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A survey on adult community-acquired pneumonia was conducted jointly by multiple centers nationwide to verify the Japanese Respiratory Society Guidelines for the Management of Community-Acquired Pneumonia in Adults (JRS2005). The efficacy and safety of piperacillin (PIPC) were investigated at the same time. PIPC is recommended as the initial treatment for patients with suspected bacterial pneumonia and pneumococcal pneumonia in JRS2005. Overall, 552 and 333 patients were registered for safety and efficacy analysis in this study, respectively. The majority of the cases in which PIPC was used had moderate disease (63.7 %), and the most common daily dosage was 4 g (73.6 %). The efficacy rate was 83.5 % overall, 81.1 % in patients with suspected bacterial pneumonia, and 92.8 % in patients with pneumococcal pneumonia. The efficacy rate with a daily dosage of 4 g was 84.9 %, and the efficacy rates achieved with a daily dosage of 4 g in patients who had mild and moderate suspected bacterial pneumonia were 90.0 and 82.6 %, respectively. The most commonly isolated causative organisms were Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae), and the bacterial eradication rates were high (97.2 and 100 %, respectively). The incidence of adverse drug reactions was 5.62 %, among which the main events were hepatic dysfunction and decreased white blood cell count. In conclusion, this study showed that PIPC is safe and effective at 4 g/day for mild-to-moderate adult community-acquired pneumonia.

Introduction: The Japanese Respiratory Society Guidelines for the Management of Community-Acquired Pneumonia (CAP) in Adults (JRS 2005) was published as a revision of the Basic Concept for the Management of CAP in Adults (JRS 2000). To evaluate the JRS 2005 criteria for differentiating between disease types and assessing the status of antimicrobial agent use in initial treatment, we conducted a prospective survey., Subjects and Methods: The survey was conducted from July 2006 to March 2007 as a nationwide joint study by 200 institutions. The study subjects included patients aged ≥16 years of age who had CAP, and patients who met the inclusion criteria were consecutively enrolled. Disease type differentiation based on JRS 2005 and JRS 2000 was conducted. Disease type diagnosis was also performed based on test results. The sensitivity and specificity of disease type differentiation were calculated. The antimicrobial agents used in the initial treatment were classified as recommended or non-recommended based on JRS 2005. The validity of non-recommended antimicrobial agent use was investigated., Results: A total of 1875 patients were analyzed. Differentiation of atypical pneumonia using the JRS 2005 criteria had higher sensitivity and lower specificity than differentiation using the JRS 2000 criteria. The antimicrobial agents recommended by JRS 2005 were used as initial treatment in a low number of cases. The efficacy of the recommended antimicrobial agents was similar to that of the non-recommended agents., Conclusions: JRS 2005 is advantageous in terms of reducing the number of items used in disease type differentiation. The recommended antimicrobial agents used for the initial treatment are believed to be appropriate., (Copyright © 2012 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Moxifloxacin is a respiratory quinolone that is expected to be useful for treating community-acquired bacterial pneumonia, but few clinical studies and not a detailed evaluation of its pharmacokinetics have been conducted in Japan in patients with pneumonia. We assessed the efficacy and safety of moxifloxacin in 18 patients with community-acquired bacterial pneumonia using pharmacokinetic-pharmacodynamic analysis. There was significant improvement in body temperature, white blood cell count, C-reactive protein, and chest X-ray score on day 3 of moxifloxacin treatment, which persisted until the completion of treatment (all p < 0.05). Nine strains, including Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Enterobacter cloacae, were isolated from sputum cultures of nine patients. The isolated strains were eradicated by moxifloxacin. The mean area under the concentration-time curve from 0 to 24 hours [AUC(0-24 h) (AUC(0-24 h,ss))], maximum plasma concentration (C(max)), and trough plasma level (C(trough)) of moxifloxacin at steady state was 52.0 μg h/ml, 4.5, and 0.9 μg/ml, respectively. Mean AUC(0-24 h,ss)/mimimum inhibitory concentration (MIC), and C(max)/MIC ratios for patients in whom MICs of moxifloxacin were determined for pathogenic bacteria were 723 and 62, respectively. The median AUC(0-24 h,ss)/MIC and C(max)/MIC ratios (based on Monte Carlo simulation employing MICs for 257 strains of S. pneumoniae collected during a respiratory infection survey by the Japanese Society of Chemotherapy in 2007) were 209.56 and 17.88, respectively. Thus, when the target for the AUC/MIC ratio was set at ≥30 and that for the C(max)/MIC ratio at ≥5, the achievement rate for these two parameters was 97.36% and 96.71%, respectively. Two patients (11%) experienced three adverse effects [one nausea, another increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], but the events were not serious. Based on these results, moxifloxacin (400 mg once daily) was considered useful for treating community-acquired bacterial pneumonia and is expected to show excellent efficacy and safety as well as suppressing the emergence of resistance.

