Lower Eradication Rate Research Articles

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

BackgroundThe Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori (H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole.MethodsSixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval.ResultsThe eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high.ConclusionDespite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection.

M1079 Histological Factors That Affect Treatment Outcome of Helicobacter pylori Eradication in Peptic Ulcers in Korea: High Grade of Gastric Atrophy Was Associated with Low Eradication Rate

M1079 Histological Factors That Affect Treatment Outcome of Helicobacter pylori Eradication in Peptic Ulcers in Korea: High Grade of Gastric Atrophy Was Associated with Low Eradication Rate

M1078 Clinical Factors Potentially Influencing Eradication of Helicobacter pylori in Peptic Ulcer in Korea: Age Over 60 and Gastric Ulcer Were Associated with Lower Eradication Rate

M1078 Clinical Factors Potentially Influencing Eradication of Helicobacter pylori in Peptic Ulcer in Korea: Age Over 60 and Gastric Ulcer Were Associated with Lower Eradication Rate

Influence of Helicobacter pylori genotype on triple eradication therapy

The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency. The aims of this study were to investigate the relationship between different genotypes of H. pylori and bacterium-related histopathological lesions in patients with duodenal ulcer and to determine the effect of genotype on triple eradication therapy. Helicobacter pylori infections were analyzed in 78 duodenal ulcer patients. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin gene (vacA) subtype status of cultured strains were studied by PCR. Histopathological findings were graded using a described grading system. The patients were treated with triple-therapy regimens consisting of a proton pump inhibitor and two antibiotics twice daily for 7 days. Endoscopy was repeated at 4 weeks post-therapy to monitor ulcer healing and H. pylori eradication. The bacteria were genotyped from 66 patients, 57 of whom had H. pylori eradicated. The absence of cagA was associated with unsuccessful treatment. No difference was found with regard to vacA subtype between the successful and unsuccessful eradication groups. On histopathological examination, high H. pylori colonization density and intestinal metaplasia were associated with low eradication rate, while a high grade of neutrophil infiltration was associated with a significantly higher eradication rate. The data confirm the importance of cagA positivity as a predictor of successful eradication. When high H. pylori colonization density and intestinal metaplasia are present, therapy appears to be less effective. Therefore, these histopathological features may be involved in an unsuccessful therapeutic outcome.

A Pilot Study Evaluating Sequential Administration of a PPI–Amoxicillin Followed by a PPI–Metronidazole–Tetracycline in Turkey

There is no effective regimen for the eradication of Helicobacter pylori in our country. It may be due to the increasing prevalence of resistance to antibiotics used for the treatment of H. pylori. Recently, a study from Turkey has revealed that a new treatment scheme consisting of sequential administration of pantoprazole plus amoxicillin for 7 days followed by pantoprazole plus metronidazole, and tetracycline for the remaining 7 days was effective in the first-line treatment of H. pylori. Therefore, we aimed to confirm efficacy of a new therapy scheme in the first-line H. pylori eradication. This is a prospective, open label, single center, pilot study and included 32 patients infected with H. pylori diagnosed by both histologic examinations, rapid urease test and (13)C-urea breath test (UBT). The patients received a 14-day sequential regimen (pantoprazole 40 mg b.d. plus amoxicillin 1000 mg b.d. for 7 days and pantoprazole 40 mg b.d., metronidazole 500 mg b.d. and tetracycline 500 mg q.d. for the remaining 7 days). Eradication was assessed with (13)C-UBT 4 weeks after completion of the therapy. Intention-to-treat and per-protocol eradication rates were determined. At intention-to-treat analysis, the eradication rate was 50% (16/32). For the per protocol analysis, the eradication rate was 57% (16/28). There were no significant adverse effects and treatment compliance was good. A new therapy consisting of sequentially administered drugs for 14 days yielded unacceptably low eradication rates. This scheme was not efficient for H. pylori eradication in our region. Further investigations are needed to determine the effectiveness of this scheme in other regions of Turkey.

Treatment of Helicobacter pylori

Since the discovery of Helicobacter pylori in the early 1980s many treatment regimes have been developed to effectively treat this infection. International guidelines have allowed consensus on the best management and improved eradication rates. In recent years, increasing antimicrobial resistance has resulted in falling eradication rates with standard therapies. In this article, we review the most recent studies and guidelines in the treatment of H. pylori. Currently, the first-line treatment remains clarithromycin, amoxicillin or metronidazole and proton pump inhibitor twice daily, but a number of recent studies have shown low eradication rates with this treatment. Increased duration of therapy has been recommended to overcome the falling eradication rates. However, conflicting findings have been reported on the benefits of extending the length of traditional therapy. Sequential therapy may be an effective alternative to standard triple therapy in regions of increased antimicrobial resistance. Probiotics reduce side-effects from traditional regimens and may improve eradication rates. A quinolone-based second-line triple therapy appears to be effective and well tolerated. Bismuth-based quadruple therapy is also an effective alternative if available. In the future, regional antimicrobial resistance and eradication rates will determine the best treatment for H. pylori.

