Klebsiella pneumoniae is a well-known opportunistic pathogen often associated with healthcare-associated infections. However, in recent years, a particularly concerning strain known as hypervirulent Klebsiella pneumoniae (hvKP) has emerged, capable of causing severe infections in healthy individuals outside of hospital settings. This phenomenon has led to a surge in community-acquired infections, raising alarms in the medical community. Here we examine the rise of community-acquired Hypervirulent Klebsiella infections, analyze case reports and discuss the implications for healthcare and public health.

The Basics of Klebsiella pneumoniae

Klebsiella pneumonia is a well-known species of gram-negative bacterium under the family Enterobacteriaceae and is among the opportunistic pathogens commonly found in the human gut as part of the normal flora. In most cases, it is non-pathogenic, but it may lead to severe infections when it invades other organs, such as the bloodstream, lungs or the urinary system. Such infections frequently occur in patients who have been hospitalized, as their immune system has been compromised. Studies in recent years have increasingly focused on hypervirulent strains of this bacterium, which can infect healthy people without any predisposing factors.

Emergence of community-acquired Hypervirulent Klebsiella pneumoniae

A subgroup of Klebsiella pneumoniae is termed as hypervirulent. The subgroup describes strains that possess enhanced virulence factors. These strains are often associated with unique genetic elements, such as plasmids that encode virulence factors like capsule production, iron acquisition systems and biofilm formation. The virulence factors enable them to invade tissues more aggressively, evade the immune system and cause severe disease. One of the most concerning features of hypervirulent Klebsiella pneumoniae is its ability to cause invasive infections, such as liver abscesses, necrotizing fasciitis and endophthalmitis, in otherwise healthy individuals.

The Growing Threat of Community-Acquired hvKP Infections

Case Reports Highlighting hvKP in Community Settings

First described in hospitals, an increasing number of recent case reports demonstrate that there has been a surge in the number of community-acquired hypervirulent Klebsiella pneumoniae infections. These were severe, rapidly progressive infections that led to complications like sepsis organ failure and even death if not treated fast.

This 63 year old Sinhalese gentleman was admitted with fever, frequent loose stools and a loss of appetite for the past one week. He had diabetes mellitus with poor glycemic control. Examination revealed only mild non-tender hepatomegaly. Investigations revealed that he had a septic process with neutrophil leukocytosis, thrombocytopenia and raised inflammatory markers with acute kidney injury. His abdomen sonography revealed a large liver abscess and two blood cultures grew Klebsiella pneumoniae. He improved fully after aspiration of the abscess and treatment with intravenously administered ceftriaxone.

Notable cases of community-acquired Klebsiella pneumoniae infections have been summarized in the case reports over the years:

• 1980s: Hypervirulent strains of Klebsiella pneumonia were recognized in Taiwan, primarily associated with liver abscesses among previously healthy hosts.

• 2003: A case report from South Korea documented endophthalmitis in a healthy middle-aged woman caused by hvKP.

Global Distribution and Epidemiology of hvKP

Worldwide, community-acquired hypervirulent Klebsiella pneumoniae infections have been reported in countries across East and Southeast Asia, with high incidence rates. This has been postulated to be due to strain-specific sequences of hypervirulent bacterial serotypes, such as K1 and K2. However, the hvKP strains have also been identified in parts of North America and Europe, pointing out that this is a global problem.

The epidemiology of hvKP is different from that of classical Klebsiella pneumoniae strains. While most hospital-associated Klebsiella infections are now associated with antibiotic resistance, hvKP strains are usually susceptible to many antibiotics. There is, however, a growing concern about the emergence of strains with hypervirulence and multidrug resistance, acquiring an overt “superbug” status, which is highly challenging to treat.

Clinical Manifestations of Hypervirulent Klebsiella pneumoniae Infections

Common Symptoms and Course of Disease

Community-acquired hypervirulent Klebsiella pneumoniae infections can occur at any site and may provide different clinical manifestations depending on the site of infection. The most common clinical manifestations are as follows:

• Liver Abscesses: There is a triad of symptoms shown by patients that include fever, abdominal pain and jaundice. The liver abscesses caused by hvKP are often single and pyogenic. In cases of pyogenic liver abscess, a K. pneumoniae liver abscess should be clinically ruled out to accurately diagnose septicemia.

• Pneumonia: hvKP often causes very severe pneumonia that can lead to respiratory failure. Clinical symptoms include cough, fever and difficulty in breathing. In contrast to the usual form of pneumonia, which is initiated with very not-so-serious presentations, the community-acquired hypervirulent Klebsiella tends to progress very quickly to severe disease that requires management in the intensive care unit.

• Endophthalmitis: A severe but infrequent eye infection that can result in blindness if it is not treated quickly. It often leads to a secondary bacteremia and can occur in one or both eyes.

