Successful Treatment of OXA-23 Acinetobacter baumannii Pneumonia with Sulbactam-Durlobactam in a Liver Transplant Recipient

Introduction

Liver transplantation (LT) is the most effective therapeutic option for patients with end-stage liver disease. Due to preoperative comorbidities, repeated antibiotic exposure, immunosuppressant therapy, and prolonged mechanical ventilation, the risk of multidrug-resistant (MDR) bacterial infections increases in LT recipients.^1,2 MDR infections have emerged as a significant threat to this group and are linked to adverse outcomes.^3,4 These infections are associated with a high 30-day mortality rate following LT, especially within the first 5 days of onset.⁵ Furthermore, mortality can reach 50% when complicated by septic shock.⁴ One of the most challenging pathogens faced in LT recipients is carbapenem-resistant Acinetobacter baumannii (CRAB), a gram-negative bacilli known for its extensive antibiotic resistance and its role in severe nosocomial infections, including ventilator-associated pneumonia (VAP), bloodstream infections, and surgical site infections.⁵

CRAB exhibits resistance to nearly all β-lactam antibiotics, including carbapenems, mainly through the production of carbapenem-hydrolyzing class D β-lactamases.⁶ Among these, OXA-23 is the most common carbapenemase genotype, with detection rates reaching up to 99% in China.⁷ The emergence of antimicrobial resistance mechanisms, combined with limited treatment options, has created significant challenges for clinical management. The 2024 Infectious Diseases Society of America (IDSA) guidance for CRAB infections first recommend combination therapy based on sulbactam-durlobactam (SUL-DUR).⁸

As noted, there is still limited data on the role of CRAB in pulmonary infections after LT. Here, we share a case of a liver transplant recipient with OXA-23-producing Acinetobacter baumannii pulmonary infection who was effectively treated with SUL-DUR in combination with meropenem.

Case Presentation

A 55-year-old male patient with a history of chronic hepatitis B and post-hepatitic cirrhosis was diagnosed with hepatocellular carcinoma (HCC) in December 2024. He underwent two sessions of transarterial chemoembolization (TACE). Positron emission tomography/Computed tomography (PET/CT) showed multiple nodules and masses in the right hepatic lobe with low metabolic activity, consistent with post-treatment changes, indicating significant tumor suppression or necrosis. No signs of malignancy or metastasis were observed elsewhere. Subsequently, the patient developed complications including portal hypertension, splenomegaly, ascites, hepatorenal syndrome, and cirrhotic cardiomyopathy. In March 2025, he presented at our transplantation center for liver transplantation. He also had bilateral emphysema, pulmonary bullae, and secondary pulmonary tuberculosis. On admission (Day 0), the clinical outcome data were summarized as follows.

• Transaminase levels were within normal limits; total bilirubin was mildly elevated at 31 μmol/L, and blood ammonia was 60 μmol/L.
• Hepatitis B viral load (high-sensitivity quantification) was 120 IU/mL, with hepatitis B surface antigen >250 IU/mL. Alpha-fetoprotein (AFP) was 22 ng/mL, and protein induced by vitamin K absence/antagonist-II (PIVKA-II) was 120 mAU/mL.
• The patient was successfully matched, with minimal risk of an immune response due to human leukocyte antigen (HLA) mismatch. Preoperative panel reactive antibody (PRA) and donor-specific antibodies (DSA) were both negative.
• Detailed laboratory values are summarized in Table 1.

Table 1 Clinical Laboratory Results

He underwent a classic allogeneic liver transplant with an organ from a brain-dead donor. The donor was a 44-year-old male who suffered a brainstem hemorrhage leading to brain death, with a documented history of fatty liver. Pathological examination of the donor liver showed approximately 30% macrovesicular steatosis in hepatocytes. Immunosuppressants were administered to prevent organ rejection. Corticosteroids and intravenous immunoglobulin (IVIG) were used for induction of immunosuppression during surgery. For postoperative maintenance therapy, three immunosuppressive drugs- including prednisolone, tacrolimus (TAC), and mycophenolate mofetil (MMF) were prescribed. On postoperative day (POD) 1, transaminase levels rose to 4500 U/L, and total bilirubin increased to 106 µmol/L. Simultaneously, the patient remained unconscious, with signs suggesting ischemia-reperfusion injury and delayed graft function. Plasma exchange was initiated. Doppler ultrasound was used to monitor graft size, blood flow, resistance index, fluid accumulation, and thrombosis. By POD 3, the patient was conscious and weaned off mechanical ventilation successfully. As per our transplant center’s antimicrobial prophylaxis protocol, the patient received piperacillin/tazobactam 4.5 g intravenously (IV) every 12 hours and caspofungin 50mg IV daily for post-transplant infection prevention.

