Shigeru Fujimura

Antibiotic Resistance of Helicobacter pylori Strains in Japanese Children

ABSTRACT The resistance of Helicobacter pylori to the recently available antibiotic treatment regimens has been a growing problem. We investigated the prevalence of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin among 51 H. pylori isolates from Japanese children. In addition, the mutations of the corresponding gene were studied by PCR and restriction fragment length polymorphism analysis. Primary resistance to clarithromycin, metronidazole, and amoxicillin was detected in 29, 24, and 0% of strains, respectively. The eradication rates in clarithromycin-susceptible and -resistant strains were 89 and 56%, respectively (P < 0.05). The prevalence of strains with acquired resistance to clarithromycin (78%) was higher than that of strains with primary resistance (P < 0.01). Among the clarithromycin-resistant strains studied, 92% showed cross-resistance to azithromycin. No acquired resistance to amoxicillin was demonstrated. The A2144G mutation in the 23S rRNA gene was detected in 11 of 12 (92%) clarithromycin-resistant strains tested, whereas the mutation was not detected in any of the 15 susceptible strains. The deletion of the rdxA gene was not demonstrated in any of the strains. The results indicate that a high prevalence of clarithromycin-resistant strains is associated with eradication failure. Testing of susceptibility to clarithromycin is recommended.

Detection of Helicobacter pylori in cow's milk

Aims: To investigate the existence of Helicobacter pylori in cows milk as one of the foods which most Japanese children eat.

Helicobacter pylori in Japanese river water and its prevalence in Japanese children

Aims:  The major transmission route of Helicobacter pylori remains unclear. In this study, we examined H. pylori in the environmental waters in Japan.

Association between Mycobacterial Genotypes and Disease Progression in Mycobacterium avium Pulmonary Infection

Background: Non-tuberculous mycobacterial lung disease, most commonly caused by Mycobacterium avium infection, tends to show variable disease progression, and significant disease predictors have not been adequately established. Methods: Variable numbers of tandem repeats (VNTR) were evaluated in 16 mycobacterial interspersed repetitive unit (MIRU) loci from M avium isolates cultured from respiratory specimens obtained from 2005 to 2007. Specifically, the association between VNTR profiles and disease progression was assessed. Results: Among the 37 subjects who provided positive respiratory cultures for M avium during the 2005–6 period, 15 subjects were treated within 10 months following a microbiological diagnosis of progressive M avium lung disease. Nine subjects underwent long-term follow-up (>24 months) without treatment for stable M avium lung disease. Based on a neighbour-joining cluster analysis used to classify M avium-positive subjects according to the VNTR profile, subjects with progressive versus stable lung disease were found to be grouped together in distinct clusters. Further analysis using logistic regression modelling showed that disease progression was significantly associated with the genetic distance of the M avium isolate from an appropriately selected reference (age-adjusted odds ratio 1.95; 95% confidence interval 1.16 to 3.30; p = 0.01 for the most significant model). A best-fit model could be used to predict the progression of M avium lung disease when subjects from the 2005–6 period were combined with those from 2007 (p = 0.003). Conclusion: Progressive lung disease due to M avium infection is associated with specific VNTR genotypes of M avium.

Primary antimicrobial resistance of Helicobacter pylori in children during the past 9 years

Background:  Antimicrobial resistance of Helicobacter pylori is a growing problem in clinical practice, particularly clarithromycin resistance. The aim of the present study was therefore to investigate the prevalence of H. pylori resistance to antimicrobial agents in Japanese children.

Combined efficacy of clarithromycin plus cefazolin or vancomycin against Staphylococcus aureus biofilms formed on titanium medical devices

In this study, we investigated the in vitro efficacy of clarithromycin (CLA) combined with cefazolin (CFZ) or vancomycin (VCM) against Staphylococcus aureus biofilms formed on titanium devices in order to confirm the efficacy of eradication therapies against device-related infection. The distribution of CLA in muscle tissue surrounding bone was also investigated by liquid chromatography/tandem mass spectrometry in 10 orthopaedic patients. Biofilm formation and eradication of S. aureus were monitored by scanning electron microscopy and using double-staining dyes, respectively. Although S. aureus biofilms were not eradicated by CLA, CFZ or VCM alone, CLA combined with CFZ or VCM destroyed biofilms, and S. aureus eradication was clearly observed 72 h later. This in vitro study showed that treatment with CLA plus CFZ or VCM destroyed staphylococcal biofilms formed on medical devices and eradicated S. aureus.

