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Desensitization in a patient with a penicillin allergy

Penicillin antibiotics are effective against a variety of infectious diseases. However, due to the incidence of allergic reactions which occur with the use of these medications, treatment of certain infectious diseases has presented clinicians with somewhat of a challenge. Questions concerning the safety and efficacy of using a penicillin in a patient who has a history of allergy to penicillin arise, and risks and benefits of treatment must carefully be weighed.

Desensitization is a procedure which has been used as an attempt to address this concern. The process involves exposing a patient over hours to days to gradually increasing doses of a medication to which the patient has an allergic history. The purpose of this procedure is to attempt to build up tolerance to the medication and blunt the allergic response by inhibiting the release of mast cell mediators though prevention of IgE crosslinking. The process has been reported to be effective in patients who have experienced IgE sensitivity to penicillin antigens. Its usefulness has not been shown in patients who have experienced late penicillin reactions (i.e contact dermatitis). It is often used in instances where no suitable alternative treatments exist, thus necessitating the administration of the drug to which the patient has experienced an allergic reaction. This situation is commonly seen in pregnant women who have syphilis in which treatment is complicated due to a previous allergic reaction to penicillin.

One study that evaluates the use of desensitization in patients with a penicillin allergy was conducted by Wendal, et al. In this study, 15 pregnant women with allergic histories to penicillin confirmed by positive skin testing, underwent desensitization with oral penicillin for the treatment of serious infections in which penicillin was the treatment of choice. Thirteen of the women were treated for syphilis, one was treated for listeriosis, and one was treated for bacterial endocarditis. All fifteen women completed the process with no serious adverse effects, and each patient was able to receive full course treatment for her infection. The only reactions noted during desensitization included urticaria (n=1) and pruritis (n=2). During treatment, the reactions noted were urticaria (n=1) and pruritis (n=2). It was concluded that oral desensitization was a safe approach to therapy in pregnant women who were allergic to penicillin and required penicillin antibiotics.

Before considering desensitization of a patient with a penicillin allergy, one must first evaluate the necessity of the antibiotic in the patient, the patient’s history of the penicillin allergy, and the current status of the allergy response in the patient. This can be done by obtaining a detailed history of the reaction, including the type of symptoms experienced, how long ago the reaction happened, and the use of related agents after the reaction occurred. Since desensitization has been reported to be effective in patients who had experienced an IgE mediated reaction (i.e. anaphylaxis, urticaria, angioedema), it is important to note the type of reaction that was experienced. Skin testing is another fundamental step to be done before desensitization can be decided. Skin testing enables the current status and extent of the patient’s allergic response to penicillin to be evaluated. A positive history and penicillin skin test should alert the clinician to increased risk of patient suffering from an allergic response if administered penicillin. If no suitable alternative exists for treatment of the patient, desensitization may be a reasonable alternative.

Once a patient is considered a candidate for the desensitization procedure based on allergic history, necessity of the antibiotic and the skin test result, the patient may undergo desensitization using either the oral or intravenous mode of administration (Table 1 and Table 2). The oral route is the preferred route since it is less likely to cause systemic allergic reactions due to incomplete absorption of the major and minor determinants of penicillin which are responsible for eliciting the allergic response. Doses of penicillin are initiated with a very small dose. The dose is then doubled every 15 minutes while observing for reaction. Once the procedure is started, it should not be interrupted due to risk of hypersensitivity returning. Furthermore, the procedure should be performed in an intensive care setting where emergency supplies are readily accessible.

 

Table 1: Protocol for oral desensitization with phenoxymethyl penicillin

Sullivan TJ. Current Therapy in Allergy. St. Louis, Mosby. 1985: 57-61

(adapted from Pharmacotherapy: a pathophysiologic approach)

 

Concentration (U/mL)

Volume (mL)

Dose (U)

Cumulative Dose (U)

1

1000

0.1

100

100

2

1000

0.2

200

300

3

1000

0.4

400

700

4

1000

0.8

800

1500

5

1000

1.6

1600

3100

6

1000

3.2

3200

6300

7

1000

6.4

6400

12700

8

10000

1.2

12000

24700

9

10000

2.4

24000

48700

10

10000

4.8

48000

93700

11

80000

1.0

80000

176700

12

80000

2.0

160000

336700

13

80000

4.0

320000

656700

14

80000

8.0

640000

1296700

Observe for 30 minutes

15

500000

0.25

125000

 

16

500000

0.50

250000

 

17

500000

1.0

500000

 

18

500000

2.25

1125000

 

 

Table 2 : Protocol for parenteral desensitization with benzylpenicillin

Weiss ME, Adkinson NF. Immediate hypersensitivity reaction to penicillin and related antibiotics. Clin Allergy 1998; 18: 515-540 (adapted from Pharmacotherapy: a pathophysiologic approach)

 

Concentration (U)

Volume (mL)

Route

1

100

0.1

ID

2

100

0.2

SC

3

100

0.4

SC

4

100

0.8

SC

5

1,000

0.1

ID

6

1,000

0.3

SC

7

1,000

0.6

SC

8

10,000

0.1

ID

9

10,000

0.2

SC

10

10,000

0.4

SC

11

10,000

0.8

SC

12

100,000

0.1

ID

13

100,000

0.3

SC

14

100,000

0.6

SC

15

1,000,000

0.1

ID

16

1,000,000

0.2

SC

17

1,000,000

0.2

IM

18

1,000,000

0.4

IM

19

Continuous IV infusion @ 1,000,000 U/hr

 

References

  1. Beringer PM, Middleton RK. Anaphylaxis and drug allergies. In : Young LY, Koda-Kimble MA, editors. Applied therapeutics : the clinical use of drugs. 6th ed. Washington : Applied Therapeutics, Inc ; 1995. p.6.1-6.21.


  2. DiPiro JT, Stafford CT, Schlesselman LS. Allergic and pseudoallergic drug reactions. In: Dipiro JT, Yee GC, Matzke GR, Wells BG, Posey ML, editors. Pharmacotherapy: a pathophysiologic approach. 4th ed. Connecticut: Appleton and Lange; 1999. p 1393-1405.


  3. Greenberger P. Desensitization and test-dosing for the drug-allergic patient [editorial]. Ann Allergy Asthma Immunol 2000 Oct ; 85(4) : 250-1


  4. Sullivan TJ. Antigen-specific desensitization to prevent allergic reactions to drugs [editorial]. Ann Allergy 1994 Nov ; 73 : 375-7


  5. Weiss ME, Adkinson NF. B-lactam allergy. In : Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Pennsylvania : Churchill Livingstone ; 2000. p. 299-305.


  6. Wendel GD, Stark BJ, Jamison RB, Molina RD, Sullivan TJ. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med 1985 May 9 ; 312(19) : 1229-32.


  7. Yin RY. A perspective on penicillin allergy. Arch Intern Med 1992 May ; 152 : 930-7.

 

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