Sulbactam-durlobactam and cefepime-taniborbactam

A 61-year-old man has been in the ICU for 10 days, on mechanical ventilation after abdominal surgery. He develops fever again, the tracheal secretion becomes purulent and a new infiltrate appears on the chest radiograph. The tracheal aspirate grows carbapenem-resistant Acinetobacter baumannii. The estimated creatinine clearance by the Cockcroft-Gault formula is 70 mL/min. He has no known allergy. The ICU team asks whether sulbactam-durlobactam is an option and someone remembers another new drug, cefepime-taniborbactam. The scene is fictional and was written for teaching.

This text uses the case as a clinical reasoning scenario for students and health professionals. Sulbactam-durlobactam (brand name Xacduro) was developed specifically against the Acinetobacter baumannii-calcoaceticus complex. Cefepime-taniborbactam is a combination still under investigation, with a spectrum aimed at resistant enterobacteria and Pseudomonas aeruginosa. The two drugs differ in target, evidence and regulatory status. The text does not replace the susceptibility report, the infection control committee or your institution's protocol. If you play the case of the day on NEXO, you will recognize the challenge: deciding with clues that arrive in sequence.

Key points

• The FDA approved Xacduro on May 23, 2023 for hospital-acquired pneumonia and ventilator-associated pneumonia caused by susceptible isolates of the A. baumannii-calcoaceticus complex, in patients aged 18 years or older.
• The dose is 1 g of sulbactam and 1 g of durlobactam every 6 hours, as a 3-hour infusion, with creatinine clearance of 45 to 129 mL/min, for 7 to 14 days.
• In the phase 3 study, 28-day mortality was 19.0 percent with sulbactam-durlobactam and 32.3 percent with colistin.
• Durlobactam does not inhibit class B metallo-beta-lactamases, and Xacduro is not active against isolates that produce them.
• Cefepime-taniborbactam received a complete response letter from the FDA in February 2024 and, as of October 2026, was not among the FDA's new approvals; it remains unapproved in the United States.
• The Brazilian guideline recommends combining two antimicrobials with in vitro activity against carbapenem-resistant A. baumannii.

Why this is a reasoning scenario

Ventilator-associated pneumonia caused by resistant Acinetobacter is one of the hardest problems in the ICU. Traditional options, such as polymyxins, have kidney toxicity and poor results (Shields and colleagues, 2023). The arrival of new drugs raises practical questions: when to use them, at what dose, with which other antibiotic and what to do when kidney function changes.

The scenario is good for training because it brings together microbiology, pharmacology and clinical decision-making. You need to tell colonization from infection, read the susceptibility report, know the spectrum of each combination and adjust the dose by creatinine clearance. The post on differential diagnosis helps you think about other causes of fever in the ICU, and the post on sepsis in nursing triage reminds you of the value of time to antibiotic.

What the scene teaches

The scene trains six habits. The first is deciding whether the isolate represents infection or colonization. The second is confirming the susceptibility of the isolate. The third is knowing the approved indication. The fourth is calculating the dose by creatinine clearance. The fifth is thinking about coverage for other germs. The sixth is monitoring adverse effects and reassessing the duration.

What is not at stake

The text does not discuss every option against Acinetobacter or the full management of pneumonia in the ICU. The final choice depends on the susceptibility report, on availability and on the infectious diseases team. The post on clinical decision-making helps you think about the sequence of tests.

Carbapenem-resistant Acinetobacter: the problem

Carbapenem-resistant A. baumannii brings long hospital stays, more deaths, more ICU admissions and more readmissions (Boutzoukas and Doi, 2025). In a review, the associated mortality reached 70 percent, against 25 percent with susceptible strains (Boutzoukas and Doi, 2025). International clones 1 and 2 predominate worldwide, but Latin America has its own epidemiology, with clones 4 and 5 frequent (Boutzoukas and Doi, 2025).

The scenario in Brazil

The guideline from the Brazilian Society of Infectious Diseases cites the 2023 Anvisa report: Acinetobacter spp. was the fourth most isolated germ in central catheter-related bloodstream infections in adult ICUs, with 2428 isolates, and had the highest carbapenem resistance rate, of 78.8 percent (Zavascki and colleagues, 2025). In a study at 14 Brazilian hospitals, carbapenem-resistant A. baumannii accounted for 9.8 percent of bloodstream infection isolates (Zavascki and colleagues, 2025).

