What is the optimal antimicrobial prophylaxis to prevent postoperative infectious complications after liver transplantation? A systematic review of the literature and expert panel recommendations

Abstract

Background Antimicrobial prophylaxis is well‐accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. Objectives To identify the optimal antimicrobial prophylaxis to prevent post‐LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short‐term outcomes, and to provide international expert panel recommendations. Data sources Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Methods Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID: CRD42021244976. Results Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. Conclusions Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

“…Regarding liver transplantation, the incidence of PJP is around 7% of all cases of pneumonia, with mortality ranging from 7% to 88% [ 63 ]. However, the overall incidence of PJ infection has fallen in recent years due to fewer immunosuppressive regimens used after LT, and according to recent data, the incidence in recipients that undergo prophylaxis is below 2% and <1% in the first year after LT. Contrarily, the incidence rises to 11% in patients without prophylaxis [ 63 , 64 ]. Considerations for PJP prophylaxis include the degree of immunosuppression preceding LT, the duration and form of post-LT immunosuppression, the absolute lymphocyte count, and the presence of a concurrent solid organ transplant.…”

“…Considerations for PJP prophylaxis include the degree of immunosuppression preceding LT, the duration and form of post-LT immunosuppression, the absolute lymphocyte count, and the presence of a concurrent solid organ transplant. In addition, in this patient cohort, prophylaxis should be explored for patients undergoing therapy for acute rejection events [ 63 , 64 ]. Most cases of PJP occurred in the first 7 months after LT [ 63 ], although Fortea et al, in their survey, recently showed a not insignificant number of PJ infections occurring beyond the usually recommended period of prophylaxis [ 65 ].…”

“…Most cases of PJP occurred in the first 7 months after LT [ 63 ], although Fortea et al, in their survey, recently showed a not insignificant number of PJ infections occurring beyond the usually recommended period of prophylaxis [ 65 ]. Currently, there is no consensus and a wide heterogeneity between centres about the need for and duration of PJP prophylaxis [ 63 , 64 ].…”

“…Some transplant centres perform retrospective, additional donor tests for latent HSV or VZV in cases of seronegative recipients (mostly children) to decide on specific anti-viral prophylaxis or treatments and follow-up. However, no evidence exists to suggest this, based on a few case reports [ 62 , 63 , 64 , 65 ].…”

Risk Factors for E2SKAPE Infections and Mortality among Liver Transplant Recipients

“…The present study also revealed that only exposure to more than two post-LT intravenous antibiotics was negatively associated with the acquisition of E 2 SKAPE infections. Despite the proven bene t of antimicrobial prophylaxis in LT programs worldwide, an optimal intervention has never been established [27]. Therefore, at the time of selecting antibiotics, it is necessary to consider individual patient characteristics, local ora and resistance patterns, culture of the preservation uid, and blood cultures obtained from the donor.…”