scholarly journals Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins.

1983 ◽  
Vol 23 (6) ◽  
pp. 918-925 ◽  
Author(s):  
A H Seeberg ◽  
R M Tolxdorff-Neutzling ◽  
B Wiedemann
Keyword(s):  
Enterobacter Cloacae ◽  
Third Generation ◽  
Beta Lactamases ◽  
Third Generation Cephalosporins

Cefepime: A Fourth-Generation Parenteral Cephalosporin

1996 ◽  
Vol 30 (12) ◽  
pp. 1414-1424 ◽  
Author(s):  
Michael A Wynd ◽  
Joseph A Paladino
Keyword(s):  
Clinical Trials ◽  
Clinical Efficacy ◽  
Fourth Generation ◽  
Third Generation ◽  
Gram Positive ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Tract Infections ◽  
Third Generation Cephalosporins

OBJECTIVE: To review the chemistry, microbiology, pharmacokinetics, therapeutic efficacy, adverse effect profile, drug interactions, dosing, and administration of cefepime, a new fourth-generation parenteral cephalosporin. DATA SOURCES: A MEDLINE search of the available literature, including clinical trials and reviews, was performed. Abstracts presented at recent scientific conferences and current publications were also reviewed. DATA SELECTION: In vitro and preclinical data were included, as well as data from Phase II and III clinical trials. DATA SYNTHESIS: Cefepime is an extended-spectrum parenteral cephalosporin antibiotic active in vitro against a broad spectrum of gram-positive and gram-negative aerobic bacteria. The gram-positive spectrum is similar to that of cefotaxime, the gram-negative spectrum is similar to that of ceftazidime, and many, though not all, organisms resistant to these two agents remain susceptible to cefepime, prompting the fourth-generation designation. Cefepime has a high affinity for penicillin-binding proteins and, due to its zwitterionic configuration, rapidly penetrates outer-membrane porin channels of bacteria. Beta-lactamases appear to have a low affinity for the drug. Cefepime has a decreased propensity to induce beta-lactamases compared with other beta-lactam antibiotics. Cefepime has a pharmacokinetic disposition similar to that of other renally eliminated cephalosporins, with a half-life of approximately 2 hours. Cefepime has demonstrated clinical efficacy against a variety of infections, including urinary tract infections, pneumonia, and skin and skin structure infections. Cefepime is generally well tolerated. CONCLUSIONS: Cefepime may have several chemical and pharmacologic advantages over currently available third-generation cephalosporins. In vitro data indicate that cefepime retains activity against some, but not all, gram-negative bacteria resistant to third-generation cephalosporins; however, clinical efficacy against infections due to resistant pathogens remains to be established. Cefepime was at least as effective as comparators during clinical trials, and may prove to be a viable alternative to other currently available agents.

scholarly journals Multiple substitutions at position 104 of β-lactamase TEM-1: assessing the role of this residue in substrate specificity

1995 ◽  
Vol 305 (1) ◽  
pp. 33-40 ◽  
Author(s):  
A Petit ◽  
L Maveyraud ◽  
F Lenfant ◽  
J P Samama ◽  
R Labia ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Active Site ◽  
Kinetic Properties ◽  
Third Generation ◽  
Wild Type Enzyme ◽  
Beta Lactamases ◽  
Class A ◽  
Extended Spectrum ◽  
Third Generation Cephalosporins

Residue 104 is frequently mutated from a glutamic acid to a lysine in the extended-spectrum TEM beta-lactamases responsible for the resistance to third-generation cephalosporins in clinical Gram negative strains. Among class A beta-lactamases, it is the most variable residue within a highly conserved loop which delineates one side of the active site of the enzymes. To investigate the role of this residue in the extended-spectrum phenotype, it has been replaced by serine, threonine, lysine, arginine, tyrosine and proline. All these substitutions yield active enzymes, with no drastic changes in kinetic properties compared with the wild-type enzyme, except with cefaclor, but an overall improved affinity for second- and third-generation cephalosporins. Only mutant E104K exhibits a significant ability to hydrolyse cefotaxime. Molecular modelling shows that the substitutions have generally no impact on the conformation of the 101-111 loop as the side chains of residues at position 104 are all turned towards the solvent. Unexpectedly, the E104P mutant turns out to be the most efficient enzyme. All our results argue in favour of an indirect role for this residue 104 in the substrate specificity of the class A beta-lactamases. This residue contributes to the precise positioning of residues 130-132 which are involved in substrate binding and catalysis. Changing residue 104 could also modify slightly the local electrostatic potential in this part of the active site. The limited kinetic impact of the mutations at this position have to be analysed in the context of the microbiological problem of resistance to third-generation cephalosporins. Although mutation E104K improves the ability of the enzyme to hydrolyse these compounds, it is not sufficient to confer true resistance, and is always found in clinical isolates associated with at least one mutation at another part of the active site. It is the combined effect of the two mutations that synergistically enhances the hydrolytic capability of the enzyme towards third-generation cephalosporins.

