OXA-48-like carbapenemases in the UK: an analysis of isolates and cases from 2007 to 2014

Findlay, Jacqueline; Hopkins, Katie L.; Loy, Richard; Doumith, Michel; Meunier, Danièle; Hill, Robert L.; Pike, Rachel; Mustafa, Nazim; Livermore, David M.; Woodford, Neil

doi:10.1093/jac/dkx012

Cited by 75 publications

(78 citation statements)

References 30 publications

(55 reference statements)

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“…Three OXA-48 variants were identified; bla OXA-48 was identified in 49 (87.5%) of 56 isolates, bla OXA-245 in 5 isolates (8.9%), and bla OXA-181 in 2 isolates (3.6%) ( Table 1; also see Table S2). OXA-48 predominated over other variants, which coincides with the results of other surveys in which OXA-48 was the most widespread (11,12). OXA-181 was first identified in India and has been reported in many different countries (United Kingdom, Canada, Australia, and Japan) (1).…”

Section: Resultssupporting

confidence: 79%

OXA-48-Like-Producing Klebsiella pneumoniae in Southern Spain in 2014–2015

Machuca

López-Cerero

Fernández-Cuenca

et al. 2019

Antimicrob Agents Chemother

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The aim of this study was to characterize the population structure of 56 OXA-48-like-producing Klebsiella pneumoniae isolates, as well as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, recovered in 2014 and 2015 from 16 hospitals in southern Spain. XbaI pulsed-field gel electrophoresis and multilocus sequence typing were performed to assess clonal relatedness. Representative isolates belonging to OXA-48-like-producing and CTX-M-15-coproducing pulsotypes were selected for characterization of blaOXA-48-like- and blaCTX-M-15-carrying plasmids by PCR-based replicon typing, IncF subtyping, whole-genome sequencing analysis, and typing of Tn1999 structures. Forty-three OXA-48-producing isolates (77%) were recovered from clinical samples and 13 from rectal swabs. All isolates showed ertapenem MIC values of ≥1 mg/liter, although 70% remained susceptible to imipenem and meropenem. Forty-nine isolates (88%) produced OXA-48, 5 produced OXA-245, and 2 produced OXA-181. Twenty-eight different pulsotypes (5 detected in more than 1 hospital) and 16 sequence types (STs) were found. The most prevalent clones were ST15 (29 isolates [52%]) and ST11 (7 isolates [13%]). Forty-five (80%) isolates were also blaCTX-M-15 carriers. The blaCTX-M-15 gene was mostly (82%) located on IncR plasmids, although ST15 and ST11 isolates also carried this gene on IncF plasmids. The composite transposon variant Tn1999.2-like was the most frequent. Among ST15 and ST11 isolates, different transposon variants were observed. The blaOXA-48 gene was mainly located on IncL plasmids, although IncM plasmids were also observed. The spread of OXA-48-like-producing K. pneumoniae in southern Spain is mainly due to ST15 and ST11 clones. Variation within clonal lineages could indicate different acquisition events for both ESBL and carbapenemase traits.

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Section: Resultssupporting

confidence: 79%

OXA-48-Like-Producing Klebsiella pneumoniae in Southern Spain in 2014–2015

Machuca

López-Cerero

Fernández-Cuenca

et al. 2019

Antimicrob Agents Chemother

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“…It is worth noting that the frequency was as high as 89.3% among the 169 KPC-Kp clinical isolates included in this study. Interestingly, similar frequencies of meropenem MIC distributions for KPc-Kp clinical isolates were recently reported in the United Kingdom (33,34). This may helpfully steer clinicians toward including (or not including) permissible HDCI meropenem in combination regimens for the empirical treatment of KPC-Kp infections.…”

Section: Discussionsupporting

confidence: 64%

Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae

Cojutti

Sartor

Righi

et al. 2017

Antimicrob Agents Chemother

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We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with carbapenemase (KPC)-producing (KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations () of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T, 100% T, 100% T, and 100% T, where "T" represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 ( = 169). Ninety-seven meropenem were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.

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“…None of the OXA-48-positive E. coli isolates were ST38, which was previously found associated with pOXA-48 (Turton et al , 2016) . Three of the seven K. pneumoniae isolates were novel STs and none of them were ST14 or ST10, previously found associated with pOXA-48 carriage (Findlay, Hopkins, Loy, et al , 2017) . Only one of the four E. cloacae isolates belonged to a previously described ST.…”

Section: Of the 43 E Colimentioning

confidence: 70%

“…This description is supported by a population genetics model based on the frequency spectrum of bacterial hosts. Such outbreak dynamics are typical of pOXA-48, although the main host is usually from the genus Klebsiella (Findlay, Hopkins, Alvarez-Buylla, et al , 2017;Findlay, Hopkins, Loy, et al , 2017) . The plasmids were highly conserved, in accordance to previous pOXA-48 outbreaks (León-Sampedro et al , no date;Skalova et al , 2017;Pulss et al , 2018;Hernández-García et al , 2019;Mahon et al , 2019) .…”

Section: Discussionmentioning

confidence: 98%

Hospital outbreak of carbapenem-resistant Enterobacteriales associated with an OXA-48 plasmid carried mostly byEscherichia coliST399

Ledda

Cummins

Shaw

et al. 2020

Preprint

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A hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance.Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak. Escherichia coli ST399 accounted for 20/55 of all the isolates. Comparative genomics with publicly available E. coli ST399 sequence data showed that the outbreak isolates formed a unique clade. The OXA-48 plasmid identified in the outbreak differed from other known plasmids by an estimated five homologous recombination events. We estimated a lower bound to the plasmid conjugation rate to be 0.23 conjugation events per lineage per year. Our analysis suggests co-evolution between the plasmid and its main bacterial host to be a key driver of the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying OXA48 as the main cause of a plasmid-borne outbreak within a hospital setting. This study supports complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak. of 30

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OXA-48-like carbapenemases in the UK: an analysis of isolates and cases from 2007 to 2014

Abstract: OXA-48-like carbapenemases are an increasing problem in the UK. This study highlights both the role of successful plasmids and the polyclonal nature of their dissemination.

Cited by 75 publications

References 30 publications

OXA-48-Like-Producing Klebsiella pneumoniae in Southern Spain in 2014–2015

OXA-48-Like-Producing Klebsiella pneumoniae in Southern Spain in 2014–2015

Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae

Hospital outbreak of carbapenem-resistant Enterobacteriales associated with an OXA-48 plasmid carried mostly byEscherichia coliST399

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