Why it is so hard to treat

All strains of A. baumannii have a chromosomal AmpC beta-lactamase, and many acquire other enzymes (Kubin and colleagues, 2025). In a series cited in a review, most resistant isolates had an acquired carbapenemase gene (Kubin and colleagues, 2025). Resistance mechanisms include beta-lactamases, altered penicillin-binding proteins (PBPs), efflux pumps and loss of porins (US Xacduro label, 5/2023). As a result, few antibiotics keep activity, and several of them are toxic.

Infection or colonization

Telling infection from colonization is one of the biggest challenges with this germ (Shields and colleagues, 2023). In ventilated patients, Acinetobacter may be in the secretion without causing pneumonia. In the patient in the scene, new fever, purulent secretion and a new infiltrate support pneumonia. The post about diagnostic uncertainty helps decide when the data are incomplete.

Sulbactam-durlobactam: how it works and what ATTACK showed

Sulbactam is a beta-lactam with its own activity against Acinetobacter, because it inhibits the penicillin-binding proteins PBP1 and PBP3, needed to build the bacterial wall (McLeod and colleagues, 2024). The problem is that many current beta-lactamases degrade sulbactam (McLeod and colleagues, 2024). Durlobactam is a diazabicyclooctane beta-lactamase inhibitor, without a beta-lactam ring, that protects sulbactam from several serine beta-lactamases (US Xacduro label, 5/2023). Durlobactam alone has no activity against these isolates (US Xacduro label, 5/2023).

Spectrum and limits

Xacduro showed in vitro activity against isolates that produce Ambler class A, C and D enzymes, including KPC and OXA-type enzymes (US Xacduro label, 5/2023). It is not active against isolates that produce class B metallo-beta-lactamases nor against those with alteration of the sulbactam target site in the PBPs (US Xacduro label, 5/2023). In laboratory series, more than 96 percent of carbapenem- and colistin-resistant isolates were susceptible to sulbactam-durlobactam (Pogue and colleagues, 2025). Production of the metallo-beta-lactamase NDM-1 is one of the described resistance mechanisms (Pogue and colleagues, 2025). Mutations near the active site of PBP3 were also found in resistant mutants (McLeod and colleagues, 2024).

The ATTACK study

In the phase 3 study, 177 adults with infection by the A. baumannii-calcoaceticus complex were randomized to sulbactam-durlobactam (91) or colistin (86) (US Xacduro label, 5/2023). Both groups also received imipenem-cilastatin 1 g every 6 hours, to cover other pathogens of hospital-acquired pneumonia (US Xacduro label, 5/2023). In the main population, with infection confirmed by a carbapenem-resistant isolate, 28-day mortality was 12 of 63 patients (19.0 percent) with sulbactam-durlobactam and 20 of 62 (32.3 percent) with colistin, and the drug was considered non-inferior (US Xacduro label, 5/2023). Clinical cure was 61.9 percent with sulbactam-durlobactam and 40.3 percent with colistin (US Xacduro label, 5/2023).

In the analyzed population, 75 percent were on mechanical ventilation, 53 percent had ventilator-associated pneumonia and the mean age was 63 years (US Xacduro label, 5/2023). A review highlights the lower rate of acute kidney injury by RIFLE criteria with sulbactam-durlobactam, 13 versus 38 percent (Pogue and colleagues, 2025). The authors note that the study was small and that other clinical trials are lacking (Pogue and colleagues, 2025).

What the guidelines say

A review reports that the most recent IDSA guidance recommends sulbactam-durlobactam as the preferred option where it is available (Iovleva and colleagues, 2025). IDSA and ESCMID recommend at least two agents with in vitro activity for severe infections by carbapenem-resistant A. baumannii (Iovleva and colleagues, 2025). The Brazilian guideline also recommends combining two antimicrobials with in vitro activity (Zavascki and colleagues, 2025). For sulbactam in ampicillin-sulbactam, a review considers it preferable to use optimized doses of at least 6 g per day of sulbactam, in combination (Shields and colleagues, 2023).

Regulatory status: FDA and other agencies

United States. The FDA approved Xacduro on May 23, 2023, under NDA 216974, as a new molecular entity and new combination, with priority review (Drugs@FDA, NDA 216974). The indication is for patients aged 18 years or older with hospital-acquired or ventilator-associated bacterial pneumonia caused by susceptible isolates of the A. baumannii-calcoaceticus complex (US Xacduro label, 5/2023). Xacduro is not indicated for pneumonia caused by other pathogens (US Xacduro label, 5/2023).

