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

Harris, Patrick N A; Ferguson, John

doi:10.1016/j.ijantimicag.2012.06.004

Cited by 110 publications

(86 citation statements)

References 131 publications

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“…bloodstream infection during third-generation cephalosporin therapy [Chow et al 1991;Choi et al 2008], but is less so for other bacteria of the group such as Serratia marcencens, Morganella morganii, and Citrobacter spp. The risk for resistance emergency and therapeutic failure is probably highest for certain sites of infection associated with high-inoculum or diminished drug concentrations [Harris and Ferguson, 2012]. Therefore, third-generation cephalosporins (and monobactams) must be avoided to treat severe infections by these bacteria despite being susceptible in vitro [Jacoby, 2009;Navarro et al 2010], but such concerns are probably less important for other sites of infections like the urinary tract [Harris and Ferguson, 2012].…”

Section: Third-generation Cephalosporinsmentioning

confidence: 99%

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Delgado-Valverde

Sojo-Dorado

Pascual

2013

Therapeutic Advances in Infection

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Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum b-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to lowlevel resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. IntroductionThe traditional first-line available options for treating serious infections caused by enterobacteria include penicillins, cephalosporins, monobactams, carbapenems, fluorquinolones, and in certain situations, aminoglycosides. The frequency of resistance to these first-line agents has been rising worldwide during the last decades [Paterson 2006;Rhomberg and Jones 2009;Houghton et al. 2010;Nordmann, et al. 2011] and now reach high proportions in many areas of the world.

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Section: Third-generation Cephalosporinsmentioning

confidence: 99%

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Delgado-Valverde

Sojo-Dorado

Pascual

2013

Therapeutic Advances in Infection

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“…This would help the physicians to optimize the current therapeutic treatment options. Although previous studies have indicated that 3 rd generation cephalosporins appears to be suboptimal choices for treating infections caused by pathogens producing AmpC β-lactamases, the role of Cefepime has been unsettled and many experts recommend resorting to Carbapenem therapy, which appear to have both excellent in vitro and vivo activity against these organism (25,26,27,28,29,30,31).…”

Section: Graphical Distribution Of Antimicrobial Susceptibility Pattementioning

confidence: 99%

AmpC β-lactamase Production in Pseudomonas aeruginosa: A Threat

Agrawal¹,

Srivastava²,

Kumar³

et al. 2017

Int.J.Curr.Microbiol.App.Sci

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“…On the other hand, AmpCs are not inhibited by inhibitors and do not hydrolyze FEP (1,(3)(4)(5). Therefore, FEP is suggested for the treatment of infections caused by AmpC producers (6)(7)(8).…”

mentioning

confidence: 99%

In Vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime

Pires

Taracila

Bethel

et al. 2015

Antimicrob Agents Chemother

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Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) ␤-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical Escherichia coli isolates obtained from a patient. The CMY-2-producing E. coli isolate (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producing E. coli isolate (CMY-33-Ec) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime. CMY-33-Ec and CMY-2-Ec were identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different ␤-lactam MICs (e.g., cefepime MIC, 16 and <0.5 g/ml for CMY-33-Ec and CMY-2-Ec, respectively). Identical CMY-2-Ec isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in E. coli strain DH10B, both CMYs conferred resistance to ceftazidime (>256 g/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 g/ml, respectively). The k cat /K m or inhibitor complex inactivation (k inact )/K i app (M ؊1 s ؊1 ) indicated that CMY-33 possesses an extended-spectrum ␤-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (ϳ4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-Ec isolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical. E nterobacteriaceae can manifest resistance to third-generation cephalosporins as a result of the production of extended-spectrum ␤-lactamases (ESBLs), chromosomal AmpC (cAmpCs), or plasmid-mediated AmpCs (pAmpCs) (1, 2). In general, ESBLs are inhibited by the commercially available ␤-lactamase inhibitors but hydrolyze well the fourth-generation cephalosporin cefepime (FEP). On the other hand, AmpCs are not inhibited by inhibitors and do not hydrolyze FEP (1, 3-5). Therefore, FEP is suggested for the treatment of infections caused by AmpC producers (6-8).In the past, AmpC variants with enhanced hydrolytic efficiency against FEP were sporadically reported in Enterobacter spp. (8-11), Serratia marcescens (12), and Escherichia coli (13-17). These chromosomal extended-spectrum AmpC ␤-lactamases (cESACs) possess specific amino acid insertions, deletions, duplications, or substitutions in the H-10 helix (also named the R2-loop) that allow better accommodation and hydrolysis of FEP in the serine active site (1,4,11,14). More ...

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

Cited by 110 publications

References 131 publications

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

AmpC β-lactamase Production in Pseudomonas aeruginosa: A Threat

In Vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime

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