In vitro exposure to macrolide antibiotics in <Emphasis Type="Italic">Helicobacter pylori</Emphasis> strains isolated from children

Clarithromycin resistance of Helicobacter pylori is a serious problem in eradication therapy. We investigated whether the use of maclorides (clarithromycin, erythromycin, and azithromycin) induces clarithromycin resistance in the organism. Twenty H. pylori strains were isolated from pediatric patients with gastrointestinal symptoms. The minimum inhibitory concentrations (MICs) of each macrolide antibiotic were determined by the Etest. Among these, 17 strains susceptible to macrolide antibiotics were used for the in vitro induction of drug resistance. In each of these 17 strains of H. pylori, 30-day exposure to clarithromycin in experiments for in vitro induction did not change the MIC of any antibiotic, nor did it induce either the A2143G or the A2144G mutation in the 23S rRNA gene. These results suggest that the use of macrolide antibiotics does not induce clarithromycin resistance in H. pylori by 23S rRNA gene mutation.     

Potent antibacterial activity of Y-754, a novel benzimidazole compound with selective action against <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Y-754, a novel benzimidazole compound, was investigated for in vitro and in vivo antibacterial activity. Unlike amoxicillin, clarithromycin, and metronidazole, the compound had no activity against common aerobic and anaerobic bacteria other than Helicobacter pylori. The minimum inhibitory concentration of Y-754 against H. pylori, at 0.025µg/ml, was nearly equal to that of amoxicillin and clarithromycin. The respective concentrations of Y-754, amoxicillin, clarithromycin, and metronidazole required to inhibit 90% of 39 isolates of H. pylori were 0.05, 0.39, 6.25, and 25µg/ml, indicating the potent activity of Y-754, including activity against clarithromycin- and metronidazole-resistant strains. The anti-H. pylori activity of Y-754 was potent even at pH 5.5 and was bactericidal at concentrations of 0.1µg/ml and above. Exposure of H. pylori to Y-754 did not result in the induction of drug-resistant mutation. Oral administration (10mg/kg twice a day for 7 days) to Mongolian gerbils infected with strain ATCC 43504 demonstrated that Y-754 was effective in H. pylori eradication and that its eradication efficacy increased in line with the progress of damage to the gastric mucosa caused by H. pylori infection. Y-754 was also efficacious in the treatment of infection by the clarithromycin-resistant strain OIT-36. The results obtained lead to the expectation that the new benzimidazole Y-754 will, in the near future, be used for H. pylori eradication therapy in peptic ulcer patients.     

Influence of daily low-dose 14-membered-ring macrolide therapy on <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in patients with chronic inflammatory disease of the airway

Our aim was to evaluate the effects of eradication and the incidence of secondary resistance by long-term low-dose daily 14-membered-ring macrolide therapy on Helicobacter pylori (H. pylori) infection in patients with chronic lower respiratory tract inflammatory disease. In a retrospective analysis, we studied the seroprevalence of H. pylori IgG in 90 patients with inflammation of the lower respiratory tract (68 had been treated with macrolide and 22 served as controls). Then, in a prospective analysis, we evaluated the eradication effect of macrolide therapy by the decline of IgG values and the ¹³C-urea breath test. Only long-term macrolide use significantly affected the seroprevalence of H. pylori IgG. However, macrolide therapy did not reduce the H. pylori IgG values in 24 patients and did not eradicate H. pylori in ¹³C-urea breath tests. Chemosensitivity testing was performed on three H. pylori strains obtained by gastric biopsy from patients in whom the disease could not be eradicated. Only one strain demonstrated a resistant character. Daily long-term low-dose 14-membered-ring macrolide therapy for patients with lower respiratory inflammatory disease may not be sufficient to eradicate H. pylori, but some strains do not acquire a resistant nature.     

Chronic <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection is associated with peripheral arterial disease

It is reported that Helicobacter pylori infection is associated with coronary atherosclerosis both epidemiologically and pathogenetically, but no conclusions have yet been reached. Therefore, we investigated the relationship between H. pylori infection and peripheral arterial disease (PAD). Sixty-nine patients with PAD attending Harasanshin General Hospital (Fukuoka, Japan) were compared with 143 controls (age-matched asymptomatic outpatients with hyperlipidemia). H. pylori infection was diagnosed by the detection of IgG antibodies, the (13)C-urea breath test, and histological examination. Multiple logistic regression analysis was used to assess the data. The 69 PAD patients and 143 controls were aged from 50 to 92 years. According to the Fontaine classification, 43/69 PAD patients (62.3%) were grade I, 25 (36.2%) were grade II, and 1 (0.14%) was grade III. The prevalence of H. pylori infection was higher in the PAD patients than in the controls (79.7% versus 44.8%; P < 0.01). Stepwise logistic regression analysis revealed that H. pylori infection and hypertension had a significant influence on the occurrence of PAD. Our results suggest that chronic H. pylori infection may be one of the risk factors for PAD.     

