In response to a previous shortage of Bicillin L-A in 2023, the FDA approved temporary importation of two equivalent IM penicillin formulations, Extencilline (benzathine benzylpenicillin) and Lentocilin S (benzathine benzylpenicillin tetrahydrate), both of which remain available (see Table 1).

SYPHILIS — IM benzathine penicillin G is the drug of choice for treatment of primary, secondary, or early latent syphilis (less than one year's duration) and for late latent (>1 year's duration), latent of unknown duration, or tertiary syphilis (gumma or cardiovascular).3 Oral doxycycline is usually recommended as an alternative when benzathine penicillin G cannot be given. Tetracycline is another alternative, but it causes more gastrointestinal adverse effects and requires more frequent dosing. Ceftriaxone appears to be effective for primary and secondary syphilis, but data are limited (see Table 2).4

Because parenteral penicillin G is the only drug with documented efficacy for treatment of syphilis during pregnancy, the CDC recommends considering use of doxycycline to treat syphilis in non-pregnant women and men during the supply shortage.2 Pregnant women with syphilis who are allergic to penicillin should be desensitized and treated with penicillin G.4

ANTISTREPTOCOCCAL PROPHYLAXIS — Long-term antimicrobial prophylaxis is recommended for prevention of recurrent episodes of streptococcal pharyngitis and acute rheumatic fever, which can worsen the severity of rheumatic heart disease. IM benzathine penicillin G once every 28 days is the drug of choice for prophylaxis. Twice daily administration of oral penicillin V is an alternative that is commonly used in nonendemic areas such as the US, but the risk of recurrence is higher with oral prophylaxis.5 Oral azithromycin or sulfadiazine can be used in patients with a confirmed allergy to penicillin.