[2S-[2α,5α,6β(S*)]]-6-[[[[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Type of sensitisation studied:

skin

Study type:

case report

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Case report: two cases of cutaneous reactions to piperacillin. 2 and 7 months later, the patients underwent skin tests with the test item and other substances.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-

EC Number:

261-868-6

EC Name:

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-

Cas Number:

59703-84-3

Molecular formula:

C23H26N5O7S.Na

IUPAC Name:

sodium;(2S,5R,6R)-6-[(2S)-2-[4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate

Test material form:

solid

Method

Type of population:

general

Ethical approval:

not applicable

Subjects:

- Number of subjects exposed: 2
- Sex: males
- Age: 38 and 42
- Race: not specified

Clinical history:

- History of allergy or casuistics for study subject or populations: Neither patient had a personal or family history of allergic diseases.
- Symptoms, onset and progress of the disease: cutaneous reactions appearing more than 48 h after the initiation of therapy (6 and 4 days), effects resolved after discontinuation of treatment (7 and 10 days).
- Exposure history: 4 g/day test item (6 and 4 days)
- Any other allergic or airway disorders: Both of the previously described subjects displayed allergologic-test negativity to penicillin determinants as well as to ampicillin and amoxicillin.

Controls:

10 healthy control subjects

Route of administration:

other: intramuscular

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)
All reagents were applied to uninvolved skin on the interscapular region of the patient’s back by using acrylate adhesive strips with small plates attached for test allergens (Curatest, Lohmann GmbH and Co KG, Neuwied, Germany).Occlusion time was 48 hours. Readings were made, 15 minutes after removal of the strips and 24 hours later.

ADMINISTRATION
- Type of application: occlusive
- Description of patch: acrylate adhesive strips with small plates attached
- Vehicle / solvent: saline ( 0.9% NaCl)
- Concentrations: 1 and 20 mg/ml
- Testing/scoring schedule: 15 minutes and 24h after removal of patch
- Removal of test substance: 48 h after application

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: Both patients presented skin-test negativity after 20 min, and delayed intradermal reactions (after 24 h in case 1 and 48 h in case 2) to the test item: erythematous, indurated wheals larger than 10 mm, which began to fade after 72 h.

CONTROLS
- Intradermal tests with PP were negative in 10 healthy control subjects, 4 of whom had previously tolerated PP.

RESULT OF CASE REPORT: The characteristics of these two cases (i.e., cutaneous reactions appearing more than 48 h after the initiation of therapy, as well as patch-test and delayed intradermal-test positivity) are indicative of delayed hypersensitivity to PP.

Applicant's summary and conclusion

Conclusions:

Two cases indicative of delayed hypersensitivity to piperacillin sodium salt were presented.

Executive summary:

A 38-year-old male receiving a dose of 4 g/day piperacillin intramuscularly after a hemorrhoidectomy developed a generalized erythematous rash after 6 days of treatment, which resolved after discontinuance of the treatment and 7 days of corticosteroid therapy. A 42 -year-old male receiving a dose of 4 g/day piperacillin intramuscularly after surgery for craneal trauma developed generalized maculopapular rash after 4 days of treatment, wich resoved 10 days after discontinuance of the treatment. Neither patient had a personal or family history of allergic diseases. Both patients underwent skin tests 2 and 7 months later, respectively, and both presented negative results after 20 min and delayed intradermal reacions after 24 and 48 h. The caracteristics of these cases are indicative of delayed hypersensitivity to piperacillin.