Comparison of the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication regimens for<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

AIMS AND METHODS: The aim of this study was to compare the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication of H. pylori infection. 235 patients with H. pylori infections and non-ulcer dyspepsia were randomly assigned to one of the following regimens: lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 250 mg (LAC250) and lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 500 mg (LAC500). All drugs were given twice daily for 7 days. The patients were assessed for prevalence of H. pylori with the CLO test. Gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4-6 weeks after completion of therapy were used for histology and culture. Bacterial sensitivity to clarithromycin and amoxicillin was determined with the E-test. RESULTS: 101 patients in the LAC250 mg group and 102 in the LAC500 group completed the study. On intention-to-treat analysis, eradication rates were 81% with LAC250 and 82% with LAC500 (p=0.88). On per-protocol analysis, eradication rates were 92% with LAC250 and 96% with LAC500 (p=0.23). Among the 203 patients (86% of the entire study group) for whom H. pylori antibiotic-sensitivity testing was technically feasible, primary resistance to clarithromycin was found in 9% and to amoxicillin in 0%. Eradication of clarithromycin sensitive/resistant strains was 94%/38% for LAC250 (p < 0.001) and 93%/40% for LAC500 (p < 0.001). CONCLUSIONS: The cure rates for the two regimens were similar, although adverse effects were more frequent with the LAC500 regimen, suggesting that 250 mg of clarithromycin b.d. may be sufficient in our patient population.     

Primary resistance in <Emphasis Type="Italic">Helicobacter pylori</Emphasis> isolated in children from Iran

Helicobacter pylori-associated infection is extre-mely common in Iran, as in other developing countries, but few data exist on the susceptibility of H. pylori to antimicrobials commonly used in the eradication schedules in this country. This study was performed to determine the resistance rate to six antimicrobial agents used in the treatment of H. pylori infection in dyspeptic Iranian children and to recommend an updated anti-H. pylori treatment regimen to use in children. All H. pylori isolated from children who were undergoing gastroscopy were prospectively collected and subcultured to yield their susceptibility to six antimicrobial agents, by E test and disk diffusion methods. Demographic data and presenting symptoms were also collected. A prospective study was carried out from January 2003 to January 2005 with 100 strains of H. pylori isolated from children (40 girls and 60 boys; age range, 1.5 to 16 years [mean, 9.22 ± 3.25 years]); the strains had been successfully subcultured to yield antimicrobial sensitivity. Overall the H. pylori resistance rate was 95% to metronidazole, 59% to amoxicillin, 16% to clarithromycin, 9% to furazolidone, 7% to ciprofloxacin, and 5% to tetracycline. The most common presenting symptom was abdominal pain. There were no statistically significant differences in antimicrobial resistance rates related to age, sex, or clinical presentation. In the Iranian children, the prevalence of H. pylori resistance was very high to metronidazole and amoxicillin, moderate to clarithromycin, and low to ciprofloxacin and tetracycline.     

Animal models for the study of <Emphasis Type="Italic">Helicobacter</Emphasis>-induced gastric carcinoma

Helicobacter pylori is considered to have a close association with gastric cancer. Many epidemiological studies have shown a strong association between chronic H. pylori infection and subsequent development of gastric carcinoma in humans. To clarify this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection was seen in the Japanese monkey model, and has recently been achieved in the Mongolian gerbil model. In these models, the sequential histopathological changes in the gastric mucosa are very similar to those in humans. The Japanese monkey model showed advances in atrophic change and p53 point mutations in the gastric mucosa during long-term observation. The Mongolian gerbil model demonstrated that H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as N-methyl-N-nitrosourea (MNU) and N-methyl-N-nitro-N-nitrosoguanidine (MNNG), and also showed that H. pylori infection alone can result in the development of gastric carcinoma. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist in the planning of eradication therapy to prevent gastric carcinoma.     

