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07 May 2023: Articles  Canada

Cryptogenic Hypervirulent Pyogenic Liver Abscess: A Case Report

Unknown etiology, Challenging differential diagnosis, Rare disease

Jennifer Leigh1ABE, Reza Naghdi1ABE*

DOI: 10.12659/AJCR.939322

Am J Case Rep 2023; 24:e939322




BACKGROUND: Klebsiella pneumoniae is a gram-negative organism known to cause pyogenic liver abscesses. It is most often caused by one of the hypervirulent strains, which are capable of causing metastatic infection. This occurs most commonly in Asia in patients without hepatobiliary disease; however, it is becoming increasingly recognized in North America.

CASE REPORT: We report a previously healthy man in his 50s who presented to hospital with 3 weeks of fever, chills, and mild abdominal pain following a minor motor vehicle collision. Ultrasound and computed tomography of his abdomen revealed a large multi-loculated liver abscess. This was drained percutaneously and grew a hypervirulent strain of Klebsiella pneumoniae known to cause metastatic infection. His blood cultures were negative. In addition to percutaneous drainage, he was treated with 8 weeks of antimicrobial therapy. Fortunately, he did not develop evidence of metastatic infection despite the hypervirulent strain. Etiology of the abscess was not clearly identified; however, it was speculated that the motor vehicle collision could have led to its development through gut translocation.

CONCLUSIONS: Presentation of Klebsiella pneumoniae liver abscesses is often nonspecific, and clinicians must have a high index of suspicion in order to ensure rapid diagnosis and treatment. Delay in diagnosis is associated with increased morbidity and mortality, and thus it is an important entity for clinicians to be aware of, especially as it becomes more prevalent in North American populations. Additionally, it is important that physicians are aware of the hypervirulent strains and screen patients clinically for evidence of metastatic infection.

Keywords: Klebsiella pneumoniae, Liver Abscess, Pyogenic, Male, Humans, Klebsiella Infections, Drainage, Fever


Klebsiella pneumoniae is a gram-negative organism first identified to be a pathogenic cause of pyogenic liver abscesses in Taiwan in the 1980s [1]. Unlike other etiologies of pyogenic liver abscess, abscesses caused by K. pneumoniae are often cryptogenic and not associated with hepatobiliary disease [2]. Infection is most often due to one of the hypervirulent serotypes (K1 or K2), which have the capability of producing metastatic infection [2,3]. This is especially more prevalent in diabetics and historically predominantly occurred in patients living in Asia [1]. It is now becoming increasingly identified as a causative agent in North Americans with no history of travel to these high-risk regions. Mortality is approximated to be 5% but increases in those with metastatic infections, such as meningitis, endophthalmitis, septic emboli, and empyema [2]. Due to the increasing prevalence in North America and cryptogenic nature of the infection, it is an important entity for clinicians to be aware of. Herein, we present a case of a previously healthy non-diabetic man who presented with a hypervirulent K. pneumoniae liver abscess (KLA) without bacteremia following a minor motor vehicle collision.

Case Report

A previously healthy man in his 50s presented to the Emergency Department (ED) with a 3-week history of intermittent abdominal pain, fever, and chills. His past medical history included an appendectomy as a child and remote wrist fracture. He was taking no prescribed medications, had no known drug allergies, and had no substance use history. He was born in South Korea and emigrated to Canada in 2002, and his last travel outside of Canada had been to South Korea greater than 2 years prior to presentation.

His symptoms started a few days after he was involved in a slow-speed traffic accident, in which another car had rear-ended him. His only injury at the time was mild whiplash. Prior to this accident he had been well. Following the event, he developed persistent daily fevers, with a temperature greater that 38°C. After the fever persisted for 3 weeks, he presented to the ED. At the time of presentation, he was febrile, with a temperature of 39.2°C, and otherwise hemodynamically stable. Physical examination revealed tenderness in the right upper quadrant of his abdomen.

