Surgical Treatment of Persistent Pseudomonas aeruginosa Bacteraemia After n-Butyl-2-cyanoacrylate for Gastric Bleeding Varices

Abstract

n-Butyl-2-cyanoacrylate (NCBA) is an effective therapeutic option for bleeding gastric varices but can sometimes be associated with adverse effects. Persistent bacteraemia is an unusual complication with a high mortality rate. We report the case of a 34-year-old man with history of cirrhosis due to Wilson’s disease and severe portal hypertension who was hospitalized as a result of upper gastrointestinal bleeding secondary to fundic varices that were treated with NCBA. Eight weeks after the bleeding episode he was readmitted with a 14-day history of fever and chills. Pseudomonas aeruginosa was isolated from blood cultures. He presented with persistent P. aeruginosa bacteraemia despite correct antibiotic treatment. A PET-CT scan was performed to rule out infection source, and inflammatory changes at the NCBA site plug were found. A presumptive diagnosis of NCBA plug infection was considered. The case was evaluated by multidisciplinary board and indicated liver transplantation as treatment. However, the patient’s bacteraemia persisted and therefore a vertical gastrectomy to remove the NCBA plug was performed. P. aeruginosa was also isolated from the plug. The patient was discharged with ceftazidime plus ciprofloxacin to complete 6 weeks after surgery and he remained asymptomatic. Any foreign material such as NCBA is susceptible to being infected and should be considered in patients with persistent breakthrough bloodstream infections. The individualized treatment is recommended in this complex scenario.

Key Summary Points

Gastric varices are commonly seen in patients with portal hypertension, especially those with cirrhosis. In some centres, they are typically treated with n-butyl-2-cyanoacrylate (NCBA).

Bacteraemia due to Pseudomonas aeruginosa may be associated with the infection of NCBA material used in the treatment of gastric varices. This aspect of the case suggests a direct link between the use of NCBA and the development of persistent bacteraemia.

The case highlights the importance of considering the NCBA plug as a potential infection source in similar clinical scenarios and the role of surgical intervention in managing such infections.

This reinforces the need to consider medical procedure materials, like NCBA, as potential infection sources, especially when antibiotic treatment against sensitive bacteria does not lead to infection resolution.

Introduction

n-Butyl-2-cyanoacrylate (NCBA) is an effective therapeutic option for bleeding gastric varices, and it is nowadays considered the gold standard haemostatic treatment in this anatomic area [1]. The treatment can eventually involve adverse effects such as rebleeding in approximately 15–20% of cases, increasing the associated morbidity and mortality rate [2, 3]. Furthermore, local vessel obstruction, systemic embolization, and fever with transient bacteraemia have been described [4, 5]. Persistent bacteraemia has been reported and it is considered an unusual complication with a moderate-high mortality rate [6–13]. The physiopathology is not entirely understood but it could be explained by the fact that NCBA forms a large conglomerate providing an ideal niche for bacterial growth.

Although technically challenging, surgical removal may be considered if antibiotic control of infection fails.

Case Description

A 34-year-old man with a history of Wilson’s disease diagnosed 10 years prior and with secondary liver cirrhosis (Child–Pugh class B7) was admitted to the hospital as a result of upper gastrointestinal bleeding secondary to fundic varices that were treated by NCBA in April 2022. Eight weeks after the bleeding episode he was readmitted with a 14-day history of fever and chills. Physical examination revealed absence of abdominal pain, bleeding signs, diarrhoea, respiratory or urinary symptoms. Laboratory tests showed a slight increase in inflammation parameters (leukocyte count was 4.6 × 10⁹/L with 92% neutrophils, and C-reactive protein was 4.42 mg/dL) and liver function tests showed aspartate aminotransferase (AST) of 43 U/L, alanine transaminase (ALT) of 50 U/L, alkaline phosphatase (ALP) of 115 U/L, gamma-glutamyl transferase (GGT) of 39 U/L, total bilirubin of 0.9 mg/dL, and INR of 1.32, similar to previous levels. Chest X-ray and urinalysis were normal and respiratory virus nucleic acid testing (influenza, respiratory syncytial virus and SARS-CoV-2) was negative. Blood and urine cultures were obtained. Ceftriaxone was started empirically and d-penicillamine was discontinued as a possible cause of drug-related fever. Once the patient was admitted, Pseudomonas aeruginosa with no pattern of resistance was isolated from blood cultures and therefore he was switched to ceftazidime. Despite the correct antibiotic treatment, he persisted with fever and chills and had repeated blood cultures with P. aeruginosa 2 weeks after starting ceftazidime 2 g every 8 h. The treatment was switched to ceftolozane/tazobactam 2 g every 8 h plus ciprofloxacin 750 mg every 12 h (MIC < 0.125 µg/ml) and amikacin 1 g every 24 h (MIC < 4 µg/ml). A thoracoabdominal computerized tomography and an echocardiography did not detect any source of infection. Two days later, PET-CT revealed inflammatory changes around the NCBA plug with no other findings; hence, in the absence of alternative infectious foci and given the persistence of bacteraemia despite effective antibiotic therapy against the bacterial strain, a presumptive diagnosis of NCBA plug infection was considered (Fig. 1). Moreover, the patient’s fever persisted and liver function was getting worse. The case was discussed in a multidisciplinary committee (involving staff from gastroenterology, hepatology, transplant surgery, infectious diseases, abdominal radiology, anaesthesia and resuscitation departments) and liver transplantation was approved as a definitive treatment of the underlying liver disease (decompensated cirrhosis).

Fig. 1.

