Evaluation of MRSASelect? chromogenic medium for the early detection of methicillin-resistant Staphylococcus aureus from blood cultures

INTRODUCTION:

Staphylococcus aureus bacteremia is associated with considerable morbidity and mortality. In theory, reducing the turnaround time in reporting of methicillin-resistant S aureus (MRSA) among patients with bactermia could assist with the rapid optimization of antimicrobial therapy.

OBJECTIVE:

To evaluate the sensitivity and specificity of MRSASelect (Bio-Rad Laboratories, USA), a chromogenic medium, in the early detection of MRSA from blood cultures growing Gram-positive cocci in clusters, and to confirm that routine use of this medium would, in fact, reduce turnaround time for MRSA identification.

METHODS:

The present study was conducted at three microbiology laboratories in Manitoba. Between April 2010 and May 2011, positive blood cultures with Gram-positive cocci in clusters visualized on Gram stain were subcultured to both MRSASelect and routine media. MRSA isolates were identified using conventional microbiological methods from routine media and using growth with the typical colony morphology (pink colony) on MRSASelect medium.

RESULTS:

A total of 490 blood cultures demonstrating Gram-positive cocci in clusters on Gram stain were evaluated. S aureus was recovered from 274 blood cultures, with 51 S aureus isolates (51 of 274 [18.6%]) identified as MRSA. MRSASelect medium had a sensitivity of 98%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.8% for the recovery and identification of MRSA directly from positive blood culture bottles. In addition, use of MRSASelect medium was found to improve turnaround time in the detection of MRSA by almost 24 h relative to conventional methods.

DISCUSSION:

These data support the utility of MRSASelect medium for the rapid identification of MRSA from positive blood cultures. Further clinical studies are warranted to determine whether the improvement in turnaround time will result in a measurable reduction in suboptimal antimicrobial therapy and/or improvement in patient outcome.     

The Efficacy of Moxifloxacin-Containing Triple Therapy after Standard Triple,Sequential, or Concomitant Therapy Failure for Helicobacter pylori Eradication in Korea

Background/Aims

Retreatment after initial treatment failure for Helicobacter pylori is very challenging. The purpose of this study was to evaluate the efficacies of moxifloxacin-containing triple and bismuth-containing quadruple therapy.

Methods

A total of 151 patients, who failed initial H. pylori treatment, were included in this retrospective cohort study. The initial regimens were standard triple, sequential, or concomitant therapy, and the efficacies of the two following second-line treatments were evaluated: 7-day moxifloxacin-containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate 300 mg 4 times a day).

Results

The overall eradication rates after moxifloxacin-containing triple therapy and bismuth-containing quadruple therapy were 69/110 (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was performed in the patients who failed standard triple therapy, and the results revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively (p=0.015). The frequency of noncompliance was not different between the two groups, and there were fewer adverse effects in the moxifloxacin-containing triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031, respectively).

Conclusions

Moxifloxacin-containing triple therapy, a recommended second-line treatment for initial concomitant or sequential therapy failure, had insufficient efficacy.     

Effect of Helicobacter pylori Eradication on the Development of Reflux Esophagitis and Gastroesophageal Reflux Symptoms: A Nationwide Multi-Center Prospective Study

Background/Aims

A two-year, prospective, nationwide multicenter study was undertaken to evaluate the effect of Helicobacter pylori eradication on the development of reflux esophagitis (RE) and gastroesophageal reflux disease (GERD) symptoms in the Korean population.

Methods

In total, 1,489 subjects without RE were enrolled at the outpatient clinics of 12 tertiary hospitals nationwide, and 452 subjects underwent follow-up (F/U) for 2 years to evaluate the development of RE and GERD symptoms.

