Original Article

Comparison of levofloxacin versus clarithromycin efficacy

in the eradication of Helicobacter pylori infection

Ali Akbar Haji- Abstract

Aghamohammadi (MD) 1 Background: Helicobacter pylori (H.pylori) infection causes multiple upper
Ali Bastani (MD) 1 gastrointestinal diseases but optimal therapeutic regimen which can eradicate infection in
Arash Miroliaee (MD) 1 all the cases has not yet been defined. This study was designed to evaluate the efficacy of
Sonia Oveisi (PhD) 2
triple levofloxacin-based versus clarithromycin-based therapy.
Saeed Safarnezhad (MD) 1
Methods: In this open-label randomized clinical trial study 120 patients who had
esophagogastroduodenoscopy (EGD) with positive rapid urease test (RUT) were enrolled
and divided into 2 groups. Case group was treated with levofloxacin (500 mg daily) plus
amoxicillin (1 gr twice a day) plus omeprazole (20 mg daily) for 2 weeks. Control group
was treated with clarithromycin (500 mg twice a day) plus omeprazole (20 mg daily) for 2
1. Department of Internal weeks. After the main course of treatment, they received maintenance treatment with
Medicine,Velayat Clinical Research omeprazole for 4 weeks. Stool antigen test was performed on them after two weeks of not
Development Unit, Qazvin having any medicine.
University of Medical Sciences,
Qazvin, Iran. Results: H.pylori eradication (intention to treat analysis) was successful in 75% of case
2. Metabolic Diseases Research group and 51.7% of control group showing a significant difference (P=0.008). H.p
Center, Qazvin University of infection eradication (per-protocol analysis) was successful in 80.4% in case group and
Medical Sciences, Qazvin, Iran.
57.4%% in control group showing significant difference (P=0.009). Drugs adverse effects
causing discontinuation treatment were seen in 5% of case group and 3.3% of control
group which have not shown a significant difference between the two groups (P=0.648).
Conclusion: Triple therapy with levofloxacin-based regimen has better efficacy than
* Correspondence: clarithromycin-based regimen and as safe as it is.
Saeed Safarnezhad, Velayat Keywords: Helicobacter pylori, Dyspepsia, Peptic ulcer, Rapid urease test, Stool antigen.
Clinical Research Development Citation:
Unit, Velayat Hospital, 22 Bahman Haji Aghamohammadi AA, Bastani A, Miroliaee A, et al. Comparison of levofloxacin versus
Blvd, Qazvin, Iran, P.O.BOX
34719-76161 clarithromycin efficacy in eradication of Helicobacter pylori infection. Caspian J Intern Med 2016;
7(4): 267-271.

Caspian J Intern Med 2016; 7(4):267-271

E-mail: T he presence of organisms was first observed more than 100 years ago and their
association with gastritis has been recognized since the 1970s (1). The true implication of
saeed_safarnezhad@yahoo.com
Tel: 0098 2833760620 these microbes was not fully realized, however, until 1982 when Marshall and Warren
Fax: 0098 2833790611 identified. Campylobacter pyloridis on culture, which was reclassified later it as H.pylori
(2). H.pylori is the most common chronic bacterial infection in humans (3, 4). It has been
demonstrated worldwide and in individuals of all ages. Conservative estimates suggest that
Received: 26 April 2016 50 percent of the world population is affected. Infection is more frequent and acquired at
Revised: 14 July 2016 an earlier age in the developing countries compared with industrialized nations (4). This
Accepted: 31 July 2016 organism is now known to cause chronic gastritis, dyspepsia, most peptic ulcers, gastric
cancers and lymphoma. Hence, eradication of H.pylori can control or cure such diseases
(5). Multiple regimens have been evaluated for H.pylori infection therapy in randomized
controlled trials (6-10). Despite the numerous studies, the optimal therapeutic regimen has not
yet been defined.
 Caspian J Intern Med 2016; 7(4):267-271
268 Haji Aghamohammadi AA, et al.

