Why Acinetobacter Infections Are So Dangerous

A Hospital Organism

Acinetobacter baumannii is a gram-negative bacterium that thrives in hospital environments. It can survive on dry surfaces for long periods, spread through contact with contaminated equipment, and colonize patients who are on ventilators or have invasive lines. Pneumonia is one of its most common serious infections.

Resistance Leaves Few Options

Acinetobacter frequently resists many classes of antibiotics. Carbapenem-resistant strains are especially difficult, because carbapenems are often the default choice for serious gram-negative infections. When these options fail, clinicians may rely on older agents such as colistin, which carry significant toxicity.

High Stakes

Patients with Acinetobacter pneumonia are often critically ill, on mechanical ventilation, and have multiple underlying conditions. Mortality is high, which is why new targeted options matter.

Key Takeaways

• Xacduro (sulbactam/durlobactam) received FDA approval on May 23, 2023, for adults 18 and older with HABP and VABP caused by susceptible Acinetobacter baumannii-calcoaceticus complex.
• It combines sulbactam with durlobactam, a beta-lactamase inhibitor that protects sulbactam from Acinetobacter enzymes.
• In the ATTACK trial, sulbactam/durlobactam met noninferiority to colistin for 28-day all-cause mortality in carbapenem-resistant Acinetobacter infections.
• The label is limited to susceptible Acinetobacter causing HABP or VABP. It is not approved for other pathogens.
• Resistance is uncommon in tested isolates overall but is reported in strains producing metallo-beta-lactamases.
• The drug is given by IV infusion in hospital settings, and dosing must account for kidney function.

What Is Xacduro

Brand and Components

Xacduro is the brand name for sulbactam for injection and durlobactam for injection, co-packaged for intravenous use. The product was developed by Entasis Therapeutics and is now marketed by Innoviva Specialty Therapeutics. The two components are supplied together and given as one regimen.

Drug Class

Sulbactam is a beta-lactam with its own activity against Acinetobacter, and it is also a beta-lactamase inhibitor. Durlobactam is a diazabicyclooctane beta-lactamase inhibitor that is not used on its own for infections.

Dosage Form

Xacduro is not a tablet. It is given by intravenous infusion in hospital or intensive care settings, where staff can monitor patients closely.

FDA Approval: May 23, 2023

The Decision

The FDA approved Xacduro on May 23, 2023, for adults 18 and older with HABP and VABP caused by susceptible Acinetobacter baumannii-calcoaceticus complex. The approval was announced the same day by the sponsor.

Advisory Committee Support

The FDA's Antimicrobial Drugs Advisory Committee voted 12 to 0 in favor of the application in April 2023, before the final decision.

Basis for Approval

Approval rested on the ATTACK phase 3 trial, which compared sulbactam/durlobactam with colistin. The FDA's review document noted that the trial was a single randomized, assessor-blinded, active-controlled study, and that a prespecified 20 percent noninferiority margin was used for 28-day all-cause mortality.

Why a Single Trial Mattered

Approval based on one pivotal trial is unusual. The FDA considered the unmet medical need, the small population of patients with carbapenem-resistant Acinetobacter, and the trial's design when making its decision.

How Sulbactam and Durlobactam Work Together

The Core Problem

Acinetobacter produces beta-lactamase enzymes, including class A, class C, and class D enzymes, that break down many beta-lactam antibiotics. Sulbactam is vulnerable to some of these enzymes, which limits its usefulness on its own.

Protection by Durlobactam

Durlobactam inhibits many of the beta-lactamases that threaten sulbactam, including class A and class C enzymes and some class D enzymes. Protecting sulbactam allows it to reach its bacterial targets.

The Result

Together, the two components restore activity against many carbapenem-resistant Acinetobacter strains. Because enzyme profiles vary, susceptibility testing determines whether a specific isolate will respond.

Sulbactam: The Partner With Its Own Activity

Activity Against Acinetobacter

Sulbactam has direct activity against Acinetobacter baumannii through binding to penicillin-binding proteins involved in cell wall synthesis. This is one reason sulbactam is considered useful for Acinetobacter infections, even though it is also a beta-lactamase inhibitor.

