July 17, 2024

The Health

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Clinical management, pathogen spectrum and outcomes in patients with pyogenic liver abscess in a German tertiary-care hospital

This retrospective observational single-center study comprises one of the largest European data sets for PLA published to date and is – to our knowledge – the largest PLA cohort in Germany. Our data show that most PLA represent complications of biliary disorders, especially malignancies, whereas PLA caused by hematogenous spread from distant infectious foci are rare. Abdominal US, especially combined with contrast-enhanced US (CEUS), is paramount for establishing the diagnosis of PLA and deciding on further diagnostics or immediate intervention. Invasive measures (puncture, drainage) were necessary in a large proportion of cases, and the observed mortality was higher than reported before14,15,16,18,34,35,36,37,38,39,40.

In general, PLA represents a rare abdominal disease in Western countries14,15,16,19,34. However, with 221 cases over a period of 7 years, PLA shows a relevant incidence in our hospital (about 32 cases per year, i.e. 2–3 cases per month). This PLA frequency is comparable to previous reports from other Western hospitals14,15,16,17,19,40,41,42,43,44.

This study also confirms some well-known PLA characteristics from the literature: the preponderance of males, “typical” symptoms (e.g. abdominal pain, fever) and the predominant involvement of the right liver lobe (Table 1)19,35,36,37,38,40,41,45,46. Biliary malignancies, cholelithiasis, and ischemic bile duct disease were the most frequent causes for PLA in our study. A possible explanation for this observation is the interdisciplinary liver center at our hospital with a large liver transplant program; a center effect is therefore likely. On the other hand, there are indications of a general shift in etiology: whereas decades ago appendicitis, trauma, post-surgical complications or hematogenous spread were common causes, in recent years diseases of the hepatic-pancreatic-biliary system have increasingly become the cause of PLA14,17,34,35,36,38,41,42,44. This is certainly due to a changed patient clientele with older and more multi-morbid patients with underlying malignant diseases or immunosuppression, paired with an increasing willingness for medical intervention.

The frequent use of US as initial imaging method is in line with other studies18,36,37,39 and reflects the wide availability, time and cost-effectiveness as well as high sensitivity for identifying liver lesions47,48. In a retrospective study of 268 patients, Lin et al. calculated a diagnostic sensitivity for US of 86%49. Irrespective of the first line imaging method, 27% of patients required further imaging in our study. Special imaging procedures such as MRI or PET-CT are primarily necessary to rule out certain differential diagnoses (e.g. metastases, cysts, echinococcosis, benign liver tumors) or to characterize smaller or multiple abscesses, the exact 3D-localization, the hepatic venous anatomy or PLA-associated diseases outside the liver. In a rational diagnostic cascade, US should be used as a first-line imaging method. Depending on US results, complex and resource-intensive diagnostic procedure such as CT, CEUS or – in special cases – MRI, PET-CT or ERCP should be complemented based on individual requirements18,22,30.

The shift in the underlying pathogens has gained particular attention in reports on PLA22,38,45. In our study Enterobacterales (58%), enterococci (42%), and streptococci (18%) accounted for the vast majority of both blood and abscess cultures. In general, the observed pathogen spectrum was similar to previous PLA studies from Europe and North America15,16,18,19,34,35,36,37,38,39,40,41,43,44,46. It should be emphasized that hypervirulent Klebsiella pneumoniae was only diagnosed in one individual case within the study period50. The high incidence of Enterobacterales and enterococci is probably related to the high incidence of biliary diseases in this study and may also reflect the specific situation at a tertiary care hospital. The antimicrobial resistance rates of the isolated bacterial strains, in particular regarding Enterobacterales, were within a manageable range and were subject to thorough consultation and, if necessary, therapy modification by the infectious diseases consultation service and the antibiotic stewardship team. Interestingly, we observed a slight decline of general resistance rates at our institution during the study period, which can be attributed to the concurrent improvement of antibiotic stewardship measures. Initial therapy with piperacillin/tazobactam or carbapenems in particular was highly effective. The low detection rate of Candida spp. confirms that a routine empirical coverage of fungi seems not to be necessary, apart from severely immunosuppressed patients (e.g. neutropenia) and suspected hepatosplenic candidiasis.

Abscess or blood cultures were obtained in less than 80% of cases and joint blood and abscess cultures in only 59%. Here, we see greater potential for diagnostic improvements, e.g. through regular training of physicians on optimal specimen collection.

Despite the use of antibiotics in almost all PLA patients, the majority required additional intervention sooner or later. This was also observed in other studies18,35,36,37,40,46. In contrast to ALA, antibiotic therapy alone is usually not sufficient to treat PLA. According to Losie et al., the absence of drainage is associated with an increased 30-day mortality in PLA (univariate OR 5.8, 95% CI 1.58–21.30, p = 0.006)34. Regarding the optimal procedure, a recent meta-analysis concluded that catheter drainage is superior to needle aspiration in terms of treatment success and duration of antibiotic therapy, especially for large PLA (diameter > 6 cm or abscess volume > 113 mL)25. A German multicenter study identified a low complication rate of < 2% in 6,420 image-guided catheter drainages of the liver51. Therefore, indications for catheter drainage in PLA patients should be generous. In selected PLA cases (e.g. multiple or large abscesses, abscess rupture, and lack of clinical improvement after drainage and antibiotic therapy), surgery should nevertheless be performed.

The all-cause fatality rate within 30 days after PLA diagnosis was relatively high (> 14%) in our cohort compared to other studies from Western countries (range 0.3–11%)14,15,16,34,35,36,37,38,39,40. However, this could also be a center effect reflecting PLA patients with severe comorbidities. A higher mortality rate in PLA patients (19%) was also reported in a Spanish study published in 200746. Interestingly, the outcomes in patients with and without underlying malignancies was similar within the first 30 days after PLA diagnosis in our analysis, but differed in the further course. Therefore, treatment procedures in patients with advanced malignant diseases should be reassessed if therapy attempts fail to resolve the PLA within one month.

Both positive blood cultures (OR 4.78) and detection of Enterobacterales (OR 3.55) were associated with increased 30-day mortality. This is consistent with data from other studies in which positive blood cultures in PLA patients were also associated with increased mortality16,37. In contrast to our results, other studies indicated an increased mortality when enterococci were detected40,42,44. It should be discussed whether empirical therapy should be extended to cover enterococci in selected patients with severe diseases, risk factors for enterococcal infections such as immunosuppression or previous long-term treatment with cephalosporins. Structured sampling of at least 2–3 blood culture sets has been shown to be effective in many infectious diseases, e.g., in the diagnosis of endocarditis, and similar strategies should be considered for the treatment of PLA. For appropriate microbiological diagnostics and individualized antibiotic treatment, we recommend consulting an infectious disease specialist as soon as PLA is suspected.

Limitations comprise the retrospective and monocentric study design with inherent information bias in a restricted study period of 7 years (inclusion of the years 2020 to 2022 was waived due to Covid-19-related differences in patient population). In particular, data on long-term mortality may be subject to bias. Hence, we opted not to extend the survival analyses beyond a follow-up period of one year. Our study only allows association analyses of culture-based pathogen detection with clinical conditions, but does not allow identification of causal pathways. Non-culturable pathogens elude such analysis, and early anti-infective therapy prior to specimen collection also affects the interpretation of the pathogen spectrum. In addition, laboratory methods may have changed over time.

A significant portion of the available data on PLA derives from comparable single center analysis and is, therefore, subject of respective limitations. This underscores the need for more comprehensive, prospective controlled studies to evaluate the optimal care of PLA patients in order to provide evidence-based treatment guidelines for the management of PLA.