Frovatriptan <Emphasis Type="Italic">vs.</Emphasis> transdermal oestrogens or naproxen sodium for the prophylaxis of menstrual migraine

Acute treatment of menstrual migraine (MM) attacks is often incomplete and unsatisfactory, and perimenstrual prophylaxis with triptans, oestrogen supplementation or naproxen sodium may be needed for decreasing frequency and severity of the attack. In this pilot, open-label, non-randomised, parallel group study we evaluated, in 38 women with a history of MM, the efficacy of frovatriptan (n=14) 2.5 mg per os or transdermal oestrogens (n=10) 25 μg or naproxen sodium (n=14) 500 mg per os once-daily for the short-term prevention of MM. All treatments were administered in the morning for 6 days, beginning 2 days before the expected onset of menstrual headache. All women were asked to fill in a diary card, in the absence of (baseline) and under treatment, in order to score headache severity. All women reported at least one episode of MM at baseline. During treatment all patients taking transdermal oestrogens or naproxen sodium and 13 out of the 14 patients (93%) taking frovatriptan had at least one migraine attack (p=0.424). Daily incidence of migraine was significantly (p=0.045) lower under frovatriptan than under transdermal oestrogens or NS. At baseline, the overall median score of headache severity was 4.6, 4.2 and 4.3 in the group subsequently treated with frovatriptan, transdermal oestrogens and naproxen sodium, respectively (p=0.819). During treatment the median score was significantly lower under frovatriptan (2.5) than under transdermal oestrogens (3.0) and naproxen sodium (3.9, p=0.049). This was evident also for each single day of observation (p=0.016). Among treatments differences were particularly evident for the subgroup of patients with true MM (n=22) and for frovatriptan vs. naproxen sodium. This study suggests that short-term prophylaxis of MM with frovatriptan may be more effective than that based on transdermal oestrogens or naproxen sodium.     

No regional spread of vancomycin-resistant enterococci with <Emphasis Type="Italic">vanA</Emphasis> or <Emphasis Type="Italic">vanB</Emphasis> in Kitakyushu,Japan

Outbreaks of vancomycin-resistant enterococci (VRE) infection occur sporadically in Japan, and their frequency has been gradually increasing. We experienced a nosocomial outbreak of VRE in two hospitals in the city of Kitakyushu, and the spread of VRE strains was suspected in this area. To examine the prevalence rate of infection and colonization of VRE in Kitakyushu, we screened a total of 24297 clinical samples from patients in hospitals and clinics in Kitakyushu from October through December 2002 for VRE. The isolates screened as positive for VRE accounted for 2.3% (566/24297) of the tested clinical samples. Polymerase chain reaction (PCR) analyses for vanA, vanB, vanC1, and vanC2/3 were performed to confirm the screening test results. Neither vanA nor vanB genes were detected in any isolates. The 265 vanC1-positive isolates were Enterococcus gallinarum, and the 150 vanC2/3-positive isolates were E. casseliflavus. Other Enterococcus species were negative in this PCR-detection test. In this study, the PCR procedure was considered reliable and successful because although neither vanA nor vanB was detected, vanC1 and vanC2/3 were completely detectable. Therefore, we concluded that the regional spread of VRE with vanA and vanB had not occurred in Kitakyushu in 2002. In the near future, the prevalence of VRE with vanA or vanB is likely to increase in Japan, as it has in other countries. We should continue to find and prevent nosocomial outbreaks of infection and colonization by VRE.     

Ultrasonic-enhanced gentamicin transport through colony biofilms of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> and <Emphasis Type="Italic">Escherichia coli</Emphasis>

The hypothesis that ultrasound increases antibiotic transport through biofilms of Escherichia coli and Pseudomonas aeruginosa was investigated using colony biofilms. Biofilms grown on membrane filters were transferred to nutrient agar containing 50µg/ml gentamicin. A smaller filter was placed on top of the biofilm and a blank concentration disk was situated atop the filter. Diffusion of antibiotic through the biofilms was allowed for 15, 30, or 45min at 37°C. Some of these biofilms were exposed to 70-kHz ultrasound and others were not. Each concentration disk was then placed on a nutrient agar plate spread with a lawn of E. coli. The resulting zone of inhibition was used to calculate the amount of gentamicin that was transported through the biofilm into the disk. The E. coli and P. aeruginosa biofilms grown for 13 and 24h were exposed to two different ultrasonic power densities. Ultrasonication significantly increased the transport of gentamicin through the biofilm. Insonation of biofilms of E. coli for 45min more than doubled the amount of gentamicin compared to their noninsonated counterparts. For P. aeruginosa biofilms, no detectable gentamicin penetrated the biofilm within 45min without ultrasound; however, when insonated (1.5W/cm²) for 45min, the disks collected more than 0.45µg antibiotic. Ultrasonication significantly increased transport of gentamicin across biofilms that normally blocked or slowed gentamicin transport when not exposed to ultrasound. This enhanced transport may be partially responsible for the increased killing of biofilm bacteria exposed to combinations of antibiotic and ultrasound.     