• Meningitis: hvKP has also been reported to be associated with bacterial meningitis, especially in patients with liver abscess. Symptoms include severe headache, neck stiffness and altered mental status.

• Necrotizing Fasciitis: This is a rapidly progressive soft tissue infection, with the damage being quite severe and life-threatening. Patients present with rapid spread of erythema, swelling and severe pain, which can lead to tissue necrosis.

Risk Factors and Populations Affected

Community-acquired Hypervirulent Klebsiella pneumoniae has been reported in children as well as adults; however, there are specifically some predisposing factors that make a person more susceptible to the infection. These predisposing factors are:

• Diabetes: Diabetic patients are at a higher risk of developing hvKP-associated liver abscess and other invasive infections.

• Immunosuppression: Immunosuppressed individuals, because of chemotherapy and corticosteroid therapy, are at an increased risk of acquiring infection.

• Geographic Location: As mentioned earlier, hvKP is considered endemic in geographical areas like East and South-East Asia.

Despite these risk factors, community-acquired hypervirulent Klebsiella infections have also been noted among patients without any predisposing conditions, hence a dreadful pathogen to the general population.

Diagnosis and Treatment of hvKP Infections

Diagnostic Challenges

Early diagnosis is crucial for successful management of hvKP, but it will always be a difficult task because of the nonspecific features of the early symptoms. Blood culture, imaging studies and molecular testing usually help in confirming the diagnosis and detection of hypervirulent signatures. Owing to their fulminant nature, clinicians should have a high index of suspicion, in particular, with patients who present with liver abscesses or rapidly progressive pneumonia.

Genomic testing is most useful for differentiating the hypervirulent strains from classic Klebsiella pneumoniae. At the genomic level, PCR assays that target virulence genes, including rmpA and magA, may be used to confirm the presence of hvKP.

Treatment Options and Antibiotic Resistance Concerns

Treatment of infections with community-acquired hypervirulent Klebsiella pneumoniae is mainly done with antibiotics, but sometimes surgical procedure is required. In contrast to classical Klebsiella pneumoniae, hypervirulent strains usually have antibiotic susceptibility including third-generation cephalosporins, carbapenems and aminoglycosides. However, the emergence of determined hypervirulent and multidrug-resistant strains is now a growing concern.

The liver abscess may also have to be drained to get rid of the pus. In the same vein, for necrotizing fasciitis, debridement of the necrotic tissue may be necessary. Such secondary complications, like septic shock and multi-organ failure, can be avoided by promptly starting an antibiotic.

Prevention and Control Measures

Surveillance will progressively become a useful tool for public health monitoring to track the spread of hvKP strains and emergence of multi-drug resistant strains. Infection control measures i.e. breaking the circulation of these hypervirulent strains to the at risk populations, have great potential in preventing the further spread, notably in healthcare places.

Preventive Strategies

Preventive strategies for hvKP include improved hand hygiene, especially in healthcare settings and judicious use of antibiotics to avoid antibiotic resistance. Public campaigns on hypervirulent strains raising awareness in the community would help prevent the spread of infection.

The increasing prevalence of infections with community-acquired hypervirulent Klebsiella pneumoniae poses a serious threat to public health. Proper diagnosis, early treatment and effective prophylaxis cannot be achieved without controlling the spread of the pathogen. With the future ahead and the medical world battling ways through, there is an urgent need for reliable testing and validation services to ensure that infections are accurately identified and effectively treated.

Microbe Investigations Switzerland (MIS) offers specialized testing and validation services tailored to the needs of manufacturers of antimicrobial products, healthcare providers and public health institutions. Contact us today to learn more about how our services can support your efforts in controlling the spread of hvKP and protecting public health.

REFERENCES

1.Premathilake, P. N. S., Kularatne, W. K. S., Jayathilake, J. P. K., & Senadhira, S. D. N. (2018). Klebsiella pneumoniae liver abscess: a case report. Journal of Medical Case Reports, 12(1). https://doi.org/10.1186/s13256-018-1924-4

2.Kain, M. J. W., Reece, N. L., Parry, C. M., Rajahram, G. S., Paterson, D. L., & Woolley, S. D. (2024). The Rapid Emergence of Hypervirulent Klebsiella Species and Burkholderia pseudomallei as Major Health Threats in Southeast Asia: The Urgent Need for Recognition as Neglected Tropical Diseases. Tropical Medicine and Infectious Disease, 9(4), 80. https://doi.org/10.3390/tropicalmed9040080.

3.Russo, T. A., & Marr, C. M. (2019). Hypervirulent Klebsiella pneumoniae. Clinical Microbiology Reviews, 32(3). https://doi.org/10.1128/cmr.00001-19