An appropriate effective regimen should be considered disease such as diabetes mellitus, hypertension, cirrhosis,
with regard to cost, side effects, and ease of administration. cerebrovascular attack, renal insufficiency, coronary artery
Triple therapy with a proton pump inhibitor (PPI), disease and gastric cancer, noncompliance to treatment or to
amoxicillin and clarithromycin is the most commonly complete duration treatment and coexistence of other
recommended for first line treatment of H.pylori and defined conditions needing to consume other antibiotics or non-
as standard protocol (11-13). However, resistant types of steroidal anti-inflammatory drugs (NSAIDs).
H.pylori to this regimen are rising (5, 14, 15) and we need to Two-hundred and thirteen patients were recruited and
evaluate more potent and available drugs in the first line 120 patients entered to the study according to the inclusion
treatment of H.pylori Previously, levofloxacin as a family criteria. After completing the consent form, 120 patients
member of flourquinolones was effective and safe for second were divided into 2 groups using balance block method
line and rescue therapy in the eradication of H.pylori (16-18) (each group contained 60 patients). The case group was
but there are little experiments about the efficacy of this drug treated with levofloxacin (500 mg daily) plus amoxicillin (1
as the first line treatment for H.pylori infection. Also, with gr twice a day) plus omeprazole (20 mg daily) for 2 weeks.
the consideration of high prevalence of H.pylori infection in The control group received clarithromycin (500 mg twice a
Iran that was reported over 90% (19, 20) we decided to day) plus amoxicillin (1 g twice a day) plus omeprazole (20
design the current study to evaluate the efficacy of triple mg daily) for 2 weeks. Maintenance treatment with
levofloxacin-based versus clarithromycin-based therapy. omeprazole was continued for 4 weeks. Two weeks after the
end of treatment period, all patients were tested by H.pylori
infection with stool antigen test using monoclonal antibody
Methods against H.pylori antigen in collected stool. The stool antigen
This study was a single-center open-label randomized test was performed using the HpSA enzyme linked
clinical trial to compare the efficacy of levofloxacin versus immunosorbent assay (ELISA) method (Premier Platinum
clarithromycin in the eradication of H.pylori infection. Our HpSA, Meridian Diagnostics, Cincinnati, OH, USA).
primary end point was the drug side effects and secondary Baseline information, demographic features, clinical and
endpoint was H.pylori infection eradication. This study was endoscopy findings were recorded. Data regarding drugs
done under the supervision of the Ethics Committee of adverse effects were provided 1 to 2 weeks after the start of
Qazvin University of Medical Sciences (reference number: treatment. At endpoint, the two groups were compared with
9943) and also was registered in Iranian Registry of Clinical respect to proportion of H.pylori eradication. Stool
Trials (IRCT registration number: IRCT2015081818124N2). examination was selected because of its cost effectiveness
The participants of this study were selected consecutively and availability. In addition, its diagnostic sensitivity and
from patients who had upper gastrointestinal symptoms and specificity are comparable with urease breath test at 94% and
had undergone esophagogastroduodenoscopy (EGD) in 92%, respectively (5). Data were analyzed with SPSS16
Velayat Hospital in Qazvin city, central Iran over a 9-month (SPSS Inc., Chicago, IL, USA). Chi-square test and Fisher’s
period from February 20 2015 to October 22 2015. exact test were used in proportions and independent t-test
The inclusion criteria were as follows: all patients was used to utilize the comparison of quantitative data. A p-
undergoing upper endoscopic procedure (EGD) with positive value of 0.05 or less was considered statistically significant.
rapid urease test (RUT) aged between 18 and 70 years old. All p-values were two-sided. The intention-to-treat (ITT)
RUT was applied to biopsies taken from the stomach antrum analysis included all patients who had taken one tablet of
mucosa, to identify the presence of infection. RUT was drugs. In the per-protocol analysis, the patients with severe
considered positive if reagent tube color containing biopsy drug side effects and those who lost follow-up examination
sample changed to red during the 24 hours after EGD. The were excluded.
exclusion criteria were as follows: pregnancy, previous
consumption of proton pump inhibitors (PPI) or bismuth and
antibiotics in the preceding month, gastrointestinal (GI) Results
bleeding or any complication of peptic ulcer disease (PUD), One hundred and twenty patients were enrolled in two
consumption of alcohol or substance; advanced chronic groups and each group contained 60 patients. In the case
Caspian J Intern Med 2016; 7(4): 267-271
Levoflonacin versus clarithromycin in eradication of H.pylori 269

group, one patient was lost to follow-up and was excluded of clinical features and endoscopy findings in both groups
and in the control group, four patients were lost to follow-up are shown in table 1. Severe side effects resulting to the
and hence, were excluded. Also, during-follow-up, 3 patients discontinuation of treatment were seen in 3(5%) cases and in
in case group and 2 patients in control group discontinued 2(3.6%) controls (P=1). Frequencies of mild and severe side
treatment because of severe drug side effects (figure 1). The effects were shown in table 2. H.pylori eradication rates for
mean age of the patients was 43.3±13.85 years old in case intention-to-treat analysis were observed in 45 (75%) cases
group and 42.85±12.78 years old in the control group. There versus 31(51.7%) controls (P=0.008). H.pylori eradication
was no statistical difference between groups (P=0.775). rates for per-protocol analysis were 45.56 (80.4%) in the
Twenty seven (45%) patients in the case group and 26 case group and 31.54 (57.4%) in the control group.
(43.3%) were males in the control group. No significant (P=0.009).
difference was found between groups (P=0.854). Frequency

