Organisation génétique des céphalosporinases acquises

Les b-lactamases de classe C (AmpC) acquises contribuent à la résistance des entérobactéries aux céphalosporines de 3ème génération. Parmi les six clusters de céphalosporinases acquises décrits dans le monde, trois émergent en région parisienne, principalement chez les espèces Klebsiella pneumoniae et Escherichia coli : les céphalosorinases DHA-1 provenant du chromosome de Morganella morganii, ACC-1 de Hafnia alvei, et CMY de Citrobacter freundii. Les gènes ampC qui codent ces céphalosporinases sont le plus souvent en position plasmidique. Plusieurs structures génétiques sont impliquées dans la mobilisation des gènes blaDHA-1, blaACC-1 et blaCMY : les séquences d insertion ISCR1 au sein d un intégron complexe, ou ISEcp1. De nombreux remaniements ultérieurs à la mobilisation de ampC expliquent la variabilité de son organisation génétique : la séquence d insertion IS26, notamment, semble avoir un rôle important dans la stabilisation de ampC sur un support génétique mobile.Acquired class C b-lactamases (AmpC) are responsible for the resistance to third-generation cephalosporins in Enterobacteriaceae. Among the six clusters of acquired cephalosporinases reported in the world, three are emerging in the Paris area, mostly in Klebsiella pneumoniae and in Escherichia coli : the enzymes DHA-1 originating from Morganella morganii, ACC-1 originating from Hafnia alvei and CMY originating from Citrobacter freundii. Acquired cephalosporinases are encoded by ampC gene, mostly plasmid-mediated. Several genetic elements are involved in the mobilization of blaDHA-1, blaACC-1 and blaCMY : insertions sequences ISCR1 associated to a complex integron, or ISEcp1. Then, different genetic rearrangements around ampC may explain the variability of ampC organization : insertion sequence IS26, notably, could have been involved in the stabilization of ampC on a mobile genetic element.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

First Detection of the Ambler Class C 1 AmpC β-Lactamase in Citrobacter freundii by a New, Simple Double-Disk Synergy Test

We report on the first detection of an AmpC-type Ambler class C 1 (ACC-1) β-lactamase in Citrobacter freundi isolated from a patient also harboring ACC-1-producing Escherichia coli and Klebsiella pneumoniae. We propose a simple cefoxitin-based double-disk synergy test (DDST) for the specific detection of ACC-1 in members of the family Enterobacteriaceae, including natural AmpC producers, in association with a cloxacillin-based DDST as a first-line AmpC-type β-lactamase screening test

Emergence of DHA-1-Producing Klebsiella spp. in the Parisian Region: Genetic Organization of the ampC and ampR Genes Originating from Morganella morganii

Eleven Klebsiella pneumoniae clinical isolates and one Klebsiella oxytoca clinical isolate showing various pulsed-field gel electrophoresis types and producing an inducible DHA-1 class C β-lactamase were isolated in the Parisian region between 1998 and 2003. The aim of this study was to compare the genetic organization of the bla(DHA-1) genes in this collection of clinical isolates. In four isolates, the Morganella morganii-derived genomic region containing bla(DHA-1) was inserted in an entire complex sul1-type integron, including a region common to In6-In7 (CR1), as previously described in a bla(DHA-1)-producing Salmonella enterica serovar Enteritidis KF92 isolate from Saudi Arabia in 1992. Different gene cassette arrays were characterized in each of these integrons. In two of them, an additional 10-kb fragment was inserted between the CR1 and the M. morganii-derived region and was similar to the sap (ABC transporter family) and psp (phage shock protein) operons originated from Salmonella enterica serovar Typhimurium. The length of the M. morganii region was variable, suggesting that several independent recombination events have occurred and that open reading frame orf513 encodes a recombinase involved in the mobilization of the resistance genes. The genetic organization of bla(DHA-1) was identical in the eight other isolates. This structure is likely derived from a complex integron following the insertion of IS26, leading to the deletion of the first part of integron. The horizontal transfer of one plasmid carrying that truncated integron was shown for seven of these isolates

Complete Nucleotide Sequence of Two Multidrug-Resistant IncR Plasmids from Klebsiella pneumoniae

