Helicobacter pylori gastritis rescue therapy
What is Helicobacter pylori?
This is an ancient bacteria (germ) able to live in the acidic stomach lining. About 40% of Australians over 60 have it in their stomach lining. Other high risk groups include close family members with peptic ulcer or gastric cancer, migrants or indigenous groups from high-prevalence areas and those from crowded living conditions, institutions or lower socio-economic groups and health professionals with higher exposure to H. pylori positive patients. Most are infected in childhood.
| Decade of birth | Prevalence range (%) |
|---|---|
| Earlier than 1920 | 53.0 |
| 1920s | 20.0–46.0 |
| 1930s | 26.0–37.0 |
| 1940s | 16.7–27.0 |
| 1950s | 11.7–24.0 |
| 1960s | 18.0–18.4 |
| 1970s | 5.0–12.4 |
| 1980s | 4.0–10.0 |
| 1990s | 4.0–8.3 |
It is a harmless coloniser without symptoms in most and a friendly preventer of disease is some. It causes gastritis (an inflamed stomach) in most, gastric or duodenal ulcers in up to 20%, and gastric cancer in up to 2%.
How is it diagnosed?
How is it treated?
Standard triple therapy (PPI+): AMX+CLR 7-14/7, MTZ+CLR 7-14/7
Rescue therapy (PPI+): AMX+LEV 10/7, CBS+TET+MTZ 7-14/7, AMX+RFB 10/7
Off-label Quadruple therapy (5th line): VPZ+AMX+RFB 7/7+ VPZ+CBS+TET 7-10/7
- bactericidals: CLR, MTZ, LEV, RFB
- avoids resistance: AMX, TET, CBS, PPI
- avoid failed combinations
First line treatment is "Triple therapy" 7-14 days (amoxycillin+ clarithromycin + esomeprazole) eg. "Nexium HP7" or, if true amoxycillin allergy, clarithromycin (500mg bd - 250mg 14+1 x 2) + metronidazole (400mg bd 21+1) + esomeprazole (40 mg bd). This cures up to 90% in clinical trials, and somewhat lower rates in Australian "real world" settings.
Causes for failure include: non-adherence and resistance (clarithromycin 8%, metronidazole 50%, amoxycillin rare) depending on country of origin.
Drug interactions need consideration with clarithromycin.
Penicillin/amoxycillin allergies rarer than thought: Amoxycillin is a very important part of the treatment for this stubborn infection. Approximately 10% of patients report unable to take penicillin due to allergy. However, up to 90% of these patients do not have a true allergy. Serious allergic reactions to amoxycillin such as anaphylaxis occur in less than 0.05%. If it is not 100% certain you have a true penicillin allergy, the doctor might send you to an allergist for a blood test and careful skin prick testing.
Rescue therapy is use as plan B, C or D and each have 60-80% cure success:
a) levofloxacin-based 10 day therapy: levofloxacin 500mg+amoxycillin 1g ( 500mg x 40+0 streamline 10402)+ PPI BD ( esomeprazole 20mg 30+1 streamline 8775)
b) quadruple therapy 7-14 days: colloidal bismuth subcitrate 120mg qid +tetracycline 500 mg qid +metronidazole 400mg tds (or qid if resistance)+ high dose PPI bd*
c) rifabutin-based 10 day therapy: amoxycillin +rifabutin+ PPI**
d: amoxycillin 375mg 120 caps + vonoprazan 20mg 30 caps + bismuth 300mg 30 caps, Furazolidone 100mg 30 caps, rifabutin 60mg 5 caps, 120mg 16 caps (10 day Webster pack as directed)
*Adverse effects are common in up to 50% but less than 5% stop therapy within 5 days due to side effects eg. nausea or vomiting, loose or dark discoloured or black stools or tongue, dry mouth or taste disturbance; clear written instruction maximise adherence. This regimen is often used after failure of levofloxacin-based triple therapy, but may be used beforehand. While taking tetracycline, your skin may be more sensitive to sunlight. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn so use careful sun protection measures.
**Rifabutin treatment is best left for those experienced in its use. First, this is expensive; second, severe leucopenia and thrombocytopenia can occur (unusual with short course under 500 mg/day); third, several drug interactions need consideration. Finally, multi-resistant strains of Mycobacterium tuberculosis are on the rise and rifabutin is an important TB drug. So use needs to be limited to avoid further increases in resistance. Rifabutin should be used only as rescue therapy after amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin have failed.
