WHO DON & Risk Assessment: Hypervirulent Klebsiella pneumoniae (hvKp) ST23

 

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While HPAI H5 and COVID currently get the bulk of our attention, they are not the only global health threats on the horizon.  We are also faced with a growing array of multidrug resistant organisms (MDROs) - both bacterial and fungal - that already claim thousands of lives each year. 

MDROs such as Candida auris, C. difficle, CRE, and MRSA cause significant morbidity and mortality in hospitalized patients, can be spread to other patients, staff, and even visitors, and are particularly problematic in nursing homes and LTCFs (Long Term Care Facilities).

Although most bacterial infections are still treatable - AMR (antimicrobial resistance) isn't some obscure future threat - as it already impacts millions of lives each year around the globe. In 2019, the CDC estimated that: More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.

In recent years HvKp - a  hypervirulent form of Klebsiella pneumoniae -  most commonly reported in Asia, has drawn our attention.  This highly invasive bacterial infection is increasingly showing signs of antibiotic resistance (see CIDRAP Hypervirulent, highly resistant Klebsiella identified in China).

• In 2020, in EID Journal: COVID-19 and Fatal Sepsis Caused by Hypervirulent Klebsiella pneumoniae, Japan, 2020, we looked at an account of an elderly COVID patient in Japan who was co-infected with HvKp, a hypervirulent form of Klebsiella pneumoniae.

• In 2019, we looked at an outbreak Extensively drug-resistant (XDR) Klebsiella pneumonia in Europe involving (XDR) K. pneumoniae, affecting four hospitals in the northeast of the state of Mecklenburg-West Pomerania.

• And in Tracking CRE in the United States, the CDC lists K. pneumoniae carbapenemase (KPC) - which was first identified in the United States around 2001- as the most common carbapenemase in the United States.

In 2021 the ECDC  - in response to two clusters of Klebsiella pneumoniae (hvKp) ST23  carrying carbapenmase genes reported by Ireland since 2019 -released a 14-page Risk Assessment.  

Last February, in ECDC Risk Assessment: Increase of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae in the EU/EEA, we learned that HvKp had spread from 4 EU/EEA nations to 10, and the number of cases has increased nearly 12-fold since that first report.  

The ECDC warned:

The probability of further spread and establishment of hvKp carrying carbapenemase genes in healthcare settings in EU/EEA countries with consequent significant impact on morbidity and mortality is therefore currently considered to be high. 

This growth has occurred around the globe, although surveillance and reporting are spotty at best.  Overnight the World Health Organization released an update - and a global risk assessment - on this emerging threat. 

Due to its length, I've only posted the summary and risk assessment. Follow the link to read the report in its entirety.  I'll have a brief postscript after the break.

Antimicrobial Resistance, Hypervirulent Klebsiella pneumoniae - Global situation

31 July 2024

Situation at a glance

In early 2024, the Global Antimicrobial Resistance and Surveillance System on Emerging Antimicrobial Resistance Reporting (GLASS-EAR) issued a request for information to assess the current global situation given the increased identification of isolates of hypervirulent Klebsiella pneumoniae (hvKp) sequence type (ST) 23 carrying resistant genes to the carbapenem antibiotics – carbapenemase genes.

 K. pneumoniae strains that can cause severe infections in healthy individuals and have been identified with increasing frequency in recent years are considered hypervirulent compared to classical strains because of their ability to infect both healthy and immunocompromised individuals and because of their increased tendency to produce invasive infections.

The presence of hvKp ST23 was reported in at least one country in all six WHO Regions. 

The emergence of these isolates with resistance to last-line antibiotics like carbapenems necessitates the administration of alternative antimicrobial treatment, which may not be available in many contexts. WHO recommends that Member States progressively increase their laboratory diagnostic capacity to allow for the early and reliable identification of hvKp, as well as reinforce laboratory capacities in molecular testing and detection and analyses of relevant virulence genes in addition to resistance genes.

The assessment of risk at the global level is moderate given the challenges with surveillance, lack of information on laboratory testing rates, track and scale of community transmission, the gap in the available data on infections, hospitalization, and the overall burden of the disease.

(SNIP)

WHO risk assessment

Globally, there is no systematic surveillance that allows for the routine identification and information collection of hvKp strains. Identification of hvKp is challenging given that it is determined by available laboratory capacity to perform genomic sequencing tests or analysis of specific markers that may indicate hypervirulence, so the prevalence of hvKp-associated infections may be underestimated. 

Assessing the current risk of hvKp at the global level aims to incorporate several risk components including 1) the emergence and sustained transmission of hvKp carrying carbapenem resistance genes, considering the public health impact of the identified resistance for the AMR related events; 2) the risk of geographical spread; 3) the risk of insufficient control capacities with available resources; and 4) the risk of resistance spread to other bacterial species via mobile genetic elements.

The risk at the global level is assessed as moderate considering that:

1. Infections caused by hvKp traditionally have occurred within communities in certain geographical regions (Asia) and are associated with high morbidity and mortality as well as high pathogenicity and limited antibiotic choices. However, recent reports from the WHO European region and the European Centre for Disease Prevention and Control (ECDC) have shown transmission in health-care settings, and several studies from China have reported clusters of health care-associated infections of hvKp; hence highlighting the importance of strict infection prevention and control (IPC) measures when managing these cases in health-care settings. With the concurrence of hypervirulence and antibiotic resistance, it is expected that there will be an increased risk of spread of these strains at both the community and hospital levels.
2. As with other resistance mechanisms, the risk of spread could increase due to high movements of people (within and between countries and regions).
3. There are very limited antimicrobial treatment options for the carbapenem-resistant hvKp isolates and these strains have the capacity to generate outbreaks.
4. The high conjugation capacity of the carbapenem-resistant hvKp (CR-hvKp) and the potential for further dissemination in clinical settings; hvKp ST23 particularly out-competes other gut bacteria facilitating colonization and spread.
5. Detection of the emergence of multi-resistant or extensively resistant pathogens requires established resistance laboratory surveillance systems as well as effective infection prevention and control programs in health-care facilities.
6. Lack of laboratory capacity contributes to the restriction of laboratory diagnosis, and this affects the sensitivity of the surveillance. Most affected countries do not have the capacity for diagnosis in the clinical setting as the laboratory diagnosis of hvKp infections depends on the availability of molecular tests.
7. There is global heterogeneity in laboratory surveillance capacity for this pathogen; because of this, there is no systematic surveillance (detection, monitoring, and reporting) of hvKp infections in most countries or regions. Outbreaks and cases are documented in a non-systematic way through laboratory surveillance for antimicrobial resistance, or retrospective epidemiological studies, making data on the prevalence of hvKp infections scarce.
8. The prevention and control of carbapenem-resistant hvKp poses significant challenges because it has not been possible to establish the extent of its dissemination in the countries of the different regions and information on this subject is currently limited.

The level of confidence in the available information and risk assessment at the global level is moderate given the challenges with surveillance, lack of information on laboratory testing rates, ability to track and determine scale of community transmission, the gap in the available data on infections, hospitalization and from the overall burden of the disease.

(Continue . . . )

Although 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 50 hours of lectures and webinars on Antimicrobial stewardship.

In this highly uncertain world, there are at least two things you can count on.

• COVID-19 won't be the last pandemic to wreak havoc around the globe

• Evolutionary pressures due to overuse and misuse of antibiotics will continue to erode our limited armamentarium of these lifesaving drugs.

We either seriously prepare to deal with these looming biological threats, or we'll suffer the consequences. 

 Again.