Cefepime-taniborbactam. In a statement dated February 23, 2024, Venatorx and Melinta reported that the FDA issued a complete response letter on the marketing application for cefepime-taniborbactam for complicated urinary tract infection, including pyelonephritis (Venatorx and Melinta statement, 2024). The letter did not point to safety or clinical efficacy problems and did not request new clinical studies; the FDA requested additional chemistry, manufacturing and controls data (Venatorx and Melinta statement, 2024). In the same statement, the combination is described as investigational, with FDA QIDP and Fast Track designations (Venatorx and Melinta statement, 2024). We found no later statement from Venatorx or Melinta. In the half-year report published on August 19, 2026, Everest Medicines, Venatorx's partner in Asia, still lists the combination in its development portfolio, at a stage before the marketing application in its territories, without indicating approval in the United States (Everest Medicines half-year report, 08/19/2026). The FDA list of new approvals for 2026, updated on October 20, 2026, does not include taniborbactam (FDA list of new approvals in 2026). Be careful not to confuse it: cefepime-zidebactam, another combination with cefepime, appears on that list, but it is a different product (FDA list of new approvals in 2026).

Other countries. This text describes only the situation in the United States, checked against primary sources. The indication and access in other countries depend on the local agency, and it is worth checking the registration and availability before use.

Contraindication and warnings

The US label lists one contraindication and some main warnings (US Xacduro label, 5/2023):

• Contraindication: history of severe hypersensitivity to sulbactam, durlobactam or other beta-lactams.
• Severe and sometimes fatal hypersensitivity reactions can occur; there was a case of anaphylactic shock in the study.
• Clostridioides difficile-associated diarrhea should be investigated if diarrhea occurs.
• Concomitant use of OAT1 transporter inhibitors, such as probenecid, is not recommended.

Dose, kidney function and preparation

The recommended dose is 1 g of sulbactam and 1 g of durlobactam every 6 hours, as a 3-hour intravenous infusion, in adults with creatinine clearance of 45 to 129 mL/min (US Xacduro prescribing information, 5/2023). The recommended duration is 7 to 14 days, guided by clinical course (US Xacduro prescribing information, 5/2023). The table summarizes the adjustments for kidney function.

Creatinine clearance (mL/min)	Frequency of 1 g of sulbactam and 1 g of durlobactam	Source
130 or more	Every 4 hours	(US Xacduro prescribing information, 5/2023)
45 to 129	Every 6 hours	(US Xacduro prescribing information, 5/2023)
30 to 44	Every 8 hours	(US Xacduro prescribing information, 5/2023)
15 to 29	Every 12 hours	(US Xacduro prescribing information, 5/2023)
Less than 15, at initiation	Every 12 hours for the first 3 doses, then every 24 hours	(US Xacduro prescribing information, 5/2023)
Drop to less than 15 during use	Every 24 hours	(US Xacduro prescribing information, 5/2023)

Creatinine clearance is estimated with the Cockcroft-Gault formula (US Xacduro prescribing information, 5/2023). On intermittent hemodialysis, the dose should be given after the end of the session (US Xacduro prescribing information, 5/2023). In patients with fluctuating kidney function, the prescribing information calls for monitoring clearance and adjusting the dose (US Xacduro prescribing information, 5/2023).

Applying it to the patient

With a clearance of 70 mL/min, the patient in the scene would receive 1 g of each component every 6 hours, over 3 hours. If clearance fell to 35 mL/min, the interval would become 8 hours. If he developed increased clearance, of 130 or more, the interval would fall to 4 hours. In the ICU, kidney function changes fast, and it is worth recalculating clearance every day. The post about diagnostic pause reminds you to check the dose before every change.

Preparation and kit

Xacduro comes in a kit with one 1 g vial of sulbactam and two 0.5 g vials of durlobactam (US Xacduro prescribing information, 5/2023). Dilution must occur within 1 hour of reconstitution (US Xacduro prescribing information, 5/2023). The vials are stored in a refrigerator, between 2 and 8 °C, and must not be frozen (US Xacduro prescribing information, 5/2023). The pharmacy needs to prepare each dose in advance, because the infusion lasts 3 hours and repeats every 6 hours. The post about interprofessional clinical reasoning shows why pharmacy and nursing are part of this decision.

Adverse effects

In the phase 3 study, serious adverse effects occurred in 40 percent with sulbactam-durlobactam and in 49 percent with colistin (US Xacduro prescribing information, 5/2023). Discontinuation due to an adverse effect occurred in 11 and 16 percent (US Xacduro prescribing information, 5/2023). The most common effects, above 10 percent, were changes in liver tests, diarrhea, anemia and low potassium (US Xacduro prescribing information, 5/2023). The list below compares selected effects.

• Changes in liver tests: 19 percent with sulbactam-durlobactam and 21 percent with colistin.
• Diarrhea: 17 and 11 percent.
• Anemia: 13 and 14 percent.
• Low potassium: 12 and 11 percent.
• Acute kidney injury: 6 and 36 percent.

