sulbactam/durlobactam

Sulbactam is a beta-lactam antibiotic and a beta-lactamase inhibitor that inhibits Acinetobacter baumannii-calcoaceticus complex penicillin-binding proteins. Durlobactam is a beta-lactamase inhibitor that protects sulbactam from being degraded by certain serine-beta-lactamases.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative pathogen:
- Acinetobacter baumannii-calcoaceticus complex.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Undergoes minimal metabolism. Primarily excreted by the kidneys, with 75–85% of sulbactam and 78% of durlobactam being excreted as unchanged drug.

Half-Life: Sulbactam: 2–3 hr; Durlobactam: 2–3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to sulbactam, durlobactam, or any beta-lactam antibiotic.

Use Cautiously in:

Renal impairment (↓ dose if CCr <45 mL/min);
CCr ≥130 mL/min;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: Consider age-related ↓ in renal function in determining dose in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmia

F and E: hypokalemia

GI: ↑liver enzymes, diarrhea, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation

GU: acute kidney injury

Hemat: anemia, thrombocytopenia

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Probenecid may ↓ renal excretion and ↑ levels of sulbactam; concurrent use not recommended.

Route/Dosage ⬆ ⬇

IV (Adults ): CCr 45–129 mL/min: Sulbactam 1 g/durlobactam 1 g every 6 hr for 7–14 days. CCr ≥130 mL/min: Sulbactam 1 g/durlobactam 1 g every 4 hr for 7–14 days.

Renal Impairment

IV (Adults ): CCr 30–44 mL/min: Sulbactam 1 g/durlobactam 1 g every 8 hr for 7–14 days. CCr 15–29 mL/min: Sulbactam 1 g/durlobactam 1 g every 12 hr for 7–14 days. CCr <15 mL/min (at baseline before initiating therapy): Sulbactam 1 g/durlobactam 1 g every 12 hr for first 3 doses; then sulbactam 1 g/durlobactam 1 g every 24 hr to complete a total treatment course of 7–14 days. CCr <15 mL/min (after initiating therapy): Sulbactam 1 g/durlobactam 1 g every 24 hr for 7–14 days.

Availability ⬆ ⬇

Lyophilized powder for injection: sulbactam 1 g/vial + durlobactam 0.5 g/vial (2 vials supplied)

Assessment ⬆ ⬇

Assess patient for infection (vital signs, wound appearance, sputum, urine, stool, WBCs) at beginning and throughout therapy.
Obtain a history before initiating therapy to determine previous use of and reaction to carbapenems, penicillins, cephalosporins or other beta lactams.
Monitor for signs/symptoms hypersensitivity reactions (rash, pruritus, laryngeal edema, anaphylaxis). If symptoms occur, discontinue sulbactam/durlobactam and treat as indicated. Keep epinephrine, antihistamine, and resuscitation equipment close by.
Monitor bowel function for diarrhea, abdominal cramping, fever, and bloody stools. If CDAD suspected, discontinue therapy and treat as clinically indicated. May begin up to several months following cessation of therapy.
Monitor for rash; may lead to severe skin reactions.

Lab Test Considerations:

Obtain specimens for culture and sensitivity before therapy. 1st dose may be given before receiving results.
May ↑ ALT and AST.
May cause hypokalemia and thrombocytopenia.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Xacduro kit includes one clear single-dose vial of sulbactam 1 g and two amber single-dose vials of durlobactam 0.5 g as sterile powders. Reconstitution: Reconstitute sulbactam 1-g vial with 5 mL of sterile water for injection; gently shake to dissolve. Solution is clear, colorless to slightly yellow; do not use if cloudy, discolored, or contains particulates. Dilution must occur within 1 hr of reconstitution. Reconstitute each durlobactam 0.5-g vial with 2.5 mL of sterile water for injection; gently shake to dissolve. Solution is clear, light yellow to orange; do not use if cloudy, discolored, or contains particulates. Dilution must occur within 1 hr of reconstitution. Diluent: Withdraw 5 mL of reconstituted sulbactam and 5 mL (2.5 mL from each vial) of reconstituted durlobactam. Add total withdrawn volume of both sulbactam and durlobactam to a 100 mL bag of 0.9% NaCl. Discard unused portion. Store solution in refrigerator. Allow solution to reach room temperature over 15–30 min before administering; stable for 24 hr if refrigerated.
Rate: Infuse over 3 hr.
Y-Site Compatibility:
- amikacin
- anidulafungin
- azithromycin
- aztreonam
- bumetanide
- calcium chloride
- calcium gluconate
- caspofungin
- cefazolin
- cefepime
- cefiderocol
- cefotetan
- cefoxitin
- ceftazidime
- ceftolozane/tazobactam
- ceftriaxone
- cefuroxime
- cisatracurium
- dexamethasone
- dexmedetomidine
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- dopamine
- doxycycline
- epinephrine
- eravacycline
- ertapenem
- esmolol
- esomeprazole
- famotidine
- fentanyl
- fluconazole
- fosphenytoin
- furosemide
- gentamicin
- heparin
- hydrocortisone
- hydromorphone
- imipenem/cilastatin
- imipenem/cilastatin/relebactam
- insulin regular
- isavuconazonium
- labetalol
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- meropenem/vaborbactam
- mesna
- methylprednisolone
- metronidazole
- micafungin
- midazolam
- milrinone
- minocycline
- morphine
- naloxone
- nicardipine
- nitroglycerin
- norepinephrine
- octreotide
- omadacycline
- ondansetron
- pantoprazole
- penicillin G potassium
- phenylephrine
- piperacillin/tazobactam
- plazomicin
- potassium chloride
- potassium phosphates
- rocuronium
- sodium bicarbonate
- sodium phosphates
- tigecycline
- tobramycin
- vancomycin
- vasopressin
Y-Site Incompatibility:
- albumin, human
- amiodarone
- ceftaroline
- ciprofloxacin
- daptomycin
- levofloxacin
- phenytoin
- propofol
- vecuronium

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to report rash or signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools).
Advise patient that serious allergic reaction may occur and to notify health care provider immediately if rash, swelling of face or airway, or difficulty breathing occur.
Caution patient to notify health care provider if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care provider. May occur up to several weeks after discontinuation of medication.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