Rene Kerstens | Eindhoven University of Technology (original) (raw)

Papers by Rene Kerstens

Antimicrobial Resistance & Infection Control, 2020

Objectives Maintenance treatment with macrolide antibiotics has shown to be effective in reducing... more Objectives Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients. A major concern with prolonged treatment with antibiotics is the development of bacterial resistance. In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients. Methods This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period. In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period. Results There was no increased risk for acquisition of macrolide resistance genes in...

Respiratory Medicine, 2019

Introduction: Maintenance treatment with macrolides are useful in preventing COPD exacerbations. ... more Introduction: Maintenance treatment with macrolides are useful in preventing COPD exacerbations. We investigated which characteristics of COPD patients with frequent exacerbations predicted the best response to maintenance treatment with azithromycin. Methods: This study was part of the COLUMBUS trial, a prospective randomized, double-blind, placebo-controlled study in 92 COPD patients with frequent exacerbations. During the 1-year treatment period, follow-up data were collected for spirometry, mMRC scores, sputum cultures and blood inflammatory markers. Results: In the azithromycin group a significant lower number of exacerbations per patient was observed in patients with the following characteristics: baseline blood eosinophil count ≥2.0% (x̄= 1.26), compared to an eosinophil count < 2.0% (x̄= 2.50; p = 0.02), GOLD stage 1-2 (x̄= 1.06), versus GOLD stage 4 (x̄= 2.62; p = 0.02) and GOLD group C (x̄= 0.45) compared to group D (x̄= 2.18; p < 0.01). Moreover, the number of hospitalizations was significantly lower in patients, with a blood eosinophil count ≥2.0% (x̄= 0.26) compared to an eosinophil count < 2.0% (x̄= 0.90; p = 0.01) and in GOLD stages 1-2 (x̄= 1.06) compared to stage 4 (x̄= 2.62; p = 0.04). Conclusion: In conclusion, azithromycin maintenance treatment appears to be effective in COPD patients with frequent exacerbations, who are either classified in GOLD stage 1-2 or GOLD C and those with a blood eosinophil count of ≥2.0%.

The American journal of surgical pathology, 2018

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) ver... more Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (...

Gut, 2010

Introduction Prucalopride (PRU) is a selective high affinity 5-HT4 agonist. Studies have shown th... more Introduction Prucalopride (PRU) is a selective high affinity 5-HT4 agonist. Studies have shown that PRU effectively improved bowel movements in patients with chronic constipation (CC). Methods Three pivotal phase III double-blind, randomised, placebo (PLA)-controlled studies were conducted, identical in design. Trials consisted of a 2-week run-in period followed by a 12-week treatment period in which patients were randomised to once daily treatment with PRU 2 mg, PRU 4 mg or PLA. Adverse events (AEs) were reported and vital signs, laboratory and ECG were recorded at baseline, weeks 4 and 12 of treatment. Combined analyses of the three trials are presented. Results Eighty-nine percent of a total of 1977 treated subjects were female, average age was 47 years, average history of constipation was 20 years and >50% of patients reported to have no spontaneous complete bowel movements during the 2-week run-in period. PRU 2 mg, PRU 4 mg and PLA were administered to 659, 657 and 661 patients, respectively. AE incidence is summarised in Abstract 008 below. The higher incidence of headache, nausea and diarrhoea in the PRU groups can be explained by the pharmacodynamic effect of PRU and mainly occurred on the first day of treatment. Most AEs (≥5%) considered at least moderate in severity and possibly related to PRU were mainly related to the GI tract with a higher incidence in the PRU groups for nausea, diarrhoea, abdominal pain and headache ranging from 2.7% to 4.7% in PLA vs 5.1% to 11.8% in PRU 2 mg and 6.1% to 16.1% in PRU 4 mg. No deaths were reported. The only SAE reported in more than one patient was abdominoplasty for two patients in the PRU 4 mg group (not related to study medication). Most frequent AEs (≥2%) leading to discontinuation were also nausea, diarrhoea, abdominal pain and headache. No clinically relevant differences were observed between PRU and PLA in laboratory parameters, in vital signs or ECG values during the trial period (Abstract 047). Abstract PTH-047 Treatment-emergent AEs PLA PRU 2 mg PRU 4 mg Most frequent AEs (≥10%), n (%) Headache 96 (14.5) 169 (25.6) 186 (28.3) Nausea 66 (10) 129 (19.6) 144 (21.9) Diarrhoea 31 (4.7) 84 (12.7) 96 (14.6) Abdominal pain 71 (10.7) 82 (12.4) 70 (10.7) n (%) with one or more AE 450 (68.1) 509 (77.2) 501 (76.3) n (%) with SAEs 18 (2.7) 13 (2.0) 19 (2.9) n (%) with AEs at least poss. related 179 (27.1) 281 (42.6) 302 (46.0) n (%) with severe AEs 97 (14.7) 123 (18.7) 139 (21.2) n (%) discontinued due to AE 24 (3.6) 39 (5.9) 64 (9.7) Conclusion Treatment during 12 weeks with PRU 2 mg and 4 mg is safe and well tolerated by patients with CC.