scholarly journals Prevalence of plasmid-mediated AmpC beta-lactamases in Enterobacteria isolated from urban and rural folks in Uganda

2019 ◽  
Author(s):  
Christine Florence Najjuka ◽  
David Patrick Kateete ◽  
Dennis K Lodiongo ◽  
Obede Mambo ◽  
Chunderika Mocktar ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Third Generation ◽  
Beta Lactamase ◽  
Beta Lactamases ◽  
Rural Districts ◽  
E Coli ◽  
Amoxicillin Clavulanate ◽  
Rural Dwellers ◽  
Encoding Genes ◽  
Third Generation Cephalosporins

Abstract Background: AmpC beta-lactamases are associated with increased resistance to third-generation cephalosporins. Here, we describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda. Methods: Stool and urine from 1,448 individuals attending outpatient clinics in Kampala and two rural districts in central Uganda (Kayunga and Mpigi) were processed for isolation of Escherichia coli and Klebsiella. Following antibiotic susceptibility testing, cefoxitin resistant isolates, and amoxicillin/clavulanate resistant but cefoxitin susceptible isolates, were tested for AmpC beta-lactamase production using the cefoxitin-cloxacillin double-disc synergy test. Carriage of plasmid-mediated AmpC beta-lactamase-encoding genes (pAmpC) and extended spectrum beta-lactamase (ESBL) encoding genes was determined by PCR. Results: Nine hundred and thirty E. coli and 55 Klebsiella were recovered from the cultured samples, yielding 985 isolates (one per participant) investigated. One hundred and twenty nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC/ESBL gene carriage. pAmpC genes were detected in 60% (67/111) of the AmpC beta-lactamase producers; pAmpC genes were also detected in 18 AmpC beta-lactamase non-producers and in 13 isolates with reduced susceptibility to third-generation cephalosporins, yielding a total of 98 isolates that carried pAmpC genes. Overall, the prevalence of pAmpC genes in cefoxitin resistant and/or amoxicillin/clavulanate resistant E. coli and Klebsiella was 59% (93/157) and 26.1% (5/23), respectively. The overall prevalence of pAmpC-positive enterobacteria was 10% (98/985); 16.4% (45/274) in Kampala, 6.2% (25/406) Kayunga, and 9.2% (28/305) Mpigi. Ciprofloxacin use was associated with carriage of pAmpC-positive bacteria, while residing in rural districts was associated with protection from carriage of pAmpC-positive bacteria. Conclusion: pAmpC beta-lactamase producing enterobacteria are prevalent in urban and rural dwellers in Uganda, therefore, cefoxitn should be included during routine susceptibility testing in this setting.

scholarly journals A highly multiplexed melt-curve assay for detecting the most prevalent carbapenemase, ESBL and AmpC genes

2019 ◽  
Author(s):  
T. Edwards ◽  
C. Williams ◽  
Y. Teethaisong ◽  
J. Sealey ◽  
S. Sasaki ◽  
...  
Keyword(s):  
16S Rdna ◽  
Simultaneous Detection ◽  
Detection Methods ◽  
Gram Negative Bacteria ◽  
Third Generation ◽  
Molecular Surveillance ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Resistance Patterns ◽  
Third Generation Cephalosporins