Results

RE was found in 33 subjects (7.3% of 452 subjects) and 14 subjects (7.3% of 192 subjects) during the first and second year of F/U, respectively. H. pylori status was not associated with the development of RE. RE was found in six (9.0%) of 67 H. pylori-negative patients, in 26 (11.2%) of 233 eradicated subjects and in eight (7.0%) of 114 noneradicated subjects (p=0.532). Multivariate analysis showed that age ≥60 years (odds ratio [OR], 7.11; 95% confidence interval [CI], 1.92 to 26.41), alcohol consumption (OR, 4.43; 95% CI, 1.03 to 19.19) and F/U cholesterol levels ≥200 mg/dL (OR, 5.03; 95% CI, 1.32 to 19.17) were significant risk factors for the development of RE. There was no significant difference in the development of GERD symptoms or weight according to H. pylori status during the 2-year F/U.

Conclusions

Eradication of H. pylori did not affect the development of reflux esophagitis or GERD symptoms among patients in outpatient gastroenterology clinics in South Korea.     

C-Reactive Protein and Prediction of 1-Year Mortality in Prevalent Hemodialysis Patients

Summary

Background and objectives

Measurement of C-reactive protein (CRP) levels remains uncommon in North America, although it is now routine in many countries. Using Dialysis Outcomes and Practice Patterns Study data, our primary aim was to evaluate the value of CRP for predicting mortality when measured along with other common inflammatory biomarkers.

Design, setting, participants, & measurements

We studied 5061 prevalent hemodialysis patients from 2005 to 2008 in 140 facilities routinely measuring CRP in 10 countries. The association of CRP with mortality was evaluated using Cox regression. Prediction of 1-year mortality was assessed in logistic regression models with differing adjustment variables.

Results

Median baseline CRP was lower in Japan (1.0 mg/L) than other countries (6.0 mg/L). CRP was positively, monotonically associated with mortality. No threshold below which mortality rate leveled off was identified. In prediction models, CRP performance was comparable with albumin and exceeded ferritin and white blood cell (WBC) count based on measures of model discrimination (c-statistics, net reclassification improvement [NRI]) and global model fit (generalized R²). The primary analysis included age, gender, diabetes, catheter use, and the four inflammatory markers (omitting one at a time). Specifying NRI ≥5% as appropriate reclassification of predicted mortality risk, NRI for CRP was 12.8% compared with 10.3% for albumin, 0.8% for ferritin, and <0.1% for WBC.

Conclusions

These findings demonstrate the value of measuring CRP in addition to standard inflammatory biomarkers to improve mortality prediction in hemodialysis patients. Future studies are indicated to identify interventions that lower CRP and to identify whether they improve clinical outcomes.     

Prevalence of plasmid-mediated quinolone resistance genes among ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from blood cultures in Korea

OBJECTIVES:

To analyze the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants in ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea.

METHODS:

A total of 102 nonduplicate isolates of ciprofloxacin-intermediate or ciprofloxacin-resistant E coli (n=80) and K pneumoniae (n=22) from blood cultures were obtained. The qnr (qnrA, qnrB, qnrS), aac(6′)-Ib-cr, qepA and oqxAB genes were detected using polymerase chain reaction (PCR) and confirmed using direct sequencing. To determine whether the PMQR-positive plasmid was horizontally transferable, conjugation experiments were performed.

RESULTS:

Of the 102 isolates, 81 (79.4%) had one or more PMQR genes; these consisted of 59 (73.8%) E coli and 22 (100%) K pneumoniae isolates. The qnr genes were present in 15 isolates (14.7%): qnrB4 was detected in 10.8% and qnrS1 was detected in 3.9%. The aac(6′)-Ib-cr, qepA and oqxAB genes were detected in 77.5%, 3.9% and 10.8%, respectively. In conjugation experiments, PMQR genes were successfully transferred from seven (8.6%) isolates. The range of minimum inhibitory concentrations of ciprofloxacin for these seven transconjugants increased to 0.5 mg/L to 1 mg/L, which was 16- to 33-fold that of the recipient E coli J53 bacteria.

