Population pharmacokinetics and pharmacodynamics of sitafloxacin in patients with community-acquired respiratory tract infections

An optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (PK–PD) analysis in patients with community-acquired respiratory tract infections (RTI). A population pharmacokinetic analysis of sitafloxacin was conducted using clinical data of five clinical pharmacology studies and one clinical PK–PD study in patients with RTIs. The pharmacokinetic parameters in individual patients were estimated by the Bayesian method to examine any correlation between pharmacokinetics and bacteriological efficacy. Efficacy data were obtained from the clinical PK–PD study, in which 50 or 100 mg sitafloxacin was administered twice daily for 7 days. In addition, an efficacy was simulated for a hypothetical dose regimen of 100 mg once daily. The fAUC(0–24h)/MIC and the fC(max)/MIC of sitafloxacin at a dose of 50 mg twice daily were 117.5 ± 78.0 and 7.3 ± 4.7 (mean ± SD), respectively. As a result of the univariate logistic regression analysis, the larger the value of fAUC(0–24h)/MIC or fC(max)/MIC becomes, the higher the bacteriological efficacies. The eradication rates for fAUC(0–24h)/MIC ≥ 30 and for fC(max)/MIC ≥ 2 were 96.4 % and 96.3 %, respectively. The PK–PD target values of sitafloxacin for the treatment of mild to moderate RTIs were considered to be fAUC(0–24h)/MIC ≥ 30 and fC(max)/MIC ≥ 2. The PK–PD parameters at the regimen of 50 or 100 mg twice daily in patients with RTIs reached the target values. Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK–PD simulations

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Strains Causing Neonatal Toxic Shock Syndrome-Like Exanthematous Disease in Neonatal and Perinatal Wards

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a new neonatal disease caused by toxic shock syndrome toxin 1 (TSST-1). We conducted a prospective surveillance study and characterized the methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from patients with NTED and compared them with the strains from patients with other MRSA infections and asymptomatic carriers. The study was performed in the neonatal intensive care unit and a general neonatal and maternal ward in the Tokyo Women's Medical University Hospital (TWMUH) from September to December 1998. Among 103 patients eligible for the study, MRSA was detected in 62 (60.2%) newborns; of these 62 newborns, 8 (12.9%) developed NTED, 1 (1.6%) had another MRSA infection, and 53 (85.5%) were asymptomatic MRSA carriers. Sixty-nine MRSA strains were obtained from the 62 newborns. DNA fingerprinting by pulsed-field gel electrophoresis showed two clusters: clone A with 8 subtypes and clone B. Sixty-seven of the 69 MRSA strains (97.1%) belonged to clone A, and type A1 was the most predominant (42 of 69 strains; 60.9%) in every neonatal and perinatal ward. All but one of the clone A strains had the TSST-1 and staphylococcal enterotoxin C genes. We also analyzed eight MRSA strains from eight NTED patients in five hospitals in Japan other than TWMUH. All the MRSA strains from NTED patients also belonged to clone A. These results suggest that a single clone that predominated in the neonatal wards of six hospitals might have caused NTED. However, the occurrence of NTED might not be dependent on the presence of an NTED-specific strain

Prevalence of Toxic Shock Syndrome Toxin 1 (TSST-1)-Producing Strains of Staphylococcus aureus and Antibody to TSST-1 among Healthy Japanese Women▿

