Sansoninto-induced Lung Injury.

A man in his 70s visited our department for dyspnea with pulmonary infiltrate that was unresolved by antibiotics. He had been taking Sansoninto for five years and doubled its dose a month ago. After discontinuing Sansoninto without any additional medications, his symptoms gradually disappeared, and pulmonary infiltration improved. Drug lymphocyte stimulation tests showed a positive result for Sansoninto. We diagnosed this patient with Sansoninto-induced lung injury. Sansoninto is a combination drug that consists of sansonin, bukuryo, senkyo, chimo, and kanzo. This paper reports the first case of Sansoninto-induced lung injury and discusses the mechanism considering its components.

Intratracheal immunization with pili protein protects against mortality associated with Pseudomonas aeruginosa pneumonia in mice.

We examined the protective effect of intratracheal immunization with Pseudomonas aeruginosa pili protein against respiratory infection caused by P. aeruginosa. Mice were immunized intratracheally or subcutaneously with purified pili protein or bovine serum albumin as a control. Intratracheally but not subcutaneously pili protein-immunized mice showed significant improvement of survival after intratracheal challenge with the PAO1 strain. Furthermore, bacterial cell counts in pili protein-immunized murine lungs were significantly decreased compared to controls at 18 h after the challenge. Antipili protein antibody titers in bronchoalveolar lavage fluid of intratracheally pili protein-immunized mice were higher than in bovine serum albumin immunized mice. However, antipili antibody titers were not increased in bronchoalveolar lavage fluid of subcutaneously pili protein-immunized mice, despite the high serum antipili antibody titers. Inoculation of P. aeruginosa induced immediate increases in interleukin-12 and interferon-gamma in bronchoalveolar lavage fluid of pili protein-immunized mice, reflecting an adequate and rapid immune response against P. aeruginosa respiratory tract infection. Our findings suggest that intratracheal pili protein immunization is effective against respiratory tract infection caused by P. aeruginosa in mice.

The expression of pro- and anti-apoptotic Bcl-2 family proteins in peribronchiolar lymphocytes from patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinctive form of small airway disease, which is characterized by chronic inflammation with lymphocyte infiltration around bronchioles. The aim of this study was to evaluate the importance of factors related to apoptosis in peribronchiolar lymphocytes of DPB. We employed immunohistochemical methods for the localization of Bax (a promoter of apoptosis), Bcl-2 (an inhibitor of apoptosis), and caspase-3 (a key executioner molecule of apoptosis) in lung tissues of five patients with DPB. In all patients, immunostaining for Bax was almost completely absent in accumulated lymphocytes around the bronchioles and in lymphocytes of the parafollicular area that correspond to a zone populated by T cells. In contrast to the reaction for Bax, Bcl-2 immunoreactivity was uniformly strong in all of the patients. The pattern of staining for caspase-3 was similar to that for Bax in all of the patients. In normal lung tissue, a few lymphocytes showed negative immunostaining for Bcl-2 and a positive reaction for caspase-3. Our results suggest that Bcl-2 protein may provide T-lymphocyte survival and hypercellularity in the bronchioles, thereby contributing to the progression of DPB.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Antibiotic-induced apoptosis in human activated peripheral lymphocytes.

Long-term administration of macrolide antibiotics reduced the number of lymphocytes in bronchoalveolar lavage fluid in patients with chronic airway inflammatory disease. To evaluate the inflammatory activity of macrolides, their effect on apoptosis of activated lymphocytes isolated from human peripheral blood was compared with that of other antibiotics. Macrolides, including clarithromycin and azithromycin, at a final concentration of 100 microg/ml accelerated apoptosis of activated lymphocytes, while other antibiotics such as fosfomycin sodium, beta-lactams--ceftazidime, piperacillin sodium and biapenem, and a quinolone, ofloxacin, did not cause significant induction of apoptosis. Our results suggest that 14- or 15-membered ring macrolides are specifically involved in the augmentation of apoptosis of activated lymphocytes, and this may be of value therapeutically for chronic airway diseases.

Synergistic cytotoxicity of acidity and 3,4-Dideoxyglucosone-3-ene under the existence of lactate in peritoneal dialysis fluid.

