The results of a randomized controlled trial conducted in Europe indicate that a common bacterial infection in women could be treated without antibiotics.
The trial investigated the efficacy of the broad-spectrum antiseptic dequalinium chloride for treating bacterial vaginosis (BV), which affects an estimated 25% of reproductive-age women and has a high recurrence rate attributed to bacterial biofilm. The standard treatments are the antibiotics clindamycin and metronidazole.
The results, published yesterday in JAMA Network Open, showed that when compared with metronidazole, dequalinium chloride was not only noninferior but also had better tolerability and fewer adverse events. The investigators also note that while dequalinium chloride has been on the market for 30 years, there are no reports of clinically relevant resistance.
"Dequalinium chloride could help reduce antibiotic consumption and thus warrants consideration as first-line treatment for BV due to its broad spectrum, efficacy, safety, tolerability, and less likelihood of resistance," the study authors wrote.
Equally effective, more tolerable than antibiotics
The phase 4 trial enrolled women aged 18 and older with symptomatic BV from 11 gynecology practices and 1 hospital in Poland, the Czech Republic, and Slovakia from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Patients were randomized 1:1 to receive dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg daily for 7 days).
The primary outcome measure was a noninferiority margin of 15 percentage points in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after treatment in the intention-to-treat (ITT) and per-protocol (PP) populations. Investigators also assessed tolerability and safety.
Of the 147 women (mean age, 36.7 years) enrolled in the trial, 72 were treated with dequalinium chloride and 75 with metronidazole. The clinical cure rate in the ITT population was 64 of 69 (92.8%) in the dequalinium chloride group and 69 of 74 (93.2%) in the metronidazole group, with an absolute difference in cure rates of –0.5 percentage points (95% confidence interval [CI], –10.8% to 9.8%).
Dequalinium chloride could help reduce antibiotic consumption and thus warrants consideration as first-line treatment for BV due to its broad spectrum, efficacy, safety, tolerability, and less likelihood of resistance.
In the PP population, the clinical cure rates were 54 of 58 (93.1%) for the dequalinium chloride group and 48 of 53 (90.6%) in the metronidazole group, with an absolute difference of 2.5 percentage points (95% CI, –9.4 to 14.4 percentage points).
"These results confirm the noninferiority of dequalinium chloride," the authors wrote.
Assessment at a second visit 20 to 40 days after treatment found that the cure rates were lower for both treatments (79.7% vs 87.3%), but dequalinium chloride remained noninferior.
Thirty of 50 (60%) patients rated the tolerability of dequalinium chloride as very good, compared with only 21 of 54 (38.9%) patients who received metronidazole. Treatment-emergent adverse events were reported by 8 patients in the dequalinium chloride group and 15 in the metronidazole group. None were considered serious, but three patients treated with metronidazole suspended treatment due to adverse events.
Alternative treatments needed
The trial is the second to find that dequalinium chloride is noninferior to the first-line antibiotic treatments for BV. An earlier trial found it was as effective as clindamycin. Although it's not approved by the US Food and Drug Administration, dequalinium chloride has been used in Europe for decades and is recommended by international and European guidelines as an alternative treatment for BV.
In a commentary that accompanies the study, researchers from the University of Maryland School of Medicine and the Johns Hopkins University School of Medicine say the findings from the two trials suggest dequalinium chloride could be a much-needed alternative treatment for BV. But they highlight three important evidence gaps.
The first is that the two trials were conducted in Europe, and vaginal microbiota composition and response to dequalinium chloride may vary regionally. The second is the lack of long-term data on BV recurrence following treatment with dequalinium chloride. Finally, data on the safety of intravaginal dequalinium chloride in pregnant women is limited.
They call for robust clinical trials to help fill these gaps and expand treatment options.
"It is imperative that we expand the toolkit of available BV treatments," the authors wrote. "Alternatives that are at least as effective as nitroimidazoles and clindamycin would be welcome additions. Treatments that effect a lasting cure would be paradigm-shifting."
