**6. Treatment**

All treatment guidelines agree that the best approach to the treatment of *H. pylori* is to be successful in the first attempt, thereby avoiding retreatment and reducing costs, anxiety, and further promotion of resistant strains [8]. *H. pylori*, in contrast to other bacterial gastrointestinal infections, requires a combination of antibiotics. Various factors, such as the slow growth rate of *H. pylori*, bacterial virulence, the inability of the drug to reach an appropriate level in the gastric mucus layer, and

#### *Current Perspective on the Treatment of* Helicobacter pylori *Infection DOI: http://dx.doi.org/10.5772/intechopen.114135*

inactivation of antibiotics at low pH levels, make it difficult to eradicate with any single antibiotic [8]. Commonly used antibiotics for treatment include metronidazole, clarithromycin, amoxicillin, tetracycline, and bismuth. In some cases, third-line treatments may involve the use of ciprofloxacin, moxifloxacin, levofloxacin, furazolidone, or rifabutin [8].

*H. pylori* treatment requires different combinations of the antibiotics mentioned above, combined with bismuth salt or an acid-suppressive agent, as none of the above-mentioned antibiotics can work as monotherapy [8]. The rationale for adding an acid-suppressive agent, either a proton pump inhibitor PPI or an H2 receptor blocker, to the regimen is that it increases gastric pH, hence extending the half-life of antibiotics and altering the microenvironment of the bacterium [8]. Moreover, some PPIs have antimicrobial activity, which helps reduce the side effects of the given antibiotics and improves compliance [2, 8]. Bismuth compounds have been used in the treatment of peptic ulcers since the 19th century. Colloidal bismuth subcitrate, bismuth subsalicylate, and ranitidine bismuth citrate are commonly used as part of anti-*H. pylori* therapy. The mode of action of bismuth salts is complex and includes inhibition of protein synthesis, adenosine triphosphate (ATP), and cell wall, working synergistically with antibiotics and increasing the efficacy of anti-*H. pylori* therapy [8].

### **6.1 Standard therapy**

The standard triple therapy for *H. pylori* treatment consists of amoxicillin/ clarithromycin and a PPI or metronidazole/clarithromycin with a PPI given daily for 7–14 days. Studies have shown that a 14-day duration of triple therapy is much more effective and achieves a higher eradication rate compared to a 7-day therapy [7]. However, this treatment has been shown to fail 20–30% of the time due to poor compliance, prescription errors, short treatment duration, or resistance [8]. Due to increasing resistance to clarithromycin, it is recommended as first-line therapy in places/regions where resistance is lower than 15% [1]. An alternative to standard triple therapy is to combine amoxicillin, metronidazole, and clarithromycin with a PPI for 10–14 days, known as a concomitant treatment, which has better eradication rates compared to standard triple therapy [1, 7]. Adding probiotic to standard triple therapy, specifically Saccharomyces boulardii and Lactobacillus, improves eradication rates, reduces adverse effects, and improves compliance [7].

#### **6.2 Sequential therapy**

Sequential therapy consists of a five-day course of a PPI and amoxicillin twice a day, followed by a five-day course of a PPI with clarithromycin and metronidazole or tinidazole. The overall eradication rate for sequential therapy is 84%, with an eradication rate of 74% in areas where clarithromycin resistance is prevalent [7]. Sequential therapy has been shown to be superior to standard triple therapy for a 7-day duration but not superior to standard triple therapy for a 14-day duration, bismuth quadruple therapy (BQT), or non-bismuth quadruple therapy [9]. Moreover, sequential therapy has comparable compliance, incidence of side effects, and therapy interruption rates compared to standard therapy [9]. It has shown positive outcomes in both pediatric and geriatric populations, with a trial enrolling patients over 65 years of age showing better outcomes in patients treated with sequential therapy compared to the standard therapy regimen [10].

#### **6.3 Bismuth-based quadruple therapy**

Bismuth-based quadruple therapy is emerging as an alternative choice for first-line treatment in multiple studies. It includes a bismuth salt (subsalicylate or subcitrate) with metronidazole, tetracycline, and a PPI, all taken four times daily for 10–14 days. The eradication rate of a 10-day bismuth-based therapy was 90.4%, and a 14-day therapy had a rate of 97.1%, indicating that an increased duration correlated with better eradication of *H. pylori* infection [11]. This therapy is primarily used when penicillin cannot be used or when clarithromycin resistance is over 15% [12]. It is often used as salvage therapy when first-line therapy fails [6]. Longer treatment durations and consideration of metronidazole resistance are highlighted as important factors for achieving higher eradication rates [12].

#### **6.4 Non-bismuth-based quadruple therapy**

Non-bismuth-based quadruple therapy, also known as concomitant therapy, involves a combination of a PPI with amoxicillin, metronidazole, or tinidazole, and clarithromycin, given twice daily for 10–14 days. It has the highest eradication rates of about 90%, even in areas of high metronidazole and clarithromycin resistance [7]. However, the success rate of a 7-day concomitant therapy has decreased due to changes in clarithromycin resistance patterns [13].

#### **6.5 Levofloxacin-based triple therapy**

Levofloxacin-based triple therapy consists of a combination of a PPI and amoxicillin given twice daily, with levofloxacin given once daily. It can be used as salvage therapy and is better tolerated than bismuth-based quadruple therapy [7]. Levofloxacin can also be given as sequential therapy, consisting of a PPI with amoxicillin for 5–7 days, followed by a PPI with levofloxacin and nitroimidazole for 5–7 days, or as quadruple therapy, composed of levofloxacin, a PPI, nitazoxanide, and doxycycline administered for 7 or 10 days [14].

#### **6.6 Rifabutin triple therapy**

Rifabutin triple therapy has also been highlighted as effective in *H. pylori* eradication, and most guidelines recommend it as salvage therapy when first-line therapy fails [2, 6]. It consists of amoxicillin 1 g, omeprazole 40 mg, and rifabutin 50 mg for 14 days [2].
