Amoxicillin

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Case reports and Literature review.

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2011

Materials and methods

Type of sensitisation studied:

respiratory

skin

Study type:

case report

Principles of method if other than guideline:

The case reports are supplemented by a systematic literature review of antibiotic occupational asthma.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Amoxicillin

EC Number:

248-003-8

EC Name:

Amoxicillin

Cas Number:

26787-78-0

Molecular formula:

C16H19N3O5S

IUPAC Name:

6-{[amino(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Method

Type of population:

occupational

Route of administration:

other: inhalation, oral and dermal.

Details on study design:

TYPE OF TEST(S) USED: skin test (prick test); specific IgE; bronchial provocation test; oral challenge.

Results and discussion

Results of examinations:

RESULT OF CASE REPORT:
All patients developed a (predominantly) late asthmatic reaction accompanied by increased bronchial hyperresponsiveness as demonstrated by a fall in histamine PC20 concentration following challenge; these findings were repeatable on further testing but not seen after identical exposure to lactose powder alone. Following diagnosis, each patient avoided further exposure at work to the causative antibiotic with improvement or resolution of their symptoms. They were advised to avoid therapeutic use of amoxicillin.

Any other information on results incl. tables

Table 1. Cases of occupational asthma from antibiotics identified at Royal Brompton Hospital in the period 1995–2009.

 

Year of diagnosis	Workplace exposure	Allergic symptoms	Latency	Specific IgE	Bronchial provocation test
					Agent	FEV1 response	Increase in histamine reactivity
1996	amoxicillin	wheeze, cough	27 years	penicilloyl G (+) penicilloyl V (+)	amoxicillin	late	yes
2000	amoxicillin	wheeze, cough	27 years	amoxicilloyl (+)	amoxicillin	late	yes

 

 

Table 2. Published cases of occupational allergy to ampicillin 1953–2009

 

Reference	Year	Country	No.	Latency	Respiratoy symtoms	Skin test	Specific IgE	Bronchial provocation test	Oral challenge
1	1980	Spain	2	#1: 1 years #2: 1 years	#1: rhinitis, dyspnoea, wheeze #2: cough, wheeze	not reported	negative	Not reported	not reported
2	1997	Belgium	1	6 months	cough, wheeze	not reported	not reported	amoxicillin: (+ER* LR*)	not reported
3	1998	Spain	1	27 years	cough, rhinitis,wheeze, dyspnea	amoxicillin (-) ampicillin (-) BP* (-) BPP* (-) MDM* (-)	amoxicillin(+) ampicillin (-) penicillin V (-)	amoxicillin: (+ER*) penicillin V (-)	amoxicillin (+LR*) penicillin V (-)

*ER: early (asthmatic) response, *LR: late (asthmatic) response.

*MDM: minor determinant (penicillin) mix,*BP: benzylpenicillin

*(B)PP: (benzyl)penicilloyl polylysine

[1] E. Losada Cosmes, M. Hinojosa Macias, R. Acover Sanchez et al., “Asma por inhalaci ´on por penicilina ambiental,”Allergologia et Immunopathologia, vol. 7, supplement, pp. 288–293, 1980.

[2] O. Vandenplas, J. P. Delwiche, and M. De Jonghe, “Asthma to latex and amoxicillin,”Allergy, vol. 52, no. 11, pp. 1147–1149, 1997.

[3] I. Jimenez, E. Anton, I. Pic´ans, I. S´anchez, M. D. Qui˜nones, and J. Jerez, “Occupational asthma specific to amoxicillin,”Allergy, vol. 53, no. 1, pp. 104–105, 1998.

 

 

Applicant's summary and conclusion

Executive summary:

Amoxicillin has been reported as a cause of work-related asthma.

Two case reports were seen and diagnosed of amoxicillin. Each of the two cases was involved in the primary manufacture or formulation of antibiotics in the United Kingdom and had presented with new onset, work-related asthmatic symptoms. All patients developed a (predominantly) late asthmatic reaction accompanied by increased bronchial hyperresponsiveness.

Previous published case reports, including a total of 4 patients, are reviewed.

Two cases of dyspnoea after inhalation of amoxicillin were described in workers in the manufacture of antibiotics; in neither case was there objective evidence of immune sensitisation to amoxicillin. A factory worker in Belgium developed occupational asthma from amoxicillin and subsequently, while employed as a nurse, to latex.

Three employees had positive skin prick tests to penicillin G and/or amoxicillin.

The patient had allergic responses to both inhaled and oral amoxicillin, but not to oral penicillin V suggesting to the authors that the responsible antigenic determinant lay in the aminohydroxyphenyl side-chain of amoxicillin.