Will the triple or quadruple rescue therapy cure my H pylori?
After 30 years of research, there is no ideal H pylori cure without side effects. Even after two "triple therapy" failures (PPI plus amoxycillin plus clarithromycin or metronidazole), H. pylori can still be cured with "quadruple" or levofloxacin-based “rescue” therapy. In "rescue" studies this levofloxacin-regimen (esomeprazole 40mg, amoxicillin 1g and levofloxacin 500mg twice a day for 10 days) worked in over 80%. Our practice experience has been 90% successful cure. Traditional "quadruple" therapy has about 70% success. Unfortunately, resistance to quinolones is easily acquired, and in countries with a high consumption of these drugs, the resistance rate is already relatively high. Levofloxacin, metronidazole and clarithromycin resistance will reduce the successful eradication rate.
Resistance of H. pylori to antibiotics in India over the past 10 years
from Dutta, A.K. Choosing optimum regimen for treating Helicobacter pylori infection: Regional data may be the quintessential guide. Indian J Gastroenterol 42, 448–451 (2023)
What are the possible risks or side effects?
Any decision to treat Helicobacter pylori involves a balance of the risk of not treating against the risk of treating.
Levofloxacin: If you decide to treat with levofloxacin, one study described no side effects in 72% and only 3% had side effects severe enough to require stopping. The most frequent side effects include nausea, headache, diarrhoea, and rashes. There are reported cases of inflamed tendons and tendon rupture and Clostridium difficile diarrhoea.
As with all medications, there is the possibility of unknown risks and late side-effects. However, after more than 15 million prescriptions in the US, the rate seems very low - less than 4 in a million.
Why is levofloxacin, tetracycline, colloid bismuth or rifabutin difficult to find in most pharmacies?
These first three drugs are not registered in Australia. This means the "Therapeutic Goods Administration (TGA) has not evaluated them either for quality, safety and or efficacy” and rifabutin is not approved by the TGA for H pylori infection. In spite of this, levofloxacin does seem simpler to take than quadruple therapy with fewer side effects. Your doctor will need to seek special access from the few special Compounding pharmacies that have supply OR in special cases seek approval from the government TGA (tel: 6232 8111) to use for your condition via a Category B form to Canberra. Levofloxacin cost is about $60-100 depending on health card status and rarely needs a category B form if you apply at the right pharmacy.
Suggested steps for TGA approval (rarely needed after 2022):
- Your doctor faxes Category B form to TGA with a request to send approval to your pharmacy*.
- Contact your pharmacist or Ramsay pharmacy (T:8425 3911, F: 8425 3910) or Cincotta (T:98971011, F:88414532) or Customised Compouding (T: 02 8049 9700, F: 1300 726 858, info@customisedcompounding.com.au) after 2 weeks to confirm levofloxacin approval. If there is a delay, call TGA direct (6232 8111) and request they fax to pharmacy
- On approval, provided you have delivered the script, you may collect the levofloxacin in person or, pay over the phone and the pharmacist will post it to you.
- For levofloxacin-base rescue therapy : take 3 medications morning and night for 10 days as directed. Levofloxacin (½ hr before, or if you forget 2 hours after food), Nexium (½ hour before food), amoxycillin (no special directions)
- Stop only if significant side effects and let your doctor know.
- Not less than 4 weeks after your last antibiotic taken and off any PPI mediation (omeprazole Losec, pantoprazole Somac, rabeprazole Pariet, esomeprazole Nexium, lansoprazole Zoton, etc) for 1-2 weeks , repeat the urea breath test. Then make an appointment to review the result with your doctor to confirm H pylori cure.
- To assist with our research and future patient care, we would appreciate if you would fill out the brief survey below (or send an email to Dr Samuel's rooms) indicating whether the levofloxacin therapy successfully cured your H pylori infection and whether you had any side effects.
*Dr Samuel has no financial interest in Ramsay, Customised Compounding, Ramadan Pharmacy or Cincotta pharmacy. They are four pharmacies with expertise in dispensing difficult to attain medicines. Others include: Ramadan Pharmacy and Easy Script Compounding Pharmacy St Marys. You might prefer to shop around as prices vary.