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.     

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.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection as an environmental risk factor for migraine without aura

Helicobacter pylori (H. pylori) infection has recently been associated with various extraintestinal pathologies and migraine. The aim of this study was to investigate the correlation of the H. pylori infection with the pathogenesis of migraine without aura, especially in cases not affected by endogenous risk factors, like hereditary pattern or hormonal fluctuations. A total of 49 outpatients (37 females and 12 males; age range: 19–47 years; mean age: 31,±14 years) affected by migraine without aura was evaluated. We divided them in 2 subgroups: a) with positive familial history, and/or with menstrual type of migraine b) with negative familial history and with menstrual unrelated type of migraine. H. pylori infection was diagnosed by the 13 C- urea breath test (INFAI — test). Control subjects consisted of 51 patients without any primary headache history (38 females; mean age of 32,±14,4 years; range 21–49 years), who underwent upper gastrointestinal (GI) endoscopy for investigation of anaemia or non ulcer dyspepsia. H. pylori detection was based on the histologic analysis of gastric mucosa biopsy. The prevalence of H. pylori infection was significantly higher in the migraineurs without aura compared to controls (p=0.016). The prevalence of H. pylori infection was significantly high in the mixed and in the female group of our patients without other predisposing factors for migraine without aura (81 and 87% respectively), while in the same groups with predisposing factors (menstruation and/or family history) the prevalence was only 36 and 37% respectively (p=0,001 for the first group and p=0,002 for the second group). Our results seem to highlight the role of H. pylori infection as a probable independent environmental risk factor for migraine without aura, especially in patients that are not genetically or hormonally susceptible to migraine.     

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.     

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.     

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.     

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.     

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.     

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.     

<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.     

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.     

Effect of arbekacin on a methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>-induced biofilm in a rat model

Biofilms are a major concern for clinicians in the treatment of infectious disease because of their resistance to a wide range of antibiotics. Arbekacin, an aminoglycoside antibiotic, is the drug of choice for the treatment of infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, it has not yet been defined whether arbekacin tends to penetrate into the biofilm structure induced by MRSA infection. In this study, we treated a biofilm mode of MRSA growth with arbekacin, using a rat air-pouch model. The model has the advantage of permitting frequent sampling of exudates for bacterial counts and antibacterial activity. A clear dose-dependent bactericidal effect was detected in rats treated with arbekacin at con-centrations between 0.3 and 10mg/kg, but 0.1mg/kg of arbekacin was ineffective against the experimental MRSA infection in rats. Morphological studies using scanning electron microscopy and histochemical staining demonstrated that an effective dosage of arbekacin induced dramatic changes in the biofilm membranous structure as well as in the inflammatory response, resulting in eradication of the biofilm structure and resolution of inflammation.     

<Emphasis Type="Italic">Anisakis simplex</Emphasis>-induced anaphylaxis

In recent years, Anisakis simplex has been shown to be an important etiologic agent responsible for food allergy and for gastrointestinal anisakiasis. We report a 61-year-old woman presenting with generalized urticaria and subsequent anaphylaxis after ingestion of raw mackerel. She rapidly recovered with administration of epinephrine and endoscopic extraction of an A. simplex larva. Serologic testing revealed specific IgE antibody to A. simplex was positive whereas that to mackerel was negative. She was diagnosed as IgE-mediated hypersensitivity to A. simplex. Patients diagnosed as fish-related or idiopathic allergy should be examined for evidence of Anisakis-induced allergy.     

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.     

