Transfer of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae from Turkey to France

Levast, Marion; Poirel, Laurent; Carrër, Amélie; Deiber, Michel; Decroisette, E.; Mallaval, Frank-Olivier; Lecomte, Claire; Nordmann, Patrice

doi:10.1093/jac/dkq504

Cited by 28 publications

(21 citation statements)

References 5 publications

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“…We report here the spread of bla OXA-48 to the species E. coli isolated from a patient without a history of prior hospitalization. This indicates a dissemination of OXA-48-producing E. coli in the community, which gave rise to recurrent importation to France after the recent identification of an OXA-48-producing K. pneumoniae strain (8). We report here two cases with a clear link to Egypt, emphasizing that OXA-48 might be endemic to the African continent, in view of other reports from Senegal, Morocco, and Tunisia.…”

mentioning

confidence: 57%

Emergence of OXA-48-Producing Escherichia coli Clone ST38 in France

Poirel¹,

Bernabeu²,

Fortineau

et al. 2011

Antimicrob Agents Chemother

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confidence: 57%

Emergence of OXA-48-Producing Escherichia coli Clone ST38 in France

Poirel¹,

Bernabeu²,

Fortineau

et al. 2011

Antimicrob Agents Chemother

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“…These findings are also supported by two case reports in which susceptible OXA-48-producing Enterobacteriaceae were successfully treated with expandedspectrum cephalosporins. A case of neonatal pneumonia caused by an OXA-48-producing K. pneumoniae isolate susceptible to ceftazidime and cefotaxime was successfully treated with a combination of cefotaxime and amikacin (20). Another patient with leukemia who developed a central line infection caused by an OXA-48-producing Escherichia coli strain, susceptible to all cephalosporins, successfully cleared their infection with a combination of ceftazidime and colistin (17).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Humanized Carbapenem and Ceftazidime Regimens against Enterobacteriaceae Producing OXA-48 Carbapenemase in a Murine Infection Model

Wiskirchen

Nordmann

Crandon

et al. 2014

Antimicrob Agents Chemother

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e Enterobacteriaceae producing the OXA-48 carbapenemase are emerging worldwide, leaving few treatment options. Efficacy has been demonstrated in vivo with ceftazidime against a ceftazidime-susceptible OXA-48 isolate but not with imipenem despite maintaining susceptibility. The relationship between phenotype and in vivo efficacy was assessed for OXA-48 producers using humanized regimens of 2 g doripenem every 8 h (q8h; 4 h infusion), 1 g ertapenem q24h, 2 g ceftazidime q8h (2 h inf), and 500 mg levofloxacin q24h. Each regimen was evaluated over 24 h against an isogenic pair (wild-type and OXA-48 Klebsiella pneumoniae strains) and six clinical OXA-48 isolates with and without other extended-spectrum ␤-lactamases in immunocompetent and neutropenic murine thigh infection models. Efficacy was determined using the change in bacterial density versus 24-h growth controls in immunocompetent studies and 0-h controls in neutropenic studies. Bacterial reductions of >1 log CFU were observed with all agents for the wild-type strain. Consistent with low MICs, ceftazidime and levofloxacin exhibited efficacy against the isogenic OXA-48 strain, whereas doripenem did not, despite having a susceptible MIC; no activity was observed with ertapenem, consistent with a resistant MIC. Similar trends were observed for the clinical isolates evaluated. Ceftazidime, levofloxacin, and ertapenem efficacy against isogenic and clinical OXA-48-producing strains correlated well with phenotypic profiles and pharmacodynamic targets, whereas efficacy with doripenem was variable over the MIC range studied. These data suggest that carbapenems may not be a reliable treatment for treating OXA-48 producers and add to previous observations with KPC and NDM-1 suggesting that genotype may better predict activity of the carbapenems than the phenotypic profile. Carbapenem resistance among the Enterobacteriaceae has been on the rise worldwide over the last decade, commonly mediated by Ambler class A ␤-lactamases such as KPC, as well as Ambler class B metallo-␤-lactamases, including VIM, IMP, and NDM-1 (1). However, carbapenem resistance secondary to the Ambler class D ␤-lactamase OXA-48 has also increasingly been reported since it was first isolated in Turkey in 2001 (1-3). While OXA-48 exhibits low-level hydrolysis of carbapenems, it does not significantly hydrolyze the extended-spectrum cephalosporins, ceftazidime and cefepime (3, 4). Consistent with in vitro hydrolysis data, an in vivo dose ranging study in an immunocompetent murine peritonitis model resulted in efficacy with ceftazidime against one ceftazidime-susceptible OXA-48-producing isolate and poor activity with imipenem, despite the isolate being imipenem susceptible (5).Discordance between in vitro MICs and in vivo efficacy with humanized regimens of carbapenems has also recently been demonstrated for KPC-and NDM-1-producing Enterobacteriaceae (6, 7). As such, an evaluation of this relationship using human simulated regimens of carbapenems and comparator agents for OXA-48 producers in vivo is warra...