Of the non-physiological compounds in glucose-rich peritoneal dialysis fluid, we investigated the synergistic cytotoxicity of acidity and 3,4-Dideoxyglucosone-3-ene(3,4-DGE) under the existence of lactate using human peritoneal mesothelial cells (HPMC). The effect of pH on cell viability at various levels of pH (5.5, 6.7, 7.15), with or without lactate was examined by adding 1N-HCl to phosphate buffer solution. We also examined the cytotoxic effects of 3,4-DGE and pH (5.5, 6.7 or 7.15). Additionally, we compared the cytotoxic effects of 3,4-DGE and pH (5.5, 6.7 or 7.15) under existence of lactate (40 meq/L) or absence of lactate. The cells were exposed to these solutions for 2 or 4 h. Cell viability was determined by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenylterazolium bromide) assay. 3,4-DGE or acidic solution alone had no significant effects on MTT viability under the absence of lactate. However, acidic solutions containing 3,4-DGE significantly decreased MTT viability under the existence of lactate. The MTT viability of HPMC was not decreased by 3,4-DGE or acidity alone under the absence of lactate. However, the combination of acidity and 3,4-DGE markedly decreased MTT viability under the existence of lactate, strongly suggesting the synergistic cytotoxicity of 3,4-DGE and acidity under the existence of lactate.

Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. METHODS: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders. CONCLUSION: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.

Long-term macrolide antibiotic therapy in the treatment of chronic small airway disease clinically mimicking diffuse panbronchiolitis.

OBJECTIVE: In the current studies, we investigated the clinical effects of long-term macrolide antibiotic therapy for patients with chronic small airway disease (CAD) that clinically and radiologically mimics but is pathologically distinct from diffuse panbronchiolitis (DPB). PATIENTS AND METHODS: Twenty-one Japanese patients were selected on the basis of clinical criteria for DPB and were categorized as DPB or CAD following histological evaluation of surgical lung biopsies. All patients received long-term macrolide therapy, and therapeutic results were compared for the DPB and CAD groups. RESULTS: Clinical, laboratory, radiological, and bacterial features, as well as neutrophilia in bronchoalveolar lavage fluid were strikingly similar in both groups. Long-term treatment with macrolides improved the clinical symptoms and PaO(2) in both groups. There was a significant improvement in forced expiratory volume in one second (FEV(1)), vital capacity (VC), and %VC in patients with DPB but not in patients with CAD. Neutrophilia in bronchoalveolar lavage fluid was also reduced following therapy in DPB patients but was refractory in CAD patients. CONCLUSION: Based on the different responses to macrolides, CAD might be associated with conditions distinct from those of DPB. Nevertheless, low-dose macrolide therapy may be applied in CAD to achieve clinical improvement, such as in respiratory symptoms and PaO(2).

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2003)].

From October 2003 to September 2004, we collected the specimen from 399 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 474 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 469 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 76, Streptococcus pneumoniae 81, Haemophilus influenzae 84, Pseudomonas aeruginosa (non-mucoid) 56, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 36, Moraxella subgenus Branhamella catarrhalis 24, etc. Of 76 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were both 38 strains (50.0%). Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 2 microg/mL. Arbekacin also showed the potent activity and inhibited the growth of all the strains at 4 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.125-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90:2 microg/ mL) and inhibited the growth of all the strains at 4 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for cefaclor (11.1%), erythromycin (43.2%), and clindamycin (40.7%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of 83 of all the strains (98.8%) at 0.063 microg/mL. Tobramycin showed the most potent activity against P. aeruginosa (both mucoid and non-mucoid) and its MIC90 was 2 microg/mL. The activity of CZOP also was preferable and its MIC90 was 4 microg/mL for the mucoid-type and 8 microg/mL for the non-mucoid type. CZOP was the most potent activities against K. pneumoniae and inhibited the growth of all the strains at 0.125 microg/mL. Also, all the agents generally showed potent activities against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (54.1%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 46.1% and 30.6% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.6%) and H. influenzae (18.1%). In contrast, S. aureus (16.9%) and S. pneumoniae (14.9%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.6%) and H. influenzae (21.5%). The bacteria relatively frequently isolated from the patients treated with cephems or macrolides were P. aeruginosa, and S. aureus was relatively frequently isolated from the patients treated with quinolones.

Association of peripheral mononuclear cells containing Chlamydia pneumoniae DNA with acute coronary syndrome and stable coronary artery disease in Japanese subjects.

To clarify the association of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells (PBMCs) with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in Japanese adults, touchdown-nested polymerase chain reaction was used to detect the presence of C. pneumoniae DNA. The prevalence of C. pneumoniae DNA in PBMCs was similar in a comparison of 88 patients (52.3%) with ACS, 164 patients (50.0%) with stable CAD, and 88 control subjects (50.0%). Temporal changes in the prevalence of C. pneumoniae DNA in PBMCs were also assessed every 3 months during a 1-year period (n=59). The prevalence was significantly higher in the first 3-month period (January through March) than in any of the other 3-month periods. In conclusion, the prevalence of C. pneumoniae DNA in PBMCs in patients with ACS or stable CAD was comparable to that in control populations. Furthermore, the presence of circulating C. pneumoniae was strongly associated with seasonal variability.

Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy.

Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.

Micro-broth dilution method with air-dried microplate for determining MICs of clarithromycin and amoxycillin for Helicobacter pylori isolates.

MICs of clarithromycin and amoxycillin for 253 isolates of Helicobacter pylori were measured by an air-dried microplate method and compared with the results obtained by the agar plate dilution method. The air-dried microplate method is performed by coating each well of a 96-well microplate with the test antibiotic and air-drying it. There were no marked differences between the air-dried microplate method and agar plate dilution methods in the MIC(50) and MIC(90) values or MIC ranges of clarithromycin obtained for the 253 isolates of H. pylori. More specifically, the MICs of clarithromycin for 114 (45.1 %) of the 253 isolates were the same by the air-dried microplate method as the agar plate dilution method, and the differences in the MICs of clarithromycin for a further 114 isolates (45.1 %) varied within one twofold dilution. The MICs of amoxycillin by the former method were in close agreement with the MICs obtained by the latter method: MICs of amoxycillin for 199 (78.7 %) of the 253 isolates were the same by both methods, and the differences in the MICs of amoxycillin for 42 isolates (16.6 %) varied within one twofold dilution. These results indicate that the air-dried microplate method is a useful method for determination of MICs, because the results obtained were in close agreement with those obtained by the standard agar plate dilution method. The air-dried microplate method is, therefore, a convenient and reliable method for determining the MICs of clarithromycin and amoxycillin for H. pylori isolates.

Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice.

Clinically important fungi such as Candida albicans and Cryptococcus neoformans are known to undergo phenotypic changes after repeated subculture or passages in vivo. However, there are no reports describing this phenomenon in Trichosporon species. This study investigated whether in-vivo passages of environmental isolates of Trichosporon asahii in mice changes their phenotype; three environmental isolates and 14 clinical isolates (from deep-seated infections) were used. The shape of the colony and cell type were observed, and the titre of glucuronoxylomannan (GXM) antigen and concentration of (1-->3)-beta-D-glucan were measured for each isolate. Changes in these features were also examined after three passages of the environmental isolates in mice. The shape of colonies and cell types were clearly different in environmental and clinical isolates. Furthermore, the clinical isolates released significantly higher levels of GXM antigen than environmental isolates (titre: log2 9.4 SD 0.7 versus log2 5.4 SD 1.4). The phenotype of passaged isolates was significantly different from the original environmental isolates with respect to the morphology of colonies and cell type and GXM release (titre: log2 10.0 SD 0.7 versus log2 5.4 SD 1.4). These results suggest that the phenotypic changes in T. asahii occur as a result of in-vivo passages. This process may allow a proportion of the fungal population to escape eradication by the host immune system, as GXM antigen is considered to protect the fungi against phagocytosis by polymorphonuclear leucocytes and monocytes in vivo.

Spontaneous remission of Epstein-Barr virus-negative non-Hodgkin's lymphoma after withdrawal of cyclosporine in a patient with refractory anemia.

A 70-year-old man presented with pancytopenia in August 2000, and the results of a bone marrow examination performed in January 2001 confirmed the diagnosis of refractory anemia. He was treated with cyclosporine (CsA) at 3.3 mg/kg per day, and the pancytopenia improved. The patient complained of epigastralgia 21 months later, and a gastric endoscopic examination showed an ulcer with a cleaved bank. A biopsy revealed diffuse large B-cell lymphoma. In situ hybridization analysis detected no Epstein-Barr virus (EBV) in the lymphoma. CsA treatment was discontinued, and a gastrectomy was performed 31 days later. A detailed histologic examination revealed no infiltration of abnormal B-cells in the resected stomach. Although EBV-positive lymphoma is a known complication of immunosuppressive therapy, no causal association between immunosuppressants and EBV-negative lymphoma has been established. The spontaneous remission observed after the withdrawal of CsA treatment suggests that immunosuppressive therapy can be a pathogenic factor in a subset of EBV-negative lymphomas.

Successful induction of long-term remission using rituximab in a patient with refractory hairy cell leukemia-Japanese variant.

