Unpredictable Cyclosporine Clearance in a Korean Patient With Aplastic Anemia With Adverse Effects: A Case Study.

ABSTRACT: A 29-year-old Korean woman with chronic aplastic anemia presented with seizures due to cyclosporine-induced posterior reversible encephalopathy syndrome, caused by unpredictable oral cyclosporine (CS) accumulation and prolonged elimination. This case demonstrates the need to monitor CS drug levels with careful dose adjustments.

The epidemiology of Helicobacter pylori resistance in a university affiliated hospital: a comparison between two time periods-a cross-sectional design.

PURPOSE: During the last few decades, the increased use of various types of antibiotics in the general population caused a significant change in regional Helicobacter pylori (H. pylori) antibiotic resistance. Our aim is to study the changes in H. pylori resistance in patients who had undergone an esophagogastroduodenoscopy (EGD) and susceptibility testing and found positive for H. pylori. The study was conducted in a university affiliated hospital between 2013-2020. METHODS: A cross-sectional study was performed on all consecutive patients who had undergone an EGD and tested positive for H. pylori at the Kaplan Medical Center, Israel. The study period was divided into two sub-periods: 2013-2016 and 2017-2020. Data on age, sex, comorbidities, previous treatments, and antimicrobial susceptibility testing for six antimicrobial agents were compared. RESULTS: The resistance rates of H. pylori to clarithromycin and dual resistance to clarithromycin and metronidazole were found significantly higher during the late period. Multivariable analysis showed that the later period, older age, and diabetes mellitus were independent predictors for antimicrobial resistance. CONCLUSIONS: Our study has shown that there is an increasing resistance of H. pylori to clarithromycin and metronidazole while its susceptibility is unaffected with time to other antibiotics. More recent cross-sectional studies with larger samples are warranted in order to evaluate the changes in the resistance patterns of H. pylori to various antibiotics with time.

All-Cause Mortality and Its Predictors in Haemato-Oncology Patients with Febrile Neutropenia.

Febrile neutropenia (FN) is one of the most important life-threatening complications in haemato-oncology. Our objective was to report all-cause mortality rates in patients ill with a hematological malignancy (HM) hospitalized with a first FN episode and to identify predictors for mortality. We conducted a historical retrospective cohort study of consecutive patients with an HM, >18 years of age, admitted between January 2012 and August 2018 for a first episode of FN. Data on all-cause mortality 12 months after admission for FN were obtained. The Kaplan-Meier curve was used to describe mortality during the follow-up period. Univariate and multivariable analyses identified predictors for 1,3 and 12-month mortality. One hundred and fifty-eight patients (mean age 69.5, 49.4% males) were included. Overall, 54 patients died (15.8%, 25.9%, and 34.1% died after 1, 3, and 12 months, respectively). Lower serum albumin, higher serum gamma-glutamyl transferase (GGT), lower estimated glomerular filtration rate (eGFR), older age, higher temperature, and lower absolute lymphocyte count at admission were independent predictors of all-cause mortality after 12 months. Further studies are needed to confirm our results and identify therapeutic strategies to improve survival.

High Metronidazole and Clarithromycin Resistance of Helicobacter Pylori Isolated from Previously Treated and Naïve Patients.

BACKGROUND: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates. OBJECTIVES: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance. METHODS: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen. RESULTS: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin. CONCLUSIONS: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.

A cat's scratch or a wolf's bite?

Bartonella henselae endocarditis mimicking systemic vasculitis has been reported in patients with valvulopathy. Herein, we describe a patient with B. henselae endocarditis involving a prosthetic pulmonic valve with positive anti-dsDNA antibodies misdiagnosed with systemic lupus erythematosus (SLE) based on the revised classification SLE criteria.

The Association of Helicobacter pylori Seropositivity with All-Cause Mortality among Colorectal Cancer Patients Undergoing PET/CT Scans.

BACKGROUND: Evidence has been emerging that Helicobacter pylori may also impact colorectal cancer (CRC). Positron emission tomography/computed tomography (PET/CT) imaging can predict overall survival in CRC patients. OBJECTIVES: To determine a possible association between H. pylori seropositivity and all-cause mortality among CRC patients evaluated by PET/CT scans. METHODS: This prospective cohort study was comprised of 110 consecutive CRC patients who had undergone a PET/CT evaluation in a tertiary academic medical center. Data included demographics, body mass index (BMI), tumor node metastasis stage at diagnosis, treatment, time from diagnosis to PET/CT, and PET/CT findings. All patients were tested for anti-H. pylori immunoglobulin G (IgG) antibodies and followed for 36 months from the day of the PET/CT scan. Mortality was documented. Univariate and multivariate Cox regression was used to estimate the hazard ratio (HR) of H. pylori serological status. RESULTS: During the follow-up period, of the 110 CRC patients 41 (37.3%) died and 69 (62.7%) survived. Of the 41 patients, 26 (63.4%) were H. pylori seropositive and 15 (36.6%) were seronegative. Multivariate analysis showed that H. pylori seropositivity was associated with increased mortality (HR 3.46, 95% confidence interval 1.63-7.32), stage IV at diagnosis, metastatic disease found on PET/CT, longer time from diagnosis to PET/CT, lower BMI, and older age. CONCLUSIONS: Our findings suggest that H. pylori infection may be a risk factor for all-cause mortality among CRC patients who are evaluated by PET/CT. Multicenter studies with larger patient groups are needed to confirm our findings.