AbstractResistance to third generation cephalosporins and carbapenems in Gram-negative bacteria is chiefly mediated by beta-lactamases including ESBL, AmpC and carbapenemase enzymes. Routine phenotypic detection methods do not provide timely results, and there is a lack of comprehensive molecular panels covering all important markers.An ESBL/carbapenemase HRM assay (SHV, TEM, CTX-M ESBLs, and NDM, IMP, KPC, VIM and OXA-48-like carbapenemases) and an AmpC HRM assay (16S rDNA control, FOX, MOX, ACC, EBC, CIT and DHA) were designed, and evaluated on 111 Gram-negative isolates with mixed resistance patterns.The sensitivity for carbapenemase, ESBL and AmpC genes was 96.7% (95%CI:82.8-99.9%), 93.6% (95%CI:85.7-97.9%) and 93.8% (95%CI:82.8-98.7%), respectively with a specificity of 100% (95%CI:95.6-100%), 93.9% (95%CI:79.8-99.3%) and 93.7% (95%CI:84.5-98.2%).The HRM assays enable the simultaneous detection of the fourteen most important ESBL, carbapenemase and AmpC genes and could be used as a molecular surveillance tool or to hasten detection of AMR for treatment management.

scholarly journals Survey and molecular genetics of SHV beta-lactamases in Enterobacteriaceae in Switzerland: two novel enzymes, SHV-11 and SHV-12.

1997 ◽  
Vol 41 (5) ◽  
pp. 943-949 ◽  
Author(s):  
M T Nüesch-Inderbinen ◽  
F H Kayser ◽  
H Hächler
Keyword(s):  
Molecular Genetics ◽  
Third Generation ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Low Resistance ◽  
Beta Lactam Antibiotics ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Third Generation Cephalosporins

Sixty isolates of Enterobacteriaceae resistant to beta-lactam antibiotics were collected over a period of 2 years in Switzerland and screened by hybridization for the carriage of SHV genes. Thirty-four positive strains were found, and their SHV genes were amplified and sequenced. SHV extended-spectrum beta-lactamases (ESBLs) were found: 13 strains contained SHV-2a, 12 harbored SHV-2, and SHV-5 was found twice. Four strains were shown to contain SHV-1. In addition, we report two new SHV variants, termed SHV-11 (non-ESBL) and SHV-12 (ESBL). In spite of the carriage of SHV ESBLs, many strains showed only low resistance to one or more third-generation cephalosporins. In addition, 26 did not transfer the blaSHV gene in mating experiments.

scholarly journals Wide Distribution and Specific Resistance Pattern to Third-Generation Cephalosporins of Enterobacter cloacae Complex Members in Humans and in the Environment in Guadeloupe (French West Indies)

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthieu Pot ◽  
Yann Reynaud ◽  
David Couvin ◽  
Célia Ducat ◽  
Séverine Ferdinand ◽  
...  
Keyword(s):  
West Indies ◽  
Enterobacter Cloacae ◽  
Farm Animals ◽  
Resistance Pattern ◽  
Third Generation ◽  
French West Indies ◽  
Produce Water ◽  
Human Samples ◽  
Resistant Strains ◽  
Third Generation Cephalosporins

Species belonging to Enterobacter cloacae complex have been isolated in numerous environments and samples of various origins. They are also involved in opportunistic infections in plants, animals, and humans. Previous prospection in Guadeloupe (French West Indies) indicated a high frequency of E. cloacae complex strains resistant to third-generation cephalosporins (3GCs) in a local lizard population (Anolis marmoratus), but knowledge of the distribution and resistance of these strains in humans and the environment is limited. The aim of this study was to compare the distribution and antibiotic susceptibility pattern of E. cloacae complex members from different sources in a “one health” approach and to find possible explanations for the high level of resistance in non-human samples. E. cloacae complex strains were collected between January 2017 and the end of 2018 from anoles, farm animals, local fresh produce, water, and clinical human samples. Isolates were characterized by the heat-shock protein 60 gene-fragment typing method, and whole-genome sequencing was conducted on the most frequent clusters (i.e., C-VI and C-VIII). The prevalence of resistance to 3GCs was relatively high (56/346, 16.2%) in non-human samples. The associated resistance mechanism was related to an AmpC overproduction; however, in human samples, most of the resistant strains (40/62) produced an extended-spectrum beta-lactamase. No relation was found between resistance in isolates from wild anoles (35/168) and human activities. Specific core-genome phylogenetic analysis highlighted an important diversity in this bacterial population and no wide circulation among the different compartments. In our setting, the mutations responsible for resistance to 3GCs, especially in ampD, were diverse and not compartment specific. In conclusion, high levels of resistance in non-human E. cloacae complex isolates are probably due to environmental factors that favor the selection of these resistant strains, and this will be explored further.

Sign in / Sign up

Export Citation Format

Share Document