We report the case of a 76-year-old man with hairy cell leukemia (HCL)-Japanese variant who underwent rituximab therapy. HCL proved refractory to treatment with pentostatin and cladribine, and the number of hairy cells in the peripheral blood continued to increase after splenectomy. The patient was treated with rituximab (375 mg/m2 intravenously weekly for 4 cycles), and hairy cells disappeared from the peripheral blood on the day after the first administration. Complete remission continued for 18 months after treatment. Although they produce high response rates in typical HCL, nucleoside analogs are associated with an inferior clinical response in HCL-Japanese variant, and repetitive administration of these agents increases the risk of serious infections. This encouraging result suggests that rituximab therapy should be considered as salvage therapy for refractory HCL-Japanese variant.

Response to cyclosporine therapy in patients with myelodysplastic syndrome: a clinical study of 12 cases and literature review.

Cyclosporine (CyA) was administered to 12 patients with myelodysplastic syndrome (MDS), and a response (major erythroid response, according to International Working Group criteria) was observed in 7 patients (58.3%). The median duration of response was 18 months (range, 3-22 months). Two patients are still responding and continuing to take CyA. Three patients stopped because of malignancy complications. To identify variables associated with responsiveness to CyA therapy, we analyzed the treatments of 72 MDS patients, comprising the 12 new patients and 60 patients previously described in the literature. Responses were observed in 44 of the 72 patients (61.1%). Univariate analyses revealed that higher daily dose of CyA (P for trend test, .007) and shorter disease duration (median, 5 months versus 17.5 months, P = .04) were factors significantly associated with response. No significant associations were observed between response and bone marrow features such as erythroid hypoplasia or hypoplastic marrow. Multivariate analysis also demonstrated that high CyA dose (>5 mg/kg per day) was significantly associated with response (P = .02). The present study showed that CyA therapy is useful for MDS patients with any marrow cellularity. Shorter disease duration is a pretreatment variable correlated with response, and a higher CyA dose results in a higher response rate.

Efficacy of long-term macrolide antibiotic therapy in patients with diffuse panbronchiolitis: comparison between HLA-B54-positive and -negative cases.

This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with diffuse panbronchiolitis (DPB). Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB. All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen. Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy. Long-term treatment with macrolides improved clinical symptoms, PaO(2), and forced expiratory volume in 1s (FEV(1)) equally in both groups. This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB.

Treatment with rokitamycin suppresses the lethality in a murine model of Escherichia coli O157:H7 infection.

The effects of rokitamycin (ROK) and levofloxacin (LEVX) were investigated in a murine model of enterohaemorrhagic Escherichia coli (EHEC) infection. After C3H/HeN mice were inoculated intragastrically with E. coli O157:H7, ROK (20mg/kg) or LEVX (1.2 mg/kg) was administered intragastrically. The death rate of the mice was noted and the faeces were collected to determine viable cell counts of EHEC and for Shiga-like toxins (SLTs) assays. After the mice were sacrificed, the kidneys and colons of some of the mice were removed for histopathological examination. The death rate of mice administered ROK (19%) was significantly lower than that of the control and LEVX-treated groups (80, 93%, respectively). Viable cell counts of EHEC in the faeces of the control and ROK-treated groups were 10(7) and 10(6) CFU/g at day 5 after the infection, respectively. LEVX reduced the bacterial count by less than 100 CFU/g at day 5. The level of SLTs in the faeces from the ROK group were lower than the LEVX-treated and control groups at day 5. The histopathological findings in the kidneys treated with LEVX showed necrotic tubular epithelial cells and those in the colon, inflammatory infiltrates. These were not seen in the ROK-treated group. These results suggested that ROK suppressed release of SLTs from the EHEC and could be useful in the treatment of EHEC infection.

Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae.

One hundred and seventy-seven strains of Streptococcus pneumoniae derived from respiratory specimens between 1987 and 2001 were evaluated for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996-2001 isolates than for the 1987-1995 isolates for all beta-lactams tested. For benzylpenicillin the MIC(90) value of the isolates derived between 1996 and 2001 was 1.56 mg/L, while that of strains isolated between 1987 and 1990 was 0.05 mg/L. Furthermore, the number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to levofloxacin of the 177 S. pneumoniae strains tested. When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, although more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the pbp 1a, 2x and 2b genes, only 30.0% of strains derived between 1996 and 2001 showed no mutations in the pbp gene. Strains having mutations in all three pbp genes (1a, 2x and 2b) by the PCR method increased from only 2.2% in the 1987-1990 derived strains to 27.5% in the 1996-2001 strains. Furthermore, 64.1 and 60.0% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, did not possess either the mefA or ermB by PCR analysis. Conversely, 75.0% of isolates from 1996 to 2001 possessed mefA and/or ermB. These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains. We believe that it is important to evaluate changes in MIC as well as genetic mutations in order to select the most appropriate therapy for S. pneumoniae infections.

Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. RESULTS: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. CONCLUSIONS: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.