Few studies have explored community experiences of our increasingly resistant bacterial landscape, and, in the sphere of sexually transmissible infections (STIs) and antimicrobial resistance, there is even greater absence of community-centred research. This is despite a growth in STI transmission worldwide, which, alongside accelerated resistance, will disproportionately affect GBTQ+ (gay, bisexual, trans, queer+) populations. In this article, drawing on semi-structured interviews conducted in 2024 with 49 cisgender and trans gay and bisexual men, trans women and gender diverse people, we explore contemporary GBTQ+ safe sex practices as they relate to the growing threat of antibiotic resistant STIs in Australia. Key themes identified where the pharmaceutical turn in safe sex practices, the tensions this produced, the complexities of condom use, and the influence of biographies on safe sex practices. We illustrate how the turn toward pharmaceutical solutions have reconfigured and continues to reconfigure safe sex, giving rise to pleasures that were hitherto ‘off-limits’ to many. However, escalating antibiotic resistance threatens to again alter community practices and relationships to STI prevention measures. Drawing on Barad, we develop these themes to theoretically conceptualise safe sex as not fixed, but as an entanglement that is relationally and iteratively (re)configured through the connections between objects, subjectivities, practices, temporalities, and the human-microbial dynamics entailed therein. Findings suggest public health and clinical communication about resistance should speak to population concerns about gut health, resistance vis-à-vis Doxy-PEP, changing definitions of safe sex, and the importance of pleasure.