Repeat and persistent rectal chlamydia infections fell measurably at a large Seattle sexual health clinic after it moved away from single-dose azithromycin in favor of a seven-day course of doxycycline, according to a 13-year analysis of electronic health records published in Open Forum Infectious Diseases.
The result matters beyond one clinic. Rectal chlamydia is the most common bacterial sexually transmitted infection among men who have sex with men. It is usually symptomless, and repeat positive tests after treatment have been a persistent frustration for patients and clinicians alike. This is among the first real-world evidence that changing what gets prescribed reduces those repeat infections at the population level.
For anyone who has tested positive and then tested positive again months later, the finding reframes a common assumption. A repeat result is not automatically a sign of new exposure or a partner's behavior. Sometimes the first course of antibiotics simply did not clear the infection.
What the Analysis Measured
Researchers led by Mary Bridget Waters of the University of Washington Department of Epidemiology used records from the Public Health Seattle and King County Sexual Health Clinic spanning January 2012 through December 2024. They identified 211 recurrent or persistent rectal chlamydia infections and 222 recurrent or persistent rectal gonorrhea infections among men who have sex with men, defining recurrence as a second positive test between 14 and 90 days after the initial diagnosis.
Gonorrhea served as the control. Because its treatment did not change over the same period, any divergence between the two trends points to the chlamydia prescribing shift rather than to broader changes in testing, sexual behavior, or clinic volume.
The analysis compared three periods: before the clinic guideline, a phased implementation period, and a fully implemented period that coincided with updated national recommendations. After full implementation, the rectal chlamydia trend declined 16.9 percent more than the rectal gonorrhea trend, a statistically significant difference. There was no abrupt drop at either implementation point, which is what a gradual prescribing change would predict.
The authors wrote that their work builds on earlier randomized trials by estimating the impact "of the implementation of new prescribing guidelines."
The Trial Evidence This Builds On
Two randomized controlled trials established the underlying comparison. A double-blind Australian trial that enrolled 625 men across five sexual health clinics found a seven-day doxycycline course superior to single-dose azithromycin for asymptomatic rectal chlamydia, with results published in the New England Journal of Medicine. A separate double-blind trial run in Seattle and Boston reached the same conclusion, reporting microbiologic cure in 100 percent of doxycycline recipients who completed the protocol compared with 74 percent of those given azithromycin. A later systematic review and meta-analysis pooling 11 studies found cure rates of 96.9% for doxycycline and 82.7% for azithromycin.
The likely explanation involves where the bacteria live. Chlamydia in the gastrointestinal tract appears harder for azithromycin to reach at effective concentrations than chlamydia in the genital tract, while doxycycline performs comparably in both. Undetected lymphogranuloma venereum, a strain that causes proctitis and requires longer treatment, may also contribute.
The trade-off is adherence. A single dose is taken in front of the clinician. A seven-day course depends on a patient picking up and finishing a prescription, and adherence outside a monitored trial is harder to guarantee. That is the practical weak point in an otherwise clear treatment advantage.
The Seattle finding also carries an equity signal worth noting. During the phased implementation period, Hispanic or Latino patients were significantly less likely to receive azithromycin than other patients, meaning they were more likely to get the more effective regimen earlier. The authors report the association without explaining it, and a single-clinic pattern should not be generalized. But prescribing differences by patient group are exactly the kind of thing that determines who benefits first when guidance changes, and they are rarely measured.
What Patients and Clinics Should Take From This
The study has real limits. It relies on health record data from a single clinic, and it cannot distinguish a genuine reinfection from a treatment failure. Both appear identical in the record. It also studied men who have sex with men, so the findings do not automatically extend to other populations or to genital infections. It was supported by funding from the National Institutes of Health.
None of that undercuts the central point. If a clinician prescribes a week of doxycycline for a rectal infection rather than a single dose, that reflects current evidence rather than an arbitrary preference, and it is worth completing even though it is less convenient than one pill.
Anyone treated for rectal chlamydia should finish the full course, avoid sex until a week after completing treatment, make sure partners are treated, and return for a retest around three months later. That retest is standard practice because repeat infection is common, not because anyone did anything wrong. Extragenital testing matters here: a urine test alone will miss a rectal infection, so people having receptive anal sex should ask specifically for a rectal swab.
Cost and access are usually manageable. Doxycycline is generic and inexpensive; public health clinics in most metro areas provide STI testing and treatment on a sliding scale or free, and many offer doxycycline as post-exposure prophylaxis for people at substantial risk. King County guidance describes that approach as effective against chlamydia and syphilis, with a weaker effect against gonorrhea. A separate real-world clinic analysis in Los Angeles found the same pattern, with prevention rates of about 90 percent for chlamydia, 86 percent for syphilis, and 55 percent for gonorrhea.
Rectal chlamydia frequently causes no symptoms at all, which is why screening rather than symptom-watching drives detection. When symptoms do occur, they include rectal pain, discharge, bleeding, a persistent urge to pass stool, or pain during receptive anal sex. Fever, severe pain, or significant bleeding warrant prompt medical evaluation. No one should self-treat with leftover antibiotics or products bought online.
Key Questions Answered
What changed at the clinic? It adopted guidance recommending a seven-day course of doxycycline instead of a single one-gram dose of azithromycin for rectal chlamydia. Recurrent and persistent infections then declined relative to gonorrhea.
How large was the effect? After full implementation, the rectal chlamydia trend fell 16.9 percent more than the rectal gonorrhea comparison trend. There was no sudden drop, only a shift in trajectory.
Why is rectal chlamydia harder to treat? Evidence suggests that azithromycin reaches lower effective concentrations in the gastrointestinal tract than in the genital tract, whereas doxycycline achieves similar concentrations in both. Undetected lymphogranuloma venereum may also play a role.
Does a repeat positive test mean a partner was unfaithful? Not necessarily. A second positive result can reflect a new exposure or an infection the first course never fully cleared, and the two are indistinguishable in clinical records.
Who should ask for a rectal swab? Anyone having receptive anal sex. Urine testing alone misses rectal infections, and most rectal chlamydia produces no symptoms.
What symptoms should prompt care? Rectal pain, discharge, bleeding, a persistent urge to pass stool, or pain during receptive anal sex. Fever, severe pain, or heavy bleeding need prompt evaluation.
Where can people get low-cost testing? County and city public health sexual health clinics in most major metro areas offer testing and treatment free or on a sliding scale, and doxycycline itself is an inexpensive generic.