Source of the list: (US Xacduro prescribing information, 5/2023). For the patient in the scene, it is worth ordering liver function tests, a complete blood count, potassium and creatinine during treatment.

Older adults

In the phase 3 study, 54 percent of patients treated with Xacduro were 65 or older (US Xacduro prescribing information, 5/2023). Because the drug is eliminated mainly by the kidneys, the prescribing information directs adjusting the dose in older adults for kidney function (US Xacduro prescribing information, 5/2023).

Cefepime-taniborbactam: what is known

Taniborbactam is a beta-lactamase inhibitor with potent activity against Ambler class A, B, C and D enzymes (Rodvold et al., 2025). This includes metallo-beta-lactamases, which durlobactam does not cover. Combined with cefepime, a fourth-generation cephalosporin, it is under study for infections caused by multidrug-resistant gram-negative bacteria (Rodvold et al., 2025). The companies' press release names extended-spectrum beta-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales and multidrug-resistant P. aeruginosa as the main targets (Venatorx and Melinta press release, 2024).

The CERTAIN-1 study

CERTAIN-1 was a phase 3, randomized, double-blind study in adults with complicated urinary tract infection (Moeck et al., 2024). Cefepime-taniborbactam was superior to meropenem on the composite endpoint of microbiological and clinical success at the test-of-cure visit (Moeck et al., 2024). In the analysis by resistance profile, patients with bacteria carrying serine carbapenemases, such as KPC-3 and OXA-48, had composite success in 5 of 6 and clinical success in all; the 3 patients with metallo-beta-lactamases had composite success (Moeck et al., 2024). These are small numbers, which show activity but do not allow firm conclusions about these subgroups.

Pharmacokinetics in the kidneys and the lung

Cefepime and taniborbactam are eliminated mainly in the urine, and renal function affects both in the same way (Dowell et al., 2022). With an eGFR of 30 to 59, clearance of both fell by 63 percent; below 30, it fell by 78 percent for cefepime and 81 percent for taniborbactam (Dowell et al., 2022). In a study in healthy volunteers, with 2 g of cefepime and 0.5 g of taniborbactam infused over 4 hours every 8 hours, both components reached the epithelial lining fluid of the lung (Rodvold et al., 2025). The ratio of lung fluid to free plasma ranged from 0.197 to 0.373 for cefepime and from 0.153 to 0.253 for taniborbactam (Rodvold et al., 2025). This regimen is investigational and is not an approved dose.

Why it does not serve the patient in the scene

As of the October 24, 2026 visit, cefepime-taniborbactam had no FDA approval (list of new FDA approvals in 2026). Everest still presented it as a product in development in August 2026 (Everest Medicines half-year report, 08/19/2026). Before any use, check the current status with the FDA. In addition, the main study was in urinary tract infection, not in pneumonia caused by Acinetobacter (Moeck et al., 2024). For the patient in the scene, the option with an approved indication in the United States is sulbactam-durlobactam, if the isolate is susceptible (US Xacduro prescribing information, 5/2023). Knowing how to tell the two drugs apart avoids confusion at handover.

What the comparison teaches

The two drugs illustrate the same idea: a new beta-lactamase inhibitor protects an old beta-lactam. The target of each one, however, is different. Durlobactam protects sulbactam against class A, C and D enzymes in Acinetobacter (US Xacduro prescribing information, 5/2023). Taniborbactam protects cefepime also against metallo-beta-lactamases, with a focus on Enterobacterales and Pseudomonas (Rodvold et al., 2025). Asking the laboratory for the resistance mechanism, when available, helps with the choice.

When the patient worsens

If the patient in the scene worsens despite treatment, it is worth repeating cultures, reviewing susceptibility and looking for other foci. If diarrhea appears, C. difficile must be investigated (US Xacduro prescribing information, 5/2023). If rash or hypotension appears soon after the infusion, consider hypersensitivity (US Xacduro prescribing information, 5/2023). The post about clinical deterioration on the ward shows how to escalate when vital signs change.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by looking for the ICD-10 code. Resistant Acinetobacter pneumonia is a good exercise because an antibiogram, a creatinine clearance or a resistance enzyme change the management. The post about case-based learning in clinical practice explains why this format fixes knowledge, and the post about simulated patient care shows how to train the handover.

Three exercises with cases

Change the renal function. State the dosing frequency if clearance fell to 20 mL/min.

Change the enzyme. State what to expect from Xacduro if the isolate produced NDM.

Change the organism. State why Xacduro would not work if the organism were resistant Klebsiella pneumoniae.

