Successful Use of Sulbactam–Durlobactam in Treating Carbapenem-Resistant Acinetobacter baumannii Pneumonia and Sepsis After Liver Transplantation: A Case Report

Introduction

Orthotopic liver transplantation (OLT) remains the most effective and primary treatment for end-stage liver disease [1,2]. In recent years, advances in transplantation techniques, new immunosuppressants, and perioperative management have significantly improved both short- and long-term outcomes for recipients and grafts [3]. However, the incidence of early postoperative infections remains high, reaching 71.4% [4], and infections continue to be among the leading causes of death in these patients [5]. Acinetobacter baumannii, a gram-negative, multidrug-resistant (MDR) pathogen, poses a significant threat, particularly in critically ill patients and transplant recipients. This pathogen is associated with high mortality rates and treatment challenges due to its ability to resist multiple classes of antibiotics, including carbapenems [6]. Acinetobacter baumannii infections are especially concerning in liver transplant recipients, as these patients often have compromised immune systems due to immunosuppressive therapy, limited antibiotic options, and an increased risk of severe, life-threatening infections. Carbapenem-resistant Acinetobacter baumannii (CRAB) is a dangerous, multidrug-resistant bacteria often affecting critically ill patients. CRAB infections have emerged as a major clinical concern, as these infections are difficult to treat and are associated with poor outcomes in immunocompromised patients. Sulbactam–durlobactam (SUL-DUR), a novel β-lactam/β-lactamase inhibitor combination, designed to overcome resistance by blocking bacterial enzymes, has shown potent antimicrobial activity against CRAB by inhibiting bacterial enzymes that degrade β-lactam antibiotics, thus restoring the efficacy of carbapenem antibiotics [7].

We successfully treated a liver transplant recipient with CRAB pneumonia and sepsis using SUL–DUR. A literature review revealed this to be the first reported case of SUL-DUR use following liver transplantation worldwide. By sharing our experience and reviewing the relevant literature, we aim to further the use of SUL-DUR in treating CRAB infections in liver transplant recipients. The purpose of this case report is to present the world’s first use of SUL-DUR following liver transplantation, to highlight its potential clinical efficacy and safety, and to encourage further evaluation in larger, multicenter studies.

Case Report

A 22-year-old woman weighing 60 kg was admitted on 18 February 2025, with fatigue, poor appetite, and nausea for approximately 2 weeks, accompanied by progressive confusion and drowsiness for 6 days.

Her illness began on 2 February 2025, when she developed malaise, loss of appetite, nausea, and vomiting without obvious precipitating factors. She denied fever, hematemesis, or melena. She self-medicated with domperidone (“Motilium”) but experienced no significant improvement. Initial liver function testing revealed marked hepatocellular injury (ALT 224.7 U/L, AST 1595 U/L, total bilirubin 130.7 μmol/L, direct bilirubin 90.8 μmol/L). Abdominal ultrasonography showed fatty liver, left renal calculi, and a poorly visualized gallbladder. That evening, she was transferred to a tertiary hospital for further evaluation. Repeat laboratory testing demonstrated progressive hepatic dysfunction (ALT 1448 U/L, AST 1167 U/L, GGT 228 U/L, ALP 164 U/L, T-BIL 156.1 μmol/L, D-BIL 116.6 μmol/L) and coagulopathy (PT 16.2 s, PTA 57%). Despite administration of hepatoprotective agents, choleretic therapy, and plasma transfusions, her bilirubin continued to rise and coagulation parameters worsened.

By 12 February, she became increasingly agitated and disoriented, with flapping tremor suggestive of hepatic encephalopathy. Lactulose enemas and oral rifaximin were initiated, yet her mental status declined further. She was transferred to the intensive care unit (ICU) on 14 February for escalating liver support, including 2 sessions of plasmapheresis, 1 session of bilirubin adsorption, and continuous renal replacement therapy (CRRT). Despite these measures, she lapsed into coma and had 3 generalized seizures on 16 February. Laboratory results the next day revealed profound hepatic failure: ALT 287 U/L, AST 183 U/L, T-BIL 363.9 μmol/L, D-BIL 249.8 μmol/L, PT 23.8 s, PTA 34%, INR 2.19, and blood ammonia 105 μmol/L.