Primary and Secondary Antibiotic Resistance of Helicobacter pylori in Israeli Children and Adolescents.

BACKGROUND: Empiric treatment for Helicobacter pylori is influenced by antibiotic susceptibility of infecting strains. A rise in the resistance rate to clarithromycin and metronidazole has been reported in pediatric populations. OBJECTIVES: To assess the primary and secondary antibiotic resistance of H. pylori isolates in Israeli children and adolescents. METHODS: A retrospective review of H. pylori isolates cultured from antral biopsies of consecutive children aged 1 to 18 years, who were referred to the Pediatric Gastroenterology Unit, Kaplan Medical Center, over a 2.8 year period, was performed. Antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was determined by E-test. Data on the age of the patient, indication for endoscopy, and antibiotic treatment for H. pylori in previously treated children was collected. RESULTS: Cultures for H. pylori yielded 123 isolates. In children not previously treated (n=95), the primary global resistance was 38% with resistance to clarithromycin 9.5%, metronidazole 32.6 %, and to both 4.2%. Respective rates of resistance in previously treated children (n=28) were 71% (P = 0.002), 29% (P = 0.02), and 61% (P = 0.007). Simultaneous resistance to both drugs was found in 18% (P = 0.02). All H. pylori strains were susceptible to amoxicillin, tetracycline, and levofloxacin. Past eradication treatment was the only independent risk factor for antibiotic resistance in multivariate analysis. CONCLUSIONS: Significantly higher resistance rates were found in previously treated patients, stressing the need to refrain from empiric treatment using the "test and treat strategy." Culture-based treatment strategy should be considered in all previously treated children.

Helicobacter pylori infection in women with Hashimoto thyroiditis: A case-control study.

An association between Helicobacter pylori (H pylori) infection as environmental risk factors for Hashimoto thyroiditis (HT) has been reported. We investigated this hypothesis in women in which HT is more common. Serum immunoglobulin G antibodies against H pylori (enzyme-linked immunosorbent assay), CagA protein (Western blot assay), circulating antibodies to thyroid antigens, mainly thyroperoxidase (TPOAbs) and thyroglobulin (TgAbs), were tested in 101 females with HT and 111 non-HT control women without a history of autoimmune disease. Thyroid function, socioeconomic status at childhood, and family history of thyroid malfunction were also studied. Forty-seven HT women (46.5%) tested seropositive for H pylori versus 48 controls (43.2%; P = 0.63). The prevalence of anti-CagA antibodies was 21.3% in HT-infected patients and 31.2% in infected controls (P = 0.352). Women with HT were older than the controls at a significance level of 0.03, and higher prevalence of hypothyroidism (69% vs 13.5%, respectively) and family history of thyroid malfunction (59% vs 34%, respectively) (P < 0.001 in both). Body mass index, diaphragmatic hernia, peptic ulcer, heartburn, use of proton pump inhibitors, childhood socioeconomic background, and crowding index showed no significant difference between HT-positive or negative individuals. Multivariate analysis demonstrated that H pylori seropositivity was not associated with HT (odds ratio 1.15, 95% confidence interval 0.57-1.83, P = 0.95) and that family thyroid malfunction was independently associated with an increased risk of HT (odds ratio 3.39, 95% confidence interval 1.86-6.18, P < 0.001). No association was found between H pylori infection and HT in women. Family history of thyroid malfunction is a risk factor for HT.

Non-pharmacological treatment of Helicobacter pylori.

Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies.

Association of Helicobacter pylori with coronary artery disease and myocardial infarction assessed by myocardial perfusion imaging.

BACKGROUND: The relationship between Helicobacter pylori infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD. OBJECTIVES: To investigate the association between CAD and H. pylori infection using MPI. METHODS: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD positivity group included patients with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients' demographic data, risk factors for CAD, and childhood socioeconomic status were recorded. RESULTS: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD positivity (odds ratio 1.83, 95% confidence interval 1.06-3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95% CI 1.44-7.84, P = 0.005). No association was noted with CagA positivity. CONCLUSIONS: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors.

Helicobacter pylori infection is associated with advanced colorectal neoplasia.

