Single Dose Based Ertapenem Prophylaxis Reduces Surgical Site Infection after Selective Hepatectomy of Hepatocellular Carcinoma: A Propensity Score Matching Study
Executive Summary
Surgical site infection (SSI) remains a significant complication following hepatectomy for hepatocellular carcinoma (HCC), contributing to increased postoperative mortality and prolonged hospital stays. While traditional prophylactic protocols often involve multiple doses of short-acting antibiotics, recent research suggests that the choice of antibiotic and the timing of administration are more critical than the duration of treatment.
A retrospective study conducted at Shengjing Hospital, China Medical University, evaluated the efficacy of a single dose of ertapenem (ER) compared to non-ertapenem (NER) antibiotics. The study, utilizing propensity score matching to ensure clinical parity between groups, concluded that a single 1.0g dose of ertapenem administered prior to skin incision significantly reduces the incidence of SSI. Specifically, the ER group demonstrated an SSI rate of 7.7% compared to 21.5% in the NER group. Furthermore, the use of ertapenem was associated with a lower risk of multidrug-resistant infections, such as MRSA and fungal infections, which were more prevalent in patients receiving extended NER antibiotic courses.
Clinical Context and Research Objective
Hepatectomy is the primary curative treatment for liver cancer. However, the procedure is classified as clean-contaminated surgery, with SSI rates typically ranging from 3.1% to 14.0%. In the Chinese patient population, HCC frequently occurs alongside chronic liver disease and cirrhosis, which introduces risk factors such as hepatic insufficiency, surgical bleeding, and weakened immunity.
The study aimed to address two primary issues in current surgical practice:
Inadequate Prophylaxis: Short-acting antibiotics may fail to maintain sufficient plasma and tissue concentrations throughout the duration of a major surgery.
Over-prescription: Extended postoperative antibiotic administration (often exceeding 24 hours) does not necessarily improve efficacy and may instead promote bacterial resistance and secondary infections.
Study Methodology
The research retrospectively analyzed data from 396 HCC patients who underwent open hepatectomy between January 2012 and June 2017. After applying exclusion criteria (e.g., preoperative infection, digestive tract surgery, or renal insufficiency), 275 patients were enrolled and divided into two cohorts:
Comparison Groups
Propensity Score Matching (PSM)
To minimize selection bias and confounding variables (such as age, BMI, diabetes, and tumor size), a 1:1 PSM analysis was performed. This resulted in two balanced groups of 65 patients each.
Analysis of Surgical Site Infections (SSI)
Following the PSM adjustment, the ER group showed a statistically significant reduction in SSI compared to the NER group. SSI was categorized into incisional infections and organ/space infections.
Post-Matching SSI Frequency
The reduction in organ/space infections—the more severe form of SSI involving the internal anatomy manipulated during surgery—was particularly notable in the ER cohort.
Bacteriological Findings and Resistance
The study isolated bacteria from 20 of the 28 total infected cases across both groups (pre-matching). The analysis highlighted a critical concern regarding the NER group: a significantly higher incidence of MRSA and fungal infections.
Isolated Pathogens: Included Gram-positive cocci (MRSA, Staphylococcus hominis, Enterococcus faecium), Gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli), and fungi (Candida tropicalis).
Resistance Correlation: The total rate of MRSA or fungal infection was 6.2% (4 cases) in the NER group, while the ER group had 0% (0 cases). This supports the theory that prolonged or excessive antibiotic courses—as seen in the NER protocol—promote drug resistance.
Pharmacokinetics and Discussion
The superior performance of ertapenem is attributed to its broad-spectrum, long-acting profile. While generally indicated for treatment rather than prophylaxis, its pharmacokinetic properties are highly suitable for major surgeries:
Sustained Concentration: A single 1.0g dose of ertapenem maintains a plasma level of 1mg/L (above the MIC90 for most pathogens) for 24 hours.
Tissue Penetration: In liver tissues, ertapenem concentrations remain at bacteriostatic levels (≥90%) for up to 360 minutes, covering the typical duration of a total hepatectomy.
Stability Across Demographics: The pharmacokinetic profile of ertapenem remains consistent regardless of the patient's age, gender, weight, or the presence of liver disease.
Conclusions
The study concludes that a single dose of ertapenem administered before selective hepatectomy for HCC is more effective in preventing SSI than traditional multi-dose regimens of other antibiotics. The findings suggest that:
Selection and Timing are Vital: The efficacy of prophylaxis depends on having a high enough concentration of the drug in the tissue at the moment of potential contamination.
Short-Course Advantage: Utilizing a single-dose regimen of a long-acting antibiotic like ertapenem provides sufficient coverage while minimizing the risk of inducing bacterial resistance (MRSA) or opportunistic fungal infections.
Resource Optimization: Single-dose prophylaxis may be more cost-effective and reduces the clinical burden associated with prolonged antibiotic administration.
