Final Reply
Neutropenia is somewhat idiosyncratic which means people who have a reaction to the rifabutin would likely develop it. As I review your past treatments my comments are:
1. Repeated treatments with clarithromycin or metronidazole are not very useful.
2. Since the acid blocker is inexpensive and relatively harmless, a much bigger dose is worth the effort and cost.
3. Similarly with amoxicillin, 1G three times daily adds some extra value and Helicobacter pylori never becomes resistant so keep using that part. It has been shown that even when it was used before, amoxicillin still has a good cure rate when given with a strong acid blocker.
4. So far, you have not used ciprofloxacin (as far as I can see). So if you use it, don't waste it by just adding it to a weak treatment. Add it to a strong treatment.
5. In Hong Kong, some years back, a cure rate of 90% was aceived in penicillin allergic people by using rifabutin and levofloxacin plus an acid blocker.
Putting this all together, you can see that our PARC treatment combines several good treatments in one.
As Helico Expert recommended, it is my first choice too.
You must discuss this with your doctor and make a decision yourself. Every patient is unique and our experience does not include people with chronic neutropenia. Depending on the cause of your neutropenia, the concern about rifabutin may be relative. In PARC, you actually only take the ciprofloxacin and rifabutin for five days (d6-d10). If you want a bigger safety factor, at least one person I know uses a lower dose of rifabutin, 150 mg per day only. If you wanted to go with that then I would suggest 150 mg two doses on day 6 then 150 mg one dose per day on days 7-10. Also, check your white cells before (on day 5) and after (on day 11-12) to see if anything happened.
Finally, lets not write off tetracycline as a possible fall-back treatment. It is a component of several good treatments and the teeth yellowing issue relates to long term use and un-erupted teeth I think. But we mainly use it when people are penicillin-allergic.
p.s. If I see anything new about this issue I will add it here below.
I looked at serveral references and have the following comments - which fit with my own experience..
A) Don't give rifabutin with clarithromycin as it increases the blood level of R and increases toxicity.
B) About half of the patients given 300 mg R for 14 days develop a reversible moderate ( 1000/mm^3 cell drop ) in the total white cells. About 1 in 20 patients has a severe drop.
C) Compared with the R doses and duration used in MAC (a type of TB in AIDS patients), the dose and duration is rather low in our PARC treatment (5 days only, and half dose if the regimen I recommended above is used).
D) My own experience from memory, in about four patients, is that the neutropenia, when it occurs, happens in patients who have clinical side effects of the rifabutin
Here is a reference I found in Medline. Your doctor might like to talk to Dr Apseloff who is the expert.
Identifier: 9753212
Authors: Apseloff G. Foulds G. LaBoy-Goral L. Willavize S. Vincent J.
Institution: Department of Pharmacology, The Ohio State University College of Medicine, Columbus 43210-1239, USA.
Title: Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers.
Journal of Clinical Pharmacology. 38(9):830-5, 1998 Sep.
Abstract
A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study was terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly. Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin. However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400% and 3,700%, respectively, of concentrations in those who received rifabutin alone. Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.
Here is some more information from a similar but earlier Apseloff paper (click to see full size):
- High and Low Dose Rifabutin Toxicity in AIDS - with azithromycin