Sulbactam and Durlobactam (Monograph)

Brand name: Xacduro
Drug class: Other Miscellaneous Antibacterials

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

Antibacterial; combination of sulbactam (a β-lactam antibacterial and β-lactamase inhibitor) and durlobactam (a β-lactamase inhibitor).

Uses for Sulbactam and Durlobactam

Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

Treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex in adults. Not recommended for treatment of HABP/VABP caused by other pathogens.

Guidelines published by the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend empiric coverage for Staphylococcus aureus in patients with clinically suspected HABP. For patients with clinically suspected VABP, empiric coverage for Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli is recommended. IDSA suggests a sulbactam-containing agent for the treatment of carbapenem-resistant Acinetobacter baumannii-calcoaceticus (CRABC) infections. Sulbactam/durlobactam, in combination with a carbapenem, is recommended as the preferred regimen.

Sulbactam and Durlobactam Dosage and Administration

General

Pretreatment Screening

• Before initiating therapy, take a complete history of any previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other β-lactams, and other allergens.

Patient Monitoring

• Monitor Cl_cr in patients with fluctuating renal function.

Other General Considerations

• To reduce development of drug-resistant bacteria and maintain effectiveness of sulbactam, durlobactam, and other antimicrobials, use sulbactam/durlobactam only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Administration

IV Infusion

Administer by IV infusion over 3 hours.

Available as a co-packaged kit containing 1 clear single-dose vial of sulbactam for injection 1 g (white to off-white powder) and 2 amber single-dose vials of durlobactam for injection 0.5 g (as solid cake or powder).

Must reconstitute and dilute commercially available powders for injection prior to administration.

Both drugs are compatible with 0.9% sodium chloride. Do not mix with other drugs or solutions containing other drugs; compatibility not established.

Reconstitution

Reconstitute the sulbactam 1 g single-dose vial with 5 mL of sterile water for injection. Gently shake to dissolve. Reconstituted vial contains 1 g of sulbactam per 5 mL of clear, colorless to slightly yellow solution. Reconstituted solution is not for direct injection; must be diluted before IV infusion. Dilution must occur within 1 hour of reconstitution.

Reconstitute each durlobactam 0.5 g single-dose vial with 2.5 mL of sterile water for injection. Gently shake to dissolve. Each reconstituted vial contains 0.5 g of durlobactam per 2.5 mL of clear, light yellow to orange solution. Reconstituted solution is not for direct injection; must be diluted before IV infusion. Dilution must occur within 1 hour of reconstitution.

Dilution

Withdraw 5 mL of reconstituted sulbactam and 5 mL (2.5 mL from each vial) of reconstituted durlobactam. Add the withdrawn volume of both drugs to a 100 mL infusion bag of 0.9% sodium chloride for injection. Discard unused portion.

Visually inspect the prepared solution; should appear as a clear, light yellow to orange solution, free of particulates. If cloudy or contains particulates, do not administer.

Bring solution to ambient room temperature (over 15 to 30 minutes) prior to infusion.

Rate of Administration

Administer prepared solution via IV infusion over 3 hours.

Dosage

Adults

HABP/VABP

IV

Dosage is based on renal function.

Patients with Cl_cr of 45 to 129 mL/minute: 1 g sulbactam and 1 g durlobactam every 6 hours.

Patients with Cl_cr ≥130 mL/minute: 1 g sulbactam and 1 g durlobactam every 4 hours.

Patients with Cl_cr <45 mL/minute: see Renal Impairment under Dosage and Administration.

Recommended treatment duration is 7-14 days. Duration should be guided by patient's clinical status.

Special Populations

Hepatic Impairment

No dosage adjustment recommended.

Renal Impairment

Dosage adjustment recommended for patients with Cl_cr <45 mL/minute; see Table 1 for recommended dosage based on Cl_cr estimated by the Cockcroft-Gault equation. The manufacturer makes no recommendations regarding dosage adjustment for patients receiving continuous renal replacement therapy (CRRT).

Geriatric Patients

Consider greater frequency of reduced renal function in geriatric patients when determining dosing. Adjust dosage based on renal function.

Cautions for Sulbactam and Durlobactam

Contraindications

• History of known hypersensitivity to sulbactam, durlobactam, or other β-lactam antibacterial drugs.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity (anaphylactic) reactions, both serious and fatal, have occurred in patients receiving β-lactam therapy. More likely to occur in individuals with a history of β-lactam hypersensitivity and/or a history of sensitivity to multiple allergens.

Prior to initiating therapy, take a complete history to identify any previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other β-lactams, and other allergens.

Discontinue sulbactam/durlobactam if an allergic reaction occurs.

Clostridiodes difficile-Associated Diarrhea

Treatment with anti-infectives alters normal colon flora; may permit overgrowth of Clostridioides difficile. Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including sulbactam/durlobactam; ranges in severity from mild diarrhea to fatal colitis.

Consider CDAD in all patients who present with diarrhea following antibacterial use; has been reported to occur over 2 months following antibacterial administration.

If suspected, assess the risk/benefit of continuing treatment. Institute appropriate medical and pharmacologic management of C. difficile, as well as surgical evaluation as clinically indicated.