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“…OXA-48 exhibits a hydrolysis profile that includes penicillins and carbapenems and that spares cephalosporins (29). Lately, the bla OXA-48 gene has been identified in different countries, such as Lebanon, Tunisia, Israel, Belgium, and France and recently in Senegal and Morocco (3,[9][10][11]14,19,[20][21][22]34). Several isolates producing OXA-48 have been involved as a source of nosocomial outbreaks (5, 11).…”

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confidence: 99%

OXA-163, an OXA-48-Related Class D β-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins

Poirel

Castanheira

Carrër

et al. 2011

Antimicrob Agents Chemother

136

160

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Two bla OXA-48 -like-positive isolates (Klebsiella pneumoniae and Enterobacter cloacae) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in Enterobacteriaceae. In both cases, sequencing identified ␤-lactamase OXA-163, differing from OXA-48 by a single amino substitution and a 4-amino-acid deletion. OXA-163 hydrolyzed penicillins, ceftazidime, and cefotaxime, whereas OXA-48 did not. However, OXA-163 had a much lower ability to hydrolyze carbapenems than OXA-48, therefore barely being considered a carbapenemase. In both isolates, the bla OXA-163 gene was located on plasmids that differed in structure and size. However, a detailed genetic analysis revealed a similar genetic context in those isolates, with the bla OXA-163 gene being bracketed by novel transposase genes, making this genetic environment different from that reported for the bla OXA-48 gene. This study identified the first class D ␤-lactamase compromising both extended-spectrum cephalosporin and carbapenem activities.Class D ␤-lactamases or oxacillinases are widely distributed among clinically relevant Gram-negative species (31). A high degree of diversity is observed at the biochemical and genetic levels among these enzymes exhibiting a narrow or broad spectrum of hydrolysis toward ␤-lactams (31). Genes encoding oxacillinases are usually embedded as gene cassettes into class 1 integrons, but other potentially mobile genetic vehicles have also been described, including insertion sequences (ISs) (31). Among class D ␤-lactamases, some enzymes confer the ability to hydrolyze carbapenems and have mostly been identified in Acinetobacter spp. (32) but rarely in Enterobacteriaceae (33). The carbapenem-hydrolyzing class D ␤-lactamase (CHDL) OXA-48 was initially identified in Turkey, first in Klebsiella pneumoniae and then in other enterobacterial species (1,5,6,15,23,29). OXA-48 exhibits a hydrolysis profile that includes penicillins and carbapenems and that spares cephalosporins (29). Lately, the bla OXA-48 gene has been identified in different countries, such as Lebanon, Tunisia, Israel, Belgium, and France and recently in Senegal and Morocco (3,[9][10][11]14,19,[20][21][22]34). Several isolates producing OXA-48 have been involved as a source of nosocomial outbreaks (5, 11). The bla OXA-48 gene has often been identified on a 70-kb plasmid featured by the replication protein RepP (6). The bla gene is usually identified in association with two IS1999 insertion sequences, forming the composite transposon Tn1999 (2). Here we report an OXA-48-related CHDL that possesses very peculiar hydrolytic properties and whose gene is associated with novel genetic structures. MATERIALS AND METHODSBacterial strains. Identification of K. pneumoniae (isolate Kp6299) and Enterobacter cloacae 2185 (isolate Enc2185) was performed by using the API 20E system (bioMérieux, Marcy l'Étoile, France). Escherichia coli TOP10 was used as the host strain for cloning, and E. coli J53 (resistant to azide) was used as the host for conjugation ...

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Transfer of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae from Turkey to France

Cited by 28 publications

References 5 publications

Emergence of OXA-48-Producing Escherichia coli Clone ST38 in France

Emergence of OXA-48-Producing Escherichia coli Clone ST38 in France

Efficacy of Humanized Carbapenem and Ceftazidime Regimens against Enterobacteriaceae Producing OXA-48 Carbapenemase in a Murine Infection Model

OXA-163, an OXA-48-Related Class D β-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins

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