Susceptibility-guided Therapy Research Articles

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Comparison of Risk and Severity of Helicobacter Pylori Infection in Non-Native Versus US Native Pediatric Patients.

Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients. We retrospectively reviewed all endoscopies with patients aged 1-21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations. In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients. Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.

Susceptibility-guided vs. empirical 10-day quadruple treatment for Helicobacter pylori-infected patients: A prospective clinical trial of first-line therapy.

BackgroundThe increasing antimicrobial resistance of Helicobacter pylori (H. pylori) has resulted in a fall in cure rates. We aimed to assess the effectiveness of first-line susceptibility-guided therapy and furazolidone-based quadruple therapy for H. pylori-infected patients.MethodsSubjects with H. pylori-infection were randomly assigned to either 10-day susceptibility-guided treatment or empiric treatment in a 2:1 ratio. Susceptibility-guided therapy was based on susceptibility to clarithromycin, and patients with susceptible strains received clarithromycin 500 mg twice daily and otherwise minocycline 100 mg twice a day was administered. Patients in the empiric therapy group was treated with furazolidone 100 mg twice a day. During treatment, all patients were given esomeprazole 20 mg twice daily, colloidal bismuth pectin 200 mg twice daily, and amoxicillin 1 g twice daily.ResultsA total of 248 patients were screened and 201 were finally included. Empiric and susceptibility-guided regimens were both successful with per-protocol eradication rates of 90.5% (57/63) vs. 88.5% (108/122) (p = 0.685) and intent-to-treat eradication rates of 85.1% (57/67) vs. 80.6% (108/134) (p = 0.435). No significant difference in eradication rates were observed among the furazolidone group, clarithromycin group and minocycline group.ConclusionBoth susceptibility-guided therapy and quadruple therapy containing furazolidone can achieve good eradication rates. For population with a high rate of resistance, quadruple therapy containing furazolidone and bismuth may be a more practical choice for first-line treatment.

Susceptibility-Guided Therapy vs. Bismuth-Containing Quadruple Therapy as the First-Line Treatment for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

BackgroundThe increased antibiotic resistance of Helicobacter pylori (H. pylori) has led to the decreased efficacy of H. pylori regimens.AimTo evaluate the efficacy, safety, and compliance of susceptibility-guided therapy (SGT) vs. bismuth-containing quadruple therapy (BQT) as the first-line treatment for H. pylori infection.Materials and MethodsThis meta-analysis was performed in accordance with the PRISMA 2009 guidelines. A systematic search in PubMed, Embase, and Cochrane databases was conducted using the combination of “H. pylori or H. pylori or Hp,” “bismuth quadruple,” and “tailored eradication OR tailored therapy OR susceptibility-guided therapy OR personalized therapy OR antibiotic susceptibility testing.”ResultsFive studies with 2,110 H. pylori-infected patients were enrolled. The pooled eradication rates of SGT and BQT were 86 vs. 78% (p < 0.05) and 92 vs. 86% (p > 0.05) by intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. SGT has a significantly superior efficacy than BQT [pooled risk ratio (RR) = 1.14, p < 0.05] in a subgroup of cultures with the susceptibility test. The pooled side effect rate was 20% in SGT and 22% in BQT, which showed no significant difference (p > 0.05). The compliances of SGT and BQT were 95 and 92%, respectively.ConclusionCompared with BQT, SGT showed a higher efficacy and similar safety as the first-line treatment of H. pylori infection in areas with high antibiotic resistance. The decision-making of first-line regimens for H. pylori infection should depend on the availability and cost-effectiveness of susceptibility tests and bismuth in local areas.

High-dose dual therapy versus culture-based susceptibility-guided therapy as a rescue regimen for Helicobacter pylori infection: a randomized controlled trial.

Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking. To compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection. A single-center, open-label, randomized controlled clinical trial. In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days. The eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT. HDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection. This clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg)

After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (&gt;90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Tailored susceptibility-guided therapy via gastric juice PCR for the first-line H. pylori eradication, a randomized controlled trial

Clarithromycin-based standard triple therapy is still commonly adopted by 81.4% of physicians in real-world practice but yields low eradication rates. Therefore, we conducted this study to compare the efficacy of gastric juice-guided therapy for first-line eradication with the standard triple therapy, in order to provide an alternative to real-world practice. A total of 182 treatment-naïve Hp-infected patients were included and randomly allocated to either susceptibility-guided therapy (SGT) with gastric juice PCR or Clarithromycin-based standard triple therapy (STT) for 7 days. The intention-to-treat eradication rates were 89% (81/91) in SGT and 75.8% in STT (p < 0.031). The per-protocol eradication rates were 91.0% (81/89) in SGT and 79.3% (69/87) in STT (p < 0.034). Among the subgroups of different antibiotic resistance, patients with SGT demonstrated superior eradication rates (91.7% vs 45.5%, p < 0.027) in the subgroup of both clarithromycin resistance and levofloxacin resistance. This prospective randomized controlled trial demonstrated the reliable efficacy of susceptibility-guided therapy via gastric juice PCR for the first-line Hp eradication. In Asia-Pacific area, where standard triple therapy is still adopted by the majority of the physicians, it is a recommended alternative to overcome the increasing antibiotic resistance.

Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area.

The increase in antibiotic resistance makes the eradication of Helicobacter pylori more difficult. Considering the limitations of the application of susceptibility-guided therapy, it is important to find an effective empirical regimen. The aim of the study is to compare the efficacy, safety, and cost-effectiveness of clarithromycin-based bismuth-containing quadruple therapy (C-BQT) and furazolidone-based bismuth-containing quadruple therapy (F-BQT) in naïve H.pylori positive patients. This was an open-label, randomized controlled, crossover trial. The trial comprised two phases. In C-F group, patients received C-BQT in the first phase; those who were still positive for H.pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment. In F-C group, patients were treated with F-BQT firstly and rescued with C-BQT. As first-line treatments, the eradication rates of C-BQT and F-BQT were 89.7% (157/175) and 92.0% (161/175) (P=0.458) in intention-to-treat analysis and 93.4% (156/167) and 95.8% (161/168) (P=0.327) in per-protocol analysis, respectively. The cumulative eradication rates of the C-F group and the F-C group were both 94.3% in intention-to-treat analysis (P=1.000). Cost-effectiveness indexes of F-BQT and C-BQT were 0.54 and 1.24 in first-line treatments. Frequencies of adverse events in F-BQT and C-BQT had no differences (36.0% in C-BQT vs 32.6% in F-BQT, P=0.499). Furazolidone-based bismuth-containing quadruple therapy should be preferred for its excellent cost-effectiveness and acceptable safety.

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.

EMPIRICAL VERSUS SUSCEPTIBILITY-BASED ERADICATION THERAPY FOR HELICOBACTER PYLORI INFECTION IN EGYPT

Background: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. Objectives: To test the effectiveness of susceptibility guided therapy vs. the empirical triple therapy for first: line H pylori treatment in a region with high antimicrobial resistance. Patients and methods: The study was performed on 82 dyspeptic H. pylori patients arranged for esophagogastroduodenoscopy at Al-Hussein University Hospital between March 2019 to march 2020. Patients were randomly divided into two groups: group A consisted of 52 patients underwent endoscopy and gastric biopsies for culture and sensitivity and treated according to sensitivity results and group B consisted of 30 patients treated by empiric triple therapy. Eradication rates and drug compliance owing to adverse effects were compared between the two groups. Results: In total, 82 patients were enrolled (52 in culture and sensitivity-based therapy group and 30 in empirical therapy group) and 50 patients (60.1%) completed the protocols. The overall resistance rates to clarithromycin, amoxicillin, metronidazole, levofloxacin, tetracycline, nitrofurantoin and rifampicin were 32.1%, 32.1%, 78.6%, 7.1%, 17.9%, 17.9% and 21.4% respectively. Empirical triple and antimicrobial susceptibility-guided eradication rates were, respectively, 53.3% and 85.7% by intention-to-treat and 64% and 96% by per-protocol analysis. Adverse events were reported in 16.6% of patients on empirical triple therapy and 21.4% of those on susceptibility-guided therapy. Conclusions: Culture-based eradication strategy demonstrated superior eradication efficacy than empirical therapy as a first-line therapy in a region with high levels of antimicrobial resistance.

