Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews

Abstract

BackgroundBenzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing to these shortages.Methods and findingsCountry-level data about BPG shortages were collected using 3 survey approaches. First, a survey designed by the WHO Department of Reproductive Health and Research was distributed to 41 countries and territories in the Americas and 41 more in Africa. Second, WHO conducted an email survey of 28 US Centers for Disease Control and Prevention country directors. An additional 13 countries were in contact with WHO for related congenital syphilis prevention activities and also reported on BPG shortages. Third, the Clinton Health Access Initiative (CHAI) collected data from 14 countries (where it has active operations) to understand the extent of stock-outs, in-country purchasing, usage behavior, and breadth of available purchasing options to identify stock-outs worldwide. CHAI also conducted in-person interviews in the same 14 countries to understand the extent of stock-outs, in-country purchasing and usage behavior, and available purchasing options. CHAI also completed a desk review of 10 additional high-income countries, which were also included. BPG shortages were attributable to shortfalls in supply, demand, and procurement in the countries assessed. This assessment should not be considered globally representative as countries not surveyed may also have experienced BPG shortages. Country contacts may not have been aware of BPG shortages when surveyed or may have underreported medication substitutions due to desirability bias. Funding for the purchase of BPG by countries was not evaluated. In all, 114 countries and territories were approached to provide information on BPG shortages occurring during 2014–2016. Of unique countries and territories, 95 (83%) responded or had information evaluable from public records. Of these 95 countries and territories, 39 (41%) reported a BPG shortage, and 56 (59%) reported no BPG shortage; 10 (12%) countries with and without BPG shortages reported use of antibiotic alternatives to BPG for treatment of maternal syphilis. Market exits, inflexible production cycles, and minimum order quantities affect BPG supply. On the demand side, inaccurate forecasts and sole sourcing lead to under-procurement. Clinicians may also incorrectly prescribe BPG substitutes due to misperceptions of quality or of the likelihood of adverse outcomes.ConclusionsTargets for improvement include drug forecasting and procurement, and addressing provider reluctance to use BPG. Opportunities to improve global supply, demand, and use of BPG should be prioritized alongside congenital syphilis elimination efforts.

Congenital Syphilis as a Measure of Maternal and Child Healthcare, Brazil

“…The most effective syphilis treatment is benzathine penicillin G ( 6 , 30 , 31 ), but despite the medication’s efficacy and affordability, syphilis continues to be a public health problem ( 2 ). Benzathine penicillin G shortages have compromised treatment for diagnosed syphilis cases in several countries ( 32 ), including Brazil ( 6 ), which in turn has seen increasing congenital syphilis cases. Countries seeking to expand and improve prenatal care, reduce adverse pregnancy outcomes, and achieve congenital syphilis elimination goals should have access to a steady supply of benzathine penicillin G ( 33 ).…”

“…Despite improvements, syphilis continues to affect a high number of pregnant women, causing high rates of perinatal illness and death ( 5 ). Elimination efforts are hindered further by a global shortage of benzathine penicillin G, a drug indicated for congenital syphilis prevention ( 6 ). …”

Syphilis management in pregnancy: a review of guideline recommendations from countries around the world

“…29 As BPG remains the only antibiotic known to treat an exposed fetus, several countries could benefit 78 by ensuring recommended treatment approaches are the best options to prevent congenital syphilis. Additionally, given the frequent global penicillin shortages, 30 language that supports forecasting to avoid stock-outs of penicillin and, when stock-outs occur, that prioritises treatment of pregnant women, could decrease potential cases of congenital syphilis. This review has limitations.…”

Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis

“…Manufacturers are additionally required to produce medication according to Good Manufacturing Practice (GMP), although there have been regulatory concerns about GMP compliance by at least one manufacturer 31. Given the hydrophobic characteristics of BPG, emulsifying agents are often added to improve the solubility including soy lecithin.…”