[Efficacy and Safety of Lorazepam Intravenously Administered in Subjects with Status Epilepticus or Repetitive Seizures].

We evaluated the efficacy and safety of lorazepam (LZP) 4 mg for adults (age, 16 years old or older) or 0.05mg/kg for children (age, 3 months to less than 16 years) as a slow intravenous injection in 26 Japanese patients with status epilepticus or repetitive seizures. The proportion of patients whose initial seizure stopped within 10 minutes and who continued seizure-free for at least 30 minutes after the completion of initial dose as the primary endpoint was 48.0% (12/25, 95%CI: 27.8%-68.7%). However, the proportion of patients whose seizures stopped within 10 minutes and who continued seizure-free for at least 30 minutes after the completion of either initial or second dose (in 10 to 30 minutes from the initial dose) was 64.0% (16/25, 95%CI: 42.5%-82.0%) in total, and 77.8% and 56.3% in adults and children, respectively. The most common adverse events (AEs) were somnolence (7.7%) and insomnia (7.7%), and almost all AEs were mild or moderate in severity. No patient experienced serious or severe LZP-related AEs. No one discontinued the study due to AEs.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Surveillance Committee of Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Clinical Microbiology in 2009: general view of the pathogens' antibacterial susceptibility.

For the purpose of nationwide surveillance of antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, the Japanese Society of Chemotherapy (JSC) started a survey in 2006. From 2009, JSC continued the survey in collaboration with the Japanese Association for Infectious Diseases and the Japanese Society for Clinical Microbiology. The fourth-year survey was conducted during the period from January and April 2009 by the three societies. A total of 684 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 635 strains (130 Staphylococcus aureus, 127 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 123 Haemophilus influenzae, 70 Moraxella catarrhalis, 78 Klebsiella pneumoniae, and 103 Pseudomonas aeruginosa). A maximum of 45 antibacterial agents including 26 ß-lactams (four penicillins, three penicillins in combination with ß-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), four aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). Incidence of methicillin-resistant S. aureus (MRSA) was as high as 58.5 %, and that of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) was 6.3 % and 0.0 %, respectively. Among H. influenzae, 21.1 % of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 18.7 % to be ß-lactamase-non-producing ABPC-resistant (BLNAR), and 5.7 % to be ß-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5 %) of ß-lactamase-producing strains has been suspected in Moraxella catarrhalis isolates. Four (3.2 %) extended-spectrum ß-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5 %) of P. aeruginosa were found to be metallo-ß-lactamase-producing strains, including three (1.9 %) suspected multi-drug resistant strains showing resistance against imipenem, amikacin, and ciprofloxacin. Continuous national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Investigation of the clinical breakpoints of piperacillin-tazobactam against infections caused by Pseudomonas aeruginosa.

The pharmacokinetics-pharmacodynamics (PK-PD) breakpoint of piperacillin/tazobactam (PIPC/TAZ) for hospital-acquired pneumonia (HAP) and Pseudomonas aeruginosa-induced bacteremia is controversial, since the susceptibility of P. aeruginosa to PIPC/TAZ is known to be lower than that set by the Clinical Laboratory Standards Institute (CLSI), ≤64 mg/L. The association between MIC levels and bacterial eradication after various PIPC/TAZ treatments was investigated. In all, 61 and 17 Japanese patients from the microbiology laboratory database with HAP and P. aeruginosa-induced bacteremia, respectively, who were treated with PIPC/TAZ (4.5 g, b.i.d., t.i.d., or q.i.d.) between 2008 and 2009 were retrospectively analyzed. Pertinent clinical data were retrieved from medical records. The MIC level was determined using the microdilution method. Appropriate empirical therapy with PIPC/TAZ was selected for all patients within 24 h of positive culture results. The microbiological effect after treatment was used to determine the efficacy of each PIPC/TAZ administration method. In PIPC/TAZ-treated HAP patients (4.5 g, t.i.d.), the microbiological efficacy was 93.3% (28/30) when the MIC was ≤16 mg/L, while it was 50.0 (5/9) and 0% (0/3) with MICs of 32 (p < 0.05) and 64 mg/L, respectively. In PIPC/TAZ-treated bacteremia patients (4.5 g, t.i.d. or q.i.d.), the microbiological efficacy was 100% (11/11) when the MIC was <16 mg/L, while it was 33.3 (1/3) and 0% (0/3) with MICs of 32 (p < 0.05) and ≥64 mg/L, respectively. The present CLSI susceptibility breakpoints do not necessarily predict clinical outcomes. The appropriateness evaluation of the current CLSI resistance breakpoint of PIPC/TAZ and the PK-PD breakpoint determination warrant further studies.

