Klebsiella pneumoniae is the most common causative organism of bacterial liver abscesses and is classified into two groups, classical K. pneumoniae and hypervirulent K. pneumoniae (1). Hypervirulent K. pneumoniae was first identified in Taiwan in 1986 as a liver abscess associated with septic endophthalmitis in young and immunocompetent hosts (2). Hypervirulent strains have a higher potential to resist phagocytosis and metastasize to distant sites forming highly mucoid colonies with capsule polysaccharide, leading to a hypermucoviscous colony phenotype. Accordingly, it is also called hypermucoviscous K. pneumoniae (1). Hypermucoviscosity has been mostly associated with serotype K1, followed by serotype K2, and is associated with the hypervirulence phenotype of Klebsiella regulated by the mucoviscosity-associated gene A (magA) and regulator of mucoid phenotype A (rmpA) (3). Klebsiella-associated invasive liver abscess syndrome with the hypermucoviscous phenotype can progress rapidly and cause severe metastatic infections such as meningitis and hydrocephalus, which are associated with high morbidity and mortality (4, 5). A rapid diagnosis followed by treatment, such as percutaneous drainage and antibiotic therapy, is the standard for improving patient outcomes with hypermucoviscous K. pneumoniae (6). For large multiloculated abscesses with percutaneous drainage failure, surgical resection is necessary for early recovery and to prevent severe secondary metastatic lesions. Herein, we present a case of successful hepatic resection in a patient with an invasive K. pneumoniae multiloculated drainage-resistant liver abscess.

An 84-year-old woman, weighing 54 kg with a height of 150 cm, was urgently admitted to the previous hospital with a diagnosis of liver abscess. Antimicrobial agents for 1 week did not improve symptoms at the previous hospital, and she was transferred to our hospital with septic shock. The patient had an implant stem after a left femur fracture and a history of asthma. There was no history of diabetes or cancer, and no history of smoking, drinking alcohol, or drug allergies. On arrival at our hospital, her initial vital signs were as follows: body temperature, 38°C; heart rate, 122 beats/min; blood pressure, 64/50 mmHg; respiratory rate, 26 breaths/min; and oxygen saturation, 91%. Her blood test revealed an increased ammonia level of 127 μg/dl, decreased serum albumin level of 1.5 g/dl, and a bilirubin level of 0.8 mg/dl. Her white blood cell count was 18200/μL, PT-INR was 1.54, d-dimer was 27.4 ng/mL, and FDP was 32.3 U/mL. Her disseminated intravascular coagulation (DIC) score was 5 points. Abdominal computed tomography showed a multiloculated liver abscess 15 cm in diameter in the right lobes of the liver extending across the right hepatic vein (Figure 1). Extrahepatic infections, such as infections of the lungs and brain, were not detected.

First, we performed percutaneous liver abscess drainage with two drainage tubes. Following transfer to the intensive care unit, intravenous meropenem followed by cefozopran was administered, according to the antibiogram. K. pneumoniae with invasive infection was confirmed by a string test in an isolated colony of K. pneumoniae, and invasive K. pneumoniae large liver abscess was diagnosed. We carried out polymerase chain reaction (PCR) with DNA from the aspirated fluid to detect the presence of hypermucoviscous K. pneumoniae as previously described (7). The PCR determined the amplification of specific genes for serotype K1, a regulator of mucoid phenotype A (rmpA), and mucoid associated gene A (magA), which was confirmed by Sanger sequencing (Figure 2). The additional abscess drainage was performed 1 week after the initial drain placement due to inadequate drainage, and finally, five drainage tubes were placed into the multiloculated liver abscess (Supplementary Figure 1). Although the abscess in the posterior segments of the liver had shrunk to a diameter of 8 cm at 4 weeks after drainage, the patient recovered from sepsis, but still had low-grade fever (occasionally 38°C), an elevated white blood cell count of 10,300/μL, C-reactive protein level of 6 U/L (Supplementary Figure 2), and continued to have symptoms of a chronic inflammation with persistent hyper mucus discharge from the liver abscess via five drainage tubes (Figure 3). We also checked for other causes of fever such as pneumonia and urinary tract infection, but no other infection related to fever was identified other than the liver abscess. We decided that further drainage treatment would be insufficient due to the multiloculated liver abscess with hyper mucus components and prolonged hospitalization with her advanced age. After explaining the patient’s condition and treatment options, a right posterior sectionectomy of the liver, including hepatic abscess, was performed. Although the abscess was not perforated, severe adhesions between the liver abscess and the right diaphragm were observed. The abscess was close to the root of Glisson’s sheath of the right posterior section; therefore, the right posterior sectionectomy of the liver, including the liver abscess, was performed (Supplementary Figure 3).

