Successful treatment of carbapenem-resistant Acinetobacter baumannii and Enterobacterales coinfection with sulbactam-durlobactam combined with aztreonam: a case report
Case Report

Successful treatment of carbapenem-resistant Acinetobacter baumannii and Enterobacterales coinfection with sulbactam-durlobactam combined with aztreonam: a case report

Siyu Yang, Zhenshun Cheng, Yuan Liu, Lan Ni, Chaojie Wei

Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China

Contributions: (I) Conception and design: S Yang, C Wei, Z Cheng; (II) Administrative support: C Wei, Z Cheng; (III) Provision of study materials or patients: S Yang, Y Liu, L Ni; (IV) Collection and assembly of data: S Yang, Y Liu, L Ni; (V) Data analysis and interpretation: S Yang, C Wei; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Chaojie Wei, MD, PhD. Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Zhongnan Road, Wuhan 430071, China. Email: chaojie_wei@163.com.

Background: Carbapenem-resistant Gram-negative bacilli (CRGNB) often cause nosocomial infections difficult to treat. Their widespread dissemination, associated high mortality, and increasing disease burden constitute a significant global public health challenge. This situation is further exacerbated by mixed CRGNB infections, which exhibit elevated mortality rates and increased therapeutic complexity. Thus, it is imperative to establish effective antibiotic strategies with minimal adverse effects to address these polymicrobial infections. We present this case to evaluate the efficacy of sulbactam-durlobactam (SUL-DUR) combined with aztreonam for treating mixed carbapenem-resistant Acinetobacter baumannii (CRAB) and metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) infections, also exploring the potential mechanisms.

Case Description: An elderly patient with uncontrolled chronic obstructive pulmonary disease (COPD) was admitted presenting with dyspnea, bloody sputum, and somnolence. Etiological workup revealed a pulmonary coinfection with CRAB and MBL-producing CRE. The infection proved refractory to multiple rounds of advanced antibiotic therapy, including meropenem, ceftazidime-avibactam, and a combination of polymyxin B with eravacycline. Guided by antimicrobial susceptibility testing (AST) and clinical guidelines, a regimen of SUL-DUR combined with aztreonam was initiated. This therapeutic strategy led to a successful clinical outcome, with no evidence of disease recurrence during a 2-month follow-up period.

Conclusions: This case highlights the significant efficacy of SUL-DUR combined with aztreonam in managing the clinically formidable challenge of mixed CRAB and MBL-producing CRE infections, offering a valuable reference for treating such conditions.

Keywords: Sulbactam-durlobactam (SUL-DUR); aztreonam; carbapenem-resistant Acinetobacter baumannii (CRAB); carbapenem-resistant Enterobacterales (CRE); case report

Received: 16 October 2025; Accepted: 10 December 2025; Published online: 26 February 2026.

doi: 10.21037/acr-2025-287

Highlight box

Key findings

• The case report presents a complex case of concurrent carbapenem-resistant Acinetobacter baumannii (CRAB) and metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) infection that responded poorly to conventional drug therapies, including susceptible eravacycline. The patient was successfully treated with a novel antibiotic combination regimen involving sulbactam-durlobactam (SUL-DUR) and aztreonam.

What is known and what is new?

• Treating CRAB and MBL-producing CRE is challenging due to their remarkable capacity to acquire resistance and the persistent scarcity of robust clinical outcome data, especially for co-infections.

• SUL-DUR combined with aztreonam is a novel regimen for CRAB and MBL-producing CRE coinfection, and shows promising efficacy due to their synergistic mechanism.

What is the implication, and what should change now?

• This report underscores the importance of selecting an appropriate antibiotic regimen for refractory multidrug-resistant bacterial infections. A rational combination therapy can significantly impact clinical outcomes. This case shows the potential synergy between SUL-DUR and aztreonam, and highlights the therapeutic promise in multiple carbapenem-resistant Gram-negative bacilli co-infections. Future studies and guidelines are encouraged to take this finding into consideration and explore the optimal indications.