Low Efficacy Rate of Moxifloxacin‐Containing Helicobacter pylori Eradication Treatment: In an Observational Study in a Turkish Population

Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.

Persistence of Helicobacter pylori infection in patients with peptic ulcer perforation

Objective. In patients with perforated peptic ulcer (PPU) the convergence between the high eradication rate of Helicobacter pylori infection and low rates of ulcer relapse after treatment has been associated with reinfection by non-virulent strains. The objective of this study was to evaluate the persistence of infection by virulent H. pylori strains and ulcer recurrence in 33 patients with PPU one year after surgery and antimicrobial treatment. Material and methods. The histological evaluation and molecular detection of H. pylori cagA and ureA genes, vacA allelic types and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses of the glmM gene products from antral mucosa specimens were performed initially, 2–5 months and 1 year after therapy. Results. The density of H. pylori colonization was temporarily decreased (p<0.05) 2–5 months after therapy. After one year, complete eradication was achieved in only 7 patients (23%) at histological examination and recurrent ulcers were found in 3/33 (9%) patients. The vacA s1a allelic type of cagA-positive strains persisted in 19/33 (58%) PPU patients with identical PCR-RFLP fingerprints in 8/9 (89%) of the patients. Conclusions. In PPU patients with a low eradication rate of H. pylori infection after surgical and antimicrobial treatment, the frequent recrudescence of the infection is mostly caused by the persisting virulent strains of the cagA and vacA s1a subtypes. In the 1-year follow-up period the recurrent ulceration can be postponed just by the lowered colonization density of H. pylori after eradicative therapy.

2‐Week Triple Therapy for Helicobacter pylori Infection is Better Than 1‐Week in Clinical Practice: a Large Prospective Single‐Center Randomized Study

Proton pump inhibitor (PPI)-based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. The aim of this study was to compare the efficacy of 1-week versus 2-week triple therapies in H. pylori-positive patients. A total of 486 consecutive H. pylori-positive patients were randomized to receive omeprazole, 20 mg b.i.d., clarithromycin 500 mg b.i.d., and either amoxicillin 1 g b.i.d. or metronidazole 500 mg b.i.d. for 1 or 2 weeks. Upper gastrointestinal endoscopy and histology were performed at entry and 2 months after the end of therapy. H. pylori status was defined according to histology and urea breath test. At intention-to-treat analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin achieved a significantly higher eradication rate than 1- or 2-week regimens with metronidazole (70% versus 52%, p = .003, versus 56%, p < .01) and the same therapy for 1-week (70% versus 57%, p = .05). At per-protocol analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin showed a significantly higher eradication rate than 1-week of amoxicillin and metronidazole (77% versus 62%; p = .03) but no difference with 1-week same regimen (66%) or 2-week metronidazole and clarithromycin regimen (72%). Compliance and tolerability were good for all regimens. Two-week therapies, independently of antibiotic combination, lead to a significant increase of H. pylori eradication rate compared to 1-week therapies, with same compliance and tolerability, even if, taking account of low-eradication rates, one must question whether the triple therapy should still be used.

Effect of a probiotic food as an adjuvant to triple therapy for eradication of Helicobacter pylori infection in children

Objective Current recommendations for treatment of Helicobacter pylori infection include a proton pump inhibitor in combination with two antibiotics. We evaluated the potential activity of a probiotic food as an adjuvant to antibiotic triple therapy for eradication of H. pylori infection in children from Buenos Aires, Argentina. Methods Sixty-five children who tested positive for H. pylori, as diagnosed by 13C-urea breath test and endoscopy, were included in this study. Patients were randomized to receive 1-wk triple therapy plus probiotic food (treated group) or milk placebo (control) that was administered for 3 mo. Probiotic food consisted of 250 mL of a commercial yogurt containing Bifidobacterium animalis and Lactobacillus casei (10 7 colony-forming units/mL). Post-treatment urea breath test controls were performed 1 and 3 mo after the end of triple therapy. Results We found no significant differences in H. pylori eradication rates (ERs) at 1 and 3 mo between the treated group (ER = 45.5% and 42.4%) and the control group (ER = 37.5% and 40.6%). Relative risks between groups were 0.87 (95% confidence interval 0.58–1.32, P = 0.345) in the first month and 0.97 (95% confidence interval 0.64–1.46, P = 0.542) in the third month. Conclusions We could not demonstrate an adjuvant effect of the studied probiotic food to triple therapy in the eradication of H. pylori infection in children in Buenos Aires, Argentina. However, we found lower ERs than those reported for the same therapeutic scheme in developed countries, indicating that bacterial resistance and alternative therapeutic strategies should be studied.

