Bacteremia due to C. jejuni in kidney transplant patients. Is immediate post-transplant immunosuppression a risk factor?

We report the case of a 52-year-old man with terminal chronic kidney disease secondary to autosomal dominant polycystic kidney disease who underwent a kidney transplant in July 2020, for which he was initially receiving quadruple immunosuppressant therapy with thymoglobulin (425 mg total), tacrolimus, mycophenolate mofetil and prednisone. Subsequently, given his poor kidney function secondary to extensive post-transplant kidney infarction, a decision was made to start belatacept (900 mg once every other week for two months, then once monthly, down-titrating the dose to a steady 500 mg monthly at present) with gradual withdrawal of tacrolimus. He received prophylaxis with trimethoprim/sulfamethoxazole and valganciclovir for six months.

In September 2020, he visited the accident and emergency department due to fever and diarrhoea with up to seven bowel movements in the past 24 hours. Laboratory testing revealed results for polymerase chain reaction (PCR) testing of 113 mg/l and leukopaenia of 2,350. He was initially diagnosed with acute gastroenteritis. After stool and blood cultures were taken, he was started on empirical therapy consisting of intravenous levofloxacin 500 mg/day. Subsequently, he remained afebrile and diarrhoea-free as of his second day of admission.

Stool PCR and stool culture detected Campylobacter jejuni. Given these results, levofloxacin was suspended and oral azithromycin 500 mg was administered for three days. At the same time, three days after incubation, quinolone-resistant C. jejuni was isolated in the blood cultures, and a decision was made to administer treatment with meropenem and order a full-body computed tomography (CT) scan to screening for malignancy; the scan was negative for neoplasms.

Once the patient's signs and symptoms resolved, his blood culture results became negative and he followed a good clinical course. After he had completed seven days of treatment with meropenem 1 g, he was discharged with a five-day regimen of oral amoxicillin/clavulanic acid 500/125 mg up to 14 days of treatment. In follow-up (six months), the patient has remained asymptomatic apart from presenting replication in the eight month of the post-transplant period.

Discussion

C. jejuni infection causes signs and symptoms of enteroinvasive diarrhoea and accounts for less than 1% of cases of bacteraemia. Such cases generally occur in the immunosuppressed population. Among patients with bacteraemia due to C. jejuni, 38% may have tumours.¹ Other commonly associated factors are human immunodeficiency virus (HIV), liver disease and hypogammaglobulinaemia.² In our case, we did not test for immunoglobulin levels, and therefore we are unaware of their potential contribution. However, we found only three reported cases in the literature of bacteraemia due to C. jejuni in kidney transplant patients.^3–5 All of them occurred in the first year of the post-transplant period, as in our case. This is probably related to high levels of immunosuppression during this period.³

With regard to immunosuppression, a higher prevalence of infections has been reported in patients induced with thymoglobulin versus basiliximab, with bacterial infections being significantly more common.⁶ In addition, the use of belatacept was linked to an increase in cytomegalovirus (CMV), Pneumocystis jirovecii and Mycobacterium tuberculosis infections.^7–9 Age and low glomerular filtration rate were identified as risk factors for infection.^8,10

The use of belatacept, though it improved the patient's glomerular filtration rate from 7 ml/min to 22 ml/min, might have been a risk factor for bacteraemia due to C. jejuni. However, in other published cases of bacteraemia in kidney transplant patients, the immunosuppressants used were different, which would make this the first reported case with belatacept.

Regarding antibiotic therapy, quinolones should be avoided since C. jejuni is quinolone-resistant in 50% of cases.² In our case, the patient was on prophylaxis with trimethoprim/sulfamethoxazole; nevertheless, it has been reported that 21%-25% of C. jejuni strains may be resistant.² In addition, there have been almost no cases of resistance to carbapenems.² The mortality rate in these patients is 15%, and the factors associated with a poor prognosis are delayed initiation of antibiotics and deficient antibiotic coverage.¹

In conclusion, bacteraemia due to C. jejuni is a very uncommon infection in kidney transplant patients that may be fostered by the choice of immunosuppression, as well as other factors such as hypogammaglobulinaemia. Therefore, suitable antibiotic coverage is important given the potentially fatal nature of this infection.

Funding

The authors declare that they received no funding to conduct this study.

Conflicts of interest

The authors declare that they have no potential conflicts of interest related to the content of this article.