Gastroenterology, 2017

Background and Aims Patient engagement, adaptation and self-management in health behaviors play a... more Background and Aims Patient engagement, adaptation and self-management in health behaviors play a critical role in improving Health Related Quality Of Life (HRQOL) and reducing health care utilization in chronic disorders. The Patient Activation Measure (PAM) is a validated tool that measures the degree to which patients are engaged to manage their own health care. PAM Level 1 denotes patients who are disengaged and overwhelmed. Level 2 indicates patients who are becoming aware, but believe that health is largely out of their control. Level 3 indicates that patients are taking action and control of their health and Level 4 indicates patients who have adopted new behaviors and are able to utilize them in stress or health-crises. Cyclic Vomiting Syndrome (CVS) is a chronic functional GI disorder that is associated with poor HRQOL, increased health care utilization and disability. There is no data on the level of patient engagement in patients with CVS; we thus sought to determine their level of engagement and its association with clinical variables. Methods The PAM questionnaire was administered prospectively to patients with CVS seen at a tertiary referral center between 2014-2015. Data on demographics, clinical characteristics, health care utilization, disease severity, and HRQOL (using the NIH PROMIS 10) were obtained. Patients were stratified into low engagement (PAM 1 & 2) and high engagement (PAM 3 & 4). The Fisher's exact test and Wilcoxon rank-sum tests were used to identify significant differences between the groups. Results Of a total of 96 patients, 58.3% were female and mean age was 35.9 + 12.8 years. PAM scores were normally distributed with a mean of 56.8 + 13.2. Twenty-five % of patients were at Level 1, 19.8% at Level 2, 40% at Level 3 and 15% at level 4. Lower patient engagement (Levels 1 & 2) was significantly associated with worse global physical and mental HRQOL (p=0.002 and 0.001), smoking tobacco (p= 0.015), more CVS related hospitalizations within the past year (4.7 vs. 2.3 P=0.030), anxiety and depression (p=0.022 and 0.007), and being a new vs. established patient in the PI's clinic (p= 0.001) (Table 1). There was no association between patient engagement and age, gender, BMI, chronic narcotic use, chronic marijuana use, duration of CVS, number of CVS episodes/year, number of urgent care visits/year or comorbid conditions such as chronic fatigue, fibromyalgia, migraines and panic disorder. Conclusion Almost half of CVS patients demonstrate poor patient engagement, which is associated with poor mental and physical HRQOL. Extra-intestinal conditions such as anxiety and depression, important drivers of patient engagement contribute to poor HRQOL. A biopsychosocial model of care addressing mental health in CVS should improve patient engagement and overall quality of life. S-117 AGA Abstracts Comparison of Demographics and Clinical Characteristics of CVS Patients with Low and High Patient Engagement * denotes p-value <0.05. Categorical variables were analyzed using Fisher's exact test and continuous variables using Wilcoxon rank-sum. Categorical variables are expressed as n (% of patients) and continuous variables expressed as mean ± standard deviation.

European Respiratory Journal, 2016

Background: It is unclear which COPD patients are most likely to benefit from long-term treatment... more Background: It is unclear which COPD patients are most likely to benefit from long-term treatment with macrolides in order to reduce exacerbation frequency. Aims and objectives: We investigated which biomarkers and characteristics of COPD patients with frequent exacerbations have the best treatment response to maintenance therapy with azithromycin. Methods: This analysis was part of the COLUMBUS trial(Clinicaltrials.gov, NCT00985244), a randomized double-blind, placebo controlled, single-center trial, which investigated azithromycin maintenance therapy compared to placebo in 92 COPD patients with frequent exacerbations during 1 year. At baseline data for spirometry, white blood cell count, concentrations of CRP-reactive protein, mid-regional pro-adrenomedullin and sputum cultures were collected. Primary endpoint was the number of exacerbations in the year of treatment. Results: In the azithromycin group(n=47) a significant lower mean number of exacerbations was observed in patients with a level of serum eosinophils ≥2,0%(n=25; 1,24) compared to patients with serum eosinophils Conclusions: In COPD patients with the frequent exacerbator phenotype a higher level of serum eosinophils, mild to moderate lung function impairment and fewer complaints show the best response to maintenance therapy with azithromycin.