Antimicrobial efficacies of several antibiotics against uterine cervicitis caused by Mycoplasma genitalium.

Mycoplasma genitalium has been shown to be one of the pathogens responsible for uterine cervicitis by many studies. However, there are no clinical recommendations for treating M. genitalium-positive uterine cervicitis. Our study retrospectively investigated the antimicrobial efficacies of several antibiotics against uterine cervicitis caused by M. genitalium. We studied a total of 257 women with M. genitalium-positive uterine cervicitis, except for those with chlamydial and gonococcal infections, who were treated with one of the following antibacterial therapies: azithromycin extended release formulation (AZM-SR) 2 g single dose, azithromycin (AZM) 1 g single dose, clarithromycin (CAM) 400 mg/day for 7 days, CAM 400 mg/day for 14 days, moxifloxacin (MFLX) 400 mg/day for 7 days, MFLX 400 mg/day for 14 days, levofloxacin (LVFX) 500 mg/day for 7 days, LVFX 500 mg/day for 14 days, sitafloxacin (STFX) 200 mg/day for 7 days, and STFX 200 mg/day for 14 days. A PCR-based assay was performed to evaluate the microbiological efficacy of eradication in these patients. M. genitalium was eradicated from the uterine cervix in 19 of the 21 (90.5%) patients treated with AZM-SR 2 g single dose, in 38 of the 42 (90.5%) patients treated with MFLX 400 mg/day for 7 days, in 42 of the 42 (100%) patients treated with MFLX 400 mg/day for 14 days, and in 12 of the 13 (92.3%) patients treated with STFX 200 mg/day for 14 days. In conclusion, AZM-SR 2 g single dose, MFLX 400 mg/day for 14 days, and STFX 200 mg/day for 14 days would each be an effective treatment for M. genitalium infection.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2008: general view of the pathogens' antibacterial susceptibility.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 ß-lactams (four penicillins, three penicillins in combination with ß-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be ß-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be ß-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of ß-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum ß-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P. aeruginosa were found to be metallo ß-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

The nationwide study of bacterial pathogens associated with urinary tract infections conducted by the Japanese Society of Chemotherapy.

This study was conducted by the Japanese Society of Chemotherapy and is the first nationwide study on bacterial pathogens isolated from patients with urinary tract infections at 28 hospitals throughout Japan between January 2008 and June 2008. A total of 688 bacterial strains were isolated from adult patients with urinary tract infections. The strains investigated in this study are as follows: Enterococcus faecalis (n = 140), Escherichia coli (n = 255), Klebsiella pneumoniae (n = 93), Proteus mirabilis (n = 42), Serratia marcescens (n = 44), and Pseudomonas aeruginosa (n = 114). The minimum inhibitory concentrations of 39 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus faecalis strains were susceptible to ampicillin and vancomycin. Although a majority of the E. faecalis strains were susceptible to linezolid, 11 strains (7.8%) were found to be intermediately resistant. The proportions of fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%, respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S. marcescens strains producing extended-spectrum ß-lactamase were 5.1%, 11.9%, 0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%, and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be multidrug resistant. These data present important information for the proper treatment of urinary tract infections and will serve as a useful reference for periodic surveillance studies in the future.

[Clinical application of azithromycin extended-release (ER) formulation to treat female sexually transmitted infection].

