Clarithromycin-containing Regimens Research Articles

Mycobacterium xenopi related spine infections: A case report and systematic literature review

Background and purposeNontuberculous mycobacteria (NTM) disease is an important infection disease throughout the world. Mycobacterium xenopi (M. xenopi) is a common NTM. Extrapulmonary infections due to M. xenopi, particularly spine infections, are a rare occurrence, but lack of research is cited as a constraint for implementing NTM control in such patients. The purposes of this paper are to describe a case of spondylodiscitis, to review the published literature on cases of M. xenopi spine infections, and to summarize the predisposing factors, diagnosis, and treatment of infection. MethodsA case of spondylodiscitis was caused by M. xenopi in a patient with systemic lupus erythematosus (SLE). Research was conducted using the PubMed, ScienceDirect, Embase, Wiley Online Library, and Scopus databases using the following search terms: “Mycobacterium xenopi”, “vertebral”, “spinal”, “spondylodiscitis”, “infection”, and “osteomyelitis”. ResultsWe retrieved 14 cases published before August 2022. The risk factors for infection were iatrogenic infections (3/14, 21.43%), SLE (4/14, 28.57%), AIDS (4/14, 28.57%), and immunocompetence without any comorbidities (3/14, 21.43%). The most common sites of infection were thoracic vertebrae (10/14, 71.43%) and lumbar vertebrae (4/14, 28.57%). A total of 14 cases were isolated and identified as M. xenopi from a toad by mycobacterial culture. The identification time was 55.00 ± 7.55 days (the present report identification time of metagenomic next generation sequencing (mNGS) was only 2 days). All patients were treated with antibiotic therapy, and the duration of treatment was 13.18 ± 2.13 months. Clarithromycin-based therapy showed a higher improvement rate (5/6, 83.33%). Surgical intervention was performed in 5 patients. Only 1 patient did not show any improvement after surgical treatment. ConclusionM. xenopi spine infection in humans presents with atypical clinical symptoms. mNGS identification may be a good choice. M. xenopi may be considered in immunocompromised patients with spinal infection. We recommend a clarithromycin-containing regimen and prolonging the duration of treatment to ensure effectiveness.

Randomised clinical trial: comparison of efficacy and adverse effects of a standard triple clarithromycin-containing regimen with high-dose amoxicillin and bismuth therapy in Helicobacter pylori eradication

The clarithromycin-based triple therapy is the most prescribed Helicobacter pylori eradication regimen in Europe; it causes adverse effects in a significant proportion of subjects, leading to discontinuation. Alternative therapies are required because of increasing clarithromycin resistance or to decrease the adverse effects. We compared the efficacy and spectrum of adverse effects of clarithromycin-based triple therapy with the high-dose amoxicillin/bismuth regimen. A randomised clinical trial enrolled healthy individuals aged 40-64 years. H. pylori was assessed with a 13C-urea breath test. In total 579 H. pylori-positive subjects were randomly allocated in two groups: group 1: clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg, all twice daily; group 2: bismuth subcitrate 240 mg twice daily, amoxicillin 1000 mg three times daily, esomeprazole 40 mg twice daily. Regimens were administered for 14 days.Information on treatment completion and adverse effects were collected via a telephone interview at 21-28 days after medication delivery. The efficacy was assessed by UBT 6 months after the treatment. We analysed 483 subjects for adverse effects (248 vs. 235 respectively). Furthermore, 316 subjects were analysed for efficacy. In per-protocol analysis, a higher efficacy was seen in group 1 (88.4 vs. 77.0%; P < 0.001); no difference was observed in compliance (90.3 and 91.2%). Therapy-related adverse effects were more common in group 1 (56.9 vs. 40.0%; P < 0.01). In intention-to-treat analysis no statistical difference in efficacy was revealed. Bismuth-based high-dose amoxicillin therapy showed a lower efficacy but was less frequently associated with adverse effects. Further research is required to examine the high-dose amoxicillin and bismuth-containing regimens in various populations to maximise eradication efficacy.

Role of Antimicrobial Susceptibility Testing before First-Line Treatment Containing Clarithromycin for Helicobacter pylori Eradication in the Clinical Setting.

