Carbapenem-resistant Klebsiella pneumoniae infection is a major cause of morbidity and mortality after solid-organ transplant and hematopoietic stem cell transplant. Here, we report a 57-year-old man with hepatitis B virus-related decompensated liver cirrhosis, huge splenic artery aneurysm, and hypersplenism who underwent liver transplant from a deceased brain-dead donor. Recipient sputum surveillance showed carbapenem-resistant Klebsiella pneumoniae when he entered the intensive care unit, and combined tigecycline, meropenem, and fosfomycin were administered. At 1 week posttransplant, the recipient’s hepatic artery was eroded by disseminated carbapenem-resistant Klebsiella pneumoniae infection, and the patient developed acute kidney injury. Our experience suggests that colonization of carbapenem-producing organisms may be included during surveillance posttransplant and that the infected graft artery must be removed instead of noninfected vessels.
Key words : Drug-resistant bacterium, Sputum culture, Surgical site infection, Vascular invasion
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is increasingly being reported worldwide and has been classified as a serious threat to our health by the World Health Organization.1,2 Mortality for patients with these resistant strains is shown to be higher than for patients with carbapenem-susceptible Klebsiella pneumoniae because of the limited antimicrobial treatments available for CRKP.3,4 Common sites of infection include the surgical site, intra-abdomen, pulmonary areas, and urinary tract.5
Here, we describe a case of disseminated CRKP infection in a liver transplant recipient, which caused graft hepatic artery rupture due to CRKP invasion.
A 57-year-old man who had been diagnosed with hepatitis B virus-related decompensated liver cirrhosis, huge splenic artery aneurysm, and hypersplenism showed pancytopenia, with white blood cell count of 0.8 × 109/L (normal range, 3.5-10.5 × 109/L), neutrophil count of 0.4 × 109/L (normal range, 2.0-7.5 × 109/L), hemoglobin level of 76 g/L (normal range, 115-155 g/L), and platelet count of 17 × 109/L (normal range, 130-380 × 109/L). A nasal swab was negative for methicillin-resistant Staphylococcus aureus, and a rectal swab was positive for extended spectrum β-lactamase Enterobacteriaceae species and negative for vancomycin-resistant enterococci colonization. A pulmonary computed tomography scan showed a small amount of exudation in both lower lungs. The patient had no fever, cough, or expectoration before transplant. He had a history of upper gastrointestinal bleeding 2 months before transplant and acute stroke 2 years before transplant without neurologic sequelae.
The patient underwent orthotopic liver transplant from an ABO-identical donor, which included splenectomy and resection of the splenic artery. Cold ischemia time of donor liver was 6.5 hours. Blood loss was about 2000 mL, and the patient required transfusion of 6 units of packed red blood cells and 1600 mL of frozen plasma during liver transplant.
The donor was 51-year-old man with severe traumatic brain injury who had stayed in the intensive care unit for 2 days. Laboratory investigations suggested no clinical infections; laboratory results showed increased white blood cell count of 15.9 × 109/L (normal range, 3.5-10.5 ×109/L) and neutrophil count of 13.6 × 109/L (normal range, 2.0-7.5 × 109/L), normal hemoglobin level of 125 g/L (normal range, 115-155 g/L), and normal platelet count of 222 × 109/L (normal range, 130-380 × 109/L). In addition, inflammatory marker tests were normal, with C-reactive protein level of 2 mg/L (normal range, 0-10 mg/L), procalcitonin level of < 0.05 ng/mL (normal range, < 0.05 ng/mL), and 1,3-β-d-glucan test of < 37.5 pg/mL (normal range, < 70 pg/mL). Blood and urine culture tests were negative. Serology tests for hepatitis B virus, hepatitis C virus, and cytomegalovirus infections were negative. The 2 recipients who had received kidneys from this donor had stable recovery without any infection.
The liver recipient received posttransplant anti-biotic prophylaxis consisting of imipenem and ganciclovir. His immunosuppressive regimen consisted of corticosteroid bolus and taper, as well as tacrolimus and mycophenolate mofetil. When the liver transplant recipient was transferred to the intensive care unit, sputum surveillance showed CRKP; however, culture of peritoneal drainage fluid was negative. The liver transplant recipient was started on combined tigecycline (200 mg/day), meropenem (6 g/day), and fosfomycin (16 g/day). Seven days later, he presented with unconsciousness and dyspnea, and his blood pressure dropped to 70/40 mm Hg and heart rate increased to 140 beats/min. Hemoglobin levels decreased from 75 to 63 g/L, and hematocrit level decreased from 23.8% to 19.9%. Portable ultrasonography scan suggested some pelvic effusion, and diagnostic abdomi-nocentesis showed uncoagulated blood.
