The patient in this case report had polycystic kidney disease combined with polycystic liver. When she was referred to our hospital, she had end-stage renal disease for which she was on regular hemodialysis treatment, and her blood culture was positive for E. casseliflavus, a rare pathogen. Continuous antibiotic treatment and monitoring indicated that she had a cystic infection in the liver. Five days before her hospitalization, she had intestinal symptoms. Thus, the intestinal bacteria could have entered the bloodstream and then disseminated through blood to result in secondary liver cyst infection.
The diagnosis and management of polycystic liver disease (PLD) cyst infections present significant challenges due to the absence of definitive laboratory test results and the difficulties associated with detecting intracystic infections through imaging studies. In clinical case reports, an elevation in serum CA19-9 levels relative to baseline measurements has been noted. However, CA19-9 is not a specific marker for cyst infection. The presence of fever (temperature > 38.5 °C for more than 3 days) without other identifiable sources of infection, detection of gas within a cyst by CT or MRI, increased FDG uptake in the cyst lining compared to the normal liver parenchyma as seen on 18FDG PET-CT, tenderness in the liver region, elevated C-reactive protein levels, increased white blood cell count (> 11,000/L), or positive blood cultures should prompt consideration of infection [5, 6]. Conventional radiological imaging has limited utility in confirming hepatic cyst infections due to the lack of reliable features that distinguish between infected and non-infected hepatic cysts [7, 8]. Inflammatory parameters, such as enhanced wall thickening, high signal intensity on diffusion-weighted imaging, fluid-fluid levels, or the presence of intracystic gas bubbles observed on CT or MRI, may support the diagnosis of a hepatic cyst infection.Lantinga [9]concluded that although analyzing cyst fluid is the definitive benchmark, employing a mix of clinical signs, biochemical indicators, and 18 F-FDG PET/CT imaging offers an effective diagnosis in situations where obtaining samples is challenging.In this case, PET-CT proved to be a promising method for detecting infection, and MRI helped determine the location of the infected cyst for interventional treatment.
The 2015 CARI guidelines suggested [3] that once multiple cystic liver infection or a suspicious infection is diagnosed, antibiotics should be used first to treat the infection. Because the infection occurs in the capsule, quinolones with strong lipid solubility are preferred. If the symptoms are not relieved within 72 h, third-generation anti-infection treatment with ceftriaxone should be added to the regimen and the antibiotic regimen should be adjusted according to drug sensitivity and culture results. In the 2022 guidelines [10], it is strongly recommended to use Fluoroquinolones and third-generation cephalosporins as first-line antibiotics for treating hepatic cyst infections, based on a level of evidence 2 and a 90% consensus. Additionally, a 4 to 6 weeks course of antibiotic therapy is advised, backed by a level of evidence 4 and a unanimous 100% consensus.Suwabe’s research indicates that in patients experiencing liver cyst infections, especially those with recurrent episodes and liver enlargement, Gram-negative bacteria constitute 74–79% of the identified pathogens, among which E. coli exhibits notable resistance to fluoroquinolone antibiotics. This study further proposes that the heightened resistance to fluoroquinolones could be associated with prolonged and repeated antibiotic usage [11].In patients with Polycystic Liver Disease (PLD) experiencing cyst infections, surgical treatment options include cyst fenestration, also known as deroofing, and segmental hepatic resection, which are applicable for patients with superficial large cysts or small to medium-sized cysts confined to a few liver segments [12, 13]. These procedures can effectively reduce cyst volume and alleviate symptoms but do not alter the natural progression of the disease. However, they are associated with high morbidity, especially in the presence of vascular abnormalities and biliary dilatation, and may lead to various postoperative complications such as ascites, hemorrhage, pleural effusion, with mortality rates exceeding 2% and a high recurrence rate [14, 15]. Therefore, the potential risks and benefits should be carefully weighed when considering these treatment options.In such scenarios, drainage of the infected cysts becomes a viable option, especially for those presenting with sizable cysts exceeding 5 cm in diameter [16, 17]. However, the intricacies of PLD necessitate a cautious approach to drainage procedures. The complexity lies in accurately pinpointing the infected cyst among many, coupled with the inherent risk of propagating the infection to neighboring cysts [6, 18]. Hence, the drainage technique—whether percutaneous or laparoscopic—should mirror the strategies employed for managing pyogenic liver abscesses, ensuring meticulous execution to mitigate potential complications [16, 17]. In this case, the patient initially presented with high fever, elevated inflammatory markers, and signs of sepsis. At the local hospital, cephalosporins and carbapenems (imipenem) were sequentially administered. Upon admission to our hospital, we initiated treatment with ampicillin/sulbactam and linezolid. However, due to persistent fever, the antibiotic regimen was changed to meropenem and linezolid. Considering the poor tissue penetration of meropenem for liver cyst infection [19], moxifloxacin was subsequently prescribed.In the present case, it was difficult to control the infection in the early stage of antibiotic treatment. Therefore, the cyst was punctured and drained under ultrasound guidance. At the first drainage, 160 mL of dark brown liquid was drawn. Following this, the patient’s body temperature reduced. Because of the separation of the cyst observed on an MR scan, cyst puncture and drainage were performed at two sites. Later, because of cyst infection, moxifloxacin was used for anti-infection treatment.