Introduction

Carbapenem-resistant Gram-negative bacilli (CRGNB) infections constitute a critical global public health threat, characterized by escalating resistance rates and unacceptably high mortality. Recognizing this urgency, the World Health Organization’s (WHO) 2017 priority list for new antibiotic development designated carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) as pathogens of “critical priority” (1). CRAB poses a distinct challenge, serving as a leading cause of ventilator-associated pneumonia (VAP) and life-threatening bloodstream infections. CRE infections represent a formidable worldwide public health menace, primarily driven by enzymatic resistance mechanisms. Alarmingly, the prevalence of metallo-β-lactamase (MBL) genes among CRE isolates in the United States surged from 4% to 20% between 2019 and 2021 (2), highlighting a rapidly evolving resistance landscape. The diverse mechanisms underpinning carbapenem resistance in Enterobacterales and Acinetobacter baumannii (A. baumannii) necessitate multifaceted therapeutic strategies. Current approaches include the repurposing of existing antibiotics, synergistic dual-therapy combinations, and the development of novel β-lactamase inhibitors and antibiotics (3). However, treating CRAB and CRE remains profoundly challenging due to their remarkable capacity to acquire resistance determinants and the persistent scarcity of robust clinical outcome data, especially for co-infections.

Given these challenges, we present a significant case of pulmonary coinfection involving both CRAB and CRE. This complex infection was successfully managed using a novel regimen of sulbactam-durlobactam (SUL-DUR) combined with aztreonam, demonstrating a promising therapeutic approach for this high-mortality clinical scenario. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-287/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 77-year-old male with a 6-year history of untreated chronic obstructive pulmonary disease (COPD) was admitted to the Respiratory Intensive Care Unit (RICU) of Zhongnan Hospital on June 9, 2025, with acute exacerbation featuring dyspnea, bloody sputum, and somnolence. Apart from COPD, the patient denied any significant comorbidities or contributory family history. He was transported by ambulance and directly admitted to our hospital. On examination, he was somnolent with conjunctival edema, reduced breath sounds, and pitting edema.

Arterial blood gas found: pH 7.161, partial pressure of carbon dioxide (pCO2) 113 mmHg, partial pressure of oxygen (PaO2) 55 mmHg , HCO3− 40.4 mmol/L, lactate 0.6 mmol/L, base excess 9.9 mmol/L.

Initial laboratory findings revealed: white blood cell count (WBC, 4.6×109/L, normal range, 3.5–9.5×109/L), platelet (65×109/L, normal range, 125–350 ×109/L), neutrophil percentage 83.4%; procalcitonin (PCT, 3.13 ng/mL, normal range, <0.05 ng/mL), C-reactive protein (252.6 mg/L, normal range, <3.0 mg/L).

Nucleic acid tests for respiratory pathogens, including influenza virus, Mycoplasma, Chlamydia, were negative (Multiplex Nucleic Acid Detection Kit for 24 Respiratory Pathogens, GeneoDx, Shanghai, China). Besides, initial sputum culture, bronchoalveolar lavage fluid (BALF) culture, and BALF next-generation sequencing (NGS) failed to identify specific pathogens. Chest X-ray showed bilateral pulmonary infiltrates (Figure 1A). The patient’s admission diagnoses included acute exacerbation of COPD, pulmonary encephalopathy, severe pneumonia, and respiratory failure. He was immediately intubated and started on meropenem (1 g, every 8 hours) and moxifloxacin (0.4 g, once daily).

Figure 1 Chest X-ray and CT findings of the patient at different time points. (A) Bilateral pulmonary infiltrates on admission, and (B) after ECMO and CRRT were weaned, no radiographic improvement was discovered. (C) With treatment of SUL-DUR combined with aztreonam for 72 hours, chest X-ray showed little improvement. (D) CT findings on 2-month follow-up after discharge. CRRT, continuous renal replacement therapy; CT, computed tomography; ECMO, extracorporeal membrane oxygenation; SUL-DUR, sulbactam-durlobactam.

From June 12, bloody sputum was repeatedly observed via suction catheter and bronchoscopy revealed no obvious bleeding source. Candida tropicalis was detected in both the sputum cultures and BALF-cultures conducted on June 12 and 14. On June 14, oxygenation worsened [PaO2/fraction of inspired oxygen (FiO2) <100 mmHg]. Based on BALF-NGS results (Enterococcus faecium: 1,558 reads, Streptococcus pneumoniae: 1,246 reads, Enterobacter hormaechei: 775 reads, Candida tropicalis: 14,124 reads), antibiotics were adjusted to ceftazidime-avibactam (2.5 g, every 8 hours), vancomycin (500 mg, every 8 hours), and micafungin (150 mg, once daily). However, clinical deterioration continued. The PaO2/FiO2 ratio dropped below 50 mmHg, oxygen saturation became difficult to maintain, bloody sputum increased. An emergency tracheostomy was performed on June 16, followed by initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and continuous renal replacement therapy (CRRT).