Many cases of neonatal toxic shock syndrome (TSS)-like exanthematous disease but few cases of menstrual TSS (mTSS) have been reported in Japan. We determined the prevalence of mucosal colonization with Staphylococcus aureus and of positive antibodies to TSS toxin 1 (TSST-1) among 209 healthy Japanese women in Tokyo. S. aureus isolates from mucosal sites were characterized with respect to TSST-1 production and resistance genotype. Antibody titers were determined for test subjects and for 133 Japanese and 137 Caucasian control women living in the United States. S. aureus was isolated from at least one site in 108 of 209 women (52%) in Tokyo. Of the 159 S. aureus isolates recovered, 14 (9%) were TSST-1 positive (12 unique strains). Twelve of 209 women (6%) were colonized with a TSST-1-producing strain; two (<1%) had vaginal colonization. Only 2 of 12 unique toxigenic strains (14%) were methicillin resistant. Of the 12 TSST-1-positive strains isolated, 6 (50%) were pulsed-field gel electrophoresis type USA200, multilocus sequence type clonal complex 30. Fewer Japanese women in Tokyo (47%) than Caucasian and Japanese women in the United States (89% and 75%, respectively) had TSST-1 antibodies. The prevalences of colonization with TSST-1-producing S. aureus were comparable in Japan and the United States, despite low seropositivity to TSST-1 in Japan. Environmental factors appear to be important in promoting the development of anti-TSST-1 antibodies, as there was a significant difference in titers between Japanese women living in Tokyo and those living in the United States. Most colonizing TSST-1-producing S. aureus strains in Japan were genotypically similar to mTSS strains found in the United States

経尿道的前立腺切除術後の感染症に対する経口抗菌剤Levofloxacin予防的投与の効果の検討

われわれは前立腺肥大症患者98例を,リスク群(術前尿路感染症を有する患者および糖尿病患者)と非リスク群とに分け,経尿道的前立腺切除術(TURP)後感染症に対する経口剤の予防的効果を検討した.術後急性期(手術日を含め7日以内)の化学療法は,リスク経口群(Ia群)ではlevofloxacin(LVFX)600mg/日を7日間,非リスク経口群(IIa群)ではLVFX400mg/日を2日間およびLVFX200mg/日を5日間投与した.対照として,リスク点滴静注群(Ib群)および非リスク点滴静注群(IIb群)では2日間のみ抗生剤の点滴静注を行い,3日から7日までは経口群(IaおよびIIa群)と同様とした.また創傷治癒期(術後7日目以降)には,4群ともにLVFX100mgを就寝前に1回服用させ,膿尿が白血球10コ/high power field以下になるまで継続した,感染症については,38.0℃以上の発熱および尿路性器感染症の有無を検討した.急性期感染症を示した症例は,Ia群(n=11):9.1%,Ib群(n=16):18.8%,IIa群(n=39):15.4%,IIb群(n=32):12.5%であった.創傷治癒期感染症は,検討できた63例のうち,リスク群(Ia+Ib群,n=15):20.0%,非リスク群(IIa+IIb群,n=48):16.7%であった.術後急性期における経口抗菌剤LVFXによる化学療法は,リスク症例,非リスク症例ともに,注射用抗生物質を併用した群に比べ感染症発症頻度に有意差を認めず,有用であった.また創傷治癒期においても,LVFXの少量就寝前1回投与法は,安全で有用であると考えられた.Recently, oral antibiotics have been evaluated in place of parenteral antibiotics for prophylactic chemotherapy against infections after transurethral resection of the prostate (TURP). We studied the prophylactic effect of levofloxacin (LVFX) on infections following TURP in 98 patients with prostatic hypertrophy. The subjects were divided into a high-risk group (patients with preoperative urinary tract infection and/or diabetes mellitus) and a low-risk group. For postoperative acute-phase prophylaxis (within 7 days of surgery), 600 mg/day of LVFX was administered orally in the high-risk oral group (Group Ia) and 200～400 mg/day was given in the low-risk oral group (Group IIa). A parenteral antibacterial agent was initially administered for 2 days in the high-risk intravenous group (Group Ib) and the low-risk intravenous group (Group IIb), after which they subsequently received the oral LVFX regimens mentioned above. In the healing phase (from postoperative day 8 onwards), 100 mg of LVFX was administered orally before bedtime until the disappearance of pyuria (less than 10 WBC/HPF) in all groups. The percentage of patients with acute phase infection was 9.1% in Group Ia (n=11), 18.8% in Group Ib (n=16), 15.4% in Group IIa (n=39), and 12.5% in Group IIb (n=32). The percentage of patients with healing phase infections was 20.0% in the high-risk group (Ia+Ib, n=15) and 16.7% in the low-risk group (IIa+IIb, n=48). Oral LVFX therapy was useful for the prevention of acute phase infections in both the high-risk group and the low-risk group. In addition, administration of a low dose of LVFX once before bedtime was safe and useful for prophylaxis in the healing phase after TURP