In this case, the blood culture before admission showed a positive result for E. casseliflavus, and the culture of the aspirated cyst fluid also confirmed the presence of E. casseliflavus. This indicates that the patient had both bacteremia and a liver cyst infection caused by this bacterium. In the United States, vancomycin-resistant Enterococcus has gradually become an important cause of invasive infections [20, 21]. A study evaluating cases of bacteremia caused by E. casseliflavus and E. gallinarum showed that malignancy (70.0%) and diabetes mellitus (20.0%) were the most common complications in these bacteremia cases, suggesting that E. casseliflavus bacteremia is more likely to occur in immunocompromised hosts [16]. During the patient’s hospitalization, tumor markers CA125 and CA199 were elevated, but no solid tumors were identified. Long-term dialysis was also identified as a risk factor for colonization by E. casseliflavus [22, 23]. In a survey conducted in the United States, the 30-day all-cause mortality rate of E. casseliflavus patients was found to be 10.4%, and the comprehensive treatment failure rate was 39.6% [24].
E. casseliflavus carries the VanC gene intrinsically and exhibits moderate resistance to vancomycin (VCM). Due to this moderate resistance, the Clinical and Laboratory Standards Institute (CLSI) considers VCM concentrations below 4 mg/dL to be susceptible for Enterococcus species, and therefore, the drug is not actively recommended for the treatment of E. casseliflavus [25, 26] In fact, the minimum inhibitory concentration (MIC) of VCM demonstrated in this case was 4 mg/dL. It is important to note that even if microbiological tests show that this microorganism is susceptible to VCM, the actual therapeutic effect of VCM is likely to be low [25, 26]. However, most strains of E. casseliflavus are sensitive to penicillin and ampicillin. Therefore, combination therapy with ampicillin and aminoglycoside drugs such as gentamicin or streptomycin is considered the standard treatment [27]. Since most E. casseliflavus strains are negative for β-lactamase, meropenem does not have a better effect than ampicillin in the treatment of enterococcal infections. Thus, in the reported cases, there is no clear indication for combination therapy with meropenem and β-lactamase inhibitors [28]. In this case, the patient was treated with meropenem and β-lactamase inhibitors, but the infection remained difficult to control. This may be explained by the deep location of the infection site within the hepatic cyst.
The difficulty in treating E. casseliflavus infection in polycystic liver disease may be attributed to several factors. Firstly, the lesions in polycystic liver disease are typically located deep within the liver, making it challenging for antibiotics to effectively penetrate the infection site. Secondly, E. casseliflavus exhibits intrinsic resistance to vancomycin under natural conditions, rendering conventional treatment with vancomycin ineffective. Additionally, the multidrug resistance and spread of resistant genes in E. casseliflavus contribute to the difficulty in treating the infection. Promising outcomes were achieved after full puncture and drainage in this case. The patient is currently undergoing regular dialysis treatment, and the levels of inflammation markers, albumin, and other nutritional indicators have returned to normal. Therefore, in cases of difficult-to-control polycystic liver infection, immediate PET-CT examination is recommended to exclude the possibility of intracystic infection and promptly perform puncture drainage as an interventional treatment.
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- Source: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03531-z