The limits on use of the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information on Curator and on Creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Is Xacduro effective against any resistant gram-negative?

No. The indication is only for hospital-acquired or ventilator-associated pneumonia caused by susceptible isolates of the A. baumannii-calcoaceticus complex (US Xacduro label, 5/2023).

What is the usual dose?

1 g of sulbactam and 1 g of durlobactam every 6 hours, over 3 hours, with clearance of 45 to 129 mL/min (US Xacduro label, 5/2023).

Does it need another antibiotic alongside?

In the study, patients also received imipenem-cilastatin for other organisms (US Xacduro label, 5/2023). The guidelines cited recommend two active agents in severe infections (Iovleva and colleagues, 2025).

Can cefepime-taniborbactam already be used?

In February 2024, the FDA issued a complete response letter (Venatorx and Melinta statement, 2024). As of October 20, 2026, the combination was not among the FDA new approvals (list of FDA new approvals in 2026), and Everest listed it in August 2026 as a product in development (Everest Medicines half-year report, 08/19/2026). Check the current status before use.

For how long should treatment last?

7 to 14 days, guided by the clinical course (US Xacduro label, 5/2023).

Final checklist

• I distinguished infection from colonization using clinical and imaging data.
• I confirmed the isolate and its susceptibility to sulbactam-durlobactam.
• I asked about metallo-beta-lactamases, which remove the activity of Xacduro.
• I calculated creatinine clearance by Cockcroft-Gault and chose the interval.
• I scheduled 3-hour infusions and the preparation with the pharmacy.
• I considered coverage of other organisms and the second active agent.
• I requested liver function tests, blood count, potassium and creatinine during treatment.
• I reviewed the 7 to 14 day duration.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Boutzoukas A, Doi Y. The global epidemiology of carbapenem-resistant Acinetobacter baumannii. JAC Antimicrob Resist. 2025. PMID 40735512.
2. Dowell JA, Marbury TC, Smith WB, et al. Safety and Pharmacokinetics of Taniborbactam (VNRX-5133) with Cefepime in Subjects with Various Degrees of Renal Impairment. Antimicrob Agents Chemother. 2022. PMID 35920662.
3. Entasis Therapeutics. XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use. Prescribing Information. Revised 5/2023. Accessed 10/24/2026. Official source.
4. Iovleva A, Fowler VG Jr, Doi Y. Treatment Approaches for Carbapenem-Resistant Acinetobacter baumannii Infections. Drugs. 2025. PMID 39607595.
5. Kubin CJ, Garzia C, Uhlemann A-C. Acinetobacter baumannii treatment strategies: a review of therapeutic challenges and considerations. Antimicrob Agents Chemother. 2025. PMID 40631987.
6. McLeod SM, O'Donnell JP, Narayanan N, et al. Sulbactam-durlobactam: a β-lactam/β-lactamase inhibitor combination targeting Acinetobacter baumannii. Future Microbiol. 2024. PMID 38426849.
7. Moeck G, Gasink LB, Mendes RE, et al. Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection. Antimicrob Agents Chemother. 2024. PMID 38780262.
8. Pogue JM, Harrington J, Wangchinda W, et al. New Perspectives on Antimicrobial Agents: Sulbactam-durlobactam. Antimicrob Agents Chemother. 2025. PMID 40844462.
9. Rodvold KA, Gotfried MH, Sabato P, et al. Plasma and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult participants. Antimicrob Agents Chemother. 2025. PMID 40476839.
10. Shields RK, Paterson DL, Tamma PD. Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections. Clin Infect Dis. 2023. PMID 37125467.
11. U.S. Food and Drug Administration. Drugs@FDA: FDA-Approved Drugs. NDA 216974, Xacduro. Accessed on 10/24/2026. Official source.
12. Venatorx Pharmaceuticals, Melinta Therapeutics. Venatorx and Melinta Provide Update on Status of U.S. New Drug Application for Cefepime-Taniborbactam. Business Wire. 02/23/2024. Accessed on 10/24/2026. Official source.
13. Everest Medicines Limited. INTERIM RESULTS ANNOUNCEMENT FOR THE SIX MONTHS ENDED 30 JUNE 2026. HKEXnews. 08/19/2026. Accessed on 10/24/2026. Official source.
14. U.S. Food and Drug Administration. Novel Drug Approvals for 2026. Updated on 10/20/2026. Accessed on 10/24/2026. Official source.
15. Zavascki AP, Chebabo A, Cunha CA, et al. Guideline for antimicrobial treatment of multidrug-resistant Gram-negative infections: practice recommendations of the Brazilian Society of Infectious Diseases. Braz J Infect Dis. 2025. PMID 41130038.