And not good ones. For those who don’t know what Doxy-PEP is, Apoorva Mandavilli provides a good, concise summary (boldface mine):

In a bid to stem the resurgence of sexually transmitted infections, the Centers for Disease Control and Prevention plans to recommend doxycycline, a widely used antibiotic, for use after an unprotected sexual encounter.

The antibiotic would be taken only by gay and bisexual men and transgender women who have had an S.T.I. within the previous year or who may be at risk for one. The scientific evidence is too limited to recommend the strategy, called doxy-PEP, to all people who might be exposed to infection-causing bacteria during sex.

The agency released draft guidelines on Monday and plans to finalize them after a 45-day public comment period.

Given how frequent STIs are–and the frequency is increasing–I don’t think we have any choice but to implement Doxy-PEP, but we need to realize this represents a public health and policy failure.

What we need to watch very carefully is how this affects resistance in non-target organisms like the Enterobacterales. Resistance to the tetracyclines is often associated with other resistance to other drugs*, especially trimethoprim and the sulfonamides. The problem isn’t that there won’t be any other drugs–I can’t imagine how DoxyPEP could directly lead to imipenem-relebactam resistance, for example, but rather, we’ll have to rachet up standard, non-critical care treatment to include newer drugs.

It would be a horrible irony for DoxyPEP to lead to an increase in resistance to other drugs in Shigella, especially lineages associated with men-who-have-sex-with-men.

I hope I’m wrong, and evolution routinely throws a ton of curve balls, but I don’t see this as a success, but as a desperate attempt to remediate policy failures, one that I hope doesn’t blow in our faces.

*Usually by linkage with other mechanisms, not some global AMR mechanism.