Laboratory investigations at presentation demonstrated an elevated white blood cell count of 16.0×109/L (reference range 3.5–10.5×109/L), hemoglobin level of 123 g/L (reference 125–170 g/L), and platelet count of 500×109/L (reference 130–380×109/L). The chemistry panel included a sodium level of 132 mmol/L (reference 136–144 mmol/L), potassium level of 4.0 mmol/L (reference 3.5–5.1 mmol/L), and creatinine level of 69 mol/L (reference 62–100 mol/L). The lactate level was within normal limits, at 1.3 mmol/L. His liver enzymes were mildly increased, with an aspartate aminotransferase level of 55 U/L (reference 12–41 U/L), alanine aminotransferase level of 55 U/L (reference 12–49 U/L), alkaline phosphatase level of 247 U/L (reference 50–112 U/L), gamma-glutamyl transferase level of 138 U/L (reference 11–105 U/L), and total bilirubin of 10 μmol/L (reference <15 μmol/L). Blood cultures were taken and eventually returned negative. His chest X-ray was clear of any infection. Urinalysis did not have any nitrites or leukocytes, and a COVID-19 nasopharyngeal PCR test was negative. An abdominal ultrasound was performed and revealed a 12.8×11.8×13.2-cm complex mass in the right lower hepatic lobe (Figure 1). This was further characterized with contrast-enhanced computed tomography (CT) of the abdomen (Figure 2), which demonstrated a multiloculated lesion with hyperenhancing capsule, septations, and mild enhancing edema measuring 11.7×9.7 cm, located in segment 7/8 and thought to be in keeping with a large hepatic abscess.

The patient was admitted to the Internal Medicine service and started on ceftriaxone 1g intravenously (i.v.) every 24 h and metronidazole 500 mg i.v. every 8 h for empiric therapy. He underwent pigtail catheter drainage of the collection within 24 h of admission. Culture of the abscess returned positive for K. pneumoniae, sensitive to amoxicillin-clavulanic acid, cefazolin, ciprofloxacin, gentamicin, sulfamethoxazole/trimethoprim, and tobramycin. The sample was sent to the National Microbiology Laboratory and the string test, which is a screen for hypermucoviscosity, returned positive. The ultimate genotype for this strain was K1, iroB, iucA, ybtA, clbA, peg-344, and rmpA, which confirmed it to be a hypervirulent strain. After 6 days of drainage, a repeat ultrasound demonstrated reduction in the size of the collection with no further drainable components, and the drain was removed. He remained on the same parenteral antibiotic regimen in hospital, with no clinical evidence of metastatic infection, and was discharged on day 10 of admission with a course of oral ciprofloxacin 500 mg twice daily and oral metronidazole 500 mg twice daily.

The patient continued his oral antibiotics for a total of 6 weeks following discharge. A repeat ultrasound performed 7 weeks later demonstrated complete resolution of the abscess, and a surveillance CT scan performed 24 weeks later confirmed no recurrence (Figure 3). Abdominal magnetic resonance imaging (MRI) with i.v. contrast was completed 8 months after his hospitalization and again confirmed ongoing resolution of the abscess and no features of cirrhosis or suspicious hepatic or biliary lesions. He has since remained clinically well, with no complications or persistent symptoms from his prior infection.

He was investigated for potential predisposing conditions including diabetes (fasting glucose was 5.7 mmol/L), hepatitis B (hepatitis B surface antigen negative, anti-hepatitis B surface antibody and anti-hepatitis B core antibody both positive, suggestive of immunity from cleared infection), and HIV (serology negative) and underwent a rheumatologic screen (anti-nuclear antibody and rheumatoid factor negative). Tumor markers were also sent and were returned within the normal range for all tests (AFP <1 ng/mL, Ca 19–9 3 U/mL, and CEA 1.4 ng/mL). Lastly, there was no radiographic evidence of malignancy on chest X-ray, abdominal MRI with i.v. contrast, or CT of the abdomen and pelvis with i.v. contrast. It was overall postulated that the patient had been colonized with this specific hyper-mucoviscous K. pneumoniae serotype, and while no definitive inciting event was identified, question was raised if his minor motor vehicle collision may have contributed.