The operative time was 4 h and 48 min, and the total blood loss was 723 ml. The resected right posterior section of the liver revealed a multiloculated and necrotic liver abscess. Histological examination showed a pyogenic liver abscess with areas of necrosis, inflammatory granulation, and a few fluid components, composed of a chronic inflammatory infiltrate consisting of lymphocytes, epithelioid macrophages, eosinophils, and neutrophils. The adjacent hepatocytes appeared atrophic (Supplementary Figure 4). The post-operative course was uneventful, with no complications. The patient was discharged on post-operative day 18. Follow-up examinations using ultrasonography showed no signs of abscess recurrence 1 year after surgery.

Liver abscesses can be divided into bacterial and amoebic liver abscesses; most of them are bacterial in origin, with K. pneumoniae reported to be the most common causative organism in bacterial liver abscesses (8). Invasive liver abscess syndrome caused by K. pneumoniae has been reported in Taiwan since the 1980s (2). K. pneumoniae is a mucoid-producing bacterium, and serotype K1 is the most common mucoid-producing strain of K. pneumoniae, followed by serotype K2 (3). In particular, magA has been identified as a gene associated with liver abscesses and metastatic lesions in K1 strains (3). Microbiological definitions of invasive liver abscess syndrome are described as K pneumoniae liver abscess caused by the K1 or K2 serotype (3). According to previous reports, some mucoid-producing strains of the genus Klebsiella are highly viscous, resistant to phagocytosis, and can spread hematogenously, resulting in secondary abscesses such as meningitis, hydrocephalus, endophthalmitis, and metastatic lung lesions (4, 5). Among these metastatic infections, endophthalmitis is the most serious complication and a poor prognostic factor for visual acuity (8). Rapid and accurate diagnosis of K. pneumoniae, such as the string test, and identification of the pathogen by metagenomic next-generation sequencing, is the key to start appropriate treatment immediately (9, 10). In our case, the patient had a positive string test, and PCR revealed amplification of the K. pneumoniae serotype K1 specific locus (wzyKPK1), rmpA, and magA fragments. Invasive liver abscess syndrome involving K1 strains is associated with an absence of immunodeficiency disorders; however, recent studies have shown that diabetes mellitus is recognized as an important risk factor for the development of the disease, as well as a poor prognostic factor for visual acuity (11). The frequency of spontaneous liver abscess rupture is as low as 3.8% (12). However, liver abscesses larger than 8 cm tend to rupture easily because of the high pressure of the contents, and ruptures presenting with peritonitis require emergency surgery (13, 14). In addition, an abscess larger than 6 cm is reported to be a significant independent risk factor for metastatic infections (15). Currently, combined antibiotic therapy based on the antibiogram and percutaneous catheter drainage of liver abscesses is the first choice of treatment for liver abscesses (16). Although many treatment strategies have been proposed for pyogenic liver abscesses, the indications for hepatic resection have not been systematically studied (17, 18). Surgical resection should be considered when there is no clinical improvement with antimicrobial therapy and percutaneous drainage, or if the liver abscess ruptures (19–21). Regarding multiloculated liver abscesses, the failure rate of percutaneous catheter drainage is high (22). Previous studies suggested that large multiloculated abscesses should be treated surgically (23). For large multiple liver abscesses with hyper mucus components, surgical resection should be performed if percutaneous drainage is inadequate, which may lead to improved prognosis and earlier recovery (24). In a report of 10 liver resections for K. pneumoniae liver abscess, including our case, 8 cases were multiloculated liver abscesses, 4 cases were operated due to failure of percutaneous abscess drainage, and 2 cases were due to abscess perforation. The post-operative course was reported to be uneventful in all cases (Table 1) (13, 19, 25–28). Regarding to the recurrence rate of liver abscess, the K1 serotype is known to be an important risk factor that influences liver abscess recurrence (29). This case report have some limitations. This was just a single case report, further accumulation of cases is necessary to establish the best therapeutic strategy for invasive K. pneumoniae liver abscess.

In conclusion, in large multiloculated abscesses after drainage failure, such as in our case, complete liver abscess resection should be performed to ensure earlier recovery and prevent metastatic disease recurrence or secondary metastatic lesions.

The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Ethics approval was obtained from the Ethical Review Board for Clinical Studies at Teikyo University Chiba Medical Center. Written informed consent was obtained from the patient for the publication of any potentially identifiable images or data included in this article.

HS was the major contributor to the writing of the manuscript. HS and HN supervised the manuscript and performed the surgical therapy. TM and MY were involved in surgical therapy and patient care. KY and SS supported the pathological examination results. KS, CK, AU, and KK supported the clinical examinations. All authors have read and approved the final manuscript.