CONCLUSIONS:

PMQR genes were highly prevalent among ciprofloxacin-nonsusceptible E coli and K pneumoniae from blood cultures in the authors’ hospital. Therefore, it is necessary to monitor for the spread of PMQR genes of clinical isolates and to ensure careful antibiotic use in a hospital setting.     

Helicobacter pylori infection: Is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients

BACKGROUND:

Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori.

AIMS:

To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy.

METHODS:

One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by ¹³C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by ¹³C-urea breath test no sooner than four weeks after the end of treatment.

RESULTS:

Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens.

CONCLUSIONS:

ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment.     

Reducing the risk of severe complications among patients with Clostridium difficile infection

BACKGROUND:

The incidence and severity of Clostridium difficile infections are increasing, and there is a need to optimize the prevention of complicated disease.

OBJECTIVE:

To identify modifiable processes of care associated with an altered risk of C difficile complications.

METHODS:

A retrospective cohort study (with prospective case ascertainment) of all C difficile infections during 2007/2008 at a tertiary care hospital was conducted.

RESULTS:

Severe complications were frequent (occurring in 97 of 365 [27%] C difficile episodes), with rapid onset (median three days postdiagnosis). On multivariable analysis, nonmodifiable predictors of complications included repeat infection (OR 2.67), confusion (OR 2.01), hypotension (OR 0.97 per increased mmHg) and elevated white blood cell count (OR 1.04 per 10⁹ cells/L). Protection from complications was associated with initial use of vancomycin (OR 0.24); harm was associated with ongoing use of exacerbating antibiotics (OR 3.02).

CONCLUSION:

C difficile infections often occur early in the disease course and are associated with high complication rates. Clinical factors that predicted a higher risk of complications included confusion, hypotension and leukocytosis. The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases, and the avoidance of unnecessary antibiotics.     

Assessment of In vivo antioxidant properties of Dacryodes edulis and Ficus exasperata as anti-malaria plants

Objective

To evaluate the phytochemical profile and potential anti-oxidant properties of Dacryodes edulis and Ficus exasperata.

Methods

Six groups of Albino rats were intoxicated with tetrachloromethane (CCl₄) for 2 d, prior to 7 d administration of 50 mg/kg, 100 mg/kg, 200 mg/kg ethanol extracts of plants and three control remidies which is Tween 80 (placebo), CCl₄ (negative control) and vitamin E (positive control). Tissue homogenates were employed in assessing the thiobarbituric acid reactive substances expressed as malondialdehyde (MDA) levels, reduced glutathione (GSH) and catalase (CAT) activities.

Results

Phytochemical profiling of the plants showed the presence of reducing sugars, flavonoids, saponins and tannins, except alkaloids and terpenoids in F. exasperata and cardiac glycosides in D. edulis. Generally, significantly different values (P<0.05) were recorded for blood than for liver homogenates. Elevated MDA levels were observed for the CCl₄ treated group (negative control). However, lower MDA levels comparable to vitamin E (positive control) were recorded for all D. edulis and the 200 mg/kg F. exasperata pre-treatments. CAT levels were significantly (P<0.05) raised in the 100 mg/kg and 200 mg/kg pretreatments for blood and the 200 mg/kg pretreatments for liver, than for Vit E. CCl₄ reduced GSH levels were reversed significantly (P<0.05) in blood by D. edulis and by the 100 mg/kg and 200 mg/kg F. exasperata pretreatments in blood and liver tissues. The mean dose-dependent analysis shows increasing fall in MDA levels with dosage.

Conclusions

The plant extracts exhibited dose-dependent oxidative stress suppressive action. This may justify their use for the traditional preparation of anti-malarial remedies.     

Nucleotide Binding Oligomerization Domain 1 Is an Essential Signal Transducer in Human Epithelial Cells Infected with Helicobacter pylori That Induces the Transepithelial Migration of Neutrophils

Background/Aims

The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner.