Background: Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST). Methods: 257 patients with H. pylori infection, with AST, performed before the eradication of clarithromycin-containing regimens were enrolled and divided into two groups: the SGT and ET groups. Results: Eradication rates in the SGT and ET groups were 85.4% and 58.4% (P < 0.01), respectively. In triple therapy (TT), eradication rates of the SGT and ET groups were 85.1% and 56.6% (P < 0.01), respectively. In sequential therapy (SET), eradication rates of the SGT and ET groups were 86.2% and 65.6% (P = 0.06), respectively. According to AST, TT had an eradication rate of 84.6% with strains susceptible to clarithromycin and amoxicillin and 11.1% with strains resistant to both. SET had an eradication rate of 89.5% with strains susceptible to clarithromycin, amoxicillin, and metronidazole, whereas it was 0% with strains resistant to clarithromycin and metronidazole. Conclusions: SGT as first-line treatment improved eradication rates of TT and SET by 28.5 (P < 0.01) and 20.6 (P = 0.06) percent points, respectively, compared with ET.

Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen.

Antibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM. We performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated. Antibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364-4615) days. During follow-up, 13 patients had a negative conversion of sputum culture. AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.

Tailored Helicobacter pylori eradication based on prior intake of macrolide antibiotics allows the use of triple therapy with optimal results in an area with high clarithromycin resistance.

the previous intake of macrolide antibiotics is associated with a failure to eradicate Helicobacter pylori (H. pylori) with clarithromycin-containing regimens. However, the standard triple therapy achieves eradication rates of over 90% in patients without a previous use of macrolides in our health area. The aim of this study was to evaluate the efficacy of an H. pylori eradication strategy based on the intake of macrolides by the patient during the previous years. one hundred and sixty-nine patients with H. pylori infection were prospectively included in the study. The electronic medical record of each patient was reviewed at the time of inclusion. Depending on their previous intake of macrolides, patients were assigned to one of two eradication regimens: group A) patients without a previous intake of macrolides received an optimized triple therapy for 14 days; and group B) patients with a previous intake of macrolides received bismuth quadruple therapy for ten days. ninety-one patients (53.84%) without a previous intake of macrolides received an optimized triple therapy (group A) and 78 patients (46.15%) with a previous intake of macrolides received bismuth quadruple therapy (group B). In group A, the H. pylori eradication rates were 90.11% in the intention-to-treat and 95.35% in the per-protocol analysis. In group B, the H. pylori eradication rates were 85.89% in the intention-to-treat and 98.5% in the per-protocol analysis. The overall eradication rates obtained using this strategy were 88.16% (95% CI: 82.32-92.02%) in the intention-to-treat and 96.75% (95% CI: 92.59-98.94%) in the per-protocol analysis. an H. pylori eradication strategy based on the intake of macrolides during the previous years achieves overall eradication rates close to 90% and allows the use of standard triple therapy in more than half of the patients from a health area with a high level of clarithromycin resistance.

Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions

In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. We searched publication databases for studies thatassessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) andprimary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). Resistance of Hpylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.

Pharmacological considerations and step-by-step proposal for the treatment of Helicobacter pylori infection in the year 2018.

Over the past 30 years, multidrug regimens consisting of a proton pump inhibitor (PPI) and two or three antibiotics have been used in treating Helicobacter pylori (H. pylori) infection. In clinical practice, the optimal regimen to cure H. pylori infection should be decided regionally. Considering the first treatment, the Maastricht V/Florence Consensus Report and the American College of Gastroenterology Clinical Management Guideline highlight that in countries with low clarithromycin resistance rates (<15%), an empiric clarithromycin-based regimen can be used. In countries with high clarithromycin resistance rates or, in the American Guideline, with a previous exposure to clarithromycin, a bismuth-containing quadruple therapy (with metronidazole and tetracycline) is the first choice. In case of persistent infection, after a previous clarithromycin-containing regimen, this drug should be avoided in second line therapy. Options after initial eradication failure include tailored therapy (choosing antibiotic combinations based on antibiotic susceptibility testing), empiric bismuth-containing quadruple therapy or triple levofloxacin-based therapy. Encouraging data are reported, both for the first-line and for rescue treatments, with the use of a formulation of bismuth subcitrate potassium, metronidazole, and tetracycline contained in a single capsule, together with a PPI. Rifabutin- and furazolidone-based regimens should also be considered in rescue regimens. Vonoprazan, a new type of potassium-competitive acid blocker that produces more potent acid inhibition than PPIs, provides improved H. pylori eradication rates in combination with antibiotics. In this review, the authors provide an overview on the current knowledge on the treatment of H. pylori infection, with focus on therapeutic challenges in this field.