BALF culture results on June 18 revealed CRAB and Enterobacter hormaechei (Table 1), and the Enterobacter hormaechei was found to be an MBL producer. Therefore, according to the antimicrobial susceptibility testing (AST), antibiotic schedule was modified to polymyxin B (500,000 units, every 12 hours) plus eravacycline (100 mg, every 12 hours), while continuing micafungin and vancomycin. Oxygenation slightly improved by June 22 (PaO2/FiO2 102 mmHg), but bloody sputum continued, necessitating bronchial artery embolization on June 23. After ECMO and CRRT were weaned on June 25 (PaO2/FiO2 200), infection markers rebounded and chest X-ray discovered no improvement of pneumonia (Figure 1B). Repeat BALF on June 27 still grew CRAB and carbapenem-resistant Enterobacter hormaechei, which still presented positive for MBL, primarily of the New Delhi Metallo-β-lactamase (NDM) type, confirming uncontrolled infection. Faced with persistent CRAB + CRE coinfection and clinical instability, and guided by updated Infectious Diseases Society of America (IDSA) guidelines for resistant Gram-negative infections, antimicrobial therapy was adjusted on June 27 to SUL-DUR (2 g, every 6 hours) combined with aztreonam (2 g, every 8 hours). To ensure synergistic concentrations, both agents were administered simultaneously via dual-channel intravenous infusion and the infusion time was more than 2 hours. Within 72 hours, the rechecked bedside chest X-ray shows little difference from the previous result (Figure 1C), but PaO2/FiO2 rose to 296 mmHg. The patient tolerated periods off mechanical ventilation, maintaining saturation of peripheral oxygen (SpO2) >95% on high-flow oxygen. Besides, by day 7 of the regimen (July 3), with the normalization of both WBC and PCT and a negative BALF culture result, all antibiotics were discontinued. Notably, no emergence of significant liver or kidney injury was observed throughout the course of this antibiotic regimen. Following successful extubation on July 5 under low-flow oxygen, the patient was transferred to a rehabilitation facility and discharged home 2 weeks later. During the follow-up assessment at 2 months, he reported feeling well. Assessment revealed resolved pulmonary inflammation on chest computed tomography (CT) (Figure 1D) and an oxygen saturation of above 95% on room air. A schematic summary of the overall patient management and key events is provided in Figure 2.

Table 1

Antibiotic sensitivity test of A. baumannii and Enterobacter hormaechei in BALF culture

Antibiotic A. baumannii Enterobacter hormaechei
MIC (μg/mL) Sensitivity MIC (μg/mL)/KB (mm) Sensitivity
Cefoperazone-sulbactam ≥64 Resistant – –
Cefepime ≥32 Resistant ≥64 Resistant
Ceftazidime ≥64 Resistant ≥64 Resistant
Cephazolin – – ≥64 Resistant
Ciprofloxacin ≥4 Resistant ≥4 Resistant
Imipenem ≥16 Resistant ≥16 Resistant
Meropenem ≥16 Resistant ≥16 Resistant
Levofloxacin ≥8 Resistant ≥8 Resistant
Amikacin – – ≤2 Susceptible
Piperacillin-tazobactam ≥128 Resistant ≥128 Resistant
Tobramycin ≥16 Resistant ≤1 Susceptible
Bactrim ≥320 Resistant ≤20 Susceptible
Tigecycline 1 Susceptible – –
Polymyxin ≤0.5 Susceptible – –
Ticarcillin-clavulanate ≥128 Resistant – –
Minocycline 8 Intermediate – –
Doxycycline ≥16 Resistant – –
Eravacycline 0.19 Susceptible 0.25 Susceptible
Ampicillin – – ≥32 Resistant
Aztreonam – – 8 Intermediate
Ceftazidime-avibactam – – 15† Resistant

†, the susceptibility testing method for ceftazidime-avibactam is the KB method. A. baumannii, Acinetobacter baumannii; BALF, bronchoalveolar lavage fluid; KB, Kirby-Bauer; MIC, minimum inhibitory concentration.

