Occupational Anaphylaxis to Piperacillin-Tazobactam in a Nurse: A Case Report

Abstract

Piperacillin–tazobactam is a widely used β-lactam antibiotic, yet occupational systemic anaphylaxis remains exceptionally rare. We report the case of a 26-year-old female nurse with persistent atopic dermatitis and previous history of allergic contact dermatitis to nickel and cobalt, who developed occupational anaphylaxis while preparing intravenous cefuroxime and piperacillin–tazobactam. She presented with acute erythematous papules, rhinorrhea, wheezing, dyspnea, and tachycardia, requiring treatment with intramuscular epinephrine, intravenous clemastine, and hydrocortisone, with complete clinical resolution. She later tolerated cefuroxime handling but developed a generalized rash following accidental skin contact with piperacillin–tazobactam powder. No cofactors were identified, and no reactions occurred outside the workplace. Skin prick testing was performed and elicited an exuberant positive response, with a wheal >20 mm, marked erythema, pruritus, and satellite vesicles after 15 minutes. Additional work-up showed positive specific IgE to penicilloyl G and amoxicillin, with negative latex and formaldehyde testing and normal baseline tryptase. This case supports piperacillin–tazobactam as a potential occupational allergen capable of inducing severe IgE-mediated reactions through non-therapeutic exposure, possibly via inhalation or skin contact during drug reconstitution. Early recognition, diagnostic confirmation, exposure avoidance, and workplace adjustments are essential to prevent recurrent reactions and reduce the risk of occupational disability. In selected cases transfer to a low-exposure work environment may be required. This case reinforces that non-therapeutic occupational exposure to piperacillin–tazobactam can lead to life-threatening IgE-mediated anaphylaxis, highlighting the need for increased awareness and structured preventive strategies in healthcare settings.

Introduction

Piperacillin–tazobactam (PTZ) is an extended-spectrum ureidopenicillin combined with a β-lactamase inhibitor, widely prescribed in hospital practice. ¹ While β-lactam antibiotics are among the most frequent causes of drug hypersensitivity, occupational systemic anaphylaxis remains extremely rare. ² Most reported occupational reactions in healthcare professionals involve dermatitis, rhinitis, or asthma. ³ Severe IgE-mediated reactions in individuals without prior therapeutic exposure are exceptional, with only a few cases described to date. The present report describes a case of occupational anaphylaxis to PTZ in a nurse and discusses its diagnostic and workplace implications.

Case Presentation

We report the case of a 26-year-old female nurse working in a cardiology ward, with persistent atopic dermatitis and a history of allergic contact dermatitis to nickel and cobalt. She had no active asthma or rhinitis and had tolerated a therapeutic course of amoxicillin–clavulanate without incident three months before the reaction. While preparing intravenous cefuroxime and PTZ, she developed acute erythematous papules, rhinorrhea, wheezing, dyspnea, and tachycardia. Symptoms progressed rapidly and required emergency treatment with intramuscular epinephrine, intravenous clemastine, and hydrocortisone, with complete resolution.

On subsequent occasions, she tolerated cefuroxime handling but developed a generalized rash after accidental skin contact with PTZ powder. No cofactors such as Non-steroidal anti-inflammatory drugs (NSAIDs), alcohol, or physical exertion were present. No systemic reactions occurred outside the work environment.

Skin prick testing (SPT) was performed with the commercially available PTZ formulation (4g/0.5g), diluted 1:10 in saline (∼20mg/mL piperacillin equivalent). This single dilution already elicited an exuberant positive reaction, with a wheal >20 mm, marked erythema, pruritus, and satellite vesicles at 15 minutes (Figure 1). Positive and negative controls were appropriate. Intradermal testing was not pursued due to the positivity of the prick test.

Figure 1.

Positive skin prick test with diluted piperacillin–tazobactam (1:1000 dilution, 0.2 mg/mL piperacillin equivalent), showing a wheal >20 mm with marked erythema and satellite vesicles at 15 minutes.

Following the strongly positive skin prick test to PTZ, additional laboratory investigations were performed. Specific IgE was positive to penicilloyl G (4.81 kU/L) and amoxicillin (3.62 kU/L), despite the patient’s previous clinical tolerance to amoxicillin–clavulanate. IgE to latex (0.04 kU/L) and formaldehyde/formalin (0.10 kU/L) were negative. Baseline tryptase was within the normal range (4.1 µg/L). These results indicate sensitization to several β-lactam determinants without consistent clinical correlation, while the PTZ prick test remains the most clinically relevant finding in this case. In addition, patch testing with latex was performed and was negative both at 48 and 72 hours after removal, further excluding latex allergy as a possible occupational cause.

The patient was reassigned to a workplace without antibiotic manipulation to prevent further occupational exposure.

Discussion

This case illustrates the potential for severe occupational reactions to PTZ. To date, only two cases of occupational systemic anaphylaxis to PTZ have been published: one case of piperacillin anaphylaxis with occupational sensitization diagnosed only by serum IgE antibody detection ⁴ and other case described a nurse with recurrent work-related episodes, finally diagnosed after a reaction following PTZ preparation, with positive skin tests to piperacillin, penicillin G, and major/minor determinants rare. ³ In both cases, as in ours, occupational exposure rather than therapeutic administration was the culprit.

Our case adds important insights. First, the skin test response was exceptionally exuberant, with a wheal >20 mm despite testing at a diluted concentration, making an irritant effect unlikely. Second, although the patient had previously tolerated amoxicillin–clavulanate and cefuroxime, this occurred before the occupational reaction and therefore, strict β-lactam avoidance was recommended. The coexistence of positive IgE to penicilloyl and amoxicillin rather suggests possible co-sensitization or cross-reactivity within the penicillin family, due to shared and side chain-specific antigenic determinants.

An important limitation of this case report is the uncertainty regarding the exact route of sensitization. The patient denied recent or frequent therapeutic exposures to piperacillin–tazobactam (PTZ), as well as any known exposure in the remote past. She had previously tolerated amoxicillin–clavulanate approximately three months prior to the index reaction, which may have contributed to prior sensitization.Occupational exposure is considered the most plausible route, supported by the temporal relationship between symptom onset and drug handling, the absence of alternative systemic exposures, and the nature of the preparation process. PTZ is supplied as a dry powder requiring reconstitution, a procedure that may generate aerosolized particles and environmental contamination, thereby enabling inhalational or cutaneous exposure. ⁵ Additionally, the patient had a history of contact sensitization, which may reflect an underlying epithelial barrier dysfunction potentially facilitating drug penetration and immune priming.

Occupational systemic allergy carries important implications. Beyond immediate morbidity, it can lead to long-term occupational disability. Preventive strategies are essential, including minimizing aerosolization during preparation (closed reconstitution systems), use of protective equipment, and workplace adjustments to reduce exposure. Education of healthcare workers on early recognition of anaphylaxis is crucial, and provision of epinephrine auto-injectors with individualized action plans is mandatory once a diagnosis is established. In many cases, transfer to a low-risk department is required, as in previously published reports.

In summary, this case reinforces that non-therapeutic occupational exposure to PTZ can cause life-threatening IgE-mediated anaphylaxis. Although rare, these reactions carry significant clinical and occupational consequences. Clinicians should recognize PTZ as a potential occupational allergen, particularly in healthcare settings, and ensure rigorous diagnostic confirmation and preventive measures.