Alternatives to intravenous penicillin G for specific infections
(Updated June 2004 - originally published October 1999)

As referenced in:
MMWR 48(42);974

A recent product recall and decreased production have caused a shortage of aqueous penicillin G. Existing supplies should be used for persons for whom alternative antibiotics would not be appropriate. There are relatively few conditions for which aqueous penicillin G is considered the treatment of choice. These include congenital syphilis, neurosyphilis, and intrapartum group B streptococcus prophylaxis. Alternative recommendations for these conditions are given below.

CONGENITAL SYPHILIS (CS)

CDC's 2002 Treatment Guidelines ¹. recommend treating infants with CS with intravenous (IV) aqueous penicillin G or intramuscular (IM) procaine penicillin G. Physicians often use IV penicillin G for children at risk for congenital syphilis, or with clinical evidence of infection. During this shortage, CDC and the American Academy of Pediatrics recommend:

1. For infants with clinical evidence of CS, check local sources for aqueous crystalline penicillin G (potassium or sodium). If IV penicillin G is limited, substitute some or all daily doses with procaine penicillin G (50,000 U/kg/dose IM a day in a single dose for 10 days).

   If aqueous or procaine penicillin G is not available, ceftriaxone may be considered with careful clinical and serologic follow-up. Ceftriaxone must be used with caution in jaundiced infants and dosed according to age and weight.² For infants ≤ 30 days old, use 75 mg/kg IV/IM a day in a single dose for 10-14 days; however, dose adjustment may be necessary based on birth weight. For older infants, this dose should be 100 mg/kg a day in a single dose. Studies that strongly support ceftriaxone for the treatment of congenital syphilis have not been done. As a result, this use requires management in consultation with an expert in the treatment of infants with congenital syphilis. Management may include a repeat CSF exam at 6 months of age if the initial exam was abnormal. Specific parameters for treatment failure are available in the 2002 Treatment Guidelines.¹

2. For infants at risk for CS without any clinical evidence of infection:
   1. Procaine penicillin G, 50,000 U/kg/dose IM a day in a single dose for 10 days; OR
   2. Benzathine penicillin G, 50,000 U/kg IM as a single dose.

      If any part of the evaluation for CS is abnormal, CSF exam is not interpretable, CSF exam was not done, or follow-up is uncertain, we recommend procaine penicillin G.

3. For premature infants at risk for CS but no other clinical evidence of infection who may not tolerate IM injections because of decreased muscle mass, IV ceftriaxone may be considered with careful clinical and serologic follow-up (see number 1). Ceftriaxone dosing must be adjusted to age and birth weight. ²

NEUROSYPHILIS

CDC's 2002 Treatment Guidelines ¹ recommend treating persons with neurosyphilis and persons with neurologic involvement with syphilis with IV aqueous penicillin G. For persons in whom compliance with therapy can be ensured, an alternative treatment regimen of IM procaine penicillin G is included in the 2002 Guidelines. During this shortage of aqueous penicillin G, CDC recommends the following:

1. For all persons with neurologic involvement with syphilis, procaine penicillin G 2.4 million units IM each day PLUS probenecid 500 mg four times a day for 10 to 14 days when IV penicillin is not available.
2. For persons with neurologic involvement with syphilis who do not tolerate IM procaine penicillin G, ceftriaxone IV/IM (2 g a day as a single dose for 10 to 14 days) may be considered with careful clinical and serologic follow-up AND in consultation with an expert in the treatment of persons with neurologic involvement with syphilis. Management may include a repeat CSF exam. Specific parameters for treatment failure are available in the 2002 Treatment Guidelines.¹
3. For persons with neurologic involvement with syphilis who report being allergic to penicillin, desensitize to penicillin and treat with procaine penicillin G OR manage in consultation with an expert in the treatment of persons with neurologic involvement with syphilis.

Some experts administer benzathine penicillin, 2.4 million units IM once per week for up to three weeks, after completing a neurosyphilis treatment regimen to provide a duration of therapy that is comparable to the treatment regimen for late syphilis in the absence of neurosyphilis.

HIV-infected persons with neurosyphilis should be treated in the same manner as persons who are not HIV-infected. Recommended follow-up of HIV-infected persons includes more frequent visits over a longer duration of time than persons who are not HIV-infected. ¹

GROUP B STREPTOCOCCUS (GBS) PROPHYLAXIS

In collaboration with ACOG, AAP, and a multi-disciplinary panel of experts, CDC has developed guidelines for preventing perinatal GBS disease. ³ These guidelines include offering intrapartum antibiotic prophylaxis to women in whom GBS carriage has been demonstrated and to particular groups of women with elevated risk of delivering children who develop GBS infection. IV penicillin G has often been used as prophylaxis. During this shortage of aqueous penicillin G, CDC recommends using IV ampicillin for GBS prophylaxis. The recommended dose is a loading dose of 2g and 1g IV every four hours until delivery.

¹ CDC. 2002 CDC Sexually Transmitted Diseases Treatment Guidelines. MMWR 2002 ;51 (RR-6):1-80.
² JD Nelson. In JD Nelson (ed.), Pocket Book of Pediatric Antimicrobial Therapy, 1998-1999, 13th edition. Baltimore: Williams & Wilkins, 1998, pp 116.
³ Prevention of Perinatal Group B Streptococcal Disease: A Public Health Perspective
⁴ CDC. Prevention of perinatal group B streptococcal disease: Revised guidelines from CDC. Morbidity and Mortality Weekly Report, 51 (RR11):1-22.

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