Comparative in vitro Activity of S-4661, a New Parenteral Carbapenem, and Other Antimicrobial Agents against Respiratory Pathogens

The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8–128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2–8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.

Efficacy of clarithromycin plus vancomycin in mice with implant-related infection caused by biofilm-forming Staphylococcus aureus

BackgroundStaphylococcal biofilms pose an important problem, especially after orthopedic surgery using foreign implants. Clarithromycin (CAM) eliminates the biofilms formed by a wide variety of aerobic and anaerobic bacteria. In a previous in vitro study, we showed that treatment with CAM and vancomycin (VCM) eradicated staphylococcal biofilms from surgical implants. To investigate the efficacy of this eradication therapy, we assessed its effects against Staphylococcus aureus on titanium plates implanted in mice.MethodsA titanium washer covered with S. aureus biofilms was implanted in the muscular tissue around the femoral bone. Mice were given intravenous injections of CAM and intraperitoneal injections of VCM twice daily beginning 72 h after implantation. To confirm eradication of biofilms and S. aureus strains, the resected washer was examined by scanning electron microscopy.ResultsDense colonization and biofilms were seen on the washer implanted in the control mice that received saline, saline plus CAM, or saline plus VCM. Treatment with CAM plus VCM eliminated the biofilms, indicating an S. aureus eradication effect.ConclusionsStaphylococcal biofilms have demonstrated resistance to most antibiotics, including VCM. Our in vivo data support the hypothesis that combined treatment using CAM plus VCM may effectively eradicate staphylococcal biofilms in patients with implant-related infection.

Non-Helicobacter bacterial flora rarely develops in the gastric mucosal layer of children

Non-Helicobacter bacteria can be cultured from the gastric mucosa in adults but in children, there are no studies about such microflora. The purpose of this study, therefore, was to clarify whether gastric biota develops in children. In 10 children and 10 adults or elderly (5 H. pylori-infected and 5 uninfected in each group), biopsy specimens of the gastric antrum and corpus and gastric juice were studied for bacterial examinations and the data were compared between both age groups in relation to H. pylori status and luminal pH. Bacterial genera and species were analyzed using both culture and real-time polymerase chain reaction (PCR) with the 52 genus- and species-specific primer sets. Non-Helicobacterbacteria in the mucosa were cultured from all adult patients, whereas microorganisms were cultured in only one child (p < .001). Gastric pH was lower in children (median, 1.4) than in adults (median, 2.6) (p < .005). The grade of endoscopic gastric atrophy was moderate or severe in 8 adults, but absent or mild in all 10 children. Among adults, there was a significant positive correlation between gastric pH and total bacterial counts of both the mucosa and juice. These data indicate that impaired gastric acid secretion associated with long-term H. pylori infection enables non-Helicobacter bacteria to colonize in the human stomach. Such microorganisms rarely colonize in the gastric mucosa in children regardless of H. pylori status.

Survey of High- and Low-Level Mupirocin-Resistant Strains of Methicillin-Resistant Staphylococcus aureus in 15 Japanese Hospitals

Background: The extent of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) in countries using mupirocin only for the eradication of nasal carriage of MRSA is unknown. Methods: During 1997, 1998, 1999, 2000, and 2001, 1,368 strains of MRSA were isolated from 15 general hospitals in the Tohoku area of Japan and tested for susceptibility to mupirocin. Results: The isolation of low-level mupirocin resistance was 0.8% in 1997, 1.1% in 1998, 0.7% in 1999, 4.0% in 2000, and 2.4% in 2001. For the first 3 years it was about 1%. However, the isolation rate of low-level mupirocin resistance in MRSA increased dramatically in 2000. High-level mupirocin resistance was not detected during these years. Conclusion: Most patients from whom low-level mupirocin resistant MRSA were found in 2000 and 2001 had previously received mupirocin treatment for eradicating nasal carriage of MRSA, and these strains were isolated from sputum or the pharynx. This result indicates that mupirocin treatment is likely to be one of the causes of mupirocin resistance and, therefore, the development of low-level mupirocin resistance in MRSA isolated from sputum or the pharynx should be considered when using mupirocin in order to improve the control of the spread of MRSA in hospitals.