Preventing Surgical Site Infections After Liver Transplantation: The Optimal Strategy

Preventing surgical site infections (SSIs) after major abdominal surgery, particularly after liver transplantation (LT), is crucial. The reported incidence of SSIs after LT varies from 10% to 37%, with the predominant organisms being gram-negative bacteria, Staphylococci, and enterococci.1 Although antibiotic prophylaxis is a cornerstone of this effort, a one-size-fits-all approach is ineffective. The type and duration of prophylactic antibiotic regimens vary widely according to patient factors, department ecology, and the practices of individual transplant centers. Given the rise of multidrug-resistant (MDR) bacteria, the choice and optimal use of a perioperative antibiotic regimen remain subjects of ongoing research and debate. The optimal strategy requires a clear distinction between 2 key approaches: perioperative antibiotic prophylaxis (PAP) and preemptive antibiotic therapy (PAT). PAP is a short-term, targeted intervention typically administered intraoperatively and not exceeding 24 h for patients without a recent history of infection or colonization by antibiotic-resistant organisms. The primary objective of PAP is to prevent SSIs and minimize the development of antimicrobial resistance by limiting antibiotic exposure. In contrast, PAT is a more aggressive approach reserved for high-risk patients. These vary between institutions2 and include recipients with acute liver failure, acute-on-chronic liver failure, sclerosing cholangitis and secondary biliary cirrhosis, high Model for end stage liver disease scores, or those with existing infections or known to be colonized with MDR bacteria. PAT is designed to treat suspected infections early. Although it can reduce overall postoperative infections, PAT carries a higher risk of selecting for extended-spectrum beta-lactamase SSIs. The choice between PAP and PAT should be based on the patient’s individual risk factors. This includes screening for colonization and existing infection at the time of transplant, as well as assessing comorbidities, surgical complexity, and the patient’s “immune net status,” which is significantly impacted by perioperative corticosteroid administration. The rise of MDR bacteria highlights the need for a careful balance. Expert panels and studies emphasize the importance of balancing infection prevention with minimizing antimicrobial resistance through judicious antibiotic use. In this issue of Transplantation, Elbaz et al3 conducted a retrospective multicenter study comparing the incidence of SSIs in 271 patients receiving PAP with narrow-spectrum antibiotics for up to 24 h, with 324 patients receiving PAT with broad-spectrum antibiotics for a median of 5 d. SSI occurred in 51 patients (19%) in the PAP group, compared with 47 (15%) in the PAT group (P = 0.7). The median time to SSI onset was 12 (8–17) d in the PAP group and 10 (5–18) d in the PAT group (P = 0.3). PAT was associated with fewer overall postoperative infectious complications and a shorter hospital stay but with increased extended-spectrum β-lactamase SSIs (47% versus 6%; P = 0.006). The authors highlighted the significant risk of bacterial resistance. They advocate for a tailored, risk-based approach as essential for optimizing patient outcomes and promoting antimicrobial stewardship. Several studies have reported that PAP has no impact on the incidence of SSIs.4,5 The International liver transplantation society reviewed the main studies dedicated to antibioprophylaxis after LT up to 2021. Of the 8 studies considered, 2 were randomized controlled trials, 4 were observational comparative studies, and 2 were observational noncomparative studies. Overall, the quality of the evidence supporting any specific regimen for preventing SSI and other bacterial infections was moderate to low. There were marked differences between studies regarding the types of antibiotics, combination regimens, and duration of therapy. Despite the low quality and contradictory nature of the published studies on the most effective antibiotic regimen, the clinical experts were highly confident, based on their experience of the high infectious risk of LT, and strongly recommended universal antibiotic prophylaxis to prevent postoperative bacterial infections.5 The choice of antibiotics should be individualized, and the length of therapy should not exceed 24 h. It is important to note that in the article by Elbaz et al,3 PAT was often administered to high-risk patients who typically required broad-spectrum antibiotics for an extended duration. However, the authors excluded recipients infected or colonized with highly resistant pathogens such as vancomycin-resistant enterococcus, broad-spectrum beta-lactamase high-resistance, or extensively drug-resistant bacteria. Infections with such MDR bacteria are notoriously difficult to treat and are associated with a high risk of patient death and severe complications after LT.6,7 This threat is substantiated by our own findings,8 where we examined 403 consecutive patients who underwent LT at our center between 2014 and 2017. The primary objective was to evaluate the 1-y mortality rate among patients who developed MDR infections after LT. Of these recipients, 147 (36.5%) developed at least 1 bacterial infection and 50 (12.4%) developed an MDR strain, with a median interval of 15 d between transplant and the first infectious episode. Among patients with MDR strains, 80% had extended-spectrum beta-lactamase bacteria, 72% had carbapenemase, and 1.4% had Methicillin-resistant staphylococcus aureus. One-year patient survival was significantly lower among those infected with an MDR strain than for those infected with a non-MDR strain or those who were not infected (76%, 89%, and 96%, respectively; P < 0.0001). In the multivariable analysis, MDR infection was significantly associated with 1-y mortality (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.48-8.23; P = 0.0041) and increased intensive care unit length of stay (34.1 ± 40.3 versus 10.2 ± 11.6 d, P = 0.0001). The risk factors that were significantly associated with posttransplant MDR infection were MDR colonization (OR, 5.38; 95% CI, 2.83-10.22; P < 0.0001), hepatic encephalopathy before transplantation (OR, 2.58; 95% CI, 1.01-6.53; P = 0.046), and reintervention after transplantation (OR, 2.32; 95% CI, 1.20-4.48; P = 0.012). These results strengthen the rationale for administering guided PAT to prevent fatal outcomes in such high-risk patient groups. However, further studies are needed to fully characterize the beneficial and detrimental effects of PAT, particularly when administered to high-risk colonized recipients. The lack of effective antibiotics for these pathogens has long been a critical challenge. The advent of new antimicrobials specifically designed to treat MDR organisms, such as the new beta-lactam/beta-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam), siderophore cephalosporins (cefiderocol), and others under development, might significantly help reduce mortality of infected recipients. Their judicious use is paramount to prevent the development of new resistance, rendering these vital tools ineffective. Close microbial monitoring before and immediately after transplantation, as well as strict adherence to hygiene practices and antibiotic therapy, is mandatory. Tailored antibiotic strategies and systematic screening for MDR organisms are critical to mitigating these risks and improving LT outcomes.