Reduced activity of <Emphasis Type="Italic">Candida</Emphasis> detachment factors in the saliva of the elderly

Saliva in healthy human subjects contains protenaceous factors that detach Candida albicans cells from plastic plates. To investigate the physiological role of the detachment activity of human saliva, we compared the activity of salivary specimens collected from the elderly (who are at greater risk of oral candidiasis) to the activity of specimens collected from children and nonelderly adults. C. albicans cells were cultured and attached to the bottoms of the wells of a 96-well plate, and saliva preparations were then added to each well. After 3h of incubation, Candida cells attached to the bottoms of the wells were counted, using the crystal violet staining method. The results showed that the activity of salivary detachment factors was significantly lower among the elderly than among nonelderly adults and children. Furthermore, the activity of salivary detachment factors was reduced in 12 of the 43 elderly subjects (27.9%), a significantly higher proportion relative to that in the children and nonelderly adults. However, there was no significant difference in the level of salivary proteins between the samples collected from elderly subjects displaying low and high salivary detachment activity. These results suggest that the increased number of people with lower salivary detachment activity among the elderly may be one of the reasons that oral candidiasis is more common among the elderly than in nonelderly adults and children.     

Application of PCR for <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> detection in children with community-acquired pneumonia

Between April 2002 and March 2003, to detect Mycoplasma pneumoniae by polymerase chain reaction (PCR), a primer set designed for the 16S rRNA gene was used to examine clinical samples from 369 children with community-acquired pneumonia. Samples were collected from 12 Japanese institutions participating in a study group concerning acute respiratory infectious diseases. The sensitivity of primers – 2 CFU per reaction tube, using M. pneumoniae M129, a standard strain – was calculated to represent 1.1 × 10³ M. pneumoniae organisms adherent to the tip of the swab used to collect clinical samples. Results for PCR were obtained within 2.6h. Cases identified by PCR, cultures, and serologic tests were 68 (18.4%), 53 (14.4%), and 76 (20.6%) respectively. Among 57 PCR-positive patients tested serologically, 56 showed a significant elevation or rise in antibody titer. PCR positivity was high among patients prescribed -lactam antibiotics (86.7%) or no antibiotic (87.0%) before PCR analysis, but was low among patients receiving macrolides, new quinolones, or tetracyclines (37.5%). We concluded that the PCR constructed by us had a high probability for confirming a diagnosis of M. pneumoniae pneumonia and for guiding antibiotic choice for patients not yet treated.     

Different susceptibilities of <Emphasis Type="Italic">Staphylococcus</Emphasis> and Gram-negative rods to epigallocatechin gallate

We examined the antibacterial effects of epigallocatechin gallate (EGCg, the main constituent of tea catechins) against various strains of Staphylococcus and Gram-negative rods. Compared to the minimum inhibitory concentrations (MICs) of EGCg against S. aureus, S. epidermidis, S. hominis, and S. haemolyticus (50–100µg/ml), higher MICs (800µg/ml) were observed against Gram-negative rods, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. And difference was observed between the binding abilities of EGCg with viable S. aureus and with E. coli. The bactericidal activity of EGCg for S. aureus was blocked dose-dependently by purified peptidoglycan but not by lipopolysaccharide or dextran. It was also found that peptone and protein, but not amino acids, in the culture medium greatly affected the antibacterial activity of EGCg. These results indicate that the structure of the bacterial cell wall and the different affinities of EGCg with the various cell wall components are responsible for the different susceptibilities of Staphylococcus and Gram-negative rods to EGCg.     

Tetracyclines for treating multidrug-resistant<Emphasis Type="Italic"> Acinetobacter baumannii</Emphasis> ventilator-associated pneumonia

Objective To report the use of tetracyclines for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).Design Observational case series.Setting The Presley Regional Trauma Center located within the Regional Medical Center, Memphis, Tennessee, USA.Patients and participants Seven critically ill trauma patients with VAP caused by A. baumannii isolates that were resistant to all antibiotics tested except for doxycycline or minocycline.Interventions Patients were treated with IV doxycycline or minocycline for an average of 13.5 (range 9–20) days.Measurements and results Doxycycline or minocycline was successful in six of seven patients.Conclusions Doxycycline or minocycline may be effective for treating multidrug-resistant A. baumannii VAP.No financial support was used for this report.