Puerperal intrauterine infection caused by <Emphasis Type="Italic">Edwardsiella tarda</Emphasis>

Edwardsiella tarda infection is uncommon and has been reported to be associated with pet reptiles and the ingestion of raw fish. The majority of the infections occur as gastrointestinal disorders in immunocompromised hosts. We report a case of puerperal intrauterine E. tarda infection in a patient with no history of predisposing illness or of the recent ingestion of raw fish; this is the first such report. The patient complained of high fever, lower abdominal pain, and increasing amounts of malodorous genital discharge; these signs and symptoms responded well to intravenous antimicrobial chemotherapy.     

An <Emphasis Type="Italic">Aeromonas veronii</Emphasis> biovar sobria infection with disseminated intravascular gas production

We report a case of Aeromonas veronii biovar sobria infection with disseminated intravascular gas production. The patient was an afebrile 15-year-old girl who had been quite healthy until the onset of the illness. She came to the hospital because of a 6-h history of increasing pain and swelling in her left thigh. On admission, no infection was suspected, and a tentative diagnosis of a ruptured left gracilis muscle was made. Because the pain increased continuously, the treatment concentrated on pain control. Unexpectedly, abrupt death occurred 23h after her admission. Postmortem computed tomographic (CT) scans showed an abundance of gas in the blood vessels of the entire body. Postmortem investigation revealed disseminated intravascular gas production, marked intravascular hemolysis, and numerous intravascular Gram-negative bacilli in all organs examined. The organisms were identified as A. veronii biovar sobria, and were highly susceptible to third-generation cephalosporins. Regarding therapeutic problems, the early administration of these antibiotics should reduce the fatality rate in such infections. It is critical to keep the possibility of such an infection in mind when a patient complains of severe muscle pain.     

Functional H-MRS findings in migraine patients with and without aura assessed interictally

The present study was aimed at investigating changes in brain metabolites due to visual cortex activation in migraineurs and normal subjects by (1)H-magnetic resonance spectroscopy (MRS). Twenty-two migraine patients with aura, 22 migraine patients without aura, and 10 control subjects were assessed. The volume of interest (about 8 cm(3)) was placed on the visual cortex area and the visual stimulus was applied using MR-compatible goggles with a flashing red light at a frequency of 8 Hz and an intensity of 14 lx. Data were acquired over 36'40". The experimental time course was: baseline phase, from 0 to 3'40" (1 spectrum); on phase (flashing light condition), from 3'40" to 29'20" (1540") (7 spectra), and off phase, from 29'20" to the end of the experiment at 36'40" (2 spectra). The main result of photic stimulation in patients with migraine with aura is the more consistent decrease (-14.61%) of the N-acetylaspartate (NAA) signal, which is significantly greater than that found in migraine patients without aura and control subjects. A parallel slight increase in the lactate peak was also detected. The above findings support little differences in brain metabolites between the two patient groups assessed in interictal periods, which suggests a less efficient mitochondrial functioning in migraine with aura patients.     

Surveillance of vancomycin-resistant <Emphasis Type="Italic">Enterococcus</Emphasis> in hospitals in Ibaraki prefecture

We surveyed the prevalence of vancomycin-resistant Enterococcus (VRE) in six hospitals in Ibaraki prefecture. Three hundred and fifty-five fecal specimens were examined and 18 Enterococcus intermediately resistant to vancomycin were isolated. All of them were vanC genotypes (16 vanC-1 and 2 vanC-2 genotypes) and susceptible or intermediately resistant to ampicillin, teicoplanin, linezolid, and quinupristin-dalfopristin. Neither the vanA nor vanB gene was detected. Two of the vanC genotypes were not motile. We concluded that VRE of either VanA or VanB phenotype or those highly resistant to the antibiotics commonly used against enterococcal infection were not epidemic in this prefecture to date. In addition, we consider that detection of vancomycin-resistant genes should be encouraged for the characterization of VRE, because the vanC genotypes are occasionally motility-negative and can be misinterpreted as other Enterococcus species.     