An emergency laparotomy was immediately performed, revealing that blood had seeped from 2 small areas of the hepatic artery in the donor segment but not at the anastomosis site (Figure 1A). We repaired the areas with direct suture, and ultraso-nography showed normal artery velocity. Two days later, the drainage was suddenly full of blood and the blood pressure was again unstable. A second laparotomy showed 3 ruptured areas in the graft hepatic artery. The pathologic hepatic artery was removed, and a deceased-donor iliac artery was used to bridge the removed area. A culture of the artery showed KPC-producing Klebsiella pneumoniae (Xpert Carba-R assay; Cepheid, Sunnyvale, CA).6 Sequence type 11 was identified by multilocus sequence typing, and hematoxylin and eosin staining showed encapsulated bacillus scattered between elastic fibers of the artery (Figure 1B). Susceptibility testing indicated that the Klebsiella pneumoniae was resistant to imipenem (minimum inhibitory concen-tration of ≥ 16 μg/mL; Table 1).
The patient developed acute kidney injury, resulting in 2 weeks of intermittent hemodialysis. He also developed a complicated abdominal infection, and continuous abdominal double-cannula lavage was required with low negative pressure drainage for effusion. The antibiotic regimen was changed to polymyxin B and meropenem to control CRKP infection. Despite these measures, the patient died due to repeated pneumonia and abdominal infection at 3 months after liver transplant.
Resistant bacterial infections are major causes of morbidity and mortality among liver transplant recipients.7 Bacterial infections, especially pos-toperative CRKP, continue to present a great challenge. The incidence of CRKP has been reported to range from 2.5% to 35%2,8 and has shown a high fatality rate of 62.5% to 82%.2,8 The survival rate is significantly lower for patients with a CRKP infection than for patients without a CRKP infection.9 With these low rates of survival, the carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae species have produced attention of global dimen-sions.
In general, the common causes of infection in vessels have been Aspergillus or Mucor species infections after liver transplant, which can lead to ischemia and necrosis; however, reports of bacterium infections are scarce.10,11 In our patient, the hepatic artery was eroded and specimen cultures demon-strated high virulence CRKP, which can carry the KPC gene. Hematoxylin and eosin staining showed that the bacteria had capsules, suggested that the bacteria had characteristics of strong invasiveness.
Vascular rupture in our patient was repaired with laparotomy; however, 2 days later, the vessel was again ruptured. The patient required the infected artery to be removed and replaced with bridging of both ends of the vessel using a deceased-donor iliac artery. A follow-up ultrasonography showed that the velocity and the resistance index of the hepatic artery were good after 2 procedures.
In our patient, we presumed that the infection had an intrinsic source. During his preoperative intensive care unit stay, he may have obtained CRKP colonization in his lung. Prolonged surgery, excessive blood loss, and immunosuppression could promote CRKP infection. Multivariate analysis has confirmed that high Model for End-Stage Liver Disease score at transplant, patients with hepatocellular carcinoma, the need for Roux-en-Y biliary choledochojejunostomy, and presence of bile leak have remained significant risk factors for CRKP infection after liver transplant.2 Another factor could be donor-derived transmission and colonization. There is a high prevalence of CRKP in China, with rates of imipenem-resistant pneumonia due to Klebsiella species increasing from 3.0% in 2005 to 20.9% in 2017 and meropenem-resistant Klebsiella pneumoniae increasing from 2.9% in 2005 to 24.0% in 2017.12 Surveillance tests of CRKP colonization and CRKP infections before liver transplant are important to select defined antibiotic strategies at an early stage. In addition, immunosuppression levels should be decreased if infection is suspected.
The colonization of carbapenemase-producing organisms may be adopted for surveillance after organ transplant, allowing tailored antibiotic prophylaxis to be given to patients with positive colonization results. Moreover, the infected graft artery must be removed.
Volume : 18
Issue : 4
Pages : 529 - 532
DOI : 10.6002/ect.2018.0384
From the 1Department of Liver Surgery and the 2Department of Laboratory
Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
*Yongbing Qian and Haomin Zhang contributed equally to this study.
Corresponding author: Yongbing Qian, Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Phone: +86 21 68383715
Figure 1. Images of Hepatic Artery Rupture and Hematoxylin and Eosin Staining
Table 1. Antimicrobial Susceptibility and Minimum Inhibitory Concentration Distributions of Carbapenem-Resistant Klebsiella pneumoniae Isolates