OBJECTIVE: The aim of this article was to evaluate the prevalence of Helicobacter pylori infection in patients diagnosed with advanced colorectal neoplasia undergoing a colonoscopy compared to patients without neoplasia. MATERIAL AND METHODS: This cross-sectional study investigated the association of neoplastic lesions diagnosed on colonoscopy with H. pylori infection in a consecutive series of subjects who had undergone a pancolonoscopy in a single academic medical center. All patients were tested by ELISA and the immunoblot technique for serum anti-H. pylori and CagA protein IgG antibodies. Multivariate analyses were adjusted for potential-relevant confounders, including age, sex, smoking, childhood socioeconomic status, and family history of colorectal cancer. RESULTS: Two hundred and seventy-three patients were included in the study: 75% (84/112), diagnosed with neoplastic colorectal lesions and 48% (77/161) without neoplastic lesions, were found to be seropositive for H. pylori infection (p < 0.001). H. pylori infection was found in 66/77 (86 %) patients with advanced neoplasia, 18/35 (51%) patients with nonadvanced neoplasia, and 48% (77/161) patients without neoplasia (p < 0.001). In the adjusted analysis, H. pylori infection was found to be associated with advanced colorectal neoplasia (odds ratio, OR 9.57; 95% CI 4.31-21.2; p < 0.001) and CRC (OR 7.98;95% CI 3.16-20.16; p < 0.001). There was no association in patients who were CagA positive. CONCLUSION: H. pylori infection is associated with the development of advanced colorectal neoplasia. More studies are needed to confirm our findings.

Helicobacter pylori and nonmalignant diseases.

The incidence of peptic ulcer disease has declined over the last few decades, particularly in Western populations, most likely as a result of the decrease in Helicobacter pylori infection and the widespread use of proton-pump inhibitors (PPI) in patients with dyspepsia. The hospital admission rate for uncomplicated duodenal and gastric ulcers has significantly decreased worldwide. In contrast, admissions for complicated ulcer disease, such as bleeding peptic ulcers and perforation, remained relatively stable. Prophylactic H. pylori eradication was found to be associated with a reduced risk of both gastric and duodenal ulcers and their complications, including bleeding in chronic users of nonsteroidal anti-inflammatory drugs. The recent Helicobacter Eradication Relief of Dyspeptic Symptoms trial presented important data relating to symptoms and quality of life of H. pylori-positive patients with functional dyspepsia (FD) and also demonstrated significant benefits from eradication compared with the control group. The new Asian consensus report on FD recommended that dyspepsia accompanied by H. pylori infection should be considered a separate disease entity from FD and that H. pylori infection should be eradicated before diagnosing FD. The association of H. pylori with gastroesophageal reflux disease (GERD) is still controversial. Treatment for H. pylori does not seem to increase GERD symptoms or reflux esophagitis. However, documented eradication of H. pylori appears to significantly improve GERD symptoms. Additional long-term intervention studies are needed to provide more information on which to base clinical decisions.

Cranberry components for the therapy of infectious disease.

Summary of the in vitro data support a beneficial effect of cranberry or its proanthocyanin constituents by blocking adhesion to and biofilm formation on target tissues of pathogens. In vivo data partially support these beneficial effects. Consumption of various cranberry products benefited young and elderly females in preventing urinary tract infections, and in conjunction with antibiotic treatment in eradicating Helicobacter pylori infections in women. Mouthwash supplemented with an isolated cranberry derivative reduced significantly the caryogenic mutans streptococci. None of the mice infected intranasal with lethal dose of influenza virus and treated with cranberry fraction died after two weeks. Further studies should focus on the active cranberry component as supplement for food and other products especially where whole juice or powder cannot be used.

Antibiotic resistance of Helicobacter pylori in Israeli children.

OBJECTIVES: To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients. MATERIAL AND METHODS: A prospective case-series design was used. The study group included 174 patients aged 1-18 years referred to the Schneider Children's Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire. RESULTS: Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy. CONCLUSIONS: H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.

Higher gastric mucin secretion and lower gastric acid output in first-degree relatives of gastric cancer patients.

BACKGROUND: Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. AIM: To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. MATERIALS AND METHODS: Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. RESULTS: Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. CONCLUSIONS: In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.

Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor.

Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.

Elevated 13C urea breath test values females infected with Helicobacter pylori.

(13)C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a high density and active bacteria and has the potential to provide a noninvasive index of bacterial growth. We describe the gender differences in delta over baseline (13)C-UBT values in 7373 patients (4531 females and 2842 males) who underwent (13)C-UBT test for the diagnosis of H. pylori infection. A significantly (P<.001) higher mean +/- SD excess delta (13)CO(2) excretion was recorded in females (24.7+/-17.4) compared to males (17.6+/-11.8) aged 10-80 years. The age-adjusted difference between sexes was 7.1 (95% confidence interval, 6.4-7.9). Our analysis demonstrates quantitatively for the first time gender associated differences in H. pylori host interaction. This study suggests that infected females have a higher bacterial load and therefore may potentially infect their children at a higher degree than males.

Susceptibility-guided vs. empiric retreatment of Helicobacter pylori infection after treatment failure.

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.