One week postoperatively, the patient developed a fever and excessive airway secretions, which quickly advanced to acute respiratory distress and septic shock. His oxygen needs increased, requiring high-flow nasal oxygen (HFNO) therapy with a fraction of inspired O2 (FiO2) of 60%. He also needed vasopressor support with norepinephrine at a dose of 0.2 mcg/kg/min. Procalcitonin levels rose to 7.13 ng/mL, and interleukin-6 levels surged to 1357 pg/mL, indicating a strong inflammatory response. Chest CT showed worsening of the infection compared to earlier imaging (Figure 1). Transnasal bronchoscopy was performed under conscious sedation, during which airway secretion samples were collected for laboratory testing. Empirical antimicrobial treatment with imipenem/cilastatin, linezolid, and caspofungin was started. On POD 9, metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) detected 1,651,915 copies/mL of Acinetobacter baumannii gene fragments (platform: Illumina, manufacturer: Hangzhou Jieyi Biotechnology). The results confirmed that the carbapenem-resistant Acinetobacter baumannii isolates carried an OXA-23-producing class D β-lactamase. Additionally, a small number of carbapenem-resistant Klebsiella pneumoniae (CRKP) gene reads (13,915 copies/mL) were identified, indicating the presence of a Klebsiella pneumoniae carbapenemase (KPC)-producing class A β-lactamase. Subsequently, only CRAB was grown in BALF cultures. In vitro antimicrobial susceptibility testing showed that CRAB was only sensitive to polymyxin, eravacycline, and tigecycline (Table 2). The antibiotic regimen was adjusted to polymyxin B 50 mg IV every 12 hours combined with eravacycline 50 mg IV every 12 hours. Despite five days of treatment, there was minimal improvement in respiratory secretions and septic shock. Infection markers remained high, and norepinephrine dependence persisted, with progressively increasing doses needed to maintain hemodynamic stability, indicating inadequate infection control. The patient had a history of preoperative hepatorenal syndrome and developed postoperative acute kidney injury (AKI), which was worsened by polymyxin therapy. About 15 days post-surgery, serum creatinine rose sixfold from baseline, and urine output declined to anuria, requiring continuous renal replacement therapy (CRRT).

Table 2 Antimicrobial Susceptibility Profile of the OXA-23 Producing Acinetobacter baumannii Isolate

Figure 1 Comparison of CT scans of the patient’s lungs before and after treatment. (A) (POD 2), (B) (POD 12), (C) (POD 20), (D) (POD 30), (E) (POD 36), (F) (POD 44). (B and C) were obtained following polymyxin B therapy, while (D–F) were taken during the subsequent meropenem-sulbactam-durlobactam therapy. The POD 44 image shows significant resolution of pneumonitis.

On POD20, a repeat chest CT showed persistent infectious consolidation in the lower lobe without radiologic improvement (Figure 1). The patient’s sputum volume had not decreased, so pulmonary bronchoscopy was performed again. BALF-mNGS analysis still detected a large number of CRAB gene reads (502,701 copies/mL). CRAB was also isolated from BALF culture. The antibiotic regimen was changed to SUL-DUR 1 g/1 g IV every 8 hours, combined with meropenem 1 g IV every 8 hours. After 5 days of treatment, the patient’s oxygenation improved, allowing successful liberation from HFNO therapy. The patient was transitioned to low-flow nasal oxygen at 2 L/min, with oxygen saturation maintained at 96–100%. On day 10 of the SUL-DUR and meropenem regimen, norepinephrine was discontinued, and procalcitonin levels gradually decreased to near-normal levels.

At the end of a 2-week course of SUL-DUR, the patient showed significant clinical improvement, including the resolution of fever, decreased sputum production, and better respiratory function. Renal function gradually improved, enabling the cessation of dialysis, while hepatic allograft function stayed stable. The timeline of the hospital stay with antibiotic treatment is shown in Figure 2. The patient was discharged on POD 44 without any complications.

Figure 2 Timeline diagram of disease and treatment course.

Discussion

Infections caused by CRAB have become a serious threat to LT recipients. A systematic review and meta-analysis reported consistently high global detection rates of CRAB, with resistance to imipenem and meropenem averaging 44.7% and 59.4%, respectively.⁹ The management of CRAB infections remains especially difficult because of their intrinsic multidrug resistance patterns and the limited effectiveness of current antimicrobial agents. SUL-DUR is a novel anti-CRAB agent, demonstrating potent inhibitory activity against the vast majority of class D carbapenemases (OXA-type β-lactamases), including OXA-23. In this report, we described a liver transplant recipient who developed OXA-23-producing Acinetobacter baumannii pneumonia complicated by respiratory failure and septic shock, and was successfully treated with a SUL-DUR-based combination of meropenem.

