Clinical and computed tomography features of extended-spectrum β-lactamase-producing Klebsiella pneumoniae liver abscess

Klebsiella pneumoniae (KP) is a key pathogen in nosocomial and community-acquired infections [1‐3]. Moreover, it is the main pathogen associated with pyogenic liver abscesses (PLAs) [4‐7]. Several studies have shown that the occurrence of PLA, caused by extended-spectrum β-lactamase–producing (ESBL-producing) KP, has been increased worldwide [8‐11]. One report showed that the prevalence of ESBL-producing KP liver abscesses (KPLAs) has increased from 1.64% in 2001 to 14.29% in 2011 in Singapore [10]. The main treatment methods for PLA include antibiotics, percutaneous drainage or aspiration, and surgery, as appropriate [12‐15]. Bacterial culture and drug sensitivity analysis allow for the determination of the involved pathogenic bacteria and effective antibiotics. However, a proportion of patients presents with negative bacterial cultures. Moreover, preparing bacterial cultures are time-consuming [13, 16]. In the clinical treatment of PLAs, antibiotics are only administered empirically before the drug sensitivity results are available. ESBL production by pathogens often causes poor efficacy of empirically selected antibiotics [17‐19]. On the other hand, early and effective antibiotic therapy decreases the mortality rate of KPLA [13]. Therefore, analysing the clinical and computed tomography (CT) features of PLAs caused by ESBL-producing KP may assist in determining the typical characteristics of ESBL-producing KPLA and enable a faster identification of these ESBL-producers.

In this study, we performed a retrospective analysis of data obtained from the medical records of patients with a first episode of KPLA. We aimed to compare the clinical and CT features of patients with ESBL-producing and non-ESBL-producing KPLA, and to determine the risk factors for ESBL-producing KPLA.

This study revealed an association between a history of biliary disease and gastrointestinal malignancies and ESBL-producing KPLA. Multivariate analysis indicated that a history of biliary disease was an independent risk factor for ESBL-producing KPLA, which is consistent with the findings of Shi et al. [21]. However, their study included liver abscesses caused by various Enterobacterales species, while our study only included KP, which is the primary pathogen associated with PLAs. Bacterial invasion via the biliary tract is among the main infectious routes in liver abscess; moreover, a PLA is a common complication after cholelithiasis surgery [22‐25]. Many studies indicated that acquisition of blaCTX-M genes and resulting CTX-M enzyme production is the main cause of resistance to aztreonam and third generation cephalosporins in KP and Escherichia coli [26, 27]. A serum epidemiological study isolated 592 strains (62.1%) of KP from stool samples from 954 healthy adults in Asian countries [28]. It is worth noting that new hypervirulent variants of Klebsiella pneumoniae (hvKP) are emerging globally, most of which exhibit antimicrobial susceptibility. In an analysis of KP strains in hospitalized patients, 33% were hvKP, of which about 17% expressed ESBL, and this data increased year by year [29]. Under pathological conditions, KP crosses the intestinal mucosal barrier and enters the liver via the portal system, which causes a PLA [30]. Patients with a history of biliary disease (especially biliary-enteric anastomosis) or gastrointestinal malignancies are more susceptible to liver infections by intestinal bacteria due to intestinal mucosal damage [4, 8, 31, 32]. Moreover, these patients often undergo surgical interventions, chemotherapy, radiotherapy, and antibiotic therapy; this could negatively influence the gut flora and the immune system and my enhance the risk of ESBL-producing KPLA.

Previous studies have reported that diabetes is an independent risk factor for KPLA [33‐35]. However, in our study, both univariate and multivariate analyses showed that diabetes was not associated with ESBL-producing KPLA. Patients with comorbid diabetes have a weaker immune function, which makes them more susceptible to serious infections, including pneumonia, meningitis, and endophthalmitis when infected by KP [35]. Therefore, administering a higher dose of antibiotics increases the risk of being infected with ESBL-producing KP [27]. However, one study has reported that diabetes could have a protective factor against ESBL-producing KP [21]. These partly contrasting findings in the above mentioned and or study may result from different KP populations with varying degrees of virulence. Molecular analyses on genetic relationship and known virulence genes of KPLA isolates were not performed; this is a limitation of the present study.

Contrast-enhanced CT is an effective method for the diagnosis of a PLA [20, 36]. CT revealed multiloculation in only half of the patients with ESBL-producing KPLA, which was significantly lesser than those with non-ESBL-producing KPLA. KPLA has been shown to typically manifest with multiloculation and poor liquification on CT [37]. Similar characteristics were reported by Kim et al., which were referred to as the “turquoise sign” [38]. In our study, 78% of the patients had evidence of multiloculation on CT. This could be attributed to the formation of granulation or congested liver tissues that are non-necrotic. The underlying pathological mechanism could be associated with the high virulence and anti-phagocytic properties of KP [39, 40]. Further studies, especially detailed molecular analyses are needed to determine why the afore mentioned signs are less common in ESBL-producing KPLA. In addition, antibiotic use may change the appearance of the liquefaction and loculation of the abscess. However, because of the retrospective nature of this study, we were unable to obtain the timeline for antibiotic administration and imaging in both groups.

KPLA is often associated with extrahepatic metastatic infections, including endophthalmitis [41]. These multi-site infections are now referred to as invasive KPLA syndrome (IKPLAS); however, its specific pathogenesis remains unclear. We previously reported that hepatic venous thrombophlebitis is an important sign of IKPLAS [8]. However, we did not find a correlation between ESBL-producing KPLA and hepatic venous thrombophlebitis. Studies have shown that hypermucoviscous KP infections induce platelet aggregation, and platelet hyperreactivity may be associated with a higher risk of vascular complications [42, 43]. Within the inflammatory microenvironment, endothelial cell activation and endothelial barrier destruction could promote bacterial migration [44, 45]. On the other hand, platelet and coagulation factor activation promotes thrombus formation. We found no correlation between ESBL-producing KPLAs and thrombophlebitis and endophthalmitis in our study. Given the small sample size, we need to be cautious about such results.

All ESBL-producing KP in the present study were susceptible to carbapenems and amikacin; this in in contrast to other studies that enrolled more patients with abdominal infection [11]. Previous studies have shown that the empiric use of carbapenem antibiotics could reduce the mortality risk associated with KPLA [17, 19]. This is especially true in patients with IKPLAS, which involves more serious conditions. The therapeutic efficacy of carbapenem antibiotics could be significantly superior to other antibiotics [3, 22], which is consistent with our findings. The carbapenem-resistant KP, which has been reported worldwide, is under scrutiny because of the few therapeutic options available for these strains [46]. To the best of our knowledge PLA caused by carbapenem-resistant KP is still very rare [22].

We found an association between ESBL-producing KPLA and a history of biliary disease and gastrointestinal malignancy. Moreover, a history of biliary disease is an independent risk factor for ESBL-producing KPLA. Patients with ESBL-producing KPLA had a higher ICU admission rate, with only half showing multiloculation on CT. Therefore, it should be noted that patients with a history of biliary disease or gastrointestinal malignancy who present with a PLA are likely to have an ESBL-producing KPLA, especially if CT findings are indicative of uniloculation. Future studies with larger sample sizes are needed to confirm our findings.