Desensitization penicillins

This section should be read in conjunction with the presentations on desensitization in Sect. 3.5. 

Although there are risks associated with desensitization to a drug, a patient may, for example, show drug resistance to a possible alternative antibiotic and there may also be the possibility of faUure to control an infection by substituting a drug that provides poorer bioavaU- 

During the stepwise dosage procedure, any dose that provokes even a mild systanic reaction 

Patient should be observed for 2 h after last dose Tor example, for benzylpenicillin or phenoxymethylpenicillin 15 min interval between steps 

Brigham and Women s Hospital, Boston, 15 patients completed 52 desensitizations, seven of which involved reactions. Six patients had limited symptoms of immediate hypersensitivity and one patient experienced acute respiratory failure to ceftazidime. Successful desensitizations were obtained with benzylpenicillin, nafcillin, cefazo-lin, and ceftriaxone. 

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Penicillin desensitization is the most common drug desensitization protocol and is required for penicillin-allergic patients when penicillin is clearly the best treatment option, e.g., when syphilis is present in pregnancy. Protocols have been adapted to most antibiotics. Tables 51-5 and 51-6 describe procedures for oral and intravenous penicillin desensitization.25... 

In a patient with a positive penicillin skin test or a history of immediate hypersensitivity to penicillin, vancomycin is the agent of choice. Vancomycin, however, kills S. aureus slowly and is generally regarded as inferior to penicillinase-resistant penicillins for MSSA. Penicillin-allergic patients who fail on vancomycin therapy should be considered for penicillin desensitization. 

Loria RC, Finnerty N, Wedner HJ. Successful use of aztreonam in a patient who failed oral penicillin desensitization. J Allergy Clin Immunol 1989 83(4) 735-7. 

Mechanism It has been stated that in patients with penicillin-specific IgE antibodies who underwent successful penicillin desensitization, the data suggest that anti-specific, mast cell desensitization is responsible for the tolerant state and that mediator depletion plays no role (190). Additionally, the clinical observation that wheal-and-flare skin responses to penicillin often become negative with successful desensitization, while IgE responses to other antigens remain unchanged, also supports an involvement of an antigen-specific mechanism. Furthermore, both clinical reactivity and skin-test reactivity return within a few days, unless a tolerant state is maintained by continued drug administration. The author stressed that these findings show that the desensitized state depends on the... 

Chisholm CA, Katz VL, McDonald TL, Bowes WA Jr. Penicillin desensitization in the treatment of syphilis during pregnancy. Am J Perinatol 1997 14(9) 553. ... 

Eor some patients allergic to penicillin, no reasonable alternatives exist, and penicillin therapy may be necessary for treatment of severe, life-threatening infection. In this situation, penicillin desensitization should be considered. Desensitization can reduce the risk of anaphylaxis but does not influence the likelihood of other types of reactions such as exfoliative dermatitis or Stevens-Johnson syndrome. 

Penicillin desensitization should be performed in a hospital setting where resuscitation equipment is readily available by a physician experienced in the risks and management of severe allergic reactions. The potential risks and benefits should be discussed with the patient. Prior to initiating the protocol, the patient should be stabilized and fluid, pulmonary, and cardiovascular function optimized. The use of... 

Benzathine penicillin 2.4 million units intramuscularly Desensitize penicillin-allergic patients during pregnancy ... 

Parenterally administered penicillin is recommended for all stages of syphilis. Alternative agents may be used in allergic individuals and include doxycycline, minocycline, tetracycline, or erythromycin base or stearate. Some patients may not respond favorably to alternative modalities. Therefore, in patients who must be administered penicillin (i.e., patients who are pregnant or have central nervous system [CNS] involvement) or are allergic, desensitization must be performed before the drug is initiated. 

Some experts administer benzathine penicillin G 2.4 million units IM once per week for up to 3 weeks after completion of the neurosyphilis regimens to provide a total duration of therapy comparable to that used for late syphilis in the absence of neurosyphilis. For nonpregnant patients pregnant patients should be treated with penicillin after desensitization. 

Pregnant patients allergic to penicillin should be desensitized and treated with penicillin. 

Desensitization Patients with a positive skin test to one of the penicillin determinants can be desensitized, a relatively safe procedure. This is recommended in instances when penicillin must be given where no proven alternatives exist. 

Patients with a history of penicillin allergy should undergo skin testing with both peniciUoyl-polylysine and minor determinant mixtures. Patients with positive skin tests should be treated with another immunologically unrelated compound or should undergo desensitization. The management of patients with a negative skin test but a history of a severe IgE-mediated reaction has to be individualized options include the use of an alternative compound, desensitization, or the controlled administration of a test dose. 

Procedure Beta-lactam desensitization should be done in an intensive care unit and any concomitant risk factors for anaphylaxis, such as use of beta-blockers should be corrected. Protocols based on incremental use of the drug orally or parenterally have been described (190,193). The oral route is preferable and is associated with a lower incidence of adverse events, but mild transient reactions are frequent (171,194,195). Pregnant women with limited antibiotic choices have been treated with immunotherapy (196). Repeated administration will maintain a state of anergy, which is often lost after withdrawal (197). At the conclusion of therapy, patients must be informed that after withdrawal, they may once again become allergic to penicillin, with a new reaction to the first subsequent application (197). 

Sullivan TJ, Yecies LD, Shatz GS, Parker CW, Wedner HJ. Desensitization of patients allergic to penicillin using orally administered beta-lactam antibiotics. J Allergy Clin Immunol 1982 69(3) 275-82. 

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

Naclerio R, Mizrahi EA, Adkinson NF Jr. Immunologic observations during desensitization and maintenance of clinical tolerance to penicillin. J Allergy Clin Immunol 1983 71(3) 294-301. 

For nonpregnant patients pregnant patients should be treated with penicillin after desensitization. 

Answer B. Indications for the use of penicillin G are currently limited for a number of reasons. The drug has a narrow spectrum, is susceptible to beta-lactamases, and may cause hypersensitivity, and alternative antibiotics are available. However, penicillin G remains the drug of choice in syphilis, usually given IM as benzathine penicillin G, but as the Na or K salt IV in neurosyphilis. What would you do for patients who are highly allergic to penicillins (Consider tetracyclines, or possibly desensitization.)... 

Erythromycin has been used in the treatment of early syphilis in patients who are allergic to penicilhn, but it no longer is recommended. Tetracychnes are the recommended alternative in penicillin-allergic patients. During pregnancy, it is recommended that patients be desensitized to penicillin. 

Therapy of syphilis with penicillin G is highly effective. Primary, secondary, and latent syphilis of <1 year s duration may be treated with penicillin G procaine (2.4 million units per day intramuscularly), plus probenecid (1.0 g/day orally) to prolong the tj for 10 days or with 1—3 weekly intramuscular doses of 2.4 million units of penicillin G benzathine (three doses in patients with HIV infection). Patients with neurosyphilis or cardiovascular syphilis typically receive intensive therapy with 20 million units of penicillin G daily for 10 days. Since there are no proven alternatives for treating syphilis in pregnant women, penicillin-allergic individuals must be acutely desensitized to prevent anaphylaxis. 

Gorevic PD, Levine BB (1981) Desensitization of anaphylactic hypersensitivity specific for the penicilloate minor determinant of penicillin and carbenicillin. J Allergy din Immunol 68 267... 

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