In recent years, the increased prevalence of macrolide-resistant Mycoplasma pneumoniae (MR-M. pneumoniae) has become a significant issue in Japan. We isolated 94 strains of M. pneumoniae, and determined the minimum inhibitory concentrations (MICs) of macrolides and other antimicrobial agents for these strains. We also performed a comparative clinical evaluation of macrolide efficacy for cases of MR-M. pneumoniae infections and cases of macrolide-sensitive Mycoplasma pneumoniae infections (MS-M. pneumoniae). Of the 94 isolates of M. pneumoniae, 64 (68.1%) were classified as MS-M. pneumoniae and 30 (31.9%) as MR-M. pneumoniae strains. The clinical study included an assessment of 47 pediatric cases of MS-M. pneumoniae and 22 pediatric cases of MR-M. pneumoniae. The patient demographics, such as sex, age, the period from the onset of the infection to the first examination, laboratory findings, diagnosis, and the severity of symptoms, showed no significant difference between the two study groups. However, the efficacy of macrolide treatment was 91.5% for MS-M. pneumoniae and 22.7% for MR-M. pneumoniae, a statistically significant difference (P < 0.01). Although M. pneumoniae infection is generally considered a treatable condition, the increasing prevalence of macrolide-resistant strains of M. pneumoniae has become a significant clinical issue in pediatric patients, and it is therefore necessary to give careful consideration to the appropriate antimicrobial therapy for MR-M. pneumoniae infection.

The efficacy and safety of gatifloxacin (GFLX) was evaluated for elderly patients with respiratory infections. Each patient received one-half (100 mg b.i.d.) or one-quarter (100 mg q.d.) of the conventional dosage of 200 mg b.i.d., after a tentative clinical dosage for GFLX was estimated based on the patient's age and body weight. The subjects were 34 patients aged 65 years or older with mild to moderate acute bronchitis, pneumonia, or chronic respiratory tract infections. The serum concentration of GFLX was measured for each patient, and population and pharmacokinetic (PPK) analysis was performed, using the Bayesian method, to calculate the AUC and maximum drug concentration (Cmax). The overall efficacy rate of GFLX for 33 patients was 87.9% (29/33 patients). GFLX was effective for 75.0% (6/8 patients) in the 100-mg dosage group and 92.0% (23/25 patients) in the 200-mg dosage group. The clinical efficacy was 90.0% (9/10 patients) for acute bronchitis, 86.7% (13/15 patients) for pneumonia, and 87.5% (7/8 patients) for chronic respiratory tract infections. The bacterial eradication rate was 85.7% (12/14 patients). No adverse events or laboratory abnormalities were observed. The AUC values were 11.2-37.5 microg.h/ml and 12.7-111 microg.h/ml for the 100-mg and 200-mg dosage groups, respectively, and the Cmax values were 1.28-3.02 microg/ml and 0.72-6.35 microg/ml, respectively, for the two groups. These results suggest that the dosage of GFLX examined in this study is clinically useful in elderly patients aged 65 or older with acute bronchitis, pneumonia, or chronic respiratory tract infections. The results of PPK analysis with the dosage management also support the efficacy of GFLX.

Objective: The aim of this study was to investigate the pathophysiology of hospital-acquired pneumonia (HAP) and the clinical efficacy of its first-line treatment and to examine the validity of "the Japanese Respiratory Society (JRS) Guidelines for management of HAP"., Methodology: The observational survey was conducted during the period of June 2002-May 2004 and patients with HAP were prospectively surveyed using the consecutive enrollment method. A total of 1,356 patients from 254 hospitals nationwide were analyzed. Clinical response to first-line antibiotics was evaluated at the end of the medication., Results: The 30-day mortality rate was 19.8%. Patients were classified into four groups according to the JRS guideline criteria. There were remarkable variances in the number of cases of each group. Mild/moderate pneumonia with no risk factors (group I) accounted for 0.3% of all cases. The mortality rate tended to be higher, as clinical conditions became more serious (group II < III < IV). Alternatively, though categorized in the same group (group III), there was a difference in the mortality rate by the severity of pneumonia (severe cases 32.2% vs. moderate cases 11.0%). First-line medication using carbapenems accounted for 61.7% of total cases. The efficacy rate of guideline-concordant therapy was significantly higher than that of guideline-discordant therapy (54.2% vs. 41.7%)., Conclusions: This is the first nationwide study on HAP in Japan. The clinical characteristics and prognosis of HAP were elucidated. Review of the current classification of the disease is required and these results provide valuable information for the next revision of the guidelines.