Not <Emphasis Type="Italic">if</Emphasis> but <Emphasis Type="Italic">when</Emphasis>; no longer <Emphasis Type="Italic">why</Emphasis> but <Emphasis Type="Italic">how</Emphasis>

There is accruing evidence that information technology can improve patient health care, with several trials of technology showing smaller numbers of medication errors, or can provide earlier detection of adverse events. Critics of this type of research point out that better resolution of events is of no value unless their direct management influences clinical outcome. Nevertheless, indirect evidence is available, such as reports indicating the importance of providing specialist neuro-critical care in the management of patients with traumatic brain injury. These studies do not indicate which aspects of critical care management are crucial, but management aimed at the earlier detection and treatment of adverse events must be partly responsible. We continue to hope for definitive controlled trial evidence that information technology-led management yields improved patient outcome, but our experience so far of funding and conducting such studies has been poor. There is no question that we need better monitoring and event detection technology for health care and that we need more research into optimising that technology, but should their adoption depend on large-scale clinical trials? Perhaps now the questions we need to focus upon are no longer if but when, and no longer why but how.     

Rizatriptan <Emphasis Type="Italic">vs.</Emphasis> ibuprofen in migraine: a randomised placebo-controlled trial

The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.     

The activity of grepafloxacin in two murine models of <Emphasis Type="Italic">Mycobacterium avium</Emphasis> infection

The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25mg/kg, 50mg/kg, 100mg/kg, and 200mg/kg) were compared to clarithromycin (CLA; 100mg/kg and 200mg/kg), ethambutol (EMB; 100mg/kg), and rifabutin (RBT; 10mg/kg) using an intranasal (IN) infection model compared to an intravenous (IV) infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10⁶ organisms and for the IV model about 10⁷ organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks. At the initiation of therapy, an early control group was killed to determine the initial organism load. Three days following the completion of therapy, drug-treated groups of mice and the late control group were killed and the response to therapy measured. The most effective agents were CLA and RBT. GRE and EMB had modest activities in both the IN and the IV models. A matched comparison between IN and IV challenges for each of the agents used revealed greater suppression of MAC in the IN model compared to the IV model.     

<Emphasis Type="Italic">Morganella morganii</Emphasis>-associated arthritis in a diabetic patient

This case report involves a 60-year-old diabetic man who developed septic arthritis as a result of the pathogen Morganella morganii. The patient had complaints of elevated body temperature, malaise, rigors and pain in the left knee, despite no history of trauma. On examination of the knee, erythema, warmth, tenderness and swelling was observed. Arthrocentesis performed on his left knee indicated the presence of straw-coloured, cloudy fluid without crystals. Bacterial identification based on biochemical and automated methods indicated the growth of M morganii. M morganii was also isolated sedimentafrom the exudate of a diabetic ulcer in the left foot, with antibiotic susceptibilities identical to those from the knee effusion. This case indicates that M morganii may be considered as a possible cause of septic arthritis in diabetic patients, especially those with diabetic foot infections.     

<Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> carriage,colonization, and infection in ICU patients

Objective We evaluated whether Pseudomonas aeruginosa associated nosocomial infections in our ICU originate mainly from patients' endogenous flora or from exogenous cross-transmission. Design and setting A 6-month prospective surveillance survey was performed according to standardized protocols at the interdisciplinary ICU of the Azienda Ospedaliera Cannizzaro. Patients The study analyzed 121 patients and focused on three different states: carriage upon admission, colonization of sterile sites, and infections during ICU stay. Results We identified 138 P. aeruginosa isolates from 45 patients. The cumulative incidence of P. aeruginosa sustained colonization in the ICU was 29.9/100 patients, and the incidence density was 16.2/1,000 patient-days. The cumulative incidence of P. aeruginosa-sustained infections in the ICU was 36.7/100 patients, and the incidence density was 19.9/1,000 patient-days. The most frequent infection type was ventilator-associated pneumonia. PFGE analysis of P. aeruginosa isolates led to the identification of a major clone represented by 60.8% of isolates involving 45.9% of patients. The impact of cross-transmission, i.e., the preventable proportion of P. aeruginosa acquisition, was estimated to be at least 59.5% of all colonization or infection episodes. Acquisition of multidrug-resistant P. aeruginosa was significantly associated with cross-transmission. Conclusions Our results suggest that the ICU personnel and environment served as reservoirs for cross-transmission and emphasize the importance of exogenous acquisition of multidrug-resistant P. aeruginosa, of reduction in antibiotic pressure, and prompt enforcement of infection control measures. This work was supported by grants to A. A. from the University of Catania, Italy.