Credit CDC - Vital Signs
#14,573
Each year we draw a little closer to a long-predicted, but highly plausible `post-antibiotic era', where even common infections become resistant to most antibiotics, and something as simple as a scraped knee, or elective surgery, could be deadly.
Completely resistant infections have - so far - been extraordinarily rare, with a few - often last resort drugs - still being effective.But this year we've seen two particularly worrisome nosocomial outbreaks in Europe, which are as notable for their spread as for their etiology.
The first (see June 2019's ECDC Rapid Risk Assessment: Large Outbreak of NDM-producing CRE in Tuscany Region, Italy), involved a multi-hospital outbreak of Carbapenum resistant CRE in the Tuscany region of Italy.
As of May, seven Tuscan hospitals had notified a total of 350 cases.The ECDC put the risk of further spread within Italy as `high', while the risk of cross border spread was deemed `moderate'.Four months later, in Oct. 7th's ECDC CDTR: Extensively drug-resistant (XDR) Klebsiella pneumonia, we looked at another European outbreak - involving (XDR) K. pneumoniae, affecting four hospitals in the northeast of the state of Mecklenburg-West Pomerania.
Today we've a detailed Eurosurveillance report on this latest event, and while not nearly as large as the Tuscan outbreak, it did spread - despite infection control measures - between a university hospital, two other hospitals and a rehabilitation clinic.I've posted some excerpts from a much longer report, but you'll want to follow the link to read it in its entirety. I'll have a postscript when you return.
Rapid communication Open Access
Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019
Sebastian Haller1, Rolf Kramer1, Karsten Becker5, Jürgen A Bohnert5, Tim Eckmanns1, Jörg B Hans6, Jane Hecht1, Claus-Dieter Heidecke5, Nils-Olaf Hübner5, Axel Kramer5, Kathleen Klaper2, Martina Littmann4, Lennart Marlinghaus6, Bernd Neumann2, Yvonne Pfeifer2, Niels Pfennigwerth6, Simone Rogge4, Katharina Schaufler7, Andrea Thürmer3, Guido Werner2, Sören Gatermann6
Between June and October 2019, a university hospital, two other hospitals and a rehabilitation clinic in north-eastern Germany (Western Pomerania, Greifswald) were affected by an outbreak of extensively drug-resistant (XDR) Klebsiella pneumoniae.
A total of 17 patients were infected or colonised. The aim of this short article is to provide detailed information on the epidemiological and microbiological results of this outbreak investigation, and thereby facilitate comparison with similar outbreaks of this emerging Klebsiella strain on international level.
(SNIP)
This is the first reported nosocomial outbreak of XDR K. pneumoniae ST307 with NDM-1, OXA-48 and CTX-M-15 in Germany. Despite established hygiene precautions, a university hospital, two other hospitals and a rehabilitation clinic in north-eastern Germany were affected. This may suggest that the outbreak clone is highly adapted to the hospital environment. Microbiological analyses of the outbreak strain are ongoing, preliminary results of susceptibility testing to disinfectants does not suggest increased disinfectant resistance.
The outbreak seemed controlled until week 44 as no new transmissions occurred. In calendar week 44, however, Case 18 was detected through admission screening in the university hospital. This case had been hospitalised during July and September on wards of the university hospital with other cases and had not been screened during these stays. Identification of this case indicates that further unknown cases may exist.
This highlights the need for close information exchange between referral hospitals and for screening of patients that were exposed to one of the outbreak facilities from June 2019 onwards. A new case was also detected through rectal screening in week 45. This case, Case 19, stayed on the ward where current cases are being cohorted and a recent transmission event seems most likely. Again an extended outbreak meeting with all stakeholders was organised in week 46 and barrier precautions were reinforced. Currently data collection of these two recent cases as well as sequencing of the isolates are being conducted. PFGE analysis of the new isolates shows that these belonged to the outbreak strain. As of calendar week 49, there have been no further cases detected.
The mode of transmission is still under investigation, but person-to-person transmission is most likely the relevant route. In this context, the following two steps are especially valuable: ensuring intensified isolation for cases and intensified case searching through systematic extended screening immediately when an outbreak is suspected, to avoid further unrecognised cases. Other outbreaks with similar pathogens have shown that systematic rectal screening is crucial to identifying colonised patients [10]. Early in-depth analysis of the molecular and phenotypic strain features supports decision making processes for treatment and outbreak control.