A prospective study of the clinical efficacy of an aminoglycoside antibiotic (streptomycin, SM) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease was carried out. In a multicenter trial, patients with pulmonary MAC disease received protocol-guided combined chemotherapy with or without SM. SM was given to the patients intramuscularly 15 mg/kg three times per week for the initial 3 months and three other antibiotics (rifampicin, ethambutol, and clarithromycin) were added and administered for over 24 months after the conversion of MAC strains. From April 1998 to December 2004, 160 HIV-negative patients were enrolled in this trial. Fourteen patients were found to be ineligible because they could not continue the treatment, and they were excluded from the analysis after randomization. Seventy-three patients were assigned to receive combined chemotherapy with SM (group A) and 73 were assigned to receive combined chemotherapy without SM (group B). The median durations of treatment were 27.6 months in group A and 28.4 months in group B. The difference in the backgrounds of the groups was not statistically significant. There were no differences in microbiological and radiological findings between the groups, but the sputum conversion rate for pulmonary MAC disease at the completion of treatment was significantly higher in group A than that in group B. Although, there were no significant differences in the sputum relapse rate and clinical improvement including both clinical symptoms and radiological findings, group A showed better initial microbiological response than group B. As for adverse reactions and abnormal laboratory findings, there were no significant differences between the groups. Based on the results of this double-blind randomized study, we support treatment including SM according to both the American Thoracic Society (ATS) and the Japanese Society for Tuberculosis (JST) guidelines for patients with pulmonary MAC disease without HIV infection.

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

From October 2002 to September 2003, we collected the specimen from 476 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 584 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 578 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 77, Streptococcus pneumoniae 103, Haemophilus influenzae 95, Pseudomonas aeruginosa (non-mucoid) 61, P. aeruginosa (mucoid) 23, Klebsiella pneumoniae 36, Moraxella subgenus Branhamella catarrhalis 29, etc. Of 77 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (MPIPC) [methicillin-susceptible S. aureus: MSSA] was 34 strains (44.2%) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) was 43 strains (55.8%). Against MSSA, imipenem (IPM) and minocycline (MINO) had the most potent antibacterial activity and inhibited the growth of all the strains at 0.25 microg/ml. Although clindamycin (CLDM) and aminoglycosides also had the potent activity, the resistant strains against those agents were detected. Cefotiam (CTM) inhibited the growth of all the strains at 1 microg/ml without the low sensitive strains. Against MRSA, vancomycin (VCM) showed the most potent activity and inhibited the growth of all the strains at 2 microg/ml. Arbekacin (ABK) also showed the relatively 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 0.25-0.5 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, the resistant strains for cefaclor (CCL), erythromycin (EM), CLDM, and tetracycline (TC) were detected in 50.5%, 76.7%, 50.5%, and 80.6% of all the strains, respectively. Against H. influenzae, LVFX showed the most potent activity and inhibited the growth of 92 of all the strains (96.8%) at 0.063 microg/ml. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and non-mucoid) and inhibited the growth of all the strains at 2 microg/ml. The antibacterial activity of CZOP was good and its MIC90 against mucoid and non-mucoid strains was 8 and 16 microg/ml, respectively. CZOP and cefpirome (CPR) were the most potent against K. pneumoniae with 0.125 microg/ml of MIC90. Also, all the agents generally showed potent activities against M. (B.) catarrhalis and the MIC90 of all drugs were 4 microg/ml or less. The approximately half the number (47.5%) of the patients with respiratory infection were aged 70 years or older. As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 35.7 and 33.8% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (22.6%). In contrast, S. aureus (16.6%) and P. aeruginosa (13.7%) were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were H. influenzae (24.5%) and S. pneumoniae (24.2%). In comparison of the isolated bacteria by pretreatment agents, P. aeruginosa was relatively frequently isolated from the patients pretreated with cephems or macrolides and H. influenzae was relatively frequently isolated from the patients pretreated with penicillins.

