No Significant Difference Between Doxycycline and Minocycline for Bone and Joint Infections
At MADID 2025, William R Mikesell, PharmD, presented data showing 20% vs 16% treatment failure rates in doxycycline and minocycline groups.
A multi-hospital retrospective cohort study conducted across Indiana University Health (IU Health) hospitals has found no significant differences in treatment outcomes between doxycycline and minocycline for managing bone and joint infections. The study, presented at MADID 2025, by William R. Mikesell, PharmD, PGY2 infectious diseases pharmacy resident at Indiana University Health, builds on the foundation laid by the OVIVA trial, which established oral antibiotics as a noninferior alternative to intravenous therapy for these infections.
The study included adult patients treated between January 1, 2016, and August 1, 2024, who received either doxycycline (n=41) or minocycline (n=38) for a minimum of two weeks of a planned six-week antibiotic course. Patients receiving additional antibiotics for unrelated infections, as well as pregnant or incarcerated patients, were excluded.
The primary endpoint was treatment failure, defined as any of the following: emergency department visit or hospital readmission for bone or joint infection, antibiotic change due to resistance, presence of a draining sinus tract or frank purulence near the bone or prosthesis, positive repeat tissue culture, or biopsy evidence of infection. Secondary outcomes included adverse effects, need for extended therapy, and early discontinuation of treatment.
Treatment failure occurred in 20% of doxycycline-treated patients and 16% of those treated with minocycline, a difference that was not statistically significant. The most common infection sites included the foot, followed by the leg, knee, hand, arm, hip, and pelvis. Staphylococcus aureus—both methicillin-resistant (MRSA) and methicillin-susceptible strains—and coagulase-negative Staphylococcus species were the predominant pathogens. Secondary outcomes such as adverse event rates, additional antibiotic duration, and early therapy discontinuation were also similar across both groups.
William R. Mikesell explained the motivation behind the study, stating, “The study originally came up because our providers at University Hospital—which treats more immunocompromised patients—prefer to use minocycline for their bone and joint infections. This is in contrast to Methodist Hospital, where they preferred doxycycline.” He added, “Some of the providers at University wanted us to look into this because they believe minocycline is a better treatment option over doxycycline. There’s research out there suggesting that doxycycline induces its own resistance in MRSA isolates—specifically if they have the TetM ribosomal protection proteins. So, they elected to use minocycline over doxycycline.”
When asked if any patient subgroups or infection sites showed a preference for one antibiotic, Mikesell said, “Overall, the research showed there was no statistical difference between the two groups. Minocycline did have less treatment failure, which we defined similarly to the AVIVA trial. That included things like if they were readmitted, if they had frank pus, repeat bacteria isolates from the sample, or any radiologic findings showing that the infection was still present.” He noted, “There wasn’t a statistically significant difference. However, there were more MRSA isolates in the minocycline group. So, I think if there were more patients in the study—and if the study was conducted over a longer period of time—there could potentially be a difference.”
Addressing future directions, Mikesell emphasized the need for prospective studies: “Well, our study was retrospective in nature. Being a resident, there’s only so much time you have. Also, our study only included a 90-day follow-up. The AVIVA trial did a full year of follow-up. I think if there were more prospective trials looking at PO antibiotic options for bone and joint infections—designed similarly to the AVIVA trial—that would be perfect.”
These findings suggest comparable clinical effectiveness between doxycycline and minocycline as oral step-down therapies for bone and joint infections, reinforcing the flexibility clinicians have when tailoring treatment. However, larger, prospective trials are needed to validate these retrospective findings and to further explore resistance patterns and optimal antibiotic selection in diverse patient populations.