Combinations containing amoxicillin–clavulanate and tetracycline are inappropriate for Helicobacter pylori eradication despite high in vitro susceptibility

The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection. The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared. The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups. Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.

Clarithromycin-Resistant Genotypes and Eradication of Helicobacter pylori

Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance. To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. Post hoc subgroup study from a multicenter, randomized trial. Two hospitals in central and southern Italy between January and December 2001. 156 patients with H. pylori infection. Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks. 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily. Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024). The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (70 euros per patient). The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

Eradication rate of Helicobacter pylori according to genotypes of CYP2C19, IL-1B, and TNF-A.

Lansoprazole, amoxicillin, and clarithromycin are commonly used drugs for eradication of Helicobacter pylori (H. pylori). A few studies reported that the eradication rate was influenced by the functional polymorphism of CYP2C19, whose product metabolizes proton pomp inhibitors including lansoprazole. This study examined the eradication rate among 67 participants in the polymorphism study who visited Daiko Medical Center, Nagoya University from July 2004 to October 2005. The participants aged 20 to 69 years were classified into three group according to CYP2C19 genotype; rapid metabolizers (RM) with *1*1 genotype, intermediate metabolizers (IM) with *1*2 or *1*3 genotype, and poor metabolizers (PM) with *2*2, *2*3, or *3*3 genotype. For the genotype classification, G681A (681G for *1 and 681A for *2) and G636A (636G for *1 and 636A for *3) were genotyped by PCR with confronting two-pair primers (PCR-CTPP). They were also genotyped for IL-1B T-31C and TNF-A T-1031C by a duplex PCR-CTPP. The eradication rate was 70.0% for RM, 93.9% for IM, and 85.7% for PM. The difference in the rate between RM and IM+PM was statistically significant (p=0.025). The eradication rate was highest for those with IL-1B -31CC; the p value was marginal among the whole subjects (chi2=3.78, p=0.05) and not significant among the RM group (chi2=1.60, p=0.21). The genotypes of TNF-A T-1031C had no associations with the eradication rate. But among the RM group, the odd ratio (OR) of the TNF-A CT for the eradication rate relative to TT was marginally reduced (OR=0.05, 95% confidence interval, 0.002-1.19). The present study confirmed the low eradication rate for RM. The reproduced finding provides evidence that the CYP2C19 genotype is useful to predict the success of the treatment. For the RM group, alternative regimens expected to be with a higher eradication rate will be recommended, especially to those with the TNF-A -1031C allele.

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

Optimal anti-Helicobacter pylori treatment has not yet been established. To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.

CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori.

Proton pump inhibitors, metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2C19, are essential drugs for Helicobacter pylori eradication. It was reported that patients with CYP2C19 wild type in Asia had lower eradication rates. This study tests the hypothesis that CYP2C19 wild type ( wt/wt ) in white patients is also associated with a higher probability of treatment failure. This was a cohort study involving 131 H pylori -positive white (German) patients treated by quadruple therapy including lansoprazole (30 mg twice daily for 5 days). Eradication success, as well as lansoprazole trough steady-state serum concentrations, was determined according to different CYP2C19 genotypes. We found 3 homozygous variant patients (2.3%) ( mt/mt, CYP2C19*2/*2 ), 42 heterozygous patients (32.1%) ( wt/mt, CYP2C19*1/*2 ), and 86 wild-type individuals (65.6%). Significant differences in eradication success could be found between wt/wt patients (80.2%) versus combined mt/mt (100%) and wt/mt patients (97.8%) ( P <.01; odds ratio, 10.8 [confidence interval, 1.4-84]), which were associated with corresponding changes in the serum levels of lansoprazole (median, 753 ng/mL for mt/mt, 59 ng/mL for wt/mt, and 21 ng/mL for wt/wt; P <.001). Apart from antibiotic resistance, CYP2C19 polymorphism was the most important influencing factor for eradication success on multivariate analysis ( P <.0001). Eradication rates of H pylori highly depend on CYP2C19 in white patients if standard doses of lansoprazole (30 mg twice daily) are administered within a quadruple regimen. Because wt/wt individuals have lower eradication rates and lower serum concentrations of lansoprazole, these patients might benefit from a higher proton pump inhibitor dosage.