The prevalence of female sexually transmitted infection (STI) in Japan is in the decreasing tendency after 2002, however it still actualizes as a social problem. Azithromycin, which is 15-member macrolide antimicrobial agent, has indication to treat the chlamydia STI in a single dose of 1 g. In April 2009, a single dose of 2 g of azithromycin extended release (ER) formulation, which is improved formulation by the viewpoint of pharmacokinetics-pharmacodynamics, was approved and has indications to treat not only chlamydial STI but also gonococcal STI. We considered the clinical application of azithromycin ER to treat female STI, including our new our own experiences because the clinical studies of azithromycin ER for STI had not been conducted. In conclusion, azithromycin ER was suggested theoretically becoming one of the choices of new treatment STI caused by not only chlamydia but also gonococcus, more clinical consideration to treat STI will be necessary in the future.

[Antimicrobial activity of oral quinolones against clinical isolates of Bifidobacterium group and Clostridium difficile].

Administrations of antimicrobial agent influence human intestinal flora, and sometimes lead to cause Clostridium difficile colitis (CDC). It has been well known that antimicrobial agents, such as clindamycin (CLDM), ampicillin (ABPC) and cephems, frequently cause C. difficile colitis, however, recently some respiratory quinolones, such as garenoxacin (GRNX) and moxifloxacin (MFLX), have paid to attention. Bifidobacterium species would be highly associated with the preservation of normal intestinal flora, while C. difficile would be associated with diarrhea related with antibiotics administration. We investigated antimicrobial activity of GRNX, MFLX and levofloxacin (LVFX) by agar dilution methods based on CLSI recommendations. Forty-seven strains Bifidobacterium species isolated from healthy human intestinal flora and 51 strains of C. difficile isolated from C. difficile colitis patients between 2004 and 2006 were subjected to this study. MIC ranges of Bifidobacterium species for GRNX, MFLX and LVFX were 0.5-16, 0.06-2, and 0.5-8 microg/mL, respectively. MIC50 s of GRNX, MFLX and LVFX against Bifidobacterium species were 2, 0.5 and 4 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against Bifidobacterium species were 8, 2 and 8 microg/mL, respectively. MIC ranges of C. difficile for GRNX, MFLX and LVFX were 0.5 - > 64, 1-64, and 0.125-32 microg/mL, respectively. MIC50s of GRNX, MFLX and LVFX against C. difficile were 2, 2 and 0.5 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against C. difficile were 64, 16 and 8 microg/mL, respectively. LVFX would preserve Bifidobacterium species, and also would be bactericidal for C. difficile, which might lead to the low rate of gastrointestinal disorder in LVFX. GRNX would preserve Bifidobacterium species, however, might be lead to CDC in some cases, since antimicrobial activity for C. difficile has been weak compared with LVFX. Since MFLX would be bactericidal for Bifidobacterium species and antibacterial activity of MFLX for C. difficile would be weak compared with LVFX, we have to pay attention to antibiotics associated diarrhea in MFLX treatment.

[Antifungal susceptibility of Candida species isolated from patient with invasive fungal peritonitis and investigation on clinical breakpoints of itraconazole].

We investigated antifungal susceptibility of 96 Candida species strains (37 strains of Candida albicans, 30 of Candida glabrata, 16 of Candida tropicalis and 13 of Candida parapsilosis) isolated from patients with invasive fungal peritonitis. Antifungal activity showed micafungin (MCFG), voriconazole (VRCZ)>itraconazole (ITCZ)>fluconazole (FLCZ). Judged by clinical breakpoints of Clinical and Laboratory Standards Institute (CLSI), FLCZ-resistant C. albicans, ITCZ-resistant C. albicans and VRCZ-resistant C. albicans were detected in the frequency of 5.4% (2/37), 21.6% (8/37) and 5.4% (2/37), respectively. We also retrospectively investigated the association of both antifungal susceptibility judged by CLSI breakpoints and clinical efficacy in 16 patients with invasive fungal peritonitis treated by injectable ITCZ. Clinical success and failure were obtained in cases of ITCZ MIC < or = 1 microg/mL and > or = 4 microg/ml, respectively. We conclude that we should re-consider CLSI breakpoints on ITCZ.