Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study

Grundmann, Hajo; Glasner, Corinna; Albiger, Barbara; Aanensen, David M.; Tomlinson, Chris; Andrašević, Arjana Tambić; Cantón, Rafael; Carmeli, Yehuda; Friedrich, Alexander; Glupczynski, Youri; Gniadkowski, Marek; Livermore, David M.; Nordmann, Patrice; Poirel, Laurent; Rossolini, Gian María; Seifert, Harald; Vatopoulos, Alkiviadis; Walsh, Timothy R.; Woodford, Neil; Monnet, Dominique; Koraqi, Andi; Lacej, Denada; Apfalter, Petra; Hartl, Rainer; Huang, Te-Din; Strateva, Tanya; Marteva-Proevska, Yulia; Butić, Iva; Pieridou-Bagatzouni, Despo; Maikanti-Charalampous, Panagiota; Hrabák, Jaroslav; Žemličková, Helena; Hammerum, Anette M.; Jakobsen, Lotte; Ivanova, Marina; Pavelkovich, Anastasia; Jalava, Jari; Österblad, Monica; Dortet, Laurent; Vaux, Sophie; Kaase, Martin; Gatermann, Sören; Tryfinopoulou, Kyriaki; Tóth, Ákos; Jánvári, Laura; Boo, Teck Wee; McGrath, Elaine; Adler, Amos; Pantosti, Annalisa; Monaco, Monica; Raka, Lul; Kurti, Arsim; Balode, Arta; Saule, Mära; Miciulevičienė, Jolanta; Mierauskaitė, Aistė; Perrin-Weniger, Monique; Reichert, Paul; Nestorova, Nina; Debattista, Sonia; Mijović, Gordana; Lopičić, Milena; Samuelsen, Ørjan; Haldorsen, Bjørg; Żabicka, Dorota; Literacka, Elżbieta; Caniça, Manuela; Manageiro, Vera; Kaftandzieva, Ana; Trajkovska-Dokic, Elena; Damian, Maria; Lixandru, Brânduşa Elena; Jelesić, Zora; Trudić, Anika; Nikš, M; Schreterova, Eva; Pirš, Mateja; Cerar, Tjaša; Oteo, Jesús; Aracil, Belén; Giske, Christian G.; Sjöström, Karin; Gür, Deniz; Cakar, Asli; Hopkins, Katie L.; Wiuff, Camilla; Brown, D. J. F.

doi:10.1016/s1473-3099(16)30257-2

Cited by 520 publications

(379 citation statements)

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“…VIM has declined, from being the exclusive carbapenemase detected in Greece until 2006 [1], to 8.4% in 2016 and is followed by double carbapenemase production (5.6%) and OXA-48 (3.6%). These findings are in accordance with those from the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project, conducted between November 2013 and April 2014, in which Grundmann et al reported for the first time that NDM was the second-ranking carbapenemase in Greece [26]. In a previous published nationwide surveillance study from January 2011 to June 2012, among 119 Greek hospitals, the prevalent mechanism of carbapenem resistance in K. pneumoniae isolates was KPC (82.6%), followed by VIM (9.7%), while the concurrent production of KPC and VIM was noted in 7.7% of the isolates [27].…”

Section: Discussionsupporting

confidence: 91%

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Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016

et al. 2018

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Section: Discussionsupporting

confidence: 91%

“…The Greek situation differs greatly from other European countries such as Spain, France, Germany, Turkey, Romania and Belgium, where OXA-48, most often linked with community-onset healthcare associated sources, is the most frequently encountered carbapenemase [26,[28][29][30][31].…”

Section: Discussionmentioning

confidence: 97%

Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016

et al. 2018

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“…The boom of international travel and tourism from China to Europe and other countries may increase the opportunities for colonization of travelers. The fact that OXA-48-producing strains have nearly outcompeted KPC and NDM producers and have become the most common CRE in several countries in Europe is alarming (11,12). These data support the need for surveillance studies, such as screening of patients who were recently hospitalized in regions of OXA-48 endemicity and were then admitted to Chinese hospitals.…”

mentioning

confidence: 66%

Coexistence of OXA-48-Producing Klebsiella pneumoniae and Escherichia coli in a Hospitalized Patient Who Returned from Europe to China

Wang

et al. 2017

Antimicrob Agents Chemother

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“…In part due to the difficulty of effectively treating infections with CRE, mortality rates can be as high as 40 to 50% (6). These infections are a worldwide problem, with recent reports indicating that CRE are widespread in the United States (7), Europe (8), and China (9). Unfortunately, resistance to "last-line" drugs, such as colistin, is emerging in CRKP strains, and in some cases, isolates are resistant to all antibiotics tested (10).…”

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confidence: 99%

Carbapenem-Resistant Klebsiella pneumoniae Exhibiting Clinically Undetected Colistin Heteroresistance Leads to Treatment Failure in a Murine Model of Infection

Band

Satola

Burd

et al. 2018

mBio

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Antibiotic resistance is a growing crisis and a grave threat to human health. It is projected that antibiotic-resistant infections will lead to 10 million annual deaths worldwide by the year 2050. Among the most significant threats are carbapenem-resistant Enterobacteriaceae (CRE), including carbapenem-resistant Klebsiella pneumoniae (CRKP), which lead to mortality rates as high as 40 to 50%. Few treatment options are available to treat CRKP, and the polymyxin antibiotic colistin is often the "last-line" therapy. However, resistance to colistin is increasing. Here, we identify multidrug-resistant, carbapenemase-positive CRKP isolates that were classified as susceptible to colistin by clinical diagnostics yet harbored a minor subpopulation of phenotypically resistant cells. Within these isolates, the resistant subpopulation became predominant after growth in the presence of colistin but returned to baseline levels after subsequent culture in antibiotic-free media. This indicates that the resistance was phenotypic, rather than due to a genetic mutation, consistent with heteroresistance. Importantly, colistin therapy was unable to rescue mice infected with the heteroresistant strains. These findings demonstrate that colistin heteroresistance may cause in vivo treatment failure during K. pneumoniae infection, threatening the use of colistin as a last-line treatment for CRKP. Furthermore, these data sound the alarm for use of caution in interpreting colistin susceptibility test results, as isolates identified as susceptible may in fact resist antibiotic therapy and lead to unexplained treatment failures. IMPORTANCE This is the first report of colistin-heteroresistant K. pneumoniae in the United States. Two distinct isolates each led to colistin treatment failure in an in vivo model of infection. The data are worrisome, especially since the colistin heteroresistance was not detected by current diagnostic tests. As these isolates were carbapenem resistant, clinicians might turn to colistin as a last-line therapy for infections caused by such strains, not knowing that they in fact harbor a resistant subpopulation of cells, potentially leading to treatment failure. Our findings warn that colistin susceptibility testing results may be unreliable due to undetected heteroresistance and highlight the need for more accurate and sensitive diagnostics.KEYWORDS Klebsiella, antibiotic resistance, clonal heteroresistance, colistin, heteroresistance A ntibiotic resistance is an increasingly urgent problem, predicted to cause 10 million annual deaths worldwide by the year 2050 (1). Klebsiella spp., including K. pneumoniae, are responsible for~10% of nosocomial infections in the United States (2),

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Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study

Cited by 520 publications

References 21 publications

Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016

Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016

Coexistence of OXA-48-Producing Klebsiella pneumoniae and Escherichia coli in a Hospitalized Patient Who Returned from Europe to China

Carbapenem-Resistant Klebsiella pneumoniae Exhibiting Clinically Undetected Colistin Heteroresistance Leads to Treatment Failure in a Murine Model of Infection

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