Figure 2 Timeline of the use of antibiotics and important events in the patient’s hospital course. BALF, bronchoalveolar lavage fluid; CRAB, carbapenem-resistant Acinetobacter baumannii; CRE, carbapenem-resistant Enterobacterales; CRRT, continuous renal replacement therapy; FiO2, fraction of inspired oxygen; NGS, next-generation sequencing; PaO2, partial pressure of oxygen; SUL-DUR, sulbactam-durlobactam; VV-ECMO, veno-venous extracorporeal membrane oxygenation.

Discussion

SUL-DUR is a β-lactam/β-lactamase inhibitor combination specifically targeting CRAB. Sulbactam inhibits penicillin-binding protein 2 (PBP2) in A. baumannii and functions as a classical β-lactamase inhibitor, while durlobactam, a novel diazabicyclooctane, potently inhibits OXA-type carbapenemases, restoring activity against multidrug-resistant/extensively drug-resistant (MDR/XDR) strains (4). The ATTACK trial demonstrated SUL-DUR’s efficacy and safety (combined with imipenem-cilastatin background therapy) for CRAB-associated hospital-acquired and ventilator-associated bacterial pneumonia (5). Besides, clinical data from real-world cases support its efficacy in CRAB pneumonia, meningitis, and bacteremia (6-8).

Coinfection with CRAB and MBL-producing CRE presents high resistance and virulence, with limited therapeutic options and poor outcomes. Both pathogens in this case were supposed to be hospital-acquired. CRAB emerged in later sputum cultures but was absent on initial NGS; Enterobacter hormaechei identified by NGS initially showed no resistant phenotype. Subsequent carbapenem exposure likely imposed selection pressure (9), and co-production of extended-spectrum β-lactamases (ESBLs) or AmpC enzymes, combined with porin loss or alteration under cephalosporin pressure, can further reduce carbapenem susceptibility (10). We hypothesize that SUL-DUR mitigates this selection pressure via bactericidal activity against Enterobacterales and protects aztreonam by inhibiting ESBLs and AmpC enzymes.

The synergy between SUL-DUR and aztreonam was central to treatment success. Aztreonam remains stable against MBLs but is susceptible to hydrolysis by ESBLs and AmpC enzymes. While avibactam protects aztreonam from such enzymes (11,12), the coexistence of MBLs with resistant serine β-lactamases [e.g., Klebsiella pneumoniae carbapenemase (KPC) variants] may compromise efficacy (13). Furthermore, most NDM-producing strains co-express ESBLs and AmpC enzymes (14,15). As a β-lactam/β-lactamase inhibitor combination with potent activity against a broad spectrum of serine β-lactamases, SUL-DUR can effectively shield aztreonam from enzymatic degradation and shows superior β-lactamase inhibition compared to avibactam (4,16,17).

Notably, aztreonam exerts its anti-NDM-producing activity by inhibiting PBP3. However, there are increasing reports of NDM-producing Escherichia coli carrying insertions in PBP3 (18,19), which significantly reduces the susceptibility of aztreonam (20). In contrast, durlobactam is stable to hydrolysis by β-lactamases such as cephamycin AmpC beta-lactamases (CMY) and NDM, and possesses intrinsic in vitro activity against Enterobacteriaceae via PBP2 inhibition. This mechanism allows durlobactam to exert potent antibacterial activity even against aztreonam-resistant Enterobacteriaceae strains.

In recent years, several novel antibiotics targeting Gram-negative bacteria, especially MDR pathogens, have entered clinical use. Agents such as ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam have expanded therapeutic options for MDR infections (21). More recently, cefiderocol, cefepime/enmetazobactam, avibactam/aztreonam, and sulbactam/durlobactam have been added to the clinical armamentarium, particularly for infections caused by MBLs-producing Gram-negative bacteria (22,23). Numerous combination regimens are currently under investigation for in vitro activity against both serine-β-lactamases and MBLs. Given the complexity of resistance mechanisms and the limited clinical efficacy data for many novel agents, rational combination therapy represents a prudent approach for managing MDR Gram-negative infections.