The patient had no history of liver disease, alcohol or drug use, and no family history of hepatic disorders. On physical examination, she was deeply comatose and jaundiced, with equal, reactive pupils, although the right eye remained fixed. Multiple ecchymoses were noted on her limbs, and mild bilateral pedal edema was present. Breath sounds were slightly diminished at both lung bases without rales, and the abdomen was flat and soft with no palpable organomegaly. Hoffmann’s sign was positive, consistent with hepatic encephalopathy. Laboratory evaluation demonstrated a markedly elevated serum ammonia level (320 μmol/L), worsened coagulopathy (INR 2.91, PTA 25%), and elevated liver enzymes (ALT 321 U/L, AST 226.7 U/L, total bilirubin 387.3 μmol/L). Chest computed tomography (CT) on admission showed no pulmonary infiltrates.

Based on these findings, a diagnosis of acute liver failure with grade IV hepatic encephalopathy and coagulopathy was established. Despite aggressive medical management, her condition deteriorated rapidly, necessitating urgent liver transplantation.

She was listed for transplantation under super-urgent status (category 1A). Metagenomic next-generation sequencing (mNGS) of peripheral blood detected SARS-CoV-2 (64 sequence reads), prompting initiation of antiviral therapy with nirmatrelvir/ritonavir (Paxlovid). On 19 February 2025 she underwent right hepatectomy and auxiliary liver transplantation using a reduced-size right liver graft from a donation after brain death (DBD) donor. The graft appeared soft and yellow-brown, with a graft-to-recipient weight ratio (GRWR) of 2.07%. Warm and cold ischemia times were 5 and 474 minutes, respectively. Intraoperative immunosuppression included basiliximab 10 mg and methylprednisolone 600 mg (10 mg/kg). Postoperatively, methylprednisolone was tapered, and tacrolimus initiation was delayed because of potential drug–drug interactions with Paxlovid. Empirical antimicrobial prophylaxis with meropenem, vancomycin, and micafungin was administered. The procedure was technically successful, with immediate graft reperfusion and stable hemodynamics.

Within several days, the patient developed intermittent fever up to 38.5 °C, persistent encephalopathy, and declining oxygen saturation. Chest imaging revealed new bilateral pulmonary infiltrates consistent with pneumonia. Bronchoscopy showed mucosal congestion and edema of the left lower bronchus with copious yellow-white secretions. Sputum mNGS identified Acinetobacter baumannii (301 788 reads), multidrug-resistant Klebsiella pneumoniae (261 313 reads), Sphingomonas paucimobilis (66 reads), and human metapneumovirus (4475 reads), with resistance genes KPC-2 and OXA-422. Given these findings, antimicrobial therapy was escalated on February 25 to sulbactam–durlobactam (1 g/1 g every 8 h), meropenem (1 g every 8 h), aztreonam, and nebulized polymyxin B. Because of the coexisting K. pneumoniae infection, meropenem was later discontinued and eravacycline was initiated. The human metapneumovirus infection was managed conservatively. Immunosuppression was temporarily modified, with tacrolimus withheld during antiviral therapy and corticosteroids used to maintain graft protection. Tacrolimus was reintroduced at a reduced dose once Paxlovid was discontinued and infection stabilized.

Repeat blood mNGS the following day revealed A. baumannii (12 694 reads) and low-level K. pneumoniae (11 reads), harboring ADC-30, OXA-171, OXA-195, OXA-422, and sul-1 resistance genes. Because inflammatory markers remained elevated, continuous venovenous hemodiafiltration (CVVHDF) was initiated (blood flow 130 mL/min; replacement fluid 1000 mL/h; dialysis fluid 3000 mL/h) for cytokine and toxin clearance. On 1 March 1 blood and sputum cultures confirmed carbapenem-resistant A. baumannii (CRAB). Susceptibility testing showed sensitivity to sulbactam–durlobactam (inhibition zone 23 mm), resistance to cefotaxime–avibactam, and sensitivity to tigecycline (MIC 0.5 μg/mL) and eravacycline (MIC 0.125 μg/mL). Sulbactam–durlobactam was therefore continued as the main therapy. Central venous catheters were replaced, and inflammatory markers (CRP, IL-6, procalcitonin, WBC) gradually declined. Follow-up sputum mNGS on 3 March showed dramatic reductions in A. baumannii (to 322 reads) and K. pneumoniae (to 23 895 reads). No bacterial growth was observed in subsequent sputum or blood cultures. Sulbactam–durlobactam was discontinued after 11 days, following clinical and microbiological resolution of infection. Table 1 shows body temperature and laboratory findings during the course of anti-infective therapy, and Figure 1 shows the dynamic changes in pulmonary CT during the clinical course.

