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 an outbreak of Klebsiella pneumoniae from the sequence type (ST) 307 producing two different carbapenemases (NDM-1 and OXA-48) first detected in Germany. Since October 21st, 2019, seventeen (17) patients have been affected, showing clinical symptoms (sepsis, pneumonia, urinary tract Infection), across three different German hospitals. This occurrence of NDM-1 and OXA-48 in Klebsiella pneumoniae is the first reported outbreak of this epidemiological combination. Since detection in Germany, this combination of the two resistance genes in Klebsiella pneumoniae has been found in one patient in Greece where the organism harbored NDM-1 and OXA-48 carbapenemases and 16 additional antimicrobial resistance genes [1].

NDM is a metallo-beta-lactamase (MBL) able to hydrolyze almost all beta-lactams, including carbapenems, for which there are no clinically approved inhibitors. NDM does not hydrolyze aztreonam. Since its first description in 2008 from a K. pneumoniae strain isolated from a patient repatriated to Sweden after hospitalization in New Delhi, India, NDM-positive strains have been causing healthcare-associated outbreaks worldwide. So far, more than twenty (20) NDM variants responsible for healthcare-associated infections have been identified in various bacterial species, primarily from the Enterobacteriaceae family, Acinetobacter spp. and Pseudomonas spp. [2,3].

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[4]. 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 [5]. 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 these 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 spread. Institutions that had more than one case had to perform screening of all their patients to avoid additional undetected 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 [6].

This outbreak should encourage further controls in hospitals, as early detection of resistant strains would help to avoid a further spread into more European hospitals and provide a path by which to optimize treatment of patients. A further spread can lead to high mortality rates due to inappropriate and delayed treatment options [7].


One action is to utilize rapid diagnostics to allow for early detection of resistant strains to avoid further spread of NDM-1 and OXA-48 and allow for early adjustment of antibiotic treatment. Our Unyvero solution can detect both NDM-1 and OXA-48 resistance genes across all five applications (Blood Culture, Hospitalized Pneumonia, Implant and Tissue Infection, Intra-abdominal-infection, Urinary Tract Infection). Each of the Unyvero panels can detect Klebsiella pneumoniae along with the associated resistance markers and provide results in 4-5 hours with a total workflow time of under 5 minutes. Such timely results are crucial to avoid further spread of organisms with these resistance markers.

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 earlier. Application of tools, like the Unyvero system, can lead to better patient outcomes to help fight the spread of antibiotic resistance organisms.


[1]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.
[2]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).
[3] 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.
[4] 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.
[5] 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
[6]Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019, Haller S., Kramer R., Becker K., Bohnert J.A., Eckmanns T., Hans J.B., Hecht J., Heidecke C.-D., Hübner N.-O., Kramer A., Klaper K., Littmann M., Marlinghaus L., Neumann B., Pfeifer Y., Pfennigwerth N., Rogge S., Schaufler K., Thürmer A., Werner G., Gatermann S.
[7] 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.