Limits Without Protection

When Acinetobacter produces enzymes that hydrolyze sulbactam, its activity drops. This is the problem durlobactam was designed to address.

Durlobactam: Protecting Sulbactam

What It Does

Durlobactam has little direct antibacterial activity against Acinetobacter. Its job is to bind and inhibit the beta-lactamases that would otherwise destroy sulbactam, so the sulbactam can act.

Enzyme Coverage

Durlobactam inhibits many class A and class C beta-lactamases and some class D enzymes. It does not inhibit metallo-beta-lactamases, which is why resistance is reported in strains that produce them.

Why It Is Co-Packaged

The two components are supplied together so that the protective inhibitor is always given with the partner antibiotic in the correct ratio.

Which Bacteria It Targets

Labeled Organisms

The label is limited to HABP and VABP caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. Susceptibility is determined by laboratory testing for each isolate.

Other Organisms Not Covered

The drug is not indicated for other pathogens. Pseudomonas aeruginosa, Klebsiella pneumoniae, and other gram-negative or gram-positive organisms are not covered by the labeled indication, even though other antibiotics may treat them.

Resistance Patterns

Reported resistance to sulbactam/durlobactam is low in tested Acinetobacter isolates overall, but strains producing metallo-beta-lactamases are reported as resistant. Local resistance data and laboratory results matter.

Approved Use and Labeling Limits

Who Is Eligible

The labeled population is adults aged 18 and older with HABP or VABP caused by susceptible Acinetobacter.

Stewardship Statement

The label emphasizes using susceptibility testing to guide treatment. Empiric use should be reassessed as culture results return.

Not Approved For

The drug is not approved for other infection types or pathogens. Children are outside the labeled age range.

The ATTACK Trial: Design

Overview

ATTACK was a randomized, assessor-blinded, active-controlled phase 3 trial comparing sulbactam/durlobactam with colistin in patients with serious Acinetobacter infections. Most participants had hospital-acquired or ventilator-associated pneumonia, and some had bloodstream infections.

Population

Participants had documented carbapenem-resistant Acinetobacter infections. The trial enrolled 181 patients, randomized between the two arms.

Comparator

Colistin was the comparator because it was a common last-resort option for carbapenem-resistant Acinetobacter. Its toxicity makes it a meaningful but imperfect benchmark.

Primary Endpoint

The primary endpoint was 28-day all-cause mortality. A secondary endpoint measured clinical cure at the test-of-cure visit.

The ATTACK Trial: Results

Mortality Outcome

In the modified intention-to-treat analysis reported in the published trial, 28-day all-cause mortality was 19 percent in the sulbactam/durlobactam group (12 of 63) compared with 32 percent in the colistin group (20 of 62). The difference was minus 13.2 percentage points, with a 95 percent confidence interval of minus 30.0 to 3.5.

Noninferiority

The result met the prespecified noninferiority criterion. The FDA accepted this single-trial evidence as sufficient for approval.

Clinical Cure

The trial also showed a significant difference in clinical cure rates favoring sulbactam/durlobactam, according to the sponsor and published reports.

Serious Adverse Events

Serious adverse events were reported in fewer patients receiving sulbactam/durlobactam than colistin in the published summary, although the trial was not designed to make strong safety comparisons.

Reading the Mortality Numbers

Small Trial, Wide Uncertainty

The trial included a limited number of patients, so the confidence interval is wide. The true difference could be smaller or larger than the point estimate suggests.

Why the Population Matters

Critically ill patients with Acinetobacter pneumonia have high baseline mortality. Outcomes depend on source control, timing of treatment, underlying illness, and supportive care, not just the antibiotic.

Applying Results to One Patient

Trial averages do not predict an individual outcome. Clinicians weigh the evidence alongside the patient's condition, culture results, and available alternatives.

Clinical Cure and Other Outcomes

Clinical Response

Clinical cure reflects whether symptoms and signs of pneumonia resolved. In ATTACK, clinical cure rates were reported to favor sulbactam/durlobactam over colistin.

Microbiological Outcomes

Microbiological eradication, meaning clearance of the organism from respiratory samples or blood, is also important. Follow-up cultures help guide the duration of therapy.