After completing sulbactam–durlobactam therapy, the patient continued to experience a low-grade fever due to persistent K. pneumoniae infection. Eravacycline and polymyxin B were maintained for another 7 days, after which her temperature normalized and chest imaging showed marked improvement. All antibiotics were discontinued on March 15, 2025. Perioperative microbiological test data are provided in Table 2 and perioperative treatment is provided in Table 3.

During the following weeks, liver function recovered steadily, with normalization of bilirubin, aminotransferase, and coagulation parameters. The patient’s mental status returned to normal, and hepatic encephalopathy resolved completely. She was transferred from the ICU to the general ward on 25 March for rehabilitation and nutritional therapy.

Whole-genome sequencing detected no pathogenic variants related to hereditary liver disorders. Metagenomic analysis of the resected native liver identified Human herpesvirus 6B (40 reads) and Human herpesvirus 7 (33 reads), while histopathology revealed massive hepatic necrosis without autoimmune or metabolic features. Despite comprehensive investigation, the cause of the acute liver failure remained indeterminate.

By early April, the patient had achieved full recovery with stable graft function and complete resolution of infection. She was discharged home in good condition after successful rehabilitation. The chronological sequence of major clinical events, treatments, and outcomes is summarized in Figure 2.

Discussion

Sulbactam–durlobactam (SUL-DUR) is a combination β-lactamase inhibitor comprising sulbactam and durlobactam, which exerts antibacterial activity through a dual mechanism. Sulbactam, a penicillin derivative, directly targets Acinetobacter baumannii penicillin-binding protein 3 (PBP3), thereby disrupting bacterial cell wall synthesis. Durlobactam is a broad-spectrum β-lactamase inhibitor that inactivates Ambler class A, C, and D serine β-lactamases, effectively protecting sulbactam from enzymatic degradation [8,9]. This dual mechanism confers potent antibacterial activity against carbapenem-resistant A. baumannii (CRAB) [10].

Based on positive results from the Phase III ATTACK trial, the U.S. Food and Drug Administration approved SUL-DUR in May 2023 for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible A. baumannii-calcoaceticus complex (ABC) [7,11]. This approval was a major advance in the treatment of CRAB infections [12,13].

In the present case, a liver transplant recipient with multi-site CRAB infections (lungs and bloodstream) achieved pathogen clearance and sustained clinical improvement following treatment with SUL-DUR in combination with meropenem and eravacycline. While SUL-DUR was the cornerstone of the patient’s treatment, the combination of multiple antibiotics and supportive care measures likely contributed to the overall positive outcome. The synergistic effect of meropenem, eravacycline, and SUL-DUR, along with the use of CVVHDF to manage systemic inflammation, was instrumental in controlling the infection.

The principal resistance mechanisms of CRAB include carbapenemase production (notably OXA-type β-lactamases) and mutations in PBP3, both of which severely limit the efficacy of conventional antibiotics. SUL-DUR overcomes these mechanisms, particularly in strains harboring OXA-type enzymes or PBP3 mutations, through the synergistic action of sulbactam and durlobactam, thereby restoring antimicrobial activity against resistant isolates.

In this case, the CRAB strain harbored resistance genes, including OXA-23, OXA-422, and ADC-30, but lacked NDM-1 metallo-β-lactamase and PBP3 mutations, consistent with previously reported CRAB resistance profiles [14,15]. Notably, SUL-DUR demonstrated a susceptibility rate of 97.7% against non-metalloenzyme-producing strains [16], which was instrumental in the patient’s favorable clinical outcome.

Additionally, the combination of SUL-DUR and meropenem may enhance bactericidal activity through “target redundancy”, whereby the agents simultaneously bind to distinct penicillin-binding proteins (PBP1a and PBP3) [17,18]. This mechanism may account for the rapid clinical response observed in this case. Following initiation of SUL-DUR, the patient’s CRAB infection was gradually brought under control, accompanied by reductions in body temperature, leukocyte count, and inflammatory markers.

In this case, the patient developed pneumonia and septicemia due to CRAB following liver transplantation, alongside co-infection with multidrug-resistant Klebsiella pneumoniae. Antibiotic therapy was escalated to a combination of SUL-DUR, meropenem, and aztreonam. While the primary focus was on controlling the CRAB infection, the treatment of K. pneumoniae co-infection also likely contributed to the patient’s overall clinical improvement. The reduction in the bacterial load of both pathogens suggests the effectiveness of the combination therapy and highlights the complexity of treating multi-pathogen infections in immunocompromised patients.