Prevalence and Pattern of Antibiotic Resistant Strains of Helicobacter Pylori Infection in ASEAN

Objective:Antibiotic resistance has significantly impact on eradication rates for H. pylori infection and remains important cause of treatment failure worldwide including ASEAN countries. The aim of this study was to survey the prevalence and antibiotic resistant pattern of H. pylori infection in ASEAN.Methods:This study was a survey among 26 experts from 9 ASEAN countries including Thailand, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore and Vietnam whom attended a meeting to develop the ASEAN consensus on H. pylori management in Bangkok in November 2015. A questionnaire was sent to each member of the consensus meeting. The detail of the questionnaire included information about prevalence of H. pylori infection, facilities to perform H. pylori culture, molecular testing for antibiotic resistance and antibiotic resistance rate in their countries.Results:H. pylori infection remain common in ASEAN ranging from 20% in Malaysia, 21-54% in Thailand and 69% in Myanmar. Most of ASEAN countries can perform H. pylori cultures and antibiotic susceptibility tests except Laos and Cambodia. In ASEAN countries, metronidazole resistant H pylori is quite common whereas amoxicillin resistance remain rare. Clarithromycin resistance results in a significant decrease in H. pylori eradication rate with clarithromycin-containing regimens. The prevalence of clarithromycin resistance varies in ASEAN countries being high in Vietnam (30%) and Cambodia (43%), moderate to high in Singapore (17%) and low in Malaysia (6.8%), Philippine (2%) and Myanmar (0%). In Thailand, clarithromycin resistance tends to higher in large cities (14%) than in rural areas (~3.7%).Conclusion:ASEAN countries should develop a standard protocol for regular susceptibility testing of H. pylori so that clinicians would be better able to choose reliably effective empiric therapies. The wide range of antibiotic resistance in ASEAN countries suggests that the preferred first line regimen should be depend on the local antibiotic resistance other than single recommendation.

Inappropriate treatment in Helicobacter pylori eradication failure: a retrospective study

Background: In recent years, success rates of empirical H. pylori therapies have fallen in many countries. Although antibiotic resistance and poor adherence are described as the main factors for treatment failure, in China, iatrogenic factors also play an important role.Objective: To investigate why patients experienced multiple failures, we performed a retrospective, single center study using questionnaires to identify causes of treatment failure other than antibiotic resistance.Methods: This study was conducted from January 2016 to July 2017 in a general hospital. Patients with at least two H. pylori treatment failures who completed the questionnaire were entered. The survey covered characteristics of the study population, regimens used, and adherence to therapy.Results: Two hundred and ninety three patients were included in the final analysis. The top three most antibiotic combinations as the first-line treatment were a PPI plus clarithromycin–metronidazole (24.6%, 72/293), clarithromycin–levofloxacin (23.5%, 69/293) and clarithromycin–amoxicillin (21.5%, 63/293). Clarithromycin-containing regimens were repeatedly used in 178 patients (60.8%) and levofloxacin-containing regimens repeatedly in 88 patients (30.0%). Fifty patients (17.1%) had poor adherence per treatment history and 32 (10.9%) stopped treatment because of nonmedical reasons.Conclusions: In order to increase the success of H. pylori eradication therapy, the effect of prior therapies needs to be given more consideration. Patient education to enhance adherence also needs to be improved.

Macrolide use in the previous years is associated with failure to eradicate Helicobacter pylori with clarithromycin-containing regimens.

There is some evidence that prior use of macrolide antibiotics is a useful predictor of the likelihood of standard triple therapy failure in Helicobacter pylori eradication. In this study, we have evaluated whether previous intake of macrolides correlates with failure to eradicate H.pylori using two different first-line clarithromycin-containing regimens. Retrospective study of 212 patients with H.pylori infection treated with one of two first-line clarithromycin-containing regimens: 108 patients treated with triple therapy for 10days and 104 patients treated with concomitant therapy for 10days. The intake of macrolides (clarithromycin, azithromycin, and other macrolides) prior to the eradication therapy was obtained from the electronic medical record, which contains information regarding all the medication prescribed to the patients since the year 2004. One hundred of 212 patients (47.2%) had received at least one treatment with macrolides during the years prior to the eradication therapy. H.pylori eradication rates were significantly lower in patients with previous use compared to patients without previous use of macrolides, both with triple therapy (60.8% vs 92.9%; P<.0001) and with concomitant therapy (85.7% vs 98.2%; P=.024). Previous use of macrolides correlates with a low H.pylori eradication rate with triple and concomitant clarithromycin-containing regimens. In addition, our study shows that in patients without previous use of macrolides, triple therapy achieves per-protocol eradication rates over 90%.

Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis

So far, a comprehensive systematic review and meta-analysis has not been done of the prevalence of primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region. We aimed to assess the trends and regional differences in primary antibiotic resistance to H pylori in the Asia-Pacific region and to examine the relation between resistance and first-line eradication. We did a systematic review and meta-analysis of primary antibiotic resistance to H pylori and the efficacy of first-line regimens in the Asia-Pacific region. We searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1990, and Sept 30, 2016; we also searched abstracts from international conferences. Both observational studies and randomised controlled trials were eligible for inclusion in the analysis of primary antibiotic resistance, but only randomised controlled trials were eligible for inclusion in the analysis of efficacy of first-line therapies. Meta-analysis was by the random-effects model to account for the substantial variations in resistance across the region. We did subgroup analyses by country and study period (ie, before 2000, 2001-05, 2006-10, and 2011-15) to establish country-specific prevalences of primary antibiotic resistance and first-line eradication rates. This study is registered with PROSPERO, number CRD42017057905. 176 articles from 24 countries were included in our analysis of antibiotic resistance. The overall mean prevalences of primary H pylori resistance were 17% (95% CI 15-18) for clarithromycin, 44% (95% CI 39-48) for metronidazole, 18% (95% CI 15-22) for levofloxacin, 3% (95% CI 2-5) for amoxicillin, and 4% (95% CI 2-5) for tetracycline. Prevalence of resistance to clarithromycin and levofloxacin rose significantly over time during the period investigated, whereas resistance to other antibiotics remained stable. 170 articles from 16 countries were included in analysis of efficacy of first-line therapies. We noted unsatisfactory efficacy (ie, <80%) with clarithromycin-containing regimens in countries where the clarithromycin resistance rates were higher than 20%. The prevalence of primary antibiotic resistance varied greatly among countries in the Asia-Pacific region, and thus treatment strategy should be adapted relative to country-specific resistance patterns. Clarithromycin-containing regimens should be avoided in countries where the prevalence of clarithromycin resistance is higher than 20%. Ministry of Health and Welfare of Taiwan, Ministry of Science and Technology of Taiwan, and Amity University.

Antibiotic susceptibility of Helicobacter pylori in Iceland

Background: Increasing resistance of Helicobacter pylori (H. pylori) to antibiotics calls for constant re-evaluation of multidrug regimens that have been used to eradicate the infection. The aim of this study was to evaluate the current antibiotic susceptibility of H. pylori in an Icelandic cohort.Methods: Patients referred for gastroscopy were recruited prospectively. Those found to have a positive rapid urease test were included in the study. Susceptibility testing was conducted by the Epsilometer test (E-test) method for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline. Results were obtained after three days of incubation in microaerophilic conditions at 37 °C, except for the metronidazole were the first 24 hours were anaerobic.Results: Of the 613 patients who underwent gastroscopy, 138 (23%) had a positive rapid urease test. H. pylori was successfully cultured from 105 (76%) of the urease test positive patients and the isolates were tested for antibiotic susceptibility. Five patients had prior H. pylori eradication. Antibiotic resistance for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline was 0%, 9%, 4%, 1% and 0%, respectively. If those who had previously undergone eradication treatment were excluded, the resistance was 0%, 6%, 3%, 1% and 0%, respectively. Clarithromycin resistance was higher amongst women than men, 13% vs. 5%, however, not significantly. Clarithromycin resistance was 60% amongst those who had previously received eradication treatment compared to 6% of those who had not (p < .0001).Conclusions: Clarithromycin resistance amongst the H. pylori isolates can be considered relatively low. Therefore, in the current cohort, standard triple-drug clarithromycin-containing regimen should remain the first-line treatment against H. pylori.

Helicobacter pylori eradication in complicated peptic ulcer: Beneficial in most?

