Xishan Biology

Introduction to Pathogens

Klebsiella pneumoniae and Klebsiella oxytoca

Klebsiella pneumoniae, a pathogen mandated for exclusion in SPF-grade mice and rats according to national standards, is classified as an opportunistic bacterium that can cause infections in experimental animals when their immune systems are compromised or under stress, thereby severely disrupting ongoing studies. While Klebsiella oxytoca is currently not listed in national standards as a mandatory test and exclusion criterion for SPF-grade rodents, growing reports and research increasingly highlight that Klebsiella oxytoca also exerts significant, yet often overlooked, effects on laboratory animals.

Introduction to Pathology

 

Klebsiella is a genus of Gram-negative, encapsulated, non-motile bacilli. Both Klebsiella pneumoniae and Klebsiella oxytoca belong to the family Enterobacteriaceae and are members of the genus Klebsiella. Currently, the K. pneumoniae group comprises seven phylogenetic groups (KP1–KP7), while the K. oxytoca group includes nine phylogenetic groups (KO1, KO2, KO3, KO4, KO6, KO8). Notably, Klebsiella pneumoniae is a common bacterium found in nature, and both it and Klebsiella oxytoca are opportunistic pathogens that spread primarily via the fecal-oral route. These bacteria commonly colonize the intestines and respiratory tracts of humans and mammals, making them one of the most prevalent hospital-acquired infection agents worldwide.

Figure 1: Acid-producing Klebsiella species

Figure 2: Acid-producing Klebsiella species

Epidemiology

 

Klebsiella pneumoniae is widely distributed in nature and most commonly causes infections such as pneumonia, urinary tract infections, and liver abscesses. In severe cases, it can lead to systemic sepsis. High-risk groups include cancer patients, newborns, the elderly, individuals with medical devices implanted, and those with compromised immune systems—groups that experience significantly higher incidence and mortality rates. With the widespread use of antibiotics, strains of Klebsiella pneumoniae have emerged that produce extended-spectrum β-lactamases (ESBLs) and carbapenem-resistant Klebsiella pneumoniae (CRE). The World Health Organization has identified these two types of Klebsiella pneumoniae (CRKp) as grave threats to global public health. ESBL-producing Klebsiella pneumoniae exhibit resistance not only to penicillins, cephalosporins, and monobactams but also to carbapenem antibiotics, including imipenem and meropenem. Notably, ESBL-producing Klebsiella pneumoniae strains have recently been detected in dogs, cats, and horses treated at veterinary hospitals. Additionally, ESBL-producing strains have been isolated from wastewater originating from poultry slaughterhouses. These findings suggest that multidrug-resistant Klebsiella pneumoniae may be spreading into animal populations, posing significant challenges for both human and veterinary medicine alike.

Klebsiella pneumoniae has two types of capsule antigens—O and K—where the K antigen serves as the basis for serotyping the bacterium. Currently, over 80 capsule serotypes have been identified, with K1 and K2 being the most virulent and also the most commonly encountered. Notably, K1 and K2 significantly enhance pathogenicity in mice, whereas all other strains either fail to cause disease in mice or exhibit only weak pathogenicity. Meanwhile, K5 is known to induce liver abscesses in humans, while K3 is restricted to the rare Klebsiella rhinoscleromatis subspecies associated with rhinoscleroma.

Figure 3: Phenotypic Characteristics of High-Virulence and Low-Virulence Klebsiella pneumoniae

Clinical symptoms

 

