Dangerous outbreak of carbapenemase-producing (NDM-1 and OXA-48) and colistin-resistant Klebsiella pneumoniae

The European Centre for Disease Prevention and Control has reported a first outbreak of Klebsiella pneumonia from the sequence type (ST) 307 in Germany producing two different carbapenemases (NDM-1 and OXA-48). Since October 21st, 2019, already 17 patients have been affected in three different German hospitals. The patients showed clinical symptoms (sepsis, pneumonia, urinary tract Infection). This combination of NDM-1 and OXA-48 is the first reported outbreak of this epidemiological combination.

The combination of the two resistance genes was found in one patient in Greece as well. Klebsiella pneumonia detected here harboured NDM-1 and OXA-48 carbapenemases and 16 additional antimicrobial resistance genes.1

NDM is a metallo-beta-lactamase(MBL)able to hydrolyse almost all beta-lactams, including carbapenems,and not inhibited by approved beta-lactamase inhibitors. NDM does not hydrolyse aztreonam. Since its first description in 2008 from a K.pneumoniae strain isolated from a patient repatriated to Sweden after hospitalisation in New Delhi, India, NDM-positive strains have been causing healthcare-associated outbreaks worldwide.So far, more than twenty NDM variants have been identified in various bacterial species responsible for healthcare-associated infections and primarily from the Enterobacteriaceae family, Acinetobacter spp. and Pseudomonas spp.[5,6].

Oxacillinase-48 (OXA-48) is a serine-beta-lactamase with hydrolytic activity against carbapenems and penicillins, but low or negligible activity against extended-spectrum cephalosporins. It was first identified in Turkey in 2001[7]. In the 2015 European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE), four countries reported regional spread (Croatia, Germany, Ireland and Italy), four countries reported interregional spread (Belgium, France, Romania and Spain), and two countries (Malta and Turkey) reported an endemic situation of OXA-48 producing Enterobacteriaceae[8]. Both, NDM-1 and OXA-48, are often associated with the presence of other beta-lactamases such as extended-spectrum beta-lactamases (ESBL) or AmpC beta-lactamases.

The outbreak of this highly resistant strains resulted in strict safety and isolation action in hospitals. In Germany, the patients were transferred to single rooms and all contact persons needed to be screened to avoid further spreads. Institutions that had more than one case have to perform screening of all their patients to avoid undetected other cases. During six weeks, once per week a screening was performed in hospitals were a patient carrying carbapenemase-producing and colistin resistant Klebsiella pneumoniae stayed overnight.2

This outbreak must lead to further controls in hospitals and an early detection of these resistances leading to adapted treatment to the patients is crucial to avoid a further spread into more European hospitals. A further spread can lead to high mortality rates due to inappropriate and late treatment options.3

One action is the early adaption of antibiotic treatment to avoid further spread of NDM-1 and OXA-48 due to fast diagnostics. Our Unyvero solution can detect both resistance genes in parallel with all five applications (Blood Culture, Hospitalized Pneumonia, Implant and Tissue Infection, Intra-abdominal-infection, Urinary Tract Infection). The different panels include Klebsiella pneumoniae and the resistance markers NDM-1 and OXA-48 and show the results in 4-5 hours with a total workflow time of under 5 minutes, which is crucial to avoid further spreads of the resistances.

With the help of the Unyvero syndromic testing system doctors get the results of patient samples faster than that of standard microbiology and can therefore adapt their treatment decisions easier. This tool leads to better patient outcomes and fights the problem of the spread of antibiotic resistances.

1Protonotariou E. Et al., 2019
2Haller S. Et al., 2019
3Guducuoglu H et al., 2017

Source: ECDC (2019), https://www.ecdc.europa.eu/en/publications-data/outbreak-Klebsiella-pneumoniae-Germany
Guducuoglu H., Gursoy NC., Yakupogullari Y., Parlak M., Karasin G., Sunnetcioglu M., Otlu B., 2017, Hospital Outbreak of a Colistin-Resistant, NDM-1- and OXA-48-Producing
J Glob Antimicrob Resist. 2019 Dec;19:81-82. doi: 10.1016/j.jgar.2019.08.020. Epub 2019 Sep 4.

Emergence of Klebsiella pneumoniae ST11 co-producing NDM-1 and OXA-48 carbapenemases in Greece.
Protonotariou E., Meletis G., Chatzopoulou F., Malousi A., Chatzidimitriou D., Skoura L.
Klebsiella pneumoniae: High Mortality from Pandrug Resistance, Microb Drug Resist. 2018 Sep;24(7):966-972. doi: 10.1089/mdr.2017.0173. Epub 2017 Dec 21.

Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019
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Littmann M., Marlinghaus L., Neumann B., Pfeifer Y., Pfennigwerth N., Rogge S., Schaufler K., Thürmer A., Werner G., Gatermann S.
5. Wu W, Feng Y, Tang G, Qiao F, McNally A, Zong Z. NDM Metallo-beta-Lactamases and Their BacterialProducers in Health Care Settings. Clin Microbiol Rev. 2019 Mar 20;32(2).
6. U.S. National Library of Medicine. Bacterial Antimicrobial Resistence Reference Gene Database[23/10/2019]. Available from: https://www.ncbi.nlm.nih.gov/pathogens/isolates#/refgene/NDM.
7. Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2004 Jan;48(1):15-22.
8. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL. Carbapenemase-producingEnterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill[Internet]. 2015 Nov 12; 20(45):[pii=30062 p.]. Available from:http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21300