Helicobacter pylori eradication therapy has a role in minimizing the complications of peptic ulcer disease, namely, bleeding, perforation, and obstruction. However, the precise role of H. pylori eradication therapy in the complicated ulcers remains inconclusive, especially in perforation and gastric outlet obstruction. The prevalence of H. pylori in peptic ulcer bleeding patients has been widely underestimated owing to the differences in diagnostic tests and patient characteristics, and hence, it is recommended that an initial negative test should be followed up by a delayed repeat testing to rule out false negativity. It is well established now that eradication of H. pylori in patients with bleeding ulcers reduces rebleeding and ulcer recurrence. Multiple studies have attributed high recurrence rates of duodenal ulcer following simple closure to a high prevalence of H. pylori infection. Eradication therapy decreases the recurrence rate of perforated ulcers, thus justifying the role of H. pylori eradication therapy following the primary surgical management of perforated ulcers. The role of H. pylori in duodenal ulcer with gastric outlet obstruction is yet to be evaluated clearly. There are some reports of resolution of gastric outlet obstruction following therapy for H. pylori, obviating the need for surgery. Clarithromycin-containing regimens are recommended as first-line in areas of low resistance, whereas bismuth-containing quadruple therapy is the first-line empirical treatment in areas of high clarithromycin resistance. Treatment of H. pylori is beneficial in most of the patients with complicated peptic ulcer disease, especially in reducing recurrence of ulcer with or without complications.

Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations

The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.

Mycobacterium avium genotype is associated with the therapeutic response to lung infection

Factors that can interfere with the successful treatment of Mycobacterium avium lung infection have been inadequately studied. To identify a potent predictor of therapeutic responses of M. avium lung infection, we analyzed variable number tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates. Associations between the VNTR profiling data and a therapeutic response were evaluated in 59 subjects with M. avium lung infection. M. avium lung infection of 30 subjects in whom clarithromycin-containing regimens produced microbiological and radiographic improvement was defined as responsive disease, while that of the remaining 29 subjects was defined as refractory disease. In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06). We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05). By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci. In conclusion, we identified four mycobacterial minisatellite loci that together were associated with the therapeutic response of M. avium lung infections.

A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication)

Introduction: Helicobacter pylori infection is generally treated with therapies that include a proton pump inhibitor (PPI) and, at least, two antibiotics being clarithromycin one of the most used. Antibiotic resistance, mainly to clarithromycin, seems to be increasing in many geographical areas, and this factor is considered a main cause leading to a treatment failure when the later therapies contain this antibiotic again. As clarithromycin is a key antibiotic in the eradication of H. pylori, the election of the rescue treatment is a matter of debate.Areas covered: The aim of this study is to systematically review the efficacy of the second-line rescue therapies after the failure of a first-line clarithromycin-containing regimen, and to link this information with the previous first-line treatment. Also, authors performed meta-analyses and inverse variance analyses with studies that met the inclusion criteria: first-line treatment must specify type and dosage; diagnosis and eradication confirmation must be performed by generally accepted tests; and second-line treatment must not be assigned depending on the antibiotic susceptibility or resistance.Expert opinion: In a routine clinical practice setting, the most adequate second-line treatment consists in a 10-day regimen of levofloxacin– amoxicillin–PPI given twice daily, unless regional or new data show high quinolone resistance. Other good options are the bismuth quadruple regimen and a metronidazole–amoxicillin–PPI therapy.

Nonbismuth Quadruple (Concomitant) Therapy: Empirical and Tailored Efficacy versus Standard Triple Therapy for Clarithromycin‐Susceptible Helicobacter pylori and versus Sequential Therapy for Clarithromycin‐Resistant Strains

Using quadruple clarithromycin-containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. 209 consecutive naive H. pylori-positive patients without susceptibility testing were empirically treated with 10-day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin-susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin-resistant strains. Eradication was confirmed with ¹³C-urea breath test or histology 8 weeks after completion of treatment. Per-protocol (PP) and intention-to-treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84-93%) and 87% (83-92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin-susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82-100%) vs 74% (58-91%), p = 0.05] and by intention to treat [92% (82-100%) vs 70% (57-90%), p = 0.02]. As for antibiotic-resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin-resistant/metronidazole-susceptible strains and 75% (3/4) vs 60% (3/5) for dual-resistant strains. Empirical 10-day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin-susceptible H. pylori and at least as effective as sequential therapy for resistant strains.