Development of Drug-Resistant Bacteria

Use in the absence of proven/strongly suspected bacterial infection or for prophylaxis is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Specific Populations

Pregnancy

No available data on the combination of sulbactam/durlobactam use in pregnant women.

Sulbactam: Limited data (in combination with ampicillin) in pregnant women; no drug-associated risk or adverse maternal or fetal outcomes reported. Sulbactam crosses the placenta. In animal studies, no harm to fetus demonstrated.

Durlobactam: No data in pregnant women. In animal studies, no drug-induced fetal malformations observed, but increased incidence of fetal skeletal variations observed.

Lactation

Sulbactam is present in human milk in low concentrations; maximum daily infant dose of 560 mcg/kg/day reported. Not known whether durlobactam is distributed into human milk. Effects of sulbactam, durlobactam, or the combination drug on breast-fed infants or milk production not known.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient data to determine if patients >65 years of age respond differently than younger patients; however, elderly patients are more likely to have renal dysfunction. Monitor renal function closely.

Hepatic Impairment

Not evaluated in patients with hepatic impairment. No major differences expected; neither sulbactam nor durlobactam undergo substantial hepatic metabolism or excretion.

Renal Impairment

Systemic exposure altered in patients with Cl_cr <45 mL/minute and Cl_cr >130 mL/minute (e.g., seriously ill patients receiving fluid resuscitation).

Common Adverse Effects

Most common adverse reactions (>10%): liver test abnormalities, diarrhea, anemia, hypokalemia.

Drug Interactions

Studies with sulbactam and CYP isoenzymes not conducted.

Durlobactam does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4. Not expected to induce CYP1A2, CYP2B6, or CYP3A4.

Sulbactam does not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptides 1B1 (OATP1B1), OATP1B3, organic cation transporter 1 (OCT1), OCT2, bile salt export pump (BSEP), organic anion transporter 1 (OAT1), OAT3, multidrug toxin extrusion protein 1 (MATE1), or MATE2-K.

Durlobactam does not inhibit P-gp, BCRP, OATP1B1, OAT1, OAT3, or OCT2.

Sulbactam and durlobactam are both substrates of OAT1. Only sulbactam is predicted to be affected; inhibition of OAT1 may increase sulbactam plasma concentrations.

Drugs Affecting or Affected by Transport Systems

OAT1 inhibitors: Concomitant administration of sulbactam/durlobactam and OAT1 inhibitors (e.g., probenecid) may increase plasma concentrations of sulbactam and is not recommended.

Sulbactam and Durlobactam Pharmacokinetics

Distribution

Plasma Protein Binding

Sulbactam: 38%

Durlobactam: 10%

Elimination

Metabolism

Minimally metabolized; largely excreted as unchanged drug.

Elimination Route

Renally excreted, mostly as unchanged drug (75-85%).

Half-life

Sulbactam: 2.15 hours

Durlobactam: 2.52 hours

Stability

Storage

Parenteral

Powder for Injection

Store vials containing sterile powders for injection in refrigerator at 2–8°C (brief excursions permitted between 8–15°C). Vials should not be frozen.

Store prepared reconstituted and diluted solution under refrigeration at 2–8°C; total time between start of reconstitution and conclusion of infusion should not exceed 24 hours. Do not freeze.

Actions

• Combination antibacterial containing sulbactam (β-lactam and β-lactamase inhibitor) and durlobactam (a diazabicyclooctane non-β-lactam, β-lactamase inhibitor).

• Bactericidal activity of sulbactam results from inhibition of Acinetobacter baumannii-calcoaceticus complex penicillin-binding proteins (PBP) PBP1 and PBP3. Inhibition of PBPs leads to the disruption of bacterial cell wall synthesis.

• Durlobactam protects sulbactam from degradation by serine-β-lactamases but has no intrinsic antibacterial activity.

• In vitro, has demonstrated activity against Acinetobacter baumannii-calcoaceticus complex isolates expressing the following serine β-lactamases: Ambler Class A (CTX-M-, TEM, PER-, and SHV-type extended spectrum beta-lactamases [ESBLs], KPC carbapenemase), Class C (ADC-type), and broad spectrum activity against Class D (OXA-type) enzymes.

• Not active against Acinetobacter baumannii-calcoaceticus complex isolates that produce Ambler Class B metallo-β-lactamases or have modification of PBPs.

• Resistance in Acinetobacter baumannii-calcoaceticus complex isolates may be attributed to the production of β-lactamases, modification of PBPs or target alteration, up-regulation of efflux pumps, or loss of outer membrane porin.

Advice to Patients

• Advise patients, their families, or caregivers that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Ask them about any previous hypersensitivity reactions to sulbactam sodium and durlobactam sodium (sulbactam and durlobactam), other beta-lactams (including cephalosporins), or other allergens.

• Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterial drugs, including sulbactam/durlobactam. Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, tell them to contact their healthcare provider.

• Patients should be counseled that antibacterial drugs, including sulbactam/durlobactam, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). Patients should be told that the medication should be administered exactly as directed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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