Clinician Alert: Long-acting benzathine penicillin G shortage

Long-acting benzathine penicillin G (brand name Bicillin® L-A & others) is the cornerstone of syphilis treatment and is again in shortage in the United States. It is hoped that supplies will start to be available again in June, 2023, but practices should be adjusted now in order to preserve supplies for individuals with syphilis -- particularly pregnant women-- who cannot be treated with alternative therapy. 

CDC guidance for response to this shortage

Providers, clinics and hospitals can respond to this shortage by:

•  Prioritizing doses of long-acting benzathine penicillin G for pregnant women with syphilis and their partners.
  • Note: Most infants with congenital syphilis require IV aqueous penicillin G, but some babies born to treated mothers are treated with long-acting benzathine penicillin G. 
• Treating non-pregnant patients with doxycycline 100 mg po bid for two weeks for primary, secondary or early latent syphilis (“early syphilis”) or for four weeks for late latent or unknown duration syphilis if your supply is already limited.
• Considering use of long-acting benzathine penicillin G for patients who are at very high risk of not successfully completing the course of doxycycline.
• Ordering their usual long-acting benzathine penicillin G supplies.
• Continuing to test for syphilis and collaborating with public health.
• Reaching out to your county STI team or health officer if you need:
  • more information about a patient’s prior treatment or test results or
  • you can’t find another source of benzathine penicillin G for a pregnant or doxycycline-allergic patient.   There are some reserves which we can access if necessary. Local Public Health Authority phone numbers
•  Avoiding use of long-acting penicillin G benzathine for treatment of infectious diseases other than early syphilis 

Background

• The lowest number of syphilis cases in the US occurred in 2000-2001 and rates have increased almost every year since then.
• There were 32% more syphilis cases reported in 2021 compared to 2020 and a total of more than 5 times as many cases in recent years than in ~ 2000.
• We need more, not less, syphilis screening, contact notification and treatment. 
• USPSTF has published guidelines for syphilis screening and OHA has slightly different guidance, including testing essentially everyone under 45 years of age for syphilis at least once if they have not been tested since 2021. OHA STI Screening Recommendations.
• Numbers and rates of congenital syphilis have been increasing since about 2013 and guidance for more aggressive screening and treatment during pregnancy has been updated.
• OHA guidance for serial syphilis testing in pregnancy (1st AND 3rd trimester testing).
• CDC guidance for syphilis screening during pregnancy. Note especially: 
  • Serologic testing should be performed at first presentation to prenatal care, at 28 weeks (early third trimester, paired with glucose tolerance testing), and again at delivery.
  • No mother or neonate should leave the hospital without maternal serologic status having been documented at least once during pregnancy.
  • Any woman who has a fetal death after 20 weeks’ gestation should be tested for syphilis.
• Any pregnant person who presents to alternative health care access points should also be tested if there is any question whether she has been consistently accessing prenatal care, including emergency departments and urgent care clinics, jails or other carceral settings, substance use disorder treatment facilities, etc

Treatment of Syphilis

• Test all patients with a positive syphilis test for HIV infection.
• Parenteral penicillin G (usually long-acting benzathine penicillin G) is the only therapy with documented efficacy for syphilis during pregnancy. Pregnant women with syphilis at any stage who report penicillin allergy should be desensitized and treated with penicillin.
• The combination long- and short-acting benzathine-procaine penicillin (Bicillin C-R), or any other combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for syphilis treatment and should not be used. 

Adult syphilis treatment if long-acting benzathine penicillin G is in short supply (current situation throughout Oregon):

Primary, secondary or early latent syphilis (“early syphilis”)

 ●     Doxycycline 100 mg orally 2 times/day for 14 days (for non-pregnant people)

Late Latent or Unknown Duration Syphilis

●     Doxycycline 100 mg orally 2 times/day for 28 days (for non-pregnant people)

Consult an infectious disease specialist for other manifestations and syphilis treatment in children.

Complete adherence to treatment regimens is absolutely required for treatment of syphilis. The use of doxycycline regimens will require support from clinics:

•  Encourage patients (or help patients) to input a reminder on their cell phone immediately 
• Use pill boxes to ensure they are taking all the required medication without fail
• Call / text reminders from clinics regarding medication adherence, prescription refills, and future appointments 
• Consider providing crackers, granola bars, etc for those with limited access to food as it may help avoid GI side effects and  improve adherence
• Clinics should be liberal with refills as patients with unstable housing often have their belongings and medicines stolen

Resources

STI Guidelines 2021 (CDC) 

Syphilis - STI Treatment Guidelines (CDC) including penicillin G benzathine access challenges

Syphilis During Pregnancy - STI Treatment Guidelines (CDC)  

Recommendation: Syphilis Infection in Nonpregnant Adolescents and Adults: Screening | United States Preventive Services Taskforce 

Oregon Health Authority: Congenital Syphilis : STD Prevention for serial syphilis testing in pregnancy

Thank you for your partnership,