Outbreak of a cutaneous Mycobacterium marinum infection in Jiangsu Haian, China

Mycobacterium marinum is a slow-growing mycobacterium. In November 2008, we diagnosed a patient with M. marinum infection who worked at a fish farm in Jiangsu Haian, China. We conducted an investigation and found 18 patients with the same infection. In suspected cases, complete data were collected including medical history, clinical manifestations, laboratory features, and responses to treatment. Therapeutic regimens, including clarithromycin monotherapy or combined treatment with clarithromycin, rifampicin, and ethambutol, were prescribed. A total of 18 patients with M. marinum infection were found. All patients showed only skin lesions. Biopsies were performed and 16 patients showed infective granulomas. Acid-fast bacilli stain (Ziehl-Neelson stain) for cutaneous samples were positive in 7 patients. Ten patients were positive in purified protein derivative tests (tubercles were ≥10 mm in diameter). In 16 patients, colonies grew after tissue samples were incubated on Löwenstein–Jensen medium at 32 °C. All the isolates were identified as M. marinum by polymerase chain reaction–restriction fragment length polymorphism analysis, by direct gene sequencing, and by genotyping using mycobacterial interspersed repetitive units. Fifteen of the 18 patients were cured using clarithromycin-containing antibiotic regimens. The history of contact with fish and aquaria plays an important role in diagnosis. Clarithromycin-containing regimens were successful in most patients with M. marinum infections limited to the skin.

Treatment outcome of combination therapy including clarithromycin for Mycobacterium avium complex pulmonary disease.

Background/AimsThe frequency of nontuberculous mycobacteria pulmonary disease in HIV-negative patients is increasing; the most common pathogen in Korea is the Mycobacterium avium complex (MAC). However, few studies have evaluated the treatment outcome of MAC pulmonary disease in Korea.MethodsThe efficacy of a clarithromycin-containing regimen for MAC pulmonary disease was studied in 42 patients treated for more than 6 months between January 2005 and December 2008. All patients were treated with a regimen consisting of clarithromycin, rifampin, and ethambutol. Streptomycin was added in 10 patients.ResultsAmong the 42 patients, a negative culture conversion was achieved in 33 (78.6%), and the median duration of treatment in these patients was 19 months (interquartile range [IQR], 16 to 22). Of the 33 patients with a negative culture conversion, 14 completed treatment. During the follow-up period (median, 10 months; IQR, 4 to 20) for the 14 patients, one relapsed at 24 months after treatment completion. The culture conversion rate was significantly higher in patients who were treated with more than 500 mg/day clarithromycin (87.1% vs. 54.5%, p = 0.038).ConclusionsThe combined regimen including clarithromycin was effective against MAC pulmonary disease. High-dose clarithromycin of more than 500 mg/day may improve the outcome of patients with MAC pulmonary disease.

Clinical Significance of Differentiation of Mycobacterium massiliense from Mycobacterium abscessus

Mycobacterium massiliense has been recognized as a separate species from Mycobacterium abscessus; however, little is known regarding the clinical impact of this differentiation. To compare clinical features and treatment outcomes between patients with M. abscessus lung disease and those with M. massiliense lung disease. We performed molecular identification of stored clinical isolates of M. abscessus complex and compared clinical characteristics and treatment outcomes between 64 patients with M. abscessus lung disease and 81 patients with M. massiliense lung disease. The clinical and radiographic manifestations of disease caused by each species were similar. Standardized combination antibiotic therapy, including a clarithromycin-containing regimen in combination with an initial 4-week course of cefoxitin and amikacin, was given to 57 patients (24 with M. abscessus and 33 with M. massiliense) for more than 12 months. The proportion of patients with sputum conversion and maintenance of negative sputum cultures was higher in patients with M. massiliense infection (88%) than in those with M. abscessus infection (25%; P < 0.001). Inducible resistance to clarithromycin (minimal inhibitory concentrations ≥ 32 μg/ml) was found in all tested M. abscessus isolates (n = 19), but in none of the M. massiliense isolates (n = 28). Treatment response rates to combination antibiotic therapy including clarithromycin were much higher in patients with M. massiliense lung disease than in those with M. abscessus lung disease. The inducible resistance to clarithromycin could explain the lack of efficacy of clarithromycin-containing antibiotic therapy against M. abscessus lung disease.