The main resistance mechanisms of CRAB include β-lactamase production, efflux pump overexpression, target-site modification, and changes in membrane permeability.⁶ The predominant mechanism in carbapenem-resistant isolates involves enzymatic hydrolysis of β-lactam antibiotics by β-lactamases, specifically class D carbapenemases of the OXA family, such as OXA-23, OXA-24/40, OXA-51, and OXA-58, which hydrolyze carbapenems through a serine-active site.¹⁰ OXA-23 has the highest global prevalence.^7,11 This Ambler class D β-lactamase confers high-level resistance to imipenem and meropenem by enzymatic hydrolysis and works together with outer membrane protein (OMP) loss, leading to typical MICs higher than 16 mg/L, which exceeds clinical breakpoints for carbapenem susceptibility.¹²

Current treatment strategies for CRAB infections mainly depend on traditional last-resort agents like colistin and tigecycline, but these face limitations such as reduced effectiveness, serious nephrotoxicity, and rising resistance.^13,14 A multicenter study conducted in the intensive care unit (ICU) found that 32.9% of polymyxin-sensitive strains developed resistance to polymyxin during treatment of CRAB with it, with a high rate of treatment failure (death or persistent bacteria).¹⁵ Polymyxin’s high nephrotoxicity restricts its use. A multicenter, randomized, active-controlled, Phase 3, non-inferiority clinical trial (ATTACK) showed that SUL-DUR is more effective and safer than polymyxin in treating severe infections like hospital-acquired pneumonia (HAP), VAP, and bloodstream infections caused by CRAB, with significantly lower nephrotoxicity rates (13% vs 38%).¹⁶

SUL-DUR, a novel β-lactam-β-lactamase inhibitor combination, targets CRAB through synergistic molecular interactions and optimized pharmacokinetic/pharmacodynamic (PK/PD) profiles.^17,18 SUL, a semi-synthetic penicillanic acid derivative, exhibits weak intrinsic inhibitory activity against class A serine β-lactamases but lacks activity against class C and D β-lactamases. Its primary antibacterial action is mediated through high-affinity binding to penicillin-binding protein (PBP) 1 and PBP3 in Acinetobacter baumannii, preventing their involvement in bacterial cell wall synthesis and exerting bactericidal activity against this pathogen.^18,19 DUR, a diazabicyclooctane inhibitor, exhibits potent inhibition of Ambler class A, C, and D enzymes.²⁰ It demonstrates potent activity against currently studied class D carbapenem-hydrolyzing OXA-type β-lactamases. Meropenem enhances this antibacterial effect by selectively targeting PBP2 and blocking its biological function in cell wall assembly. By blocking enzymatic degradation of SUL and Meropenem, DUR improves their penetration to PBP targets, increasing bactericidal effectiveness against Acinetobacter baumannii.^18,21 The combination of SUL-DUR with carbapenem shows significant synergistic bactericidal effects against carbapenemase-producing strains.²²

A growing body of clinical reports demonstrates the successful use of SUL-DUR-based combinations, often with a carbapenem, in treating critically ill patients with extensively drug-resistant Acinetobacter baumannii infections. These include cases of nosocomial pneumonia,^23,24 severe burn injury,^11,25 and meningitis.^26,27 All other patients received a carbapenem during SUL-DUR therapy to cover potential co-infecting pathogens. The 2024 IDSA guidance recommends SUL-DUR, combined with meropenem or imipenem-cilastatin, as the preferred treatment for CRAB infections.⁸ Given the complexity of this patient group, data on its use in solid organ transplantation are very limited. To date, successful treatment of CRAB infections with sulbactam-durlobactam has been reported in kidney and lung transplant recipients.^28,29 To our knowledge, we first present the successful use of an antimicrobial regimen combining SUL-DUR and meropenem in a liver transplant recipient.

In our case, the patient developed hepatorenal syndrome before LT. After surgery, acute renal failure complicated the course and was attributed to hypoxic-ischemic reperfusion injury. Due to limited treatment options, polymyxin was used for CRAB infection. However, the pulmonary infection remained uncontrolled, and polymyxin worsened AKI. The antimicrobial therapy was then changed to a SUL-DUR-based regimen. After two weeks of targeted treatment, the infection was successfully controlled, and kidney function returned to normal.

Conclusion

We present a case of a liver transplant recipient with OXA-23-producing Acinetobacter baumannii infection who failed initial therapy with polymyxin and eravacycline, then developed worsening renal insufficiency. Successful eradication was achieved after switching to a combination of SUL-DUR and meropenem. This case highlights the potential clinical utility of SUL-DUR-based combination therapy for managing CRAB infections in solid organ transplantation, especially liver transplant recipients for whom conventional treatments may be contraindicated due to toxicity or resistance. Currently, real-world clinical data on SUL-DUR for CRAB infections in liver transplant recipients remain limited, emphasizing the need for large-scale clinical studies.