Focal FDG uptake around the NCBA plug in the gastric fundus is visible on FDG PET/CT (arrow)

Partial gastrectomy was extensively deliberated upon but ultimately dismissed owing to anatomical peculiarities, specifically the presence of multiple feeding collaterals beneath the NCBA plug. Similarly, placement of a transjugular intrahepatic portosystemic shunt (TIPS) as a bridge therapy to decompress varices prior to surgery was also discarded because of the potential risk of infection (endotipsitis) as positive blood cultures persisted. The Catalonian Liver Transplant Board was consulted, and accepted prioritised inclusion of the patient on the transplant waiting list. The patient received a deceased donor liver transplant 29 days later. Two days after that, ceftolozane-tazobactam was stopped; however, 10 days after discontinuing antibiotics the patient presented with another episode of P. aeruginosa bacteraemia, and antibiotics were therefore restarted. It was confirmed that the source of infection was the plug, even after the decompression of gastric varices and the resolution of portal hypertension. It was then decided to surgically remove the NCBA plug with a vertical gastrectomy 1 month after the transplant (Fig. 2). P. aeruginosa with identical resistance pattern as in the blood cultures was isolated in the surgical sample of the NCBA plug. After the surgery, fever resolved after 72 h, and the patient was discharged with a plan to complete a 6-week course of ceftazidime plus ciprofloxacin. Blood cultures performed 48 h after stopping antibiotic therapy were negative and the patient has remained asymptomatic ever since. Figure 3 shows clinical and analytical characteristics as well as the susceptibility pattern of the isolates.

Fig. 2.

Postoperative specimen including infected NCBA plug in gastric varices

Fig. 3.

Susceptibility pattern of the isolated strain and a timetable of antibiotic consumption, fever, blood cultures and inflammatory biomarkers

Discussion

We present a case of persistent P. aeruginosa bacteraemia secondary to NCBA infection that was successfully treated with a sequential surgical treatment, orthotopic liver transplant followed vertical gastrectomy with prolonged systemic antibiotic therapy.

Variceal cyanoacrylate injection has been reported to cause transient bacteraemia with no subsequent complications [4]. However, recurrent bacteraemia is a rare complication and only ten cases have been reported to the date in the literature [6–13]. Three of the ten reported cases died despite effective antibiotics. The physiopathology is not well understood, but the hypothesis is that disruption of the mucosa in the upper gastrointestinal tract after the injection of a cyanoacrylate plug promotes the passage of viable bacteria. Additionally, NCBA forms a large conglomerate providing an ideal niche for bacterial growth. Other theories have been postulated such as the previous contamination of the needle or the side channel of the endoscope [9]. All the reported cases in the literature were men except one woman [7]. They all presented with bleeding gastric varices secondary to cirrhosis and/or portal hypertension and received an effective antibiotic treatment with different duration (2–24 weeks). However, only four underwent surgery: a 60-year-old and a 77-year-old patient who underwent surgical debridement of the cyanoacrylate plug and a partial gastrectomy, respectively. Unfortunately, both died few days after the surgery [6, 10]. In a third case, a 54-year-old woman, died from septic shock despite multiple antibiotic treatments, a gastrectomy and a thrombectomy of the splenic vein [7]. The timeline of these events, however, is not clearly defined. The last one was a 46-year-old patient who also underwent a liver transplant with no initial control of the infection source and recurrent bacteraemia 10 days after the transplant, achieving clearance of the bacteraemia [9].

Our case is unique because of several facts. Firstly, this is the second case of P. aeruginosa reported as the etiological agent of NCBA infection, and ours represents the fourth reported patient in which the cyanoacrylate plug was surgically removed [6, 7, 10]. Secondly, a two-step approach with liver transplant in order to reduce portal hypertension and partial gastrectomy as an effective treatment in the same patient has not been documented elsewhere in the literature.

Furthermore, PET-CT scan has been only performed in three other cases and it should be considered as a useful tool for its diagnosis [7, 11, 13].

Our patient is the youngest reported case, which likely contributed to his survival of two high-risk surgical procedures. Last, this case highlights the importance of source control, which is fundamental in managing uncontrolled sepsis.

Conclusion

Any foreign material such as NCBA should be considered in the search of an infection source, especially in patients with persistent breakthrough bloodstream infections. This complex scenario should not discourage surgery; a combined approach with prolonged antibiotic treatment and extensive multidisciplinary management is warranted.

Author Contributions

Alex Soriano, Gabriela Chullo, Sabina Herrera, Jorge Boan, Elisa Pose, Maria Londono, Virginia Hernandez-Gea, Miguel Angel Verdejo, Juan Carlos Garcia-Valdecasas, Cristina Pitart, Yiliam Fundora, Alex Soriano, and Marta Bodro contributed significantly to the patient’s care and evolution. Each author has actively participated in the case management and the drafting of this case report, and has approved the final version submitted for publication.

Funding

No funding or sponsorship was received for this study or publication of this article.

Declarations

Conflict of Interest

Abiu Sempre, Gabriela Chullo, Sabina Herrera, Jorge Boan, Elisa Pose, Maria Londono, Virginia Hernandez-Gea, Miguel Angel Verdejo, Juan Carlos Garcia-Valdecasas, Cristina Pitart, Yiliam Fundora, Alex Soriano, and Marta Bodro declare that there are no conflicts of interest regarding the publication of this paper. Alex Soriano is an Editor-in-Chief of Infectious Diseases and Therapy and was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethical Approval

Ethical approval was not required for this study as it involves a case report of clinical practice conducted and agreed upon by the patient. Informed consent was obtained from the patient, ensuring adherence to ethical standards in the handling and presentation of case details.