Supporting this strategy, Koenig et al. used a broth disk elution assay to evaluate SUL-DUR combined with aztreonam against CRAB and observed no antagonism (24). Another study verified that SUL-DUR has no antagonistic interactions with 17 other antimicrobials (e.g., ciprofloxacin, vancomycin, fluconazole), confirming its safety in combination regimens (25). In vitro studies also indicate synergistic potential when aztreonam is paired with relebactam against Enterobacterales, a finding corroborated by a clinical report from Pipitò et al., in which imipenem/relebactam plus aztreonam successfully treated an MDR Klebsiella pneumoniae sternal infection (26-28). Consistent with this evidence, SUL-DUR was used to protect aztreonam from hydrolysis in the present case.

Notably, resistance to SUL-DUR can emerge, mainly via substitutions in the PBP3 determinant (typically near the active serine site S336 or sulbactam-binding domain) or MBL production (29-31). Nevertheless, combining SUL-DUR with aztreonam may help circumvent these resistance mechanisms.

The “dual-channel simultaneous extended infusion” strategy ensured both drugs reached and maintained synergistic therapeutic concentrations at the infection site. In a study on the treatment of NDM plus OXA48-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, ceftazidime/avibactam was administered first, followed by supplementary aztreonam. The resulting pharmacokinetic/pharmacodynamic indices exceeded those required for optimal bactericidal activity, and the regimen also suppressed the emergence of drug resistance (32). In addition, extending the infusion duration of β-lactam antibiotics prolongs the time the drug concentration remains above the minimum inhibitory concentration, thereby enhancing antibacterial efficacy (33,34). Although current guidelines and literature lack explicit recommendations regarding the efficacy and safety of simultaneous infusion, and no evidence specifically supports its necessity when SUL-DUR and aztreonam are combined, the infusion strategy applied here provided crucial pharmacokinetic support for rapid infection control and likely contributed substantially to the treatment success. Further studies are warranted to investigate optimal infusion methods for this drug combination.

Within just 3 days of starting SUL-DUR plus aztreonam, the PaO2/FiO2 ratio surged from critically low levels (<50 mmHg, ECMO-dependent) to near-normal (296 mmHg), enabling ventilator weaning, reducing hemoptysis, and improving consciousness. Inflammatory markers continued to decline over 7 days (Figure 3). The 2024 IDSA guidelines recommend aztreonam combined with novel β-lactamase inhibitor combinations (e.g., ceftazidime-avibactam) for MBL-producing CRE based on AST (35). Extending this principle, the combination of SUL-DUR and aztreonam proved innovative and effective for concurrent CRAB and MBL-producing CRE infection. Notably, ECMO and CRRT provided vital organ support, creating a therapeutic window for antibiotic efficacy. As these supportive measures were discontinued 48 hours prior to antibiotic administration, their impact on the pharmacokinetics/pharmacodynamics of SUL-DUR and aztreonam was deemed negligible. This case offers valuable insights for managing lethal co-infections.

Figure 3 Trends of PCT and WBC counts. PCT, procalcitonin; SUL-DUR, sulbactam-durlobactam; WBC, white blood cell.

Patient perspective

The patient’s son: I am deeply satisfied with the treatment my father received and would like to express my sincere gratitude to all the medical staff for saving my father’s life.

Conclusions

This case report details the challenging management of an elderly, critically ill COPD patient with CRAB and CRE pulmonary coinfection. Following ECMO/CRRT support and multiple failed advanced antibiotic regimens, targeted therapy with dual-channel simultaneous infusion of SUL-DUR and aztreonam achieved rapid and significant clinical and microbiological success, saving the patient’s life. This case strongly demonstrates the potent synergistic potential of this combination. By providing complementary mechanisms, it offers a highly promising therapeutic option for CRAB and MBL-producing CRE co-infections.

Acknowledgments

We would like to acknowledge the patient and his family who gave informed consent for this publication.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-287/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-287/prf

Funding: This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (project No. 2024ZD0522702).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-287/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/acr-2025-287
Cite this article as: Yang S, Cheng Z, Liu Y, Ni L, Wei C. Successful treatment of carbapenem-resistant Acinetobacter baumannii and Enterobacterales coinfection with sulbactam-durlobactam combined with aztreonam: a case report. AME Case Rep 2026;10:57.

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