The Phase III ATTACK trial demonstrated that SUL-DUR is associated with a significantly lower incidence of nephrotoxicity compared to polymyxins (13% vs 38%) [19]. In the present case, CVVHDF was employed to mitigate systemic inflammation, and SUL-DUR dosing was adjusted according to pharmacokinetic parameters. No renal impairment or other serious adverse effects were observed, suggesting that SUL-DUR is safe for use in immunosuppressed populations, including liver transplant recipients, and may offer an advantage in critically ill patients [20].

In clinical practice, SUL-DUR can be combined with other antibiotics to enhance antibacterial efficacy. In this case, combination therapy resulted in successful infection control. The regimen – including SUL-DUR, meropenem, aztreonam, and nebulized polymyxin – underscores the necessity of combination approaches for the management of multidrug-resistant infections. Preclinical studies suggest that combining SUL-DUR with β-lactam agents such as imipenem can produce a synergistic effect [17,18]. In our patient, the addition of meropenem to SUL-DUR likely broadened the antibacterial spectrum by targeting multiple PBP sites while potentially reducing the emergence of resistance.

Furthermore, dynamic monitoring of sputum via tNGS revealed a marked reduction in pathogen load, confirming the microbiological efficacy of combination therapy. McLeod et al reported no antagonistic interactions between SUL-DUR and 17 commonly used antibiotics [21]. Additionally, Ruiz et al demonstrated that SUL-DUR exhibits physical compatibility with 90.5% of 95 intravenous medications tested, with incompatibilities limited to 9 agents – albumin, amiodarone hydrochloride, cefoperazone, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium bromide, and propofol – when administered via Y-site infusion [22].

Liver transplant recipients are particularly susceptible to multidrug-resistant infections due to ongoing immunosuppression and frequent exposure to invasive procedures, resulting in high mortality rates. This case is the first reported instance of successful SUL-DUR use following liver transplantation, offering a potential reference for its application in critically ill and immunocompromised patients. Given the increasing burden of CRAB infections, the successful treatment of CRAB septicemia in our patient supports the expansion of SUL-DUR use to bloodstream infections [23]. Future investigations should evaluate its role in additional indications, such as urinary tract and other systemic infections, and pursue multicenter clinical trials to validate its long-term efficacy.

In this case, next-generation sequencing (NGS) was employed to identify resistance genes, guiding the targeted administration of SUL-DUR in accordance with molecular epidemiology-based treatment strategies, as emphasized in prior reviews [16,24]. The detection of OXA-23 and ADC-30 did not compromise the efficacy of SUL-DUR, highlighting the importance of ongoing surveillance of resistance mechanisms to inform treatment selection. NGS also enabled dynamic quantification of bacterial sequence reads, facilitating real-time assessment of therapeutic response.

While this case supports the potential of SUL-DUR in managing multi-drug-resistant infections in liver transplant recipients, the findings are based on a single-patient observation. Larger, multicenter studies are needed to evaluate the generalizability of these results and confirm the long-term efficacy and safety of SUL-DUR in transplant populations and other high-risk groups. Future real-world studies in high-risk populations, such as organ transplant recipients, are warranted to confirm the durability of SUL-DUR’s efficacy, assess the risk of resistance development, and investigate sequential therapy strategies with novel agents such as cefiderocol [25–27]. This is a single case report, and the observed clinical success cannot be generalized. The concomitant use of multiple antibiotics and supportive therapies also limits attribution of the outcome solely to SUL-DUR. Larger multicenter studies and real-world investigations are warranted to confirm its efficacy, safety, and potential role in treatment guidelines for transplant populations.

Conclusions

Although based on a single case, this report suggests that sulbactam–durlobactam (SUL-DUR) may be a promising therapeutic option for treating CRAB infections in high-risk patients such as liver transplant recipients. The observed clinical success supports previous findings from Phase III clinical trials and highlights the potential utility of SUL-DUR in complex, multidrug-resistant infections. However, due to the lack of a control group and the concurrent use of other antimicrobials, the specific contribution of SUL-DUR to the overall outcome cannot be conclusively determined. Further research in broader patient cohorts is essential to validate these findings and to establish standardized therapeutic protocols for CRAB infections in transplant recipients.