Helicobacter pylori: today's treatment, and possible future treatment.

Helicobacter pylori induces chronic superficial gastritis which in some patients may lead to peptic ulcer disease, while a subset of infected individuals develop gastric cancer or gastric lymphoma. Consensus guidelines recommend that patients with a known H. pylori infection receive eradication treatment. Successful treatment requires that antibiotics be used in combination with acid suppressants or bismuth, and although the list of effective antibacterials is short, regimens such as amoxicillin and clarithromycin or metronidazole and clarithromycin with the proton pump inhibitor omeprazole have achieved eradication rates of approximately 90% in trials. However lower eradication rates are probably more common, and strains resistant to clarithromycin or metronidazole, or both, are of concern. Stable amoxycillin resistance has also been reported. Efforts are underway to discover and develop novel therapeutics, both H. pylori specific antibacterial drugs and a therapeutic vaccine. Impetus to these efforts has been provided by the availability of the genome sequences of two different H. pylori isolates. In the case of drug discovery, a genome-based strategy facilitates the expeditious selection of novel lethal targets not used by today's antibiotics, providing the opportunity to identify novel classes of antibacterials. Vaccine discovery and development has largely focused on a small number of antigens selected by conventional means. Recent reports that mucosal and serum antibody titers do not appear to be essential for protection against H. pylori in murine models suggest that that a wider range of H. pylori proteins than those previously considered may be able to induce protective immunity. Progress towards development of new H. pylori therapeutics is discussed.

Formulary Management of Eradication Therapies for Helicobacter pylori

Objective: To use the System of Objectified Judgement Analysis (SOJA) method for the rational selection of Helicobacter pylori eradication therapies for formulary inclusion. Design: Drug selection for the eradication therapy of H. pylori is made by means of the SOJA method. In this formulary decision-making model, selection criteria for a given class of drugs are prospectively defined and weighted by a panel of experts. The following criteria (relative weight) were used: variability of pharmacokinetics; drug interactions; resistance to antibacterials; efficacy; general adverse effects; complexity of the regimen; acquisition cost and clinical documentation. Only published studies with at least 30 evaluable patients were considered, at least 3 studies had to be available per treatment regimen and efficacy had to be assessed on an intent-to-treat basis. Main outcome measures and results: The regimens containing clarithromycin and an imidazole antibacterial in combination with omeprazole or ranitidine bismutrex showed the highest scores for eradication of H. pylori. The combinations amoxicillin/clarithromycin and omeprazole or lansoprazole showed slightly lower eradication rates and were more costly. The eradication rates obtained with 2-drug regimens were low, resulting in a low overall SOJA score. No quadruple regimens could be included, as none of the regimens fulfilled the inclusion criteria. This was also true for the classical triple therapy with bismuth/metronidazole/tetracycline. Conclusion: The present score is specific for the Netherlands, as Dutch acquisition costs and data on resistance were used. In other countries, with different degrees of imidazole and clarithromycin resistance, other regimens may be more appropriate. The SOJA score will be regularly updated through the internet to include relevant new studies or new successful eradication regimens. The interactive program offers groups of physicians the opportunity to discuss the optimal H. pylori eradication regimen, based on their weighting of the criteria.

Re-treatment after Helicobacter pylori eradication failure.

Currently, highly effective Helicobacter pylori eradication therapies are used, and although eradication failures still appear in a considerable proportion of cases, the therapeutic efficacy in such refractory cases has been only exceptionally studied. Therefore, our aim was to evaluate the appropriate attitude when eradication therapy fails. In 127 duodenal ulcer patients, several therapies with omeprazole (O) plus one or two antibiotics [amoxycillin (A), clarithromycin (C), metronidazole (M)] had failed to eradicate H. pylori. Re-treatment was administered depending on initial therapy; in no case was the same regimen repeated, and antibiotics with resistance risk (as C or M) were only re-administered using combination regimens with bismuth (B): O + A + C + B (when C was re-administered) and O + bismuth triple therapy (BTT) (when M was re-administered). First therapy and eradication rates, with the corresponding second therapy, were: BTT re-treatment in O + A failure achieves a relatively low eradication rate, probably lower than BTT for the first time, suggesting that other regimens should be tried. The following re-treatments are recommended in H. pylori eradication failure: in O + A failure, BTT (or O + BTT, as BTT re-treatment could be less effective than the initial BTT treatment); in O + C failure, O + A + M; in O + A + C failure, O + BTT; in O + A + M failure, O + A + C; and, finally, in O + C + M failure, O + BTT (or O + A + C + B).

Group A Beta-hemolytic Streptococcal Infections

Group A Beta-hemolytic Streptococcal Infections

Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis.

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.