacy in vivo, which mirrored its in vitro activity; this was not the case for carbapenems. Therefore, ceftazidime may be recommended for the treatment of infections due to OXA-48 producers if they do not coproduce an extended-spectrum ␤-lactamase or a plasmid-mediated AmpC cephalosporinase.

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“…␤-Lactam/␤-lactamase inhibitor combinations and most cephalosporins and penicillins should be avoided because of in vitro resistance, the potential for AmpC induction or selection of high-enzyme-level mutants, and documented poor clinical outcomes with ceftazidime, cefotaxime (244), and, in an animal model, piperacillin-tazobactam (329). Whether cefepime can be used is unsettled.…”

Section: Treatment Of Ampc-producing Organismsmentioning

confidence: 99%

AmpC β-Lactamases

2009

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SUMMARY AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal blaAmpC gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum β-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC β-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

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Broad-spectrum -lactams for treating experimental peritonitis in mice due to Escherichia coli producing plasmid-encoded cephalosporinases

Cited by 14 publications

References 30 publications

Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model

Inoculum Effect on the Efficacies of Amoxicillin-Clavulanate, Piperacillin-Tazobactam, and Imipenem against Extended-Spectrum β-Lactamase (ESBL)-Producing and Non-ESBL-Producing Escherichia coli in an Experimental Murine Sepsis Model

Broad-Spectrum β-Lactam Antibiotics for Treating Experimental Peritonitis in Mice Due to Klebsiella pneumoniae Producing the Carbapenemase OXA-48

AmpC β-Lactamases

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