We performed a nationwide survey of 1,258 patients to assess the treatment of community-acquired pneumonia in Japan. Cases were classified as bacterial pneumonia in which the causal organism was unknown (Type A) or presumed (Type B), atypical pneumonia (Type C), severe pneumonia (Type D), or pneumonia in certain specific morbid states (Type E). Our objectives were to assess the actual use of antimicrobials and to determine the usefulness of the "Guidelines on Respiratory Infections--Basic Concepts in the Medical Care of Community-Acquired Pneumonia in Adults", developed by the Guideline-Drafting Committee of the Japanese Respiratory Society (JRS), in differentiating these categories of patients. We also hoped to elicit constructive opinions that would contribute to future revisions of these guidelines. The findings showed that pneumonia was classified as "bacterial pneumonia in which the causal organism was unknown" in approximately half (50.2%) of the patients studied. The next most common classification was "severe pneumonia", followed by "atypical pneumonia", "bacterial pneumonia in which the causal organism was presumed", and "pneumonia in certain specific morbid states", in that order. Our results suggest that the JSR guidelines, including the methods for differentiating between bacterial pneumonia and atypical pneumonia, are useful and appropriate, and that antimicrobial agents were generally selected in accordance with the guidelines. We also identified a number of issues to be addressed in future updates of the guidelines, including criteria for physiological assessment, handling of cases in which physical findings and laboratory test results are not in agreement, age-related issues (especially the treatment of patients 65 years of age and older), the differentiation between bacterial pneumonia and atypical pneumonia, the weighing of underlying diseases and complications, and guidelines regarding the use of adjuvant therapy.

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.

Objectives: To investigate the in vitro activity of cethromycin, a new ketolide, against Chlamydia pneumoniae., Methods: The in vitro activity of cethromycin against 20 isolates of C. pneumoniae was compared with the activities of telithromycin, erythromycin A, azithromycin and clarithromycin against those isolates., Results: The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of the isolates were killed by cethromycin were both 0.016 mg/L (range 0.016-0.031 mg/L). Cethromycin was the most active antibiotic tested in this study., Conclusions: Our results appear to indicate that cethromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C. pneumoniae.

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).

Two cases of recurrent pneumonia due to Chlamydia pneumoniae are described. C. pneumoniae was continuously detected from the nasopharynx in both patients by the polymerase chain reaction and/or culture even with appropriate antibiotic therapy during the first episode. After eradication of C. pneumoniae with long-term macrolide therapy, the respiratory symptoms of both patients completely disappeared and no relapse was observed. These data indicate that new treatment strategies may be necessary to eradicate the organism in patients prone to persistent infection.

The in vitro activity of telithromycin, a new ketolide, was compared with those of roxithromycin, azithromycin, clarithromycin and erythromycin A against 20 strains of Chlamydia pneumoniae. The MICs and minimal chlamydiacidal concentrations of telithromycin for the 20 C. pneumoniae strains both ranged between 0.031 and 0.25 mg/L. Telithromycin was twice as active as roxithromycin, azithromycin and erythromycin A, but less active than clarithromycin. These results appear to indicate that telithromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C. pneumoniae.

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

Using a new plaque cloning technique, we obtained unique Chlamydia trachomatis strains which were confirmed to be free of the 7.5-kb common plasmid and glycogen in inclusions. The in vitro susceptibility of these strains to various chemotherapeutic agents was tested by comparison with their parent strains and clinical isolates possessing the common plasmid. No difference was detected for any of the agents tested, indicating that the 7.5-kb common plasmid is unrelated to the drug resistance of C. trachomatis.

An efficient and stereoselective synthesis of the C13-C23 part (8) was achieved starting from methyl (R)- and (S)-3-hydroxy-2-methylpropionates (9) via coupling of the C13-C17 aldehyde (6), prepared by Evans asymmetric aldol reaction, with the C18-C21 iodoalkene (5b) by taking advantage of the 3,4-dimethoxybenzyl protecting group.

The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).

We report on two patients with sulbactam/ampicillin (SBT/ABPC)-induced pneumonitis. Both patients were being treated with SBT/ABPC for respiratory-tract infections. Following the initiation of SBT/ABPC chemotherapy, however, chest X-ray films showed a shift of shadow in patient 1 and new pulmonary infiltration shadows in patient 2. Bronchoalveolar lavage fluid (BALF) findings showed a marked increase in the total cell count and percentage of eosinophils in patient 1 and of lymphocytes in patient 2. The results of lymphocyte stimulation tests were SBT/ABPC positive for both patients. SBT/ABPC therapy was therefore discontinued and corticosteroid therapy started. Both patients were subsequently relieved of their symptoms demonstrated significantly lower and pulmonary infiltrate levels. Based on these findings, both patients were given a diagnosis of SBT/ABPC-induced pneumonitis. It has been widely reported that CD 4/CD 8 ratio in BALF decreases in cases of drug-induced pneumonitis. However, some reports have cited increase in the CD 4/CD 8 ratio. In our two patients as well, the CD 4/CD 8 ratio increased. These results, together with the findings from several other case reports, indicate that the CD 4/CD 8 ratio may not be good basis for diagnosing drug-induced pneumonitis. Recently, the incidence of drug-induced pneumonitis has been rising. To our knowledge this is the first report documenting cases of SBT/ABPC-induced pneumonitis.