International audienceWe report here the complete nucleotide sequence of two IncR replicons encoding multidrug resistance determinants, including β-lactam ( bla DHA-1 , bla SHV-12 ), aminoglycoside ( aphA1 , strA , strB ), and fluoroquinolone ( qnrB4 , aac6′-1b-cr ) resistance genes. The plasmids have backbones that are similar to each other, including the replication and stability systems, and contain a wide variety of transposable elements carrying known antibiotic resistance genes. This study confirms the increasing clinical importance of IncR replicons as resistance gene carriers

An unusual community-acquired invasive and multi systemic infection due to ExoU-harboring Pseudomonas aeruginosa strain: Clinical disease and microbiological characteristics

International audienceCommunity-acquired Pseudomonas aeruginosa infections are rare. Most cases involve patients either with underlying immunosuppression or structural chronic lung diseases. We report here an atypical case of a severe community-acquired invasive infection due to a hypervirulent ExoU-producing strain, in an immunocompetent patient

No Neck Pain: Meningococcemia

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Meningococcal purpura fulminans and severe myocarditis with clinical meningitis but no meningeal inflammation: a case report

Abstract Background During fulminant meningococcal septicaemia, meningococci are often observed in the cerebrospinal fluid (CSF) although the patients have frequently no meningeal symptoms. Meningococcal meningitis, by contrast, usually features clinical meningeal signs and biochemical markers of inflammation with elevated white blood cell count (pleiocytosis) in the CSF. Cases of typical symptomatic meningitis without these biochemical features are uncommon in adults. Case presentation A 21-year-old male presented with meningococcal purpura fulminans and disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome requiring hospitalization in the Intensive Care Unit. Despite typical meningeal clinical signs, lumbar puncture showed no pleiocytosis, normal glycorachia and normal proteinorachia, whereas the lactate concentration in the CSF was high (5.8 mmol/L). CSF culture showed a high inoculum of serogroup C meningococci. On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week. During the hospitalization, distal ischemic and necrotic lesions were observed, predominantly on the fingertips, which were treated with local and systemic vasodilators. Conclusions We report a rare case of adult meningococcal disease characterized by an intermediate form of meningitis between purulent meningitis and meningeal inoculation from fulminant meningococcal septicaemia, without classical signs of biological inflammation. It highlights the diagnostic value of CSF lactate, which may warrant administration of a meningeal dosing regimen of beta-lactam antibiotics. This case also demonstrates the potential severity of meningococcal myocarditis; we discuss its pathophysiology, which is distinct from other sepsis-related cardiomyopathies. Finally, the observed effects of vasodilators on the meningococcal skin ischemia in this case encourages future studies to assess their efficacy in DIC-associated necrosis

A Plasmid-Borne Shewanella algae Gene, qnrA3, and Its Possible Transfer In Vivo between Kluyvera ascorbata and Klebsiella pneumoniae▿

The plasmid-borne quinolone resistance gene qnrA1 is prevalent in multidrug-resistant Enterobacteriaceae. A chromosomally encoded homologue in Shewanella algae, qnrA3, has been described. We isolated two qnrA3-positive strains, one of Klebsiella pneumoniae (He96) and one of Kluyvera ascorbata (Kas96), from the feces of an immunocompromised outpatient. The qnrA3 allele was identical to that of S. algae except for 5 nucleotides and differed from qnrA1 by 29 nucleotides affecting three amino acids. The analysis of the qnrA3 genetic environment showed that qnrA3 was inserted downstream from an ISCR1 element at a recombination crossover site described for other resistance genes, including qnrA1, and immediately upstream from IS26, a situation not described before. IS26 preceded an incomplete class 1 integron which contained, among other genes, aac(6′)-Ib-cr, another transferable quinolone resistance gene, and the β-lactamase gene blaOXA-1/30. The 10-kb fragment encompassing qnrA3 was compared to previously described qnrA1-containing plasmids and multidrug-resistant plasmids; it shares identical sequences with pC15a, pHSH2, pQR1, pQKp311H, and pSAL-1 but with rearrangements, deletions, and mutations. Conjugal transfer of qnrA3 was highly efficient (10−2) from K. pneumoniae He96 or K. ascorbata Kas96 to Escherichia coli J53 but less so (10−5) from either donor to a clinical strain of Enterobacter cloacae. This first description of a plasmid-borne copy and of the in vitro transfer of qnrA3 is taken to illustrate its likely in vivo transfer from S. algae to the Enterobacteriaceae