Longer-Term Recovery

Survivors of severe pneumonia may face prolonged ventilation, weakness, or other complications. Rehabilitation and follow-up care matter.

Resistance and Susceptibility Testing

Why Testing Matters

Acinetobacter resistance mechanisms vary, and some strains are not susceptible to sulbactam/durlobactam. Testing the specific isolate before and during treatment is essential.

Metallo-Beta-Lactamases

Strains producing metallo-beta-lactamases are reported as resistant because durlobactam does not inhibit those enzymes. Laboratories may test for these enzymes when clinically appropriate.

Monitoring Resistance

Hospitals track Acinetobacter resistance patterns. Clinicians should review local antibiograms and infection prevention guidance when choosing therapy.

Dosing and Administration

IV Infusion

Xacduro is given by intravenous infusion in hospital settings. Pharmacists prepare the regimen according to the label, and nurses monitor the infusion.

Labeled Regimen

The labeled regimen uses fixed amounts of sulbactam and durlobactam given at set intervals. Confirm the current dose, infusion time, and duration in the prescribing information on DailyMed rather than relying on this summary.

Duration

Treatment length depends on the infection, response, and culture results. The ICU team sets the plan and reviews it daily.

Missed Doses

Hospital staff manage missed or delayed doses. Patients should not try to make up doses on their own.

Kidney Function and Dosing

Why Kidney Function Matters

Sulbactam and durlobactam are cleared by the kidneys. Reduced kidney function increases drug exposure, so the label includes dose adjustments based on kidney function.

Monitoring

Critically ill patients often have fluctuating kidney function. Clinicians check creatinine regularly and adjust doses as needed.

Dialysis

Patients on dialysis need individualized planning with nephrology and pharmacy teams.

Common Side Effects

Gastrointestinal Effects

Nausea, vomiting, and diarrhea can occur. Persistent or bloody diarrhea needs prompt evaluation because C. difficile infection can occur with nearly all antibiotics.

Infusion-Site Reactions

Pain, redness, or swelling at the IV site can occur. Nurses monitor lines and report problems.

Laboratory Changes

Changes in liver tests, blood counts, and electrolytes may occur. Care teams monitor labs during critical illness.

Serious Risks and Warnings

Hypersensitivity Reactions

Serious allergic reactions can occur with beta-lactam antibiotics. Hives, facial swelling, trouble breathing, or hypotension require immediate treatment.

C. difficile Infection

C. difficile can cause severe diarrhea and colitis. Any new or worsening diarrhea during or after treatment should be reported promptly.

Other Warnings

The current prescribing information lists additional warnings and precautions. Read the label for full details before clinical use.

Who Should Not Receive Xacduro

Known Allergy

People with a known allergy to sulbactam, durlobactam, or other beta-lactam antibiotics should not receive Xacduro without specialist review.

Infections Outside the Label

The drug is not approved for infections caused by non-Acinetobacter organisms or for infections outside HABP and VABP.

Children

The labeled population is adults 18 and older. Use in children is outside the labeled indication.

Drug Interactions

Medication Review

ICU patients often receive many medications. Give your care team a full list, including prescriptions, infusions, and supplements. Pharmacists check for interactions before starting therapy.

Nephrotoxic Drugs

Medicines that affect the kidneys deserve attention because kidney function influences dosing decisions.

How Xacduro Compares With Other Options

Colistin

Colistin was the comparator in ATTACK. It is an older last-resort agent with significant kidney and nerve toxicity. Xacduro offers a targeted alternative for susceptible Acinetobacter.

Carbapenems

Carbapenems are often first-line for gram-negative infections, but carbapenem-resistant Acinetobacter is common in some hospitals. Choice depends on susceptibility results and local patterns.

Other Newer Agents

Other newer options exist for resistant gram-negative infections. Each has its own spectrum, labeling, and safety profile, so choice depends on the organism and patient.

Care in the ICU Setting

Source and Supportive Care

Antibiotics are only one part of treating ventilator-associated pneumonia. Ventilator management, positioning, airway care, and infection prevention all matter.