Gut, 2010

Introduction Treatment of severe chronic constipation (CC) is suboptimal. This study evaluates th... more Introduction Treatment of severe chronic constipation (CC) is suboptimal. This study evaluates the combined efficacy results of prucalopride (PRU) in three identical pivotal, randomised, placebo (PLA)-controlled trials. The objective of each trial was to compare the efficacy and safety of a 12 week once daily treatment of 2 mg or 4 mg PRU with PLA in CC. Methods All three trials were of identical design with three parallel treatment groups: PLA, PRU 2 mg and PRU 4 mg. Treatment phase followed a 2-week run-in. Two trials were executed in the US and one in Europe, Canada, Australia and South Africa. The main inclusion criterion was ≤2 spontaneous complete bowel movements (SCBM) per week in combination with straining, sensation of incomplete evacuation or hard stools, at least 25% of the time. The primary efficacy parameter was the percentage of patients with an average of ≥3 SCBM/week over the 12-week treatment period. The two main secondary endpoints were the percentage of patients with an average increase of ≥1 SCBM/week and the percentage of patients with an improvement ≥1 on the satisfaction subscale of the validated quality of life instrument, PAC-QOL. Other endpoints were based on number of (S) BM, time to first BM, stool consistency, straining and patient-reported global evaluation of severity of constipation. Data analysis followed intent-to-treat (ITT) principles. Results Total 1924 ITT patients, 89% female, average age 47 years, average duration of constipation ∼20 years, prior treatments rated inadequate for 83%. Main Complaints: Infrequent defecation (30%), abdominal bloating (24%), abdominal pain (14%), during 2-week run-in ∼57% of the patients had no SCBM, and average weekly number of SCBM was 0.47. In each individual trial the results for the primary endpoint and secondary endpoints were significantly better for both PRU groups compared to PLA. For the three trials combined, the percentage of patients with an average of ≥3 SCBM per week over the 12 week treatment period (primary endpoint) were 11.3%, 23.6% end 24.7% for PLA, PRU 2 mg and PRU 4 mg, respectively (both p<0.001 PRU vs PLA); similar for subjects who rated their previous therapy as inadequate. Response was highest in week 1 of treatment and stable over the remaining 11 weeks. PRU 2 mg and 4 mg consistently showed significant differences with PLA on all other secondary endpoints. Except for higher incidences of diarrhoea, nausea and headache on first day of treatment, PRU was well tolerated. Conclusion Both 2 and 4 mg PRU significantly improve bowel function and associated symptoms in CC compared to PLA. Results are reflected consistently in all observed efficacy parameters, including QOL.

The American Journal of Gastroenterology, 2000

Dumping syndrome is one of the most common causes of morbidity after gastric surgery. An estimate... more Dumping syndrome is one of the most common causes of morbidity after gastric surgery. An estimated 25-50% of operated patients have some manifestations of dumping symptoms. The hallmark feature of dumping syndrome is diarrhea, which occurs following a meal. As a class, 5HT 3 receptor antagonists slow colonic transit resulting in decreasing stool frequency and hardening of stool consistency. Alosetron hydrochloride (Lotronex®) is a potent and selective 5HT 3 receptor antagonist that has recently been approved for the treatment of diarrhea-predominant female IBS patients. This study was conducted to determine the effects of alosetron in the treatment of the symptoms of dumping syndrome. Methods: 14 male and female patients who had undergone a partial or total gastrectomy or gastric surgery and who exhibited, during the screening period, chronic diarrhea (defined as an average of Ն4 bowel movements per day, characterized as loose/watery in consistency) were eligible to enroll in this single-center, randomized, double blind, placebo-controlled pilot study. After a one-week screening period to collect adequate symptoms, patients were randomly assigned to 3 weeks treatment with placebo or alosetron 1 mg BID followed by a one-week follow-up period. Patients kept a diary card of daily bowel functions. Results: 14 patients (7 to alosetron; 7 placebo), with mean baseline of 4.4 stools per day for the alosetron group and a mean baseline of 4.7 stools per day for the placebo group, were randomized. In the alosetron group, a decrease in the mean number of stools per day was seen after the first week of treatment and benefit persisted throughout all three weeks of treatment. Mean stool consistency at baseline was 4.5 for alosetron and 4.0 for placebo (stool consistency rated as 1 ϭ very hard, 2 ϭ hard, 3 ϭ formed, 4 ϭ loose and 5 ϭ watery). Over the 3-week treatment period stools became firmer on alosetron as compared to placebo (change from baseline Ϫ0.7 vs. 0.2, respectively). Conclusions: This small pilot study demonstrates the utility of alosetron in reducing the number of stools per day and increasing stool firmness in patients with dumping syndrome. 432 Impact of Lotronex® (Alosetron HCL) on workplace productivity and activity time in females with non-constipated irritable bowel syndrome (IBS)

