Oral Vancomycin (OV), a highly controlled antibiotic most commonly used to treat Clostridium Difficile infections, has emerged over the last 20 years as an effective treatment for PSC, but there are important nuances to consider:
- The brand of vancomycin (manufacturer) appears to matter significantly in certain patients,
- The proper dose of Vancomycin is key to the results, and
- Additionally, the specific situation of a given patient: age, disease stage, and phenotype may all have an impact of the effectiveness of OV for any specific patient
- Vancomycin is not a cure - patients must take OV continuously
History of Vancomycin for PSC
Dr. Ken Cox at Lucile Packard Children's and Stanford University Hospital was the first to report positive results from treating a PSC patient with oral vancomycin in 1993. Dr. Cox was treating a pediatric patient who had both a Clostridium Difficile infection and PSC with oral vancomycin to address the C. Diff. Dr. Cox noted that in addition to resolving the C. Diff. Infection, the patient’s PSC also appeared to resolve while on OV.
Based on this result, Dr. Cox continued to use OV as a treatment for his pediatric PSC patients, with consistent and regular success over the following years. With the support of the Children's PSC Foundation, Dr. Cox tracked these results as part of a clinical trial from 2002 to 2016. The published paper of Dr. Cox’s clinical findings from use of OV to treat PSC can be found on our “Resources” page here: Research & Resources
Over time, Dr. Cox and his colleagues, including Dr. Yinka Davies, who is currently treating patients with PSC with OV in her practice at Sutter Health, identified important nuances in the use of OV for PSC.
The Brand or Manufacturer of Vancomycin
Over the years, the team at Stanford noticed that patients who were prescribed certain brands of OV did not have the same positive results that had been experienced by most patients.
The Dose of OV
Through their years of experience in treating PSC with OV, the Stanford team has been able to develop a very specific protocol for dosing of OV that appears to be most effective. They were also able to identify the key indicators of success and make adjustments to the OV dose for individual patients based on each patient's response.
The Stanford Protocol Today
After many years of clinical results and learning, Dr. Cox, Yinka Davies, and now Dr. Cox’s clinical practice successor at Stanford, Dr. Leina Alribadi, have developed a clear protocol that they use as the standard of care for PSC patients:
- Lupin brand OV: Stanford doctors now specifically prescribe OV produced by Lupin pharmaceutical company as they have seen consistent success with Lupin OV across all patients.
- Patients taking OV from other manufacturers have seen more variability in the results. One hypothesis for this variability in results from different brands is that the dissolution rate of the capsules may differ, which could impact the bioavailability of the drug. Here is a case report on this topic.
- Some patients taking OV from ANI Pharmaceuticals have seen positive results.
- Opening the capsule, which is not generally recommended for any medication, has also shown to improve results with brands of OV that have not been as consistently effective. In this case, patients, or their parents, either 1) pull the capsule apart and dissolve the OV powder into water and drink the solution or 2) remove the top half of the capsule and swallow the other half with the medicine in it.
- Dose: The Stanford Protocol suggests starting at 500 mg 3x/day for patients who weigh more than 30 kg and to increase the dosage until the patient’s symptoms normalize. For children under 18 who weigh less than 30 kg, the Stanford protocol suggests 50 mg/kg/day. The most common dose is 500 mg 3x per day, though others respond better to a higher or lower dose.
Patients who have attempted to stop OV treatment after seeing success have had recurrence of the disease, which suggests that OV is modulating some disease mechanism but not eradicating the disease. There have also been instances of patients stopping OV treatment and then restarting OV due to recurrence and then not seeing the same positive result from the OV therapy.
There are patients who have been on OV as treatment for PSC, with continuous success, for over 20 years.
Through the 20+ years of treating patients with OV for PSC there are no reported cases of Vancomycin Resistant Enterococcus (VRE) - an infection of bacteria that is resistant to Vancomycin. VRE infections can be life threatening and are always a concern when someone is being treated with vancomycin. However, this concern has not yet been an issue for PSC patients on OV.
Additionally, OV is a large molecule drug that is not absorbed into the bloodstream and, therefore, simply passes through the digestive tract. This reduces the possibility of other complications with taking OV over long periods of time.
Opening the Capsule
Why would a patient have improved results by opening the OV capsule prior to ingesting the OV as described above?
The hypothesis is that capsules from different manufacturers have different dissolution rates. That is, the capsules from different manufacturers dissolve in different ways and at different rates. If so, this would impact the bio-availability of the drug inside the capsule because capsules that dissolve quickly would expose the drug early in the digestive tract, and capsules that dissolve slowly would expose the drug later in the digestive tract. This difference in bio-availability based on different capsule dissolution rates could impact the ability of the drug inside the capsule to have the effect needed in the areas of the digestive tract in which it is needed.
By opening the capsule, all of the OV inside the capsule becomes available in the patient’s GI tract right away and passes through the entire GI tract fully available to the microbiota of the GI tract, therefore, providing the most bio-availability of the drug throughout the GI tract.
Again, this is hypothetical, but it is a goal of the Children’s PSC Foundation to support an analysis of the dissolution rates of varying capsules from different OV manufacturers to attempt to clarify why doctors and their patients have different levels of success with OV based on manufacturer.
The Debate Over Vancomycin
Because of the reported success with OV for PSC at Stanford, there have been other clinical trials of OV for PSC by other health care institutions, and, unfortunately, some of these trials have not been successful. Additionally, there have been patients who have tried OV for PSC and not had positive results. Therefore, there are people in the PSC community who do not support the use of OV for PSC. However, these unsuccessful trials or attempts at treatment may not have taken into account the nuances described above based on the learnings and experience of the Stanford team.
Even so, the success of OV as a treatment for PSC has been breaking through and steadily building momentum simply based on actual results for patients. As a result, more and more physicians at health care institutions around the US, who have been following the Stanford Protocol, are seeing success and are now using OV as their standard treatment for PSC with consistent success.
The Children's PSC Foundation is dedicated to supporting research and trials that will 1) build on the knowledge from the success of oral vancomycin for PSC to better understand the mechanisms at play to potentially lead to a cure for PSC, 2) address any debate about the role of oral vancomycin through further data collection and evidence gathering - ideally a double blind placebo controlled trial, and 3) explore other areas of potential treatment or cure for PSC such as the auto-immune activity in the liver and the dysbiosis in the microbiome.