Rapid Emergence of Resistance to Cefepime During Treatment

Limaye, Ajit P.; Gautom, Romesh; Black, Douglas J.; Fritsche, Thomas R.

doi:10.1086/516917

Cited by 37 publications

(17 citation statements)

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“…K. pneumoniae strains expressing PACBL are usually susceptible in vitro to zwitterionic cephalosporins and carbapenems, unless other mechanisms of resistance coincide (5,6,20,33,17,23). This may be related to the increased stability of such compounds with respect to AmpC-type beta-lactamases and their excellent penetration through the outer membrane (18,20).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

Pichardo

Rodríguez-Martínez²,

Pachón-Ibáñez

et al. 2005

Antimicrob Agents Chemother

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Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type ␤-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porindeficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1؋, 2؋, 4؋, 6؋, and 8؋ MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 g/ml, respectively. ⌬T/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

Pichardo

Rodríguez-Martínez²,

Pachón-Ibáñez

et al. 2005

Antimicrob Agents Chemother

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“…Péchère and Vladoianu (20) showed that ceftazidime-resistant E. cloacae strains contained a subpopulation of cefepime-resistant strains and that cefepime often failed to cure peritonitis due to ceftazidimeresistant E. cloacae strains in a murine experimental model. Furthermore, Limaye et al (14) described the emergence of cefepime-resistant E. aerogenes strains during cefepime treatment of a patient with septicemia and hepatic abscess with an E. aerogenes strain which was initially susceptible to ceftazidime but became resistant after ceftazidime use. These observations led Meideros (17) to caution against cefepime use in the treatment of high-inoculum ceftazidime-resistant Enterobacter infections.…”

Section: Discussionmentioning

confidence: 99%

“…An alarming observation in our study was the finding of occasional strains that were resistant to both cefepime and imipenem. Although no information was available on use of antimicrobial agents in the patients colonized with such strains, this phenotype has been reported to emerge during imipenem therapy (2,5,8,9,14,15). The vast majority of isolates were also resistant to ciprofloxacin, similarly to strains in France (4).…”

Section: Discussionmentioning

confidence: 99%

National Epidemiologic Surveys of Enterobacter aerogenes in Belgian Hospitals from 1996 to 1998

et al. 2001

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Two national surveys were conducted to describe the incidence and prevalence of Enterobacter aerogenes in 21 Belgian hospitals in 1996 and 1997 and to characterize the genotypic diversity and the antimicrobial resistance profiles of clinical strains of E. aerogenes isolated from hospitalized patients in Belgium in 1997 and 1998. Twenty-nine hospitals collected 10 isolates of E. aerogenes, which were typed by arbitrarily primed PCR (AP-PCR) using two primers and pulsed-field gel electrophoresis. MICs of 10 antimicrobial agents were determined by the agar dilution method. Beta-lactamases were detected by the double-disk diffusion test and characterized by isoelectric point. The median incidence of E. aerogenes colonization or infection increased from 3.3 per 1,000 admissions in 1996 to 4.2 per 1000 admissions in the first half of 1997 (P < 0.01). E. aerogenes strains (n ‫؍‬ 260) clustered in 25 AP-PCR types. Two major types, BE1 and BE2, included 36 and 38% of strains and were found in 21 and 25 hospitals, respectively. The BE1 type was indistinguishable from a previously described epidemic strain in France. Half of the strains produced an extended-spectrum betalactamase, either TEM-24 (in 86% of the strains) or TEM-3 (in 14% of the strains). Over 75% of the isolates were resistant to ceftazidime, piperacillin-tazobactam, and ciprofloxacin. Over 90% of the strains were susceptible to cefepime, carbapenems, and aminoglycosides. In conclusion, these data suggest a nationwide dissemination of two epidemic multiresistant E. aerogenes strains in Belgian hospitals. TEM-24 beta-lactamase was frequently harbored by one of these epidemic strains, which appeared to be genotypically related to a TEM-24-producing epidemic strain from France, suggesting international dissemination.

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“…Although clinical and in vitro efficacy is usually seen for cefepime against Enterobacter, clinical failures were soon recognised after its introduction, especially in high-inoculum infections with strains exhibiting ceftazidime resistance [79]. This may occur by a two-step process involving selection of hyperproducing AmpC mutants and changes in cell wall permeability [80].…”

Section: Cefepime Resistancementioning

confidence: 99%

Antibiotic therapy for inducible AmpC β-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?

Harris

Ferguson

2012

International Journal of Antimicrobial Agents

110

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Rapid Emergence of Resistance to Cefepime During Treatment

Abstract: and cefepime therapy in a murine peritonitis model. J Antimicrob Chemo-

Cited by 37 publications

References 1 publication

Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

National Epidemiologic Surveys of Enterobacter aerogenes in Belgian Hospitals from 1996 to 1998

Antibiotic therapy for inducible AmpC β-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?

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