Methods

Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor κB (NF-κB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified.

Results

Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-κB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-κB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls.

Conclusions

Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-κB activation and IL-8 expression in H. pylori-infected human epithelial cells.     

Levofloxacin,Metronidazole, and Lansoprazole Triple Therapy Compared to Quadruple Therapy as a Second-Line Treatment of Helicobacter pylori Infection in Korea

Background/Aims

Several rescue therapies have been recommended to eradicate Helicobacter pylori infection in patients with a failure of first-line eradication therapy, but they still fail in more than 20% of cases. The aim of this study was to evaluate the efficacy and safety of levofloxacin, metronidazole, and lansoprazole (LML) triple therapy relative to quadruple therapy as a second-line treatment.

Methods

In total, 113 patients who failed first-line triple therapy for H. pylori infection were randomly assigned to two groups: LML for 7 days and tetracycline, bismuth subcitrate, metronidazole and lansoprazole (quadruple) for 7 days.

Results

According to intention-to-treat analysis, the infection was eradicated in 38 of 56 patients (67.9%) in the LML group and 48 of 57 (84.2%) in the quadruple group (p=0.042). Per-protocol analysis showed successful eradication in 38 of 52 patients (73.1%) from the LML group and 48 of 52 (92.3%) from the quadruple group (p=0.010). There were no significant differences in the adverse effects in either treatment group.

Conclusions

LML therapy is less effective than quadruple therapy as a second-line treatment for H. pylori infection. Therefore, quadruple therapy should be considered as the primary second-line strategy for patients experiencing a failure of first-line H. pylori therapy in Korea.     

Effects of hydro-ethanol extract of Citrullus colocynthis on blood glucose levels and pathology of organs in alloxan-induced diabetic rats

Objective

To evaluated the differential effects of ethanol extraction of Citrullus colocynthis (C. colocynthis) on the blood glucose concentration and pathology of pancreas, liver, lungs, kidney and gastrointestinal tract in the alloxan induced diabetes in rats.

Methods

Diabetes mellitus was induced in 20 adult female Albino rats, using intraperitoneal injection of 120 mg/kg alloxan. The diabetic rats were randomly assigned into two equal groups. The first group was treated with the extract of C. colocynthis seed (300 mg/kg) and the rats of the second group, as an untreated diabetic group, received ordinary diet. Ten non diabetic rats remained as a normal control group.

Results

The results of this study indicate that C. colocynthis was able to reduce blood glucose significantly compared with the control diabetic group (P<0.05). Histopathologically, alloxan resulted in severe necrotic changes in the pancreatic islets, especially in the central area of the islets. Tissue sections of the pancreas in the treated rats demonstrated enhanced regeneration of B cells and increased size of pancreatic islets. Liver of the treated diabetic rats revealed significant improvement of the hepatic tissue compared to those of the untreated diabetic rats.

Conclusions

The present study indicated a significant anti-hyperglycemic effect of C. colocynthis seed and supported its traditional usage in treatment of diabetes mellitus.     

Inverse relationship between the inflammatory marker pentraxin-3, fat body mass, and abdominal obesity in end-stage renal disease

Summary

Background and objectives

Pentraxin-3 (PTX3) belongs to the same pentraxin superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat accumulation in ESRD is considered a chronic inflammatory state, but the relationship of PTX3 to this phenomenon is unknown. This study assesses plausible associations between PTX3 and surrogates of fat mass deposits in dialysis patients.

Design, setting, participants, & measurements

Circulating levels of PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric and nutritional surrogate markers of fat tissue in two cohorts comprising 156 prevalent hemodialysis (HD) and 216 incident dialysis patients.

