Can Xacduro be safely used in a patient with an anaphylactic pencillin allergy?

Comment by InpharmD Researcher

There is currently insufficient evidence to determine whether Xacduro (sulbactam/durlobactam) can be safely administered to patients with a history of penicillin-induced anaphylaxis. Sulbactam is a β-lactam antimicrobial that also functions as a penicillanic acid sulfone β-lactamase inhibitor, whereas durlobactam is structurally distinct as a novel diazabicyclooctane (DBO) β-lactamase inhibitor. In Xacduro clinical trials, patients with a history of hypersensitivity to any β-lactam were excluded, and the prescribing information lists a history of severe hypersensitivity to Xacduro components or other β-lactam antibacterial drugs as a contraindication to its use. Published evidence regarding the individual components is limited: only a single case report (Table 1) has definitively implicated sulbactam as the allergenic component in a patient with hypersensitivity to ampicillin–sulbactam, and no published literature has evaluated the cross-reactivity of durlobactam in patients with penicillin allergy. Consequently, the safety of Xacduro in patients with a history of penicillin-induced anaphylaxis remains unknown, and its use in this population should generally be avoided in accordance with the prescribing information.

Background

Sulbactam, developed by Pfizer in the late 1970s, is a penicillanic acid sulfone β-lactamase inhibitor originally designed to restore the activity of ampicillin by inhibiting selected class A β-lactamases (e.g., SHV and CTX-M), thereby reducing ampicillin minimum inhibitory concentrations against susceptible gram-positive and gram-negative organisms. In contrast, durlobactam is a novel diazabicyclooctane (DBO) β-lactamase inhibitor designed to retain potent inhibition of class A and C β-lactamases while expanding activity against class D β-lactamases (e.g., OXA-23, OXA-24, and OXA-58) commonly produced by Acinetobacter species, addressing a key limitation of earlier β-lactamase inhibitors. [1]

A 2019 review identified 12 published reports of hypersensitivity reactions following administration of ampicillin–sulbactam or cefoperazone–sulbactam. Only one case definitively implicated sulbactam, involving a healthcare worker with contact urticaria confirmed by allergy testing (Table 1). In approximately half of the reports, the causative agent could not be distinguished between the β-lactam and sulbactam components, whereas the remaining cases provided evidence that the β-lactam (ampicillin or cefoperazone) was the more likely culprit. The authors concluded that although sulbactam can rarely cause hypersensitivity, either component of combination products may be responsible. Therefore, in patients with suspected allergy to ampicillin–sulbactam or cefoperazone–sulbactam, allergy evaluation should include testing of both the β-lactam and sulbactam components to accurately identify the offending agent. [2]

Background References: [1] Papp-Wallace KM, McLeod SM, Miller AA. Durlobactam, a Broad-Spectrum Serine β-lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species. Clin Infect Dis. 2023;76(Suppl 2):S194-S201. doi:10.1093/cid/ciad095
[2] Stover KR, Barber KE, Wagner JL. Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors. Pharmacy (Basel). 2019;7(3):77. Published 2019 Jun 28. doi:10.3390/pharmacy7030077
Relevant Prescribing Information

CONTRAINDICATIONS [3]
XACDURO is contraindicated in patients with a history of known severe hypersensitivity to the components of XACDURO (sulbactam and durlobactam), or other beta-lactam antibacterial drugs.

WARNINGS AND PRECAUTIONS [3]
Hypersensitivity Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. These reactions are more likely to occur in individuals with a history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. Hypersensitivity was observed in patients treated with XACDURO in clinical trials. Before initiating therapy with XACDURO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta lactams, and other allergens. Discontinue XACDURO if an allergic reaction occurs.

CLINICAL PHARMACOLOGY [3]
12.4 Microbiology
Mechanism of Action
XACDURO is a co-packaged product containing sulbactam and durlobactam. Sulbactam is a beta-lactam antibacterial and Ambler Class A serine beta-lactamase inhibitor that has bactericidal activity due to its inhibition of Acinetobacter baumannii-calcoaceticus complex (ABC) penicillin-binding proteins PBP1 and PBP3, which are essential enzymes required for bacterial cell wall synthesis.

Durlobactam is a diazabicyclooctane non-beta-lactam, beta-lactamase inhibitor, that protects sulbactam from degradation by certain serine-beta-lactamases. Durlobactam alone does not have antibacterial activity against ABC isolates.

Relevant Prescribing Information References: [3] Xacduro (sulbactam and durlobactam kit). Prescribing information. La Jolla Pharmaceutical Company; 2025
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Can Xacduro be safely used in a patient with an anaphylactic pencillin allergy?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

The simultaneous occurrence of contact urticaria from sulbactam and allergic contact dermatitis from ampicillin in a nurse

Design

 Case report 

Case presentation

 A 24-year-old nurse developed pruritic erythema of the fingers within 30 minutes of preparing injectable antibiotics after 3 months of working in a pediatric ward, with progression over several months to pruritic papulovesicles and scaly eczematous plaques involving all fingers. She had a history of allergic rhinitis but no atopic dermatitis. Scratch and patch testing with commonly used β-lactam antibiotics demonstrated immediate wheal-and-flare reactions to Sulbacillin® (ampicillin/sulbactam, 100 mg/mL) and delayed positive patch test reactions to both Sulbacillin® and Augmentin® (amoxicillin/clavulanate, 100 mg/mL). Further testing with individual components at concentrations of 100, 10, and 1 mg/mL identified an immediate reaction to sulbactam on scratch testing and delayed vesicular eczematous reactions to ampicillin on patch testing, while control testing in 10 healthy healthcare workers was negative for sulbactam and serum-specific IgE testing to penicillin derivatives was negative. Based on the clinical history and allergy testing, she was diagnosed with contact urticaria caused by sulbactam and allergic contact dermatitis caused by ampicillin. Her symptoms improved with topical corticosteroids, and complete resolution without recurrence was achieved after reassignment to a hospital unit where she no longer handled aminopenicillins.

Study Author Conclusions

 To our knowledge, this is the first reported case of immediate hypersensitivity to sulbactam presenting as contact urticaria, in combination with delayed allergic contact dermatitis to ampicillin. Although a contribution from preservatives could not be completely excluded, the patient's selective reactions to pure sulbactam and pure ampicillin, together with negative responses to other β-lactam antibiotic preparations, strongly suggest that these agents were the causative allergens.
Table 1 References:
[4] Kwon HJ, Kim MY, Kim HO, Park YM. The simultaneous occurrence of contact urticaria from sulbactam and allergic contact dermatitis from ampicillin in a nurse. Contact Dermatitis. 2006;54(3):176-178. doi:10.1111/j.0105-1873.2005.0739h.x