Efficacy of Cefepime in the Treatment of Infections Due to Multiply Resistant Enterobacter Species

We, Sanders; Jh, Tenney; Re, Kessler

doi:10.1093/clinids/23.3.454

Cited by 126 publications

(53 citation statements)

References 11 publications

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“…These data reflect the geno-and phenotypic heterogeneity of E. asburiae. In former studies, it played only a minor role as a clinical pathogen (9,12,40). In our study, one strain of the E. asburiae cluster (EN373) was isolated from the blood culture of a neonate (18).…”

Section: Discussionmentioning

confidence: 88%

Population Genetics of the Nomenspecies Enterobacter cloacae

Hoffmann

Roggenkamp

2003

Appl Environ Microbiol

245

270

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The genetic heterogeneity of the nomenspecies Enterobacter cloacae is well known. Enterobacter asburiae, Enterobacter cancerogenus, Enterobacter dissolvens, Enterobacter hormaechei, Enterobacter kobei, and Enterobacter nimipressuralis are closely related to it and are subsumed in the so-called E. cloacae complex. DNA-DNA hybridization studies performed previously identified at least five DNA-relatedness groups of this complex. In order to analyze the genetic structure and the phylogenetic relationships between the clusters of the nomenspecies E. cloacae, 206 strains collected from 22 hospitals, a veterinarian, and an agricultural center in 11 countries plus all 13 type strains of the genus and reference strain CDC 1347-71 R were examined with a combination of sequence and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses of the three housekeeping genes hsp60, rpoB, and hemB as well as ampC, the gene of a class C ␤-lactamase. Based on the neighbor-joining tree of the hsp60 sequences, 12 genetic clusters (I to XII) and an unstable sequence crowd (xiii) were identified. The robustness of the genetic clusters was confirmed by analyses of rpoB and hemB sequences and ampC PCR-RFLPs. Sequence crowd xiii split into two groups after rpoB analysis. Only three strains formed a cluster with the type strain of E. cloacae, indicating that the minority of isolates identified as E. cloacae truly belong to the species; 13% of strains grouped with other type strains of the genus, suggesting that the phenotypes of these species seem to be more heterogeneous than so far believed. Three clusters represented 70% of strains, but none of them included a type or reference strain. The genetic clustering presented in this study might serve as a framework for future studies dealing with taxonomic, evolutionary, epidemiological, or pathogenetic characteristics of bacteria belonging to the E. cloacae complex.Enterobacter cloacae has become increasingly important as a nosocomial pathogen, accounting for up to 5% of hospitalacquired septicemias, 5% of nosocomial pneumonias, 4% of nosocomial urinary tract infections, and 10% of postsurgical peritonitis cases (18,35,39). Besides its clinical significance, E. cloacae plays an important role as a pathogen in plants (2, 34) and insects (15) and is ubiquitous in the terrestrial and aquatic environments (22). This diversity of habitats is mirrored by the genetic variety of the nomenspecies E. cloacae, which has been demonstrated in several studies by biotyping and serotyping (16, 47), ribotyping and phage typing (46), pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) (18), and internal transcribed spacer-PCR and random amplification of polymorphic DNA (RAPD)-PCR (6). The 16S ribosomal DNA (rDNA) sequences of E. cloacae did not form a coherent cluster but built a patchy tree, in which the clusters of E. cloacae strains interfused with those of Enterobacter aerogenes, Escherichia coli, Citrobacter species, and Leclercia species. This refl...

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Section: Discussionmentioning

confidence: 88%

Population Genetics of the Nomenspecies Enterobacter cloacae

Hoffmann

Roggenkamp

2003

Appl Environ Microbiol

245

270

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“…The clinical implications of these types of enzymes are unknown. Since inducible expression of chromosomal AmpC ␤-lactamases is associated with a significant risk of therapeutic failure with all ␤-lactam drugs except carbapenems and dipolar methoxyiminocephalosporins (28,32), the question arises whether inducible expression of plasmid-mediated AmpC ␤-lactamases confers a similar or greater risk of therapeutic failure than constitutive expression of plasmid-mediated AmpC ␤-lactamases. If the risk is greater, it will be important for clinical laboratories not only to be able to detect imported AmpC ␤-lactamases but also to be able to test for inducibility.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Newer β-Lactamases in Klebsiella pneumoniae Isolates from 24 U.S. Hospitals

Moland

Black

Ourada

et al. 2002

Antimicrob Agents Chemother

109

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Despite the discovery of novel ␤-lactamases such as extended-spectrum ␤-lactamases (ESBLs), imported AmpC, and carbapenem-hydrolyzing ␤-lactamases at least a decade ago, there remains a low level of awareness of their importance and how to detect them. There is a need to increase the levels of awareness of clinical laboratories about the detection of newer ␤-lactamases. Therefore, a study was conducted in 2000 to investigate the occurrence of these ␤-lactamases in Klebsiella pneumoniae isolates at 24 U.S. medical centers. To enhance the likelihood of detecting imported AmpC and carbapenem-hydrolyzing ␤-lactamases, participating laboratories were permitted to include archived strains (1996 to 2000) that were intermediate or resistant to either cefoxitin or imipenem. The ␤-lactamase production of 408 isolates positive by screening of 1,123 isolates was investigated by ESBL phenotypic confirmation tests; and for AmpC and carbapenem-hydrolyzing ␤-lactamases, three-dimensional tests, isoelectric focusing, ␤-lactamase inhibitor studies, spectrophotometric assays, induction assays, and molecular tests were used. ESBL-producing isolates were detected at 18 of the 24 sites (75%), imported AmpC-producing isolates were detected at 10 sites (42%), inducible imported AmpC-producing isolates were detected at 3 sites (12.5%), and a molecular class A carbapenem-hydrolyzing enzyme was detected at 1 site (4%). No class B or D carbapenem-hydrolyzing enzymes were detected. ESBLs and imported AmpC ␤-lactamases were detected at a significant number of sites, indicating widespread penetration of these enzymes into U.S. medical institutions. Because these enzymes may significantly affect therapeutic outcomes, it is vital that clinical laboratories be aware of them and be able to detect their occurrence.

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“…Nonetheless, cefepime has cured infections due to multiply resistant Enterobacter spp. including those with reduced susceptibility to ceftazidime (286), and in a prospective, randomized study of ICU patients with nosocomial pneumonia having P. aeruginosa as the most common isolate, cefepime proved to be just as effective as imipenem (350). The jury is still out, but cefepime seems to be an exception to the recommendation to avoid all cephalosporin therapy even if an AmpC-producing isolate tests susceptible to an individual agent.…”

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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Efficacy of Cefepime in the Treatment of Infections Due to Multiply Resistant Enterobacter Species

Cited by 126 publications

References 11 publications

Population Genetics of the Nomenspecies Enterobacter cloacae

Population Genetics of the Nomenspecies Enterobacter cloacae

Occurrence of Newer β-Lactamases in Klebsiella pneumoniae Isolates from 24 U.S. Hospitals

AmpC β-Lactamases

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