Digestion, 2003

Background: Chronic constipation (CC) is common and there is a need for more effective and better... more Background: Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin 4 receptor agonist with enterokinetic properties. Aims: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre. Methods: After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study). Results: Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters. Conclusions: Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.

Value in Health, 2009

for the propensity score this remained significantly higher (HR 2.93, 95% CI 1.42, 6.02) for thos... more for the propensity score this remained significantly higher (HR 2.93, 95% CI 1.42, 6.02) for those with concurrent aspirin, but was non-significant in those with no concurrent aspirin (HR 1.48, 95% CI 0.76, 2.89). In contrast, in the SCCS the relative incidence (RI) of GI hospitalisation for COX-2 s vs tNSAIDs was 0.73 (0.604, 0.998) in those with no concurrent ulcer healing drugs. CONCLUSIONS: Traditional cohort analysis methods only weakly adjust for confounding, especially confounding by indication. Case-only designs give results more akin to trials. Interpretation still requires care as each design makes crucial assumptions.

American Journal of Gastroenterology

Gastroenterology, 2013

Introduction: In patients with chronic constipation (CC), treatment with the selective, highaffin... more Introduction: In patients with chronic constipation (CC), treatment with the selective, highaffinity 5-HT4 receptor agonist prucalopride is associated with improvements in colonic transit time (CTT) that correlate with bowel movement frequency. The aim of this analysis was to assess the relationship between CTT and gastrointestinal symptoms in relation to prucalopride use. Methods: An integrated analysis was conducted of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with CC. CC was defined as ≤3 spontaneous complete bowel movements per week as well as straining, sensation of incomplete evacuation, or hard stools for ≥25% of stools. Patients with secondary constipation were excluded. CTT was assessed at pre-selected study sites at the start and end of treatment, using radio-opaque markers, when the patients were not taking laxatives. Slow CTT was defined as ≥48 hours and very slow CTT as ≥96 hours. At every visit, patients assessed the presence and severity of their symptoms (absent, very mild, mild, moderate, marked, severe and very severe). Results: Overall, 280 patients had CTT assessments at both baseline and final visit and were included in this analysis. Of these, 112 were treated with placebo, 98 with prucalopride 2mg and 70 with prucalopride 4mg. Average patient age was 43 years; average duration of constipation was 19 years; and 93% of patients were female. Overall, mean baseline CTT was 66 hours (range: 2-144 hours) and 70% of patients (n = 196) had slow CTT. After treatment with prucalopride 2mg and 4mg, CTT was reduced by 12 hours (95% confidence interval [CI]: -18.9, -5.1) and 14 hours (CI: -20.5, -7.4), respectively; CTT increased by 0.5 hours (CI: -4.5, +5.5) with placebo. Of patients with slow CTT at baseline, 16%, 68% and 65% had normal CTT after treatment with placebo, prucalopride 2mg and prucalopride 4mg, respectively. A higher proportion of patients with slow or very slow CTT at the end of the study had severe/very severe abdominal pain/cramps, straining symptoms or unproductive calls to defecate, compared with patients with normal CTT (Figure 1). Severe/very severe urgency was less common in the slow and very slow CTT groups than in patients with normal CTT. For other symptoms such as fatigue, abdominal bloating, flatulence and distension, a relationship with CTT was less clear. Conclusions: This study is the first to show a relationship between idiopathic slow CTT and symptom severity in patients with CC. Slower CTT is associated with a greater need to strain, unproductive calls to defecate and abdominal pain/cramps. Figure 1. Relationship between transit time at the end of treatment and the proportion of patients with severe or very severe symptoms for (A) abdominal pain/cramps and straining and (B) unproductive calls to defecate and urgency. CTT, colonic transit time.