Antibiotic Resistance and Therapy Outcome in H. pylori Eradication Failure Patients.

Helicobacter pylori (H. pylori) eradication fails in a definite amount of patients despite one or more therapeutic attempts. Curing these patients is progressively more difficult, due to development of antibiotic resistance. Current guidelines suggest testing antibiotic susceptibility in H. pylori isolates following two therapeutic attempts. Aim: to evaluate the development of antibiotic resistance, MIC values trends and therapeutic outcomes in patients who failed at least one H. pylori eradication therapy. Methods: consecutive patients, referred to perform upper gastrointestinal endoscopy (UGIE) to our Unit from January 2009 to January 2019 following at least one therapeutic attempt were considered. Bacterial resistance towards clarithromycin, metronidazole and levofloxacin was tested. Patients received either a susceptibility-guided therapy or Pylera®. Results: a total of 1223 patients were H. pylori positive, and antibiotic susceptibility was available for 1037. The rate of antibiotic resistance and MIC values significantly increased paralleling the number of previous therapeutic attempts. Eradication rates of antibiogram-tailored therapies remained stable, except for the sequential therapy if used as a third line. As a rescue treatment, the Pylera® therapy achieved cure rates comparable to those of the other culture-guided therapies. Conclusions: A significant increase in the secondary resistance towards the three tested antibiotics was observed, both as rate and MIC values, in correlation with the number of therapy failures. These findings should be considered when administering an empirical second-line therapy. Pylera® therapy eradication rates are comparable to culture-tailored therapies.

Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review.

Although susceptibility-guided therapy is frequently recommended for Helicobacter pylori infection, the evidence available to date supporting this strategy is limited. The aim of the present article is to review the advantages and limitations of the susceptibility-guided and the empirical strategies to treat this infection. We performed a bibliographic search to identify studies investigating H. pylori susceptibility-guided therapy. Culture is not the only way to assess antibiotic resistance, as different polymerase chain reaction-based approaches have been developed as alternative methods. For detecting H. pylori antimicrobial resistance, a molecular approach based on a stool sample might enable more convenient, time-saving methods. Unfortunately, the antimicrobial susceptibility cannot be obtained in all cases. Furthermore, antibiotic susceptibility testing in clinical practice yields useful information only for a few antibiotics: clarithromycin, metronidazole, and quinolones. In addition, susceptibility towards clarithromycin and metronidazole in vitro does not necessarily lead to eradication in vivo. In the case of H. pylori therapy failure, we should not re-administer any of the antibiotics against which H. pylori has probably become resistant. Our updated meta-analysis showed that susceptibility-guided treatment is not better than empirical treatment of H. pylori infection in first-line therapy if the most updated quadruple regimens are empirically prescribed, and similar efficacy results were also demonstrated with the two strategies for second-line therapy. Cumulative H. pylori eradication rate with several successive rescue therapies empirically prescribed reaches almost 100%. Finally, the studies that have evaluated the cost-effectiveness of the susceptibility-guided treatment have achieved contradictory results. In summary, we can conclude that the evidence is too limited to support the generalized use of susceptibility-guided therapy for H. pylori treatment in routine clinical practice, either as first-line or as rescue treatment. Nevertheless, it would be recommended that susceptibility tests are performed routinely, even before prescribing first-line treatment, in specialized centers with an interest in H. pylori management.

2019 J. Leonard Goldner Award Winner: A Novel Intraoperative Technique Seeding Morselized Bone Tissue into Pediatric Blood Culture Bottles Improves Microbiological Diagnosis in Patients with Foot and Ankle Osteomyelitis