Klebsiella pneumoniae can cause suppurative otitis media and meningitis in common marmosets; meningitis in rhesus monkeys; and liver abscesses, bacteremia, endophthalmitis, bronchopneumonia, and mesenteric lymphadenitis in African green monkeys. In mice, infection with Klebsiella pneumoniae primarily leads to pneumonia following respiratory tract infection. Common symptoms include difficulty breathing, sneezing, weight loss, reduced appetite, hunched posture, and roughened fur. Severely affected mice may develop systemic abscesses, conjunctivitis, and enlarged cervical lymph nodes; female mice may even exhibit uterine fluid accumulation. Immunocompromised mice often succumb to the infection, with the disease typically lasting 5 to 7 days. Pathological changes are mainly observed in the lungs, where pulmonary hemorrhage and fluid accumulation are evident, along with hepatic congestion and enlargement. The intestinal walls also show signs of congestion. In rats, abscesses commonly form in the cervical and inguinal lymph nodes, often leading to fistula formation on the adjacent skin surface. Additionally, mesenteric lymph nodes and kidneys may develop abscesses. In guinea pigs, the bacteria can induce anorexia, respiratory distress, and ultimately death, accompanied by seropurulent lesions in the thoracic and abdominal cavities, as well as conditions such as mastitis, splenomegaly, hepatic coagulative necrosis, and granular degeneration of renal tubular cells.

Klebsiella pneumoniae typically causes suppurative pneumonia in humans. It also induces subcutaneous, intra-abdominal, and hepatic abscesses in mice, as well as keratoconjunctivitis and meningitis, and infections of the oral cavity and salivary glands. In aged mice, it leads to uterine and ovarian infections, including purulent endometritis, salpingitis, perioophoritis, and peritonitis. In rats, the primary manifestation is intestinal damage occurring specifically in the cecum, along with purulent otitis media, urogenital tract infections, and pneumonia. Rabbits, meanwhile, develop hemorrhagic ileocolitis, serous fluid accumulation in the thoracic cavity, and exhibit pale, enlarged livers.

Treatment and Removal

 

Treatment typically involves lomefloxacin hydrochloride (a fluoroquinolone antibiotic), colistin B, and gentamicin (which are poorly absorbed when taken orally but are well-suited for injection). Amoxicillin-clavulanate is also used, as it can produce β-lactamase. Strains originating from non-human primates not only exhibit resistance to ampicillin, cephalothin, amoxicillin, and clavulanate, but also show cross-resistance to drugs like enrofloxacin and gentamicin. Moreover, co-infected captive macaques may harbor mixed or recurrent infections involving different bacterial strains. Both rhesus monkeys and crab-eating macaques can serve as asymptomatic carriers, maintaining subclinical infections. For this reason, certain institutions maintain strict physical separation between African green monkeys and macaque species.

Klebsiella species colonize facilities and are notoriously difficult to eliminate, often spreading within environments via items such as clothing, gloves, and scrapers. With the emergence and spread of carbapenem-resistant Enterobacteriaceae, colistin is now considered the last-line treatment for infections caused by carbapenem-resistant bacterial isolates.

It is understood that Klebsiella pneumoniae infections show regional variations. Below is our company's detection rate of Klebsiella pneumoniae over the past five years for your reference.

Figure 5: Trends in the Detection Rate of Klebsiella pneumoniae Over the Past Five Years

References

 

1. Paczosa, Michelle K., and J. Mecsas. "Klebsiella pneumoniae: Launching an Offense with a Robust Defense." Microbiology and Molecular Biology Reviews 3 (2016): 80.

2. Cox, Brandi L., et al. "Resistance of Klebsiella pneumoniae to the Innate Immune System of African Green Monkeys." Veterinary Microbiology 176.1-2 (2015): 134–142.

3. Russo, Thomas A., and C. M. Marr. "Hypervirulent Klebsiella pneumoniae." Clinical Microbiology Reviews 32.3 (2019).

4. Joseph, Laura, et al. "From Klebsiella pneumoniae Colonization to Dissemination: An Overview of Studies Utilizing Murine Models." Microorganisms 9.6:1282.

5. Bleich, A., et al. "Klebsiella oxytoca: Opportunistic Infections in Laboratory Rodents." *Laboratory Animals* 3 (2008): 42.

6. Alison, Darby, and colleagues. "Cytotoxic and Pathogenic Properties of Klebsiella oxytoca Isolated from Laboratory Animals." *PLOS One* 9.7 (2014): e100542.

7. Zhang Shiyu. Isolation and Identification of Klebsiella pneumoniae, and Study on Its Pathogenicity in Mice [D]. Nanjing Agricultural University [2023-07-19]. DOI: 10.7666/d.Y2528138.

 

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