American Journal of Gastroenterology

Blood

R115777 is an oral selective inhibitor of farnesyltransferase which disrupts critical signaling p... more R115777 is an oral selective inhibitor of farnesyltransferase which disrupts critical signaling pathways resulting in antiangiogenic, antiproliferative and apoptotic effects. Single-agent activity of R115777 in patients (pt) with MDS, with manageable toxicity, was previously reported in single-institution studies. The current multicenter study assesses the response rate (IWG-criteria) and survival of R115777 in pt with high-risk MDS, defined by FAB classification as RAEBt and RAEB or CMML with ≥10% bone marrow (BM) blasts. Starting dose of R115777 was 300 mg bid for the first 21 days of every 28-day cycle. Eighty-two pt were enrolled (median age 67 yrs; range 39–86) with RAEBt (n=23), RAEB (n=40) and CMML (n=19). Thirty-six pt (44%) had IPSS score high, 32 (39%) int-2 and 14 (17%) int-1. Fifty-two pt were therapy-naïve, while 30 (37%) had received prior therapy for MDS. Pt were treated for a median of 3 cycles (range: 6 to 553+ days), with 78% relative dose intensity. Pt discontinu...

Leukemia Research, 2005

Purpose: To assess response rate and survival with tipifarnib (ZARNESTRA ®) in a multicenter stud... more Purpose: To assess response rate and survival with tipifarnib (ZARNESTRA ®) in a multicenter study in patients with MDS, defined by FAB classification as RAEB-t, RAEB, or CMML with ~>10% bone marrow blasts and IPSS scores INT-1 or higher.

Blood, 2007

tipifarnib in intermediate-to high-risk myelodysplastic syndrome A multicenter phase 2 study of t... more tipifarnib in intermediate-to high-risk myelodysplastic syndrome A multicenter phase 2 study of the farnesyltransferase inhibitor (4217 articles) Neoplasia (3368 articles) Clinical Trials and Observations Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: This multicenter phase 2 study evaluated the use of tipifarnib (R115777) in patients with poor-risk myelodysplastic syndrome (MDS; French-American-British classification). Patients (n ‫؍‬ 82) received tipifarnib 300 mg orally twice daily for the first 21 days of each 28-day cycle. Twenty-six patients (32%) responded to tipifarnib: 12 (15%) complete responses (CRs) and 14 (17%) hematologic improvements; 37 patients (45%) had stable disease (modified International Working Group criteria, 2006). Among the 12 CRs, the median response duration was 11.5 months (range, 2.0-21.9 months), the median time to progression was 12.4 months (range, 3.9-23.8 months), and 7 were still alive at time of analysis (all > 3 years). Median overall survival was 11.7 months (95% CI, 9.4-15.0). Grade 3-4 neutropenia (18%) and thrombocytopenia (32%) were the most common treatment-related adverse events; severe nonhematologic adverse events were rarely reported. In this study, durable responses and acceptable side effects were observed. Tipifarnib is an active agent for the treatment of patients with intermediate-to high-risk MDS. (Blood. 2007;109:4158-4163)

Antimicrobial Agents and Chemotherapy, 2010

PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis ... more PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days. Eight subjects received once daily standard antituberculosis treatment as positive control. The primary efficacy endpoint was the mean rate of change in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log 10 CFU/day/ml (؎ standard deviation [SD]). The drug demonstrated increases that were dose linear but less than dose proportional in serum concentrations in doses from 200 to 1,000 mg daily. Dosing of 1,200 mg gave no additional exposure compared to 1,000 mg daily. The mean daily CFU fall under standard treatment was 0.148 (؎0.055), consistent with that found in previous studies. The mean daily fall under PA-824 was 0.098 (؎0.072) and was equivalent for all four dosages. PA-824 appeared safe and well tolerated; the incidence of adverse events potentially related to PA-824 appeared dose related. We conclude that PA-824 demonstrated bactericidal activity over the dose range of 200 to 1,200 mg daily over 14 days. Because maximum efficacy was unexpectedly achieved at the lowest dosage tested, the activity of lower dosages should now be explored.

Antimicrobial Resistance & Infection Control, 2020

Respiratory Medicine, 2019

The American journal of surgical pathology, 2018

Gut, 2010

Gastroenterology, 2017

European Respiratory Journal, 2016

Gut, 2010

The American Journal of Gastroenterology, 2000

Digestion, 2003

Value in Health, 2009

American Journal of Gastroenterology

Gastroenterology, 2013

American Journal of Gastroenterology

Blood

Leukemia Research, 2005

Blood, 2007

Antimicrobial Agents and Chemotherapy, 2010