Category:Basic Sciences/Biologics, DiabetesIntroduction/Purpose:Bone infection in the foot is a challenging pathology that frequently leads to amputation and major disability. Agent identification and antimicrobial susceptibility-guided therapy is the key for a successful treatment. Standard culture methods for bone tissue have demonstrated poor sensitivity. It has been reported that synovial fluid culture sensitivity is enhanced when seeded into pediatric blood culture bottles (PBCB), however, its performance for bone infection has yet to be determined. The aim of this study was to evaluate a novel method to obtain and process infected bone tissue using PBCB and comparing it with the standard technique.Methods:Patients admitted at a single university hospital with foot osteomyelitis between 2008 and 2017 were recruited prospectively. The diagnosis was made by clinical, laboratory and imaging findings. A representative sample of infected bone tissue was obtained for each patient and simultaneously processed using the standard technique for solid tissue cultures (SCM) and a morselized bone sample that was seeded into a PBCB (BacT/ALERT® PF). Culture sensitivity and number of agents detected for each technique were compared using the McNemar and the Mann Whitney tests respectively.Results:Over the period studied, 107 patients fitted the inclusion criteria. Of these, 63 patients had a diabetic-related infection. The causative agent was identified in 60.7% using the SCM and in 97.2% using PBCB (p < 0.001). We detected a mean of 1.05 bacteria species using SCM and 1.67 using PBCB (p<0.01). PBCB retrieved 1 bacterial species in 50.5% of the samples and 2 or more bacterial species in 46.7%. The SCM detected 1 bacterial species in 29% of the samples and 2 or more bacterial species in 31.7%.Conclusion:In this cohort, culture technique using morselized bone tissue seeded in PBCB identified the causative agent in a significantly larger percentage than SCM. Additionally, this method identified a larger number of agents. These findings demonstrate that this novel, simple and reproducible technique for culturing bone tissue samples allows a better microbiological diagnosis, without additional intraoperative risks, compared with standard methods.

Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment.

Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line Hpylori treatment in a region with high antimicrobial resistance. We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised Hpylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20mg and amoxicillin 1g b.d. plus clarithromycin 500mg, metronidazole 400mg b.d., or levofloxacin 500mg daily for susceptible infections or bismuth 220mg b.d. and metronidazole 400mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20mg, bismuth 220mg b.d., amoxicillin 1g and metronidazole 400mg t.d.s. Primary outcome was Hpylori eradication. Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P=1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P=0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI -3.1% to 3.2%) and 6.2% intent-to-treat (-0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n=50), MEA (n=8) or quadruple (n=16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

Susceptibility-guided therapy for Helicobacter pylori infection treatment failures

Background:Empirical therapy of Helicobacter pylori frequently results in treatment failure due to unrecognized antimicrobial resistance. The aim of this study was to investigate the effectiveness of susceptibility-guided therapy for rescue treatment of H. pylori infection in China.Methods:This was a prospective study of consecutive 200 patients infected with H. pylori with one or more treatment failures. The therapy chosen was susceptibility based using the most effective, best-tolerated regimens first and a locally proven, reliably effective regimen for multidrug-resistant infections. All patients received 14-day triple therapy, i.e. esomeprazole 20 mg and amoxicillin 1 g twice a day plus clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, or levofloxacin 500 mg daily, or, for multidrug-resistant infections, amoxicillin-containing bismuth quadruple therapy with esomeprazole 20 mg twice a day, bismuth 220 mg twice a day, amoxicillin 1 g three times a day, and metronidazole 400 mg four times a day. Antibiotic resistance was determined by agar dilution.Results:The eradication rate of susceptibility-guided therapy overall was 94.5% (189/200, 95% confidence interval: 90.4–97.2%). Around 28% (56/200) of patients carried strains susceptible to one of the tested antibiotics and were prescribed the triple therapy. A total of 144 multidrug-resistant patients received bismuth quadruple therapy. The eradication rates were all greater than 90%, i.e. 91.7% (11/12), 92.3% (12/13), and 93.5% (29/31) in those who received clarithromycin, metronidazole, and levofloxacin-containing triple therapy and 95.1% (137/144) for the bismuth quadruple therapy. There were no differences in eradication rates between the subgroups.Conclusions:Although susceptibility-guided therapy proved high efficacious despite the high proportion of multidrug-resistant strains, the strategy suggested the best approach for this population would be empirical amoxicillin-containing bismuth quadruple therapy. ClinicalTrials.gov identifier: NCT03413020.

Efficacy of a 14-day quadruple-therapy regimen for third-line Helicobacter pylori eradication.