The first case (index patient) presented no typical risk factors for K. pneumoniae infection such as a recent hospital stay or recent travel, and is therefore unlikely to be the primary case that brought the outbreak strain into the university hospital. As exemplified by the detection of Case 18, there may have been undetected cases, especially during the early phase of the outbreak. All but one case (of the 19 cases) had a history of hospitalisation in the university hospital, which is the only tertiary hospital in the affected region. Transmissions within the other institutions involved cannot be ruled out. Cooperation between institutions and public health authorities should be intensified, e.g. by fostering close, local collaboration between health facilities, health departments, laboratories and further stakeholders in MDRO-networks. This has already been proven to be successful for controlling outbreaks with other XDR pathogens [11].
The emergence of XDR K. pneumoniae dramatically limits treatment options. Only a few outbreaks of K. pneumoniae with the carbapenemase combination of NDM-1 and OXA-48 have been described [12,13].
Furthermore, presence of both carbapenemases NDM-1 and OXA-48 were identified in other K. pneumoniae sequence types [14,15], but rarely in ST307 [16]. However, CTX-M-15-associated K. pneumoniae ST307 with OXA-48 and colistin resistance was reported in a Serbian hospital in 2015 [7]. Wyres et al. [17] recently described CTX-M-15-associated K. pneumoniae ST307 as a highly successful, globally emerging lineage with remarkable level of plasmid conservation.
Clinical and laboratory staff need to increase vigilance in order to improve early detection of XDR outbreaks. Early extensive screening and a high level of isolation precautions are needed to avoid further spread of these pathogens. As consequence of this outbreak, the detection of an XDR enterobacterial strain in an area with low endemicity emphasizes the need for increased awareness and risk mitigation measures to avoid transmission events.(Continue. . . .)
Carrying genes encoding for both NDM-1 (New Delhi metallo-ß-lactamase-1) and OXA-48 carbapenemases, this new, highly resistant resistant strain becomes even harder to treat and control.
As time goes by, these bacteria continue to learn new ways to undermine our antibiotic armamentarium.Complicating matters, these AMR abilities can be transferred via Plasmids – tiny snippets of DNA that can be easily transferred between different types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species).
It may help if you think of plasmids as vehicles that can travel between different types of bacteria, and the resistance genes (like NDM-1) as one of its passengers.While most current resistant infections are still treatable - antimicrobial resistance already impacts millions of lives each year around the globe. The CDC's HAI ( healthcare-associated infections) website describes the insidious spread of CRE in the United States over the past 20 years.
Tracking CRE in the United States
Bacteria are constantly finding new ways to avoid the effects of antibiotics. For example, some Enterobacteriaceae can produce enzymes called carbapenemases that break down antibiotics including carbapenems, making the drugs ineffective. Carbapenem antibiotics are typically reserved to treat multidrug-resistant bacterial infections, so when bacteria develop resistance to them, treatment options can be extremely limited.
As of 2018, CDC is tracking carbapenemase enzymes in CRE using data generated by the Antibiotic Resistance Laboratory Network (AR Lab Network) and CDC laboratories. The AR Lab Network is not a surveillance network and therefore does not represent testing of every isolate in each state.
The AR Lab Network routinely tests for the following carbapenemases:
- K. pneumoniae carbapenemase (KPC): This was first identified in the United States around 2001 and is the most common carbapenemase in the United States.
- New Delhi Metallo-beta-lactamase (NDM): A less common carbapenemase in the United States but concerning because it can be resistant to even more antibiotics than KPC.
- Verona Integron-Enconded Metallo-beta-lactamase (VIM): A less common carbapenemase in the United States but concerning because it can be resistant to even more antibiotics than KPC.
- Imipenemase (IMP): A less common carbapenemase in the United States but concerning because it can be resistant to even more antibiotics than KPC.
- Oxacillinase-48-like (OXA-48-like): A less common carbapenemase in the United States.
While I cover AMR topics from time to time in this blog, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about the growing global threat of AMR.
You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 24 hours of lectures and webinars on Antimicrobial stewardship.Some of my more recent blogs on the threat of antibiotic resistance include:
WHO Update - Carbapenem-resistant Pseudomonas aeruginosa Infection – Mexico
UK Launches 5-year Action Plan Against Antimicrobial Resistance
WHO Report: Wide Differences In Antibiotic Use Between Countries
The Lancet: Attributable Deaths & Disability Due To Infections With Antibiotic-Resistant Bacteria - EU 2015
mBio: The Gathering Storm: Is Untreatable Typhoid Fever on the Way?
WHO: First Global Antimicrobial Surveillance System (GLASS) Report
