Class C β-lactamases or cephalosporinases can be classified into two functional groups (1, 1e) with considerable molecular variability (≤20% sequence identity). These enzymes are mostly encoded by ...chromosomal and inducible genes and are widespread among bacteria, including Proteobacteria in particular. Molecular identification is based principally on three catalytic motifs (
SXSK,
YXN,
KTG), but more than 70 conserved amino-acid residues (≥90%) have been identified, many close to these catalytic motifs. Nevertheless, the identification of a tiny, phylogenetically distant cluster (including enzymes from the genera
,
, and
) has raised questions about the possible existence of a C2 subclass of β-lactamases, previously identified as serine hydrolases. In a context of the clinical emergence of extended-spectrum AmpC β-lactamases (ESACs), the genetic modifications observed
and
(point mutations, insertions, or deletions) during the evolution of these enzymes have mostly involved the Ω- and H-10/R2-loops, which vary considerably between genera, and, in some cases, the conserved triplet
YXN. Furthermore, the conserved deletion of several amino-acid residues in opportunistic pathogenic species of Acinetobacter, such as A. baumannii, A. calcoaceticus, A. pittii and A. nosocomialis (deletion of residues 304-306), and in Hafnia alvei and H. paralvei (deletion of residues 289-290), provides support for the notion of natural ESACs. The emergence of higher levels of resistance to β-lactams, including carbapenems, and to inhibitors such as avibactam is a reality, as the enzymes responsible are subject to complex regulation encompassing several other genes (
R,
D,
G, etc.). Combinations of resistance mechanisms may therefore be at work, including overproduction or change in permeability, with the loss of porins and/or activation of efflux systems.
We report two cases of bacteremia due to Clostridium difficile from two French hospitals. The first patient with previously diagnosed rectal carcinoma underwent courses of chemotherapy, and ...antimicrobial treatment, and survived the C. difficile bacteremia. The second patient with colon perforation and newly diagnosed lung cancer underwent antimicrobial treatment in an ICU but died shortly after the episode of C. difficile bacteremia. A review of the literature allowed the identification of 137 cases of bacteremia between July 1962 and November 2016. Advanced age, gastro-intestinal disruption, severe underlying diseases and antimicrobial exposure were the major risk factors for C. difficile bacteremia. Antimicrobial therapy was primarily based on metronidazole and/or vancomycin. The crude mortality rate was 35% (21/60).
Objectives: Over a 3 year period (2000–2003) 21 Escherichia coli, 5 Klebsiella pneumoniae, 1 Serratia marcescens and 1 Proteus mirabilis producing CTX-M-type β-lactamase were collected from five ...different hospitals in Paris, France. This study was conducted to analyse the genetic environment of these 28 blaCTX-M genes. Methods: Antimicrobial susceptibility testing was performed by the disc diffusion method and MICs of various β-lactams were determined by an agar dilution method. PCR was used to detect and sequence alleles encoding CTX-M, TEM, SHV and CMY enzymes. The genetic environment was analysed by amplification and direct sequencing using various set of PCR primers or cloning in pBK-CMV. Results: Sequence analysis revealed that these isolates contained seven different blaCTX-M genes: blaCTX-M-1 (4 strains), blaCTX-M-2 (2 strains), blaCTX-M-3 (4 strains), blaCTX-M-9 (1 strain), blaCTX-M-14 (5 strains), blaCTX-M-15 (11 strains), blaCTX-M-24 (1 strain). TEM-1 was associated with CTX-M-type enzymes in 15 isolates. Two strains produced both CTX-M-15 and SHV-2 or CTX-M-14 and CMY-2. In 25 strains the insertion sequence ISEcp1 was located upstream of the 5′ end of the blaCTX-M gene. Among these strains, in five isolates, ISEcp1 was disrupted by insertion sequences such as IS26 (in three of them) or IS1 or IS10. Insertion sequence IS903 was found downstream of blaCTX-M-14 or blaCTX-M-24. Examination of the other three blaCTX-M genes (two blaCTX-M-2 and one blaCTX-M-9) by cloning, sequencing and PCR analysis revealed the presence of complex Class 1 integrons, In35, an integron similar to In60 and a novel integron. Conclusions: This work further confirmed the predominant role of ISEcp1 in the mobilization of blaCTX-M genes of the CTX-M-1 cluster and the presence of In35, of an integron similar to In60 and a novel complex Class 1 integron.
With the β-Lacta test, production of extended-spectrum β-lactamases (ESBLs) was assayed in 200 urine samples showing Gram-negative bacilli during direct microscopic examination. While 168 samples ...tested negative, all samples yielding ESBL-producing Enterobacteriaceae after culture gave positive (n = 30) or uninterpretable (n = 2) results. The sensitivity and specificity of ESBL detection were 94% and 100%, respectively.
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