Figure 1. Schematic representation of groups in study

Table 1. Frequency of patient symptoms and EGD† finding in both groups

Groups Clarithromycin Levofloxacin P-value*
Symptom (N=60) (N=60)
Epigastrium pain 38(63.3%) 37(61.7%)
Nonspecific abdominal pain 7(11.7%) 12(20%)
Nausea 1(1.7%) 3(5%) 0.440
Bloating 11(18.3%) 8(13.3%)
Early satiety 3(5%) 0(0%)
EGD† Finding
Esophagitis 3 (5%) 4(6.7%)
Antral erythema 29(48.3%) 22(36.7%)
Gastro-duodenal erosion 7(11.7%) 10(16.7%)
Gastric ulcer 6(10%) 9(15%) 0.740
Duodenal ulcer 4(5%) 2(3.3%)
Esophagitis& Antral erythema 7(11.7%) 5(8.3%)
Non-ulcer dyspepsia 5(8.3%) 8(13.3%)
(Normal EGD)
* P value less than 0.05 is significant †Esophagogastroduodenoscopy
 Caspian J Intern Med 2016; 7(4):267-271
270 Haji Aghamohammadi AA, et al.

Table 2. Side effects of treatment in both groups eradication rate but studies in India and Western countries
Groups Clarithromycin Levofloxacin P- had higher eradication rates (14, 21, 17, 18).
Side effects (N=56) (N=59) value Overall in our study, drug side effects were seen in 8.5%
Nausea 4(7.1%) 2(3.4%) of the patients in case group and 12.5% in the control group.
Skin rash& itching 0(0%) 2(3.4%) 0.280 Additionally, severe side effects causing discontinuation of
Diarrhea 3(5.4%) 1(1.7%) treatment regiments were seen in 5% of patients in case
None 49(87.5%) 54(91.5%) group and in 3.6% of patients in control group indicating
* P-value less than 0.05 is significant levofloxacin is as safe as clarithromycin. These findings are
consistent with other studies (15, 17, 18). The cost of
Discussion treatment may partly affect in the decision to select treatment
Extensive efforts have been made to determine regimen. Regarding the higher cost of levofloxacin, this
individuals with H.pylori infection requiring eradication. At issue may prevent the use of levofloxacin as the first line of
present, there is a broad consensus to eradicate H.pylori empiric treatment for H.pylori infection. This study has
infection in peptic ulcer disease and dyspepsia (5). These limitations regarding its insufficient sample size particularly
patients were the main participants in our study. in showing significant adverse effects between the two
In our study, eradication rate was 75% in case group and groups. In addition, we did not collect data regarding the
51.7% in the control group according to intention- to-treat efficacy of treatment on clinical features of patients.
analysis. In addition, eradication rates were 80.4% in case In conclusion, the results of this study show that
group and 57.4% in control group according to per-protocol levofloxacin-based triple therapy is preferable to
analysis. These differences indicate that levofloxacin-based claritromycin-based regimen in H.pylori eradication to
triple therapy is more effective than clarithromycin based achieve an optimal eradication rate of 80% or more as
therapy in the eradication of H.pylori infection. In an earlier recommended in treatment guideline (5). Nonetheless, the
study by Gopal et al. (21) on 74 patients with peptic ulcer cost of treatment and the possible higher rate of severe
perforation, H.pylori eradication rates were 69% and 79% in reaction should be considered in the selection of this
clarithromycin-based regimen versus 80% and 87% in regimen.
levofloxacin-based regimen on intention to treat and per-
protocol analysis respectively.
In another study (14) of patients with dyspepsia, H.pylori Acknowledgments
infection eradication rates were 66.67% for clarithromycin Authors of this article are thankful for the valuable
triple therapy and 94.87% for levofloxacin, based triple cordial and dedicated cooperation of Clinical Research
therapy as first line regimens. Development Unit of Velayat Hospital.
Similar results have been reported in a study of Chinese
population (22) with eradication rates of 74.5% and 78.2% in Funding: This study was funded by Qazvin University of
clarithromycin triple therapy, versus 82.4% and 83% in Medical Sciences.
levofloxacin based-triple therapy regimen according to Conflict of Interest: There is no conflict of interest in this
intention to treat and per-protocol analysis, respectively. study.
Discrepancies across various studies may be explained by
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