The European Centre for Disease Prevention and Control (ECDC) has issued guidance recommending against population-level use of doxycycline for post-exposure prophylaxis (doxy-PEP) against sexually transmitted bacterial infections. Instead, doxy-PEP should primarily be used to prevent syphilis, specifically in target groups at the highest risk of infection. 

The guidance follows research that shows doxy-PEP may contribute to antimicrobial resistance (AMR) in those who take it and possibly even among the broader population. 

Three large randomized controlled trials reported that doxy-PEP reduces the incidence of chlamydia and syphilis by around 80% and gonorrhea by up to 50%. However, the same studies also found that doxy-PEP is linked to tetracycline resistance in certain species of gonorrhea, staphylococcus, and streptococcus.

Meanwhile, other research indicates that doxy-PEP is linked to decreased susceptibility of gonorrhea to cefixime, a mainstay treatment option alongside ceftriaxone. 

Doctors should use their clinical judgement when considering doxycycline, Otilia Mårdh, MD, medical epidemiologist and scientific officer of HIV, sexually transmitted infections (STIs), and viral hepatitis at the ECDC, told Medscape News Europe. 

“If recommended, doxy-PEP should be used as part of a broader sexual health approach, including prevention counselling, regular STI testing and treatment, vaccination, and HIV prevention, where appropriate. The need for doxy-PEP should be reviewed periodically,” she said. 

Different Perspectives

Mårdh stressed that how doxy-PEP is prescribed depends on national clinical guidelines that take local STI epidemiology into account. 

While some countries like Belgium restrict its use to research settings, others like the US advocate doxy-PEP for all men who have sex with men (MSM) and transgender women who have had a bacterial STI in the past year. Countries like France, Germany, Netherlands, and the UK fall somewhere in between.

According to a recent article published in Frontiers of Microbiology, where a country falls within this spectrum depends on how much their framework tilts towards prioritizing the reduction of STI incidence over protecting the overall health of individuals and populations. 

“Some doctors are mainly worried about increases in STIs and so think doxy-PEP is great as it reduces chlamydia and syphilis infections. Others are very worried about antibiotic resistance,” Chris Kenyon, MBchB, MPH, PhD, head of the Unit of Sexually Transmitted Infections at the Institute of Tropical Medicine, Antwerp, Belgium, and co-author of the article, told Medscape News Europe. 

Those concerned about AMR, he noted, know that while short-term antibiotic use reduces infection rates, long-term use selects for resistance. 

“If we think beyond the short-term gains, rolling out doxy-PEP outside of research settings is therefore a bad idea as we will just be making resistance worse. It’s a bit like cocaine: great in the short term but a really bad idea if you factor in the long-term effects,” he explained. 

Prescribing Doxy-PEP

Many factors need to be considered before prescribing doxy-PEP. The case against it, said Mårdh, is driven by concern for accelerated AMR in STI pathogens and bystander organisms. 

“These concerns may outweigh the benefits of reducing chlamydia and syphilis incidence, particularly given the uncertainty about how long these reductions can be sustained,” she said. 

Efficacy in reducing incident chlamydia and syphilis among those with a higher burden of bacterial STIs may drive a decision to prescribe doxy-PEP, she added, noting factors such as low cost, good tolerability, as well as additional benefits like reduced anxiety, lower stigma, and increased empowerment around sexual health. 

Christoph Spinner, MD, specialist in internal medicine and infectious diseases and professor at the Technical University of Munich, Germany, said that doxy-PEP’s high efficacy against syphilis and chlamydia means it should be prescribed on a case-by-case basis among persons at a high risk of STI and especially MSM living with HIV or using HIV PrEP. 

He added that potential users should be counselled and told that gonorrhea resistance against doxycycline is high in Europe and thus it only offers weak protection. 

A recent study conducted in Belgium found that educating patients on the potential effects of doxy PEP on AMR reduced willingness to use it from 80% to 60% and increased concerns about side effects and AMR from 50% to 70%. 

At present, doxycycline is the only antibiotic with sufficient evidence from clinical trials to support its use as post exposure prophylaxis for bacterial STIs, said Mårdh. 

“Evidence for other antibiotics is limited or absent and their use could pose a higher risk for antimicrobial resistance,” she added. 

Beyond considering doxy PEP for prophylaxis, Kenyon recommended use of condoms as a “better alternative.” 

Kenyon reported no relevant financial relationships. Spinner reported affiliations with GSK, Gilead, Pfizer, and ViiV. 

Annie Lennon is a medical journalist. Her writing appears on Medscape, WebMD, and Medical News Today, among other outlets.