Natamycin plus lactulose for vaginal yeast infection: a trial

This trial found higher short-term clinical recovery with one fixed-dose vaginal natamycin–lactulose product than with lactulose alone or the specific natamycin comparator in its per-protocol population. It does not establish how the product compares with recommended azole regimens or change treatment guidance.

The study adds a direct comparison for one combination product in acute vulvovaginal candidiasis. Its comparators and short follow-up set narrow limits on what the result can say about other treatments or durable benefit.

Six sites in Belarus and Russia randomized 218 females aged 18–60 with symptomatic, microscopy-positive VVC and vaginal pH ≤4.5. Pregnancy, lactation, and recurrent VVC were excluded; Table 1 described all participants as White. The primary per-protocol analysis included 209 participants.

Participants used one vaginal suppository nightly for six days: natamycin 100 mg plus lactulose 300 mg, lactulose 300 mg alone, or Pimafucin natamycin 100 mg. The trial was open-label to participants and treating staff; outcome assessors were blinded at visits 2 and 3. The primary outcome was clinical recovery around day 7.

At day 7, clinical recovery was 71/87 (81.6%) with the combination, 15/35 (42.9%) with lactulose, and 55/87 with Pimafucin. The article prints 62.3% for 55/87 (which calculates to 63.2%) and reports an 18.4-point combination difference. At day 20–27, clinical recovery was 79/87 (90.8%), 22/35 (62.9%), and 68/87 (78.2%), respectively.

For day-7 microscopic recovery, the paper prints 69/87 (75.9%) for the combination and 65/87 (71.3%) for Pimafucin; the counts calculate to 79.3% and 74.7%. Lactulose was 16/35 (45.7%). At visit 3, the reported counts were 79/87 (90.8%), 26/35 (74.3%), and 77/87 (88.5%); the paper reported no combination-versus-Pimafucin difference at either visit.

The article also prints 61/87 (71.1%) for day-7 overall clinical plus microscopic recovery; 61/87 calculates to 70.1%. In the safety set, any adverse event occurred in 6/91 (6.59%), 0/36, and 10/90 (11.1%), with no serious adverse events reported. Normal lactobacilli counts at visit 3 were a surrogate outcome: 48/91 (52.2%), 12/36 (33.3%), and 29/90 (32.2%).

These results apply narrowly to the tested products and the selected, nonpregnant adults with acute VVC at the study sites. The trial did not compare with standard azole treatment, enroll people with recurrent VVC, or establish product availability, safety advice, or preferred treatment in the United States, Poland, or another market.

Participants and treating clinicians knew the assigned product, the primary analysis was per protocol after post-randomization exclusions, and the study stopped early at an interim efficacy boundary. It was registered after the trial ended, followed participants for about a month, and did not report an imputation strategy in the main text. All participants were described as White. The main article also contains the unresolved count/percentage and endpoint-description discrepancies listed above. Lactobacilli results are surrogate measurements, not evidence that future episodes are prevented.

This is a contextual, product-specific signal from one short-term trial. It does not set the evidence level for broader acute VVC treatment claims or support a treatment hierarchy.

No practical change follows from this study alone. It does not compare the fixed-dose product with recommended azole regimens, establish local access or contraindications, or change the current next step for treatment decisions.

JSC “AVVA RUS” funded the study and makes the combination product. The paper reports that OVM, SAT, and EAL were employees of AVVA RUS JSC. The declarations inspected did not report the sponsor's role in study design, conduct, analysis, manuscript preparation, or publication decisions.

Original article, published February 20, 2025. Trial registration: NCT06411314, retrospectively registered May 13, 2024.