経尿道的前立腺切除術後の感染症に対する経口抗菌剤Levofloxacin予防的投与の効果の検討

われわれは前立腺肥大症患者98例を,リスク群(術前尿路感染症を有する患者および糖尿病患者)と非リスク群とに分け,経尿道的前立腺切除術(TURP)後感染症に対する経口剤の予防的効果を検討した.術後急性期(手術日を含め7日以内)の化学療法は,リスク経口群(Ia群)ではlevofloxacin(LVFX)600mg/日を7日間,非リスク経口群(IIa群)ではLVFX400mg/日を2日間およびLVFX200mg/日を5日間投与した.対照として,リスク点滴静注群(Ib群)および非リスク点滴静注群(IIb群)では2日間のみ抗生剤の点滴静注を行い,3日から7日までは経口群(IaおよびIIa群)と同様とした.また創傷治癒期(術後7日目以降)には,4群ともにLVFX100mgを就寝前に1回服用させ,膿尿が白血球10コ/high power field以下になるまで継続した,感染症については,38.0℃以上の発熱および尿路性器感染症の有無を検討した.急性期感染症を示した症例は,Ia群(n=11):9.1%,Ib群(n=16):18.8%,IIa群(n=39):15.4%,IIb群(n=32):12.5%であった.創傷治癒期感染症は,検討できた63例のうち,リスク群(Ia+Ib群,n=15):20.0%,非リスク群(IIa+IIb群,n=48):16.7%であった.術後急性期における経口抗菌剤LVFXによる化学療法は,リスク症例,非リスク症例ともに,注射用抗生物質を併用した群に比べ感染症発症頻度に有意差を認めず,有用であった.また創傷治癒期においても,LVFXの少量就寝前1回投与法は,安全で有用であると考えられた.Recently, oral antibiotics have been evaluated in place of parenteral antibiotics for prophylactic chemotherapy against infections after transurethral resection of the prostate (TURP). We studied the prophylactic effect of levofloxacin (LVFX) on infections following TURP in 98 patients with prostatic hypertrophy. The subjects were divided into a high-risk group (patients with preoperative urinary tract infection and/or diabetes mellitus) and a low-risk group. For postoperative acute-phase prophylaxis (within 7 days of surgery), 600 mg/day of LVFX was administered orally in the high-risk oral group (Group Ia) and 200～400 mg/day was given in the low-risk oral group (Group IIa). A parenteral antibacterial agent was initially administered for 2 days in the high-risk intravenous group (Group Ib) and the low-risk intravenous group (Group IIb), after which they subsequently received the oral LVFX regimens mentioned above. In the healing phase (from postoperative day 8 onwards), 100 mg of LVFX was administered orally before bedtime until the disappearance of pyuria (less than 10 WBC/HPF) in all groups. The percentage of patients with acute phase infection was 9.1% in Group Ia (n=11), 18.8% in Group Ib (n=16), 15.4% in Group IIa (n=39), and 12.5% in Group IIb (n=32). The percentage of patients with healing phase infections was 20.0% in the high-risk group (Ia+Ib, n=15) and 16.7% in the low-risk group (IIa+IIb, n=48). Oral LVFX therapy was useful for the prevention of acute phase infections in both the high-risk group and the low-risk group. In addition, administration of a low dose of LVFX once before bedtime was safe and useful for prophylaxis in the healing phase after TURP