Pyogenic liver abscesses are traditionally thought to be polymicrobial in nature, especially those found in the Western hemisphere [3]. However, K. pneumoniae is becoming an increasingly recognized monomicrobial cause of pyogenic liver abscess in North America. Epidemiologic data suggests that infection, especially caused by the hypervirulent K1 serotype, occurs more often in men of Asian descent and those with underlying diabetes mellitus, and is negatively associated with hepatobiliary pathology, which tends to cause more polymicrobial infections [2–4]. It is postulated that KLA development can occur following gut translocation through a mucosal defect or compromised mucosal barrier in healthy individuals who are colonized [5]. Interestingly, KLA can distract from an occult colorectal malignancy, as there is a rare but previously reported association between the two [6].

The clinical presentation of pyogenic liver abscesses is diverse and nonspecific, with more common symptoms including fever, chills, and abdominal pain [2]. There are certain CT imaging findings that make a pyogenic liver abscess more likely to be due to K. pneumoniae, and this includes findings of a single abscess, unilobar involvement, solid appearance, multilocular, and association with thrombophlebitis, many of which were seen in the present case [7]. There is a higher likelihood of hematogenous spread in KLA, as well as metastatic sites of infection with the hypervirulent strains, which can lead to devastating infection including endogenous endophthalmitis, meningitis, septic emboli, empyema, and osteomyelitis. This occurs more commonly in diabetic patients and those with an abscess of 5 cm or larger and is associated with increased mortality [2,8,9]. There are a number of biomarkers for hyper-virulence that have been identified, and this is important as these are correlated with an increased likelihood of severe disease or death [10]. Some of these were identified in the strain from the present case, including peg-344, iroB, rmpA, and iucA [10]. The K1 serotype is an independent risk factor for endogenous endophthalmitis, and this was also identified in the present case [11,12].

Treatment for KLA includes antimicrobial therapy, often in combination with percutaneous drainage of the collection [13,14]. Indications for surgical management include ruptured abscess, incomplete percutaneous drainage, persistent primary pathology, multi-loculated abscess, and failure to improve after 4 to 7 days of percutaneous drainage [14]. Isolates usually show resistance to ampicillin and penicillin, and thus third and fourth generation cephalosporins are considered first-line therapy [15,16]. While there has been evidence to suggest that anaerobic coverage is not required in KLA, epidemiologic data has suggested that close to half of pyogenic liver abscesses in Canada are polymicrobial [17,18]. Since abscess sampling was not completed until 24 h after antibiotic initiation in our patient, which could in turn effect the microbiologic yield, anaerobic coverage was continued for the course of his treatment. Extended duration of antimicrobial therapy is typically recommended, with 2 to 3 weeks of parenteral antibiotics followed by oral administration, for a total 4 to 6 weeks of antibiotic course, although there is evidence to support early initiation of oral antimicrobial therapy as well [19].

The exact trigger for abscess formation in our patient was never identified, as he had no clear abdominal pathology, bacteremia, or risk factors. Review of the literature identifies a few case reports of the development of pyogenic liver abscesses in patients without any prior hepatobiliary pathology following blunt force abdominal trauma, including motor vehicle collisions [20,21]. These cases were associated with liver lacerations following the trauma, which our patient was not known to have following his minor accident. Given that the patient had been well before the accident and developed his symptoms only afterward, we suspect that either a mild injury from the accident or gut translocation at time of impact may have caused the abscess to develop in this case. There were no symptoms or prior imaging to suggest that this abscess had been a chronic process.


K. pneumoniae is an important invasive cause of pyogenic liver abscess that is becoming increasingly recognized in North America, including in otherwise healthy individuals, such as our patient. It is often caused by the hypervirulent K1 or K2 serotypes, which place patients at risk of increased complications and worsened morbidity and mortality. Clinicians need to have a high index of suspicion in order to diagnose pyogenic liver abscesses. Their presentation is often nonspecific, and they can develop in patients with no clear risk factors, such as in this case. If it is not on the differential diagnosis and a physician does not think to look for it, the diagnosis can be missed or delayed. Rapid diagnosis and treatment are important in the management of this disease, and it is an important entity for clinicians to be aware of. Diagnostic work-up should include screening for metastatic complications, and empiric therapy for any pyogenic liver abscess should include coverage of K. pneumonia.


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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923