Disease Outbreak News
Antimicrobial Resistance, Hypervirulent Klebsiella pneumoniae - Global situation
31 July 2024
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:
- 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.
- As with other resistance mechanisms, the risk of spread could increase due to high movements of people (within and between countries and regions).
- There are very limited antimicrobial treatment options for the carbapenem-resistant hvKp isolates and these strains have the capacity to generate outbreaks.
- 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.
- 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.
- 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.
- 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.
- 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.
WHO advice
1. Awareness and laboratory capacity to identify carbapenem resistance hvKp
- Countries should strengthen clinical and public health awareness for the detection of carbapenem resistance (CR)-hvKp. The isolation of invasive isolates of K.pneumoniae with associated carbapenem resistance should prompt consideration of further testing (where available). The ability to differentiate hvKp from classical Klebsiella pneumoniae is needed for optimal clinical management. Furthermore, the sites of infection due to hvKp could dictate modifications of the antimicrobial regimen to optimize tissue concentrations [e.g., prostate, central nervous system] and may affect the duration of therapy. This is even more important for antimicrobial resistant hvKp (e.g., CR-hvKp) due to more limited treatment options. There is a need to raise awareness among clinicians and diagnostic laboratory services to detect suspected hvKp infections based on the typical clinical picture of community-acquired hvKp infections, unusual spread of K. pneumoniae infections within the body, or clusters of healthcare-associated K. pneumoniae infections related to increased severity and mortality.
- WHO in liaison with Member States should implement a consensus definition of hvKp as there is no current agreement on the definition, partly due to the diversity of genetic backgrounds and the complexity of virulence mechanisms, which results in a lack of understanding of the prevalence, identification, and diagnosis of hvKp infections. To date, multiple virulence factors and phenotypes have been well characterized and some of these features serve as a marker for hvKp. Until such a consensus definition is agreed upon, countries should continue to use with caution current available schemes to detect hvKp such as the detection of biomarkers, Kleborate virulence scores or other available methods.
- Countries should reinforce the central role of the national reference laboratories in molecular testing and in detection and analyses of relevant virulence genes in addition to resistance genes. Develop effective methods and strategies to screen for hypervirulence in the routine diagnostic laboratory, as well as clinical case definitions that would aid the detection of samples for higher characterization.
2. Prospective data collection and surveillance
- Countries should develop a surveillance system (if not already in place) for the systematic collection of microbiological and clinical data that includes invasive infections and monitors the number of cases at the national level, accounting for body sites where CR-hvKp may be present, such as the eyes (endophthalmitis), lungs, and central nervous system.
- Develop algorithms for the detection, confirmation, and characterization of hypervirulence from the clinical presentation of infections to the genetic characterization of virulence markers and the interpretation of the results, as well as a need for a menu of methodologies that allow Member States to detect these isolates regardless of the available resources.
- Evaluate clinical outcomes as well as creating a surveillance system to monitor antibiotic treatment when CR- hvKp infections are suspected or confirmed.
- Countries should continue to report new cases of CR-hvKp to WHO via GLASS-EAR and other available global and regional channels.
3. Infection prevention and control (IPC) measures
- Health-care facilities should be familiar with the general IPC measures (standard and transmission-based precautions) required when managing all patients in both acute care and long-term care facilities
- Enhanced IPC measures should be in place for the prompt management of suspected and/or confirmed cases and contacts of carbapenem-resistant hvKp in both acute care and long-term care facilities as per WHO Guideline and Implementation manual to prevent and control the spread of carbapenem-resistant organisms at the national and health care facility level.
- Enhanced IPC control measures for CR-hvKp in both acute care and long-term care facilities are analogous to the enhanced control measures for carbapenem-resistant ‘classic’ K. pneumoniae, hence the infection control requirements described in the guidelines are still valid.