Penicillin Desensitization — A Case Review

The penicillin class of antibiotics are often life-saving and their use may be required despite prior evidence of allergic manifestations to these drugs. A case report of a patient with subacute bacterial endocarditis who was allergic to penicillin yet requiring treatment with it is presented. The mechanisms and manifestations of penicillin allergy, skin testing for penicillin allergy and the theory and procedures for penicillin desensitization are also discussed.

and incontinence. On 8-28-75, edema and petechiae of the lower extremítíes and a new díastolíc heart murmur were noted. Blood cultures were positive for enterococcus sensitive to penicillin. The diagnosis of subacute bacterial endocarditis due to enterococcus was made at this time and intravenous potassium penicillin G 2,400,000 units every four hours and streptomycin 500 mg intramuscularly twice daily were initiated.

On 9-1-75, the patient developed a florid rash with pruritus over his entire body. Despite the rash, penicillin was continued along with diphenhydramine. This therapy proved to be ineffective with the rash increasing in intensity and becoming unbearable to the patient. Penicillin was discontinued and cephalothin 2 g intravenously every four hours was initiated with continuation of streptomycin. Repeat blood cultures ten days later remained positive for enterococcus. The murmurs became louder progressing to Grade IV systolic and diastolic over both the mitral and aortic areas. Cephalothin was discontinued and vancomycin 500 mg intravenously every six hours was substituted. The patient's renal function began to slowly deteriorate as evidenced by a blood urea nitrogen of 60 mg% and serum creatinine of 2.5 mg%. One day prior to admission, the vancomycin dose was decreased to 500 mg every eight hours. It was decided to transfer the patient to The New York Hospital for re-evaluation and possible desensitization to penicillin.

The patient was admitted to The New York Hospital on 10-2-75 with a blood urea nitrogen of 49 mg% and a serum creatinine of 2.5 mg%. Blood cultures on admission showed no growth. The initial decision was to continue with vancomycin 500 mg intravenously every eight hours and streptomycín 500 mg intramuscularly twice daily unless renal function further deteriorated or ototoxicity developed. The plan was to continue treatment for a duration of six weeks. On 10-6-75, the vancomycin dose was lowered to 250 mg every six hours. Desired therapeutic response was not being obtained on this regimen and renal function continued to worsen (creatinine clearance of 15 ml/minute and a serum creatinine of 3.4 mg%). In view of these findings, it was elected to desensitize the patient to penicillin.

A penicillin desensitization schedule was outlined (see Table 1) and therapy was initiated on 10-7-75 without premedication with antihistamines or corticosteroids. Adequate precautions were observed. The patient had intravenous 5 percent dextrose running, along with a tourniquet and tracheostomy set at the bedside. Syringes of epinephrine (1 mg), aminophylline (250 mg), diphenhydramine (50 mg), and methylprednisolone (125 mg) were prepared and ready at the bedside for suppression of allergic and/or anaphylactic episodes. The patient received injections of potassium penicillin G at 20 minute intervals, first intradermally, then subcutaneously and intramuscularly, and finally intravenously. The patient was closely observed during the desensitization and was at no time left unattended. Before each injection, the patient was questioned and examined for manifestations of allergic reactions. Table 1 summarizes the penicillin desensitization schedule. The starting dose of 0.01 U. of penicillin was increased ten-fold at 20 minute intervals up until the drug was begun intravenously. The desensitization was performed over a period of approximately two and one-half hours without complication. After the desensitization procedure was completed, a continuous intravenous infusion of penicillin (20 million units daily) was begun. Due to the degree of renal impairment, the pharmacist recommended alternating 10 million units of sodium penicillin G with 10 million units of potassium penicillin G with careful monitoring of the electrolytes. The dose of streptomycin was decreased to 500 mg daily. The day following desensitization, the patient complained of pruritus without evidence of rash. Diphenhydramine 50 mg was administered orally every four hours as needed, providing relief.

The patient continued to do well until 10-24-75 when his gait was noted to be increasingly unsteady. Caloric responses were noted to be hypoactive and the patient complained of nausea with occasional vomiting. Signs and symptoms were suggestive of vestibular toxicity. As a result, the dose of streptomycin was decreased to 250 mg daily.

Shortly thereafter, the patient began to complain of dysuria, frequency, and occasional incontinence. A cystoendoscopy was performed showing bladder neck obstruction with bilateral reflux, indicating the necessity for urologic surgery. A cardiac catheterization was also performed that demonstrated marked aortic regurgitation and the necessity for valve replacement.

Surgical intervention was deferred at this time at the patient's request. The patient completed his six-week course of antibiotics on 11-12-75 and was discharged on 11-22-75. He is to be readmitted in the near future for cardiac and urologie surgical procedures.