PurposeTo assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication.MethodsWe enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylori culture. Seven patients were lost to follow-up. Patients were treated according to the results of antibiotic-susceptibility testing reports (cultured group, n=39). Those who failed the H. pylori culture were prescribed 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily (empirical group, n=24). A follow-up urea breath test was performed 8 weeks later.ResultsAntibiotic-resistance rates were 79.5% (clarithromycin), 94.9% (levofloxacin), 66.7% (metronidazole), 2.6% (amoxicillin), and 0 (tetracycline). Eradication rates attained by the cultured and empirical group were 89.7% (95% CI 72.7%–97.1%) and 58.3% (95% CI 36.6%–77.9%) in per-protocol analysis (P=0.004) and 81.4% (95% CI 66.6%–91.6%) and 51.8% (95% CI 31.9%–71.3%) in intention-to-treat analysis (P=0.014), respectively. Culture-guided therapy was the only clinical factor influencing the efficacy of H. pylori eradication (OR 0.16, 95% CI 0.04–0.60; P=0.006). Despite the high metronidazole-resistance rate (66.7%) after two treatment failures, the eradication rate in patients with this condition was 84%.ConclusionEmpirical 14-day modified quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment. The success rate of third-line susceptibility-guided treatment was near 90%. This report is valuable as a reminder to medical practitioners that rather than a try-and-see approach, susceptibility-guided therapy should always be considered whenever possible for patients who have undergone several treatment failures.

Multidrug resistant Proteus mirabilis and Escherichia coli causing fulminant necrotising fasciitis: a case report

BackgroundNecrotizing fasciitis is a rare soft tissue infection characterized by rapid progressive necrosis with relative sparing of underlying muscles. This case is reported to highlight the emergence of multidrug resistant microbes in recent days which limits the use of empiric antibiotic therapy and necessitates early cultures and sensitivity enabling targeted antibiotic therapy. Factors that lead to antimicrobial resistance especially in sub-Saharan Africa have also been discussed.Case presentationWe report the case of a 52-year-old black man who was referred to our centre for the management of cellulitis and suppurating ulcers of the right leg which had progressed to a wet gangrene. Following physical examination and work-up, a diagnosis of fulminant necrotizing fasciitis of the right leg caused by multidrug resistant Proteus mirabilis and Escherichia coli was made. Despite the broad-spectrum empiric antibiotic therapy and aggressive multiple surgical debridement, necrosis progressed leading to an above-knee amputation.ConclusionNecrotizing fasciitis is a surgical emergency that requires prompt diagnosis and aggressive surgical debridement in order to reduce morbidity and mortality. The emergence of multidrug resistant organisms in recent days have limited the use of empiric antibiotic therapy, necessitating early culture and sensitivity and the use of susceptibility-guided antibiotic therapy. Timely action to control the use of antibiotics in sub-Saharan Africa will reduce multidrug resistance and delay the arrival of post-antibiotics era.

Providencia stuartii Aortic Prosthetic Valve Endocarditis with Formation of Paravalvular Pseudoaneurysm

Infective endocarditis (IE) is characterized by high morbidity and mortality. Providencia stuartii infections are very rare and mainly acquired in a hospital setting, being isolated primarily in urine cultures of patients with longterm urinary catheters; rarely causing bacteremia and endocarditis. The authors present a case of a 74-year-old male patient with vascular risk factors and a biological aortic prosthetic valve hospitalized for urosepsis with P. stuartii bacteremia. He underwent antibiotic susceptibility-guided therapy, resulting in both negative urine and blood cultures. However, the patient was later re-admitted due to persistent P. stuartii urosepsis and bacteremia. A transesophageal echocardiogram revealed endocarditis of the prosthetic aortic valve, complicated with extensive aortic root pseudoaneurysm, fistulized into the left atrium. Given the co-comorbidities and extent of the disease, he was not a candidate for surgical intervention and therefore maintained broad-spectrum antibiotic therapy. Unfortunately, the patient didn’t respond to best medical treatment and died of septic shock.

Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

AIMTo evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODSA total of 1034 patients infected by Helicobacter pylori (H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire.RESULTSIntention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate.CONCLUSIONAntimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.