Results

In both cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body mass index (FBMI) derived from anthropometrics and leptin, whereas there was a positive association with adiponectin. In prevalent HD patients, those with larger waist circumference (above gender-specific median values) had lower PTX3, higher CRP, and higher IL-6 levels. This was also true in multivariate analyses. In both cohorts, multivariate regression analyses showed that PTX3 was negatively and CRP (or IL-6) was positively associated with FBMI.

Conclusions

Although CRP and IL-6 were directly associated with body fat, PTX3 levels showed negative correlations with surrogates of adipose tissue in two independent cohorts of ESRD patients. Understanding the underlying reasons behind these opposite associations may have clinical relevance given the survival advantage described for obese patients on dialysis.     

Comparison of the Eradication Rate between 1- and 2-Week Bismuth-Containing Quadruple Rescue Therapies for Helicobacter pylori Eradication

Background/Aims

First-line therapies against Helicobacter pylori, including proton pump inhibitors (PPIs) plus two antibiotics, may fail in up to 20% of patients. ''Rescue'' therapy is usually needed for patients who failed the first-line treatment. This study evaluated the eradication rate of bismuth-containing quadruple rescue therapy over a 1- or 2-week period.

Methods

We prospectively investigated 169 patients with a persistent H. pylori infection after the first-line triple therapy, which was administered from October 2008 to March 2010. The patients were randomized to receive a 1- or 2-week quadruple rescue therapy (pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.). After the ''rescue'' therapy, the eradication rate, compliance, and adverse events were evaluated.

Results

The 1-week group achieved 83.5% (71/85) and 87.7% (71/81) eradication rates in the intention to treat (ITT) and per-protocol (PP) analyses, respectively. The 2-week group obtained 87.7% (72/84) and 88.9% (72/81) eradication rate in the ITT and PP analyses, respectively. There was no significant difference in the eradication rate, patient compliance or rate of adverse events between the two groups.

Conclusions

One-week bismuth-containing quadruple therapy can be as effective as a 2-week therapy after the failure of the first-line eradication therapy.     

Failure of a Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of H. pylori Eradication in H. pylori-Infected Patients with Functional Dyspepsia

Background/Aims

The role of Helicobacter pylori eradication in patients with functional dyspepsia (FD) is still uncertain. We originally planned a randomized clinical study to observe dyspeptic symptoms after H. pylori eradication therapy. However, we failed to complete the study; therefore, we analyzed the factors that affected the failure of the study.

Methods

Interviews and questionnaire surveys were conducted to analyze the factors that induced early termination from the study.

Results

Many patients were screened by gastroenterologists at 11 tertiary referral hospitals between July 2009 and August 2010; however, only 4 patients met the enrollment criteria. Most patients who visited our clinics had been experiencing FD symptoms for less than 6 months or were already taking medication. They also demanded to continue taking medications and using other drugs. Only 3 of the 4 patients signed informed consent.

Conclusions

The application of the current Rome III criteria to FD is difficult to evaluate in Korean patients with dyspeptic symptoms because of the early medical evaluation. Most Korean patients who were diagnosed with FD by the Rome III criteria did not overcome their fear of being unable to use rescue medications during the study period.     

Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

Background/Aims

This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori.

Methods

We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d., levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week.

Results

In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively.

Conclusions

A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori.     

Cystatin C,CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

Background

In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease.

Objective

To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL.

Methods

This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome.

Results

In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r²: 0.277, p < 0.05).

Conclusion

CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.     

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Background/Aims

The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies.

Methods

A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C¹³-urea breath test.

Results

Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795).

Conclusions

The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.     

Effect of angiotensin-converting enzyme inhibition on C-reactive protein levels: The Ramipril C-Reactive pRotein Randomized evaluation (4R) trial results

BACKGROUND:

Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied.

METHODS:

A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo-treated patients.

RESULTS:

The mean (± SD) age was 53±9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was −13.2% (95% CI −22.3% to −3.2%) in the placebo group compared with −21.1% (95% CI −29.9% to −11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial.

CONCLUSIONS:

A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.