Infection Prevention

Hospitals use hand hygiene, equipment cleaning, and isolation to limit Acinetobacter spread. These measures protect current and future patients.

Family Communication

Families of ICU patients should ask the team about goals of care, expected timeline, and how the antibiotic fits into the overall plan.

Antibiotic Stewardship

Culture First

Respiratory and blood cultures with susceptibility results should guide therapy. Empiric choices should be reviewed as results return.

Protecting the Drug

Because resistance can develop, Xacduro should be reserved for infections that need it. Overuse of any antibiotic accelerates resistance.

Reporting Resistance

Unexpected resistance patterns should be reported to infection prevention teams and public health authorities.

Availability and Cost

Availability

Xacduro is available through hospital pharmacies and specialty distributors. Availability depends on the facility, so the care team can confirm stock.

Cost

Xacduro is a branded specialty antibiotic and is expensive. Costs are usually bundled into the hospital stay. Ask the hospital financial counselor or insurer for current figures.

Coverage

Coverage for FDA-approved indications is generally more straightforward. Prior authorization may be required, and pharmacy staff can help.

Pregnancy, Breastfeeding, and Children

Pregnancy

Pregnant patients with pneumonia need urgent evaluation. Decisions about Xacduro should involve obstetric and infectious disease teams, weighing benefits against limited data.

Breastfeeding

Discuss breastfeeding with the care team before treatment.

Children

The labeled population is adults 18 and older. Use in children requires specialist judgment outside the label.

Questions to Ask Your Care Team

• Did the culture identify Acinetobacter, and is the isolate susceptible to sulbactam/durlobactam?
• Why was this drug chosen over other options, including colistin or a carbapenem?
• How will kidney function be monitored and the dose adjusted?
• What signs of allergy or diarrhea should be reported right away?
• How will the team decide when to stop treatment?

Frequently Asked Questions

Q: What is Xacduro used for?

A: Xacduro is approved for adults 18 and older with hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Acinetobacter.

Q: When was it approved?

A: The FDA approved it on May 23, 2023.

Q: Is Xacduro a pill?

A: No. It is given only by intravenous infusion in hospital settings.

Q: How well did it work in the main trial?

A: In ATTACK, 28-day all-cause mortality was 19 percent with sulbactam/durlobactam and 32 percent with colistin in the published analysis. The drug met noninferiority, but the trial was small.

Q: Does it treat other bacteria?

A: No. The label is limited to susceptible Acinetobacter causing HABP or VABP.

Q: Can Acinetobacter become resistant to it?

A: Yes. Resistance is uncommon in tested isolates overall but is reported in strains producing metallo-beta-lactamases. Testing is essential.

Q: Who should not receive it?

A: People with a known allergy to sulbactam, durlobactam, or other beta-lactams should not receive it without specialist review.

Medical Disclaimer

This article is for general education only and does not provide medical advice, diagnosis, or treatment. Pneumonia acquired in hospital is a serious condition managed by critical care and infectious disease teams. Do not start, stop, or change any antibiotic without guidance from your care team. For dosing, warnings, and interactions, consult the current U.S. prescribing information on DailyMed. If you or a family member has trouble breathing, fever with chills, confusion, or low blood pressure, seek emergency care immediately.

Sources and Further Reading

• U.S. FDA approval of Xacduro (sulbactam and durlobactam), May 23, 2023, and FDA press announcement on the approval
• Innoviva Specialty Therapeutics announcement of FDA approval, May 23, 2023
• FDA integrated review of NDA 216974 (Xacduro), May 22, 2023
• ATTACK trial (NCT03894046): Efficacy and safety of sulbactam-durlobactam versus colistin for serious infections caused by Acinetobacter baumannii-calcoaceticus complex, The Lancet Infectious Diseases, 2023
• Advisory committee vote summaries from the FDA Antimicrobial Drugs Advisory Committee, April 2023
• Xacduro U.S. Prescribing Information, including dosing, warnings, and renal guidance

This article reflects information available as of October 2026. Confirm current prescribing details with your healthcare provider and the latest FDA labeling. For more on MyOnlineMedShop, visit our blog or contact us.