Purpose: Bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) after liver transplantation (LT) is a rising threat during postoperative care. An alternative antibiotic treatment approach comprises ceftazidime-avibactam. This retrospective cohort study evaluated a novel ceftazidime-avibactam-centered bundle therapy (CCBT) for CRKP BSIs in LT recipients. Patients and methods: Among 728 LT recipients, 25 patients with CRKP BSIs were included. The CCBT comprised: (1) prompt infection source control; (2) early ceftazidime-avibactam initiation (< 3 days post-culture); (3) immunosuppression adjustment (discontinuation of calcineurin/mechanistic target of rapamycin inhibitors/mycophenolate until blood culture clearance); and (4) intravenous immunoglobulin (IVIG, 300 mg/kg/day for 5 days). The controls received empirical anti-infection therapy comprising polymyxin- and tigecycline-based combination regimens, or amikacin and polymyxin used in combination with meropenem according to drug susceptibility results. Outcomes included microbiological clearance, mortality, immune/liver function recovery, recurrence, and complications. Results: Patients were distributed into CCBT (n=15) and control (n=10) groups. The CCBT group had a higher blood culture clearance rate (100% vs 50%; P =0.005) and longer post-infection median survival time (407 vs 18.5 days; P =0.011) than the control group. Liver enzyme (aspartate aminotransferase, alanine aminotransferase, direct bilirubin) levels improved significantly ( P < 0.05) and normalized in the CCBT group. The CCBT group also exhibited significant rebounds in natural killer, CD4+, and CD8+ cell numbers post-recovery ( P < 0.01), indicating immune reconstitution. Despite immunosuppression withdrawal, rejection occurred in only 2 CCBT group patients (Banff scores 3 and 5), which were managed successfully with steroid pulses. Perioperative complications (bile leaks, hepatic artery issues) showed no intergroup differences. Conclusion: A multidisciplinary bundle integrating ceftazidime-avibactam, IVIG and immunosuppression minimization significantly improved survival and microbiological outcomes in patients with CRKP BSI after LT, compared with antibiotic therapy alone. Multicenter studies are merited to confirm whether wider implementation of this multidisciplinary bundle would improve outcomes in patients with CRKP BSI after LT. Keywords: carbapenem-resistant Klebsiella pneumonia , liver transplantation, ceftazidime-avibactam, bloodstream infection, bundle treatment
Guo et al. (Sun,) studied this question.