sitafloxacin and Respiratory-Tract-Infections

The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC0-24h divided by the minimum inhibitory concentration (MIC) (fAUC0-24h/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C peak divided by the MIC (fC peak/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC0-24h/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC peak/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C peak is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Community-Acquired Infections; Female; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae

Sitafloxacin is a newly approved oral fluoroquinolone in Thailand for treatment of respiratory tract and\ urinary tract infections. Initial in vitro susceptibility testing showed its effect on Escherichia coli with extended-spectrum betalactamases (ESBL), Klebsiella pneumoniae with ESBL, Pseudomonas aeruginosa, and carbapenem resistant Acinetobacter baumannii. To retrospectively review in vitro susceptibility to sitafloxacin on clinical isolates from HRH Princess Maha Chakri\ Sirindhorn Medical Center, Srinakharinwirot University (SWU) and Samitivej Sukhumvit Hospital (SVH).. Between January 2014 and June 2015, all clinical isolates from SWU and SVH that were added to test\ in vitro susceptibility to sitafloxacin were included in the present study. The susceptibility for sitafloxacin was identified by disk diffusion method with inhibition zone diameter 19 mm or greater, considered to be sensitive, and smaller than 16 mm considered to be resistance. The comparative activities of sitafloxacin to other antibiotics were determined by organisms. All bacteria with count numbers of more than 30 would be shown in results.. Among 1,288 clinical isolates from 1,163 clinical specimens that were added in vitro susceptibility test to sitafloxacin, there were 728 clinical isolates from SWU and 560 clinical isolates from SVH. The most common specimens were sputum (482), urine (385), pus (96), and blood (81). Organisms with comparative activities included E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, and Stenotrophomonas maltophilia. The susceptible percentage of sitafloxacin was 72.69% for all E. coli (n = 216) (68.26% for E. coli with ESBL and 86.96% for E. coli without ESBL), 39.31% for all K. pneumoniae (n = 173) (50% for K. pneumoniae with ESBL, 61.11% for K. pneumoniae without ESBL and 13.11% for carbapenem resistant enterobacteriaceae (CRE) strain of K. pneumoniae), 60.66% for P. aeruginosa (n = 366), 66.32% for A. baumannii (n = 386) and 93.94% for S. maltophilia (n = 33). Sitafloxacin had more susceptible percentage as compared to ciprofloxacin for all strains of E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii and more susceptible percentage as compared to levofloxacin for S. maltophilia. Although sitafloxacin might not have good activity against CRE strain of K. pneumoniae, at least some (13.11%) were susceptible as compared to 0% for ciprofloxacin.. Sitafloxacin had more susceptible percentage to E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, and S. maltophilia compared to comparative fluoroquinolones. It should be considered an antibiotic for treatment of respiratory tract and urinary tract infections caused by the resistant strains of these bacteria with susceptible proven of in vitro susceptibility.

Topics: Academic Medical Centers; Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Gram-Negative Bacteria; Humans; In Vitro Techniques; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections; Stenotrophomonas maltophilia; Thailand; Urinary 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.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria; Community-Acquired Infections; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Respiratory Tract Infections; Young Adult

To determine comparative in vitro activity of sitafloxacin against clinical isolates of bacteria from Thai patients with urinary tract infection and those with lower respiratory tract infection.. 1,255 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus spp, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis isolated from different Thai patients with urinary tract infection and those with lower respiratory tract infection in 2010 were included. The minimum inhibitory concentrations (MICs) of sitafloxacin, ciprofloxacin, levofloxacin, moxifloxacin, imipenem, amikacin, ampicillin, ceftazidime, ceftriaxone, penicillin, piperacillin/tazobactam, vancomycin, azithromycin and trimethoprim/sulfamethoxazole were determined by standard agar dilution method.. The MIC50 and MIC90 values of sitafloxacin against all tested bacteria were lowest when compared with those of levofloxacin, ciprofloxacin and moxifloxacin. Sitafloxacin was active against 51% of methicillin-resistant S. aureus (MRSA) isolates. The activity of sitafloxacin against multidrug-resistant (MDR) Gram-negative bacteria, such as, extended spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumomiae, P. aeruginosa and A. baumannii was comparable to or more than that of some beta-lactam/beta-lactamase inhibitors, cephalosporins or carbapenems.. Sitafloxacin is more active than levofloxacin, ciprofloxacin and moxifloxacin against isolated bacteria from Thai patients with urinary tract and lower respiratory infections including antibiotic resistant bacteria, such as MRSA, ESBL-producing Gram-negatives, carbapenem-resistant A. baumannii.

Topics: Anti-Bacterial Agents; Aza Compounds; Bacteria; Ciprofloxacin; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Ofloxacin; Quinolines; Respiratory Tract Infections; Thailand; Urinary Tract Infections

We investigated the efficacy and safety of sitafloxacin (STFX) in patients with mild to moderate community-acquired pneumonia or secondary infections of chronic respiratory tract diseases. The results showed that the efficacy rate was 96.5% (111/115) in patients analyzed for efficacy. The efficacy rate by STFX administration method was 93.9% (46/49) at 50mg b.i.d., 100% (37/37) at 100 mg q.d. and 96.6% (28/29) at 100mg b.i.d. In chest X-rays, the image improvement rate in 102 patients with shadows before treatment was 94.1% (96/102). The image improvement rate by STFX administration method was 90.5% (38/42) at 50 mg b.i.d., 97.1% (33/34) at 100mg q.d. and 96.2% (25/26) at 100mg b.i.d. Side effects occurred in five out of 115 patients (4.3%). Abnormalities in hepatic function test values appeared in two patients and abnormalities in renal function test values appeared in three patients. In four cases, the abnormalities were very mild and STFX administration was continued without any treatment. In the other patient, the abnormal value rapidly returned to normal after STFX administration was discontinued. These findings indicated that STFX can be used safety in routine practice by adjusting the administration within the approved dose based on patient characteristics. Good therapeutic effects can be expected in patients with respiratory tract infections.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Female; Fluoroquinolones; Humans; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Respiratory Tract Infections; Severity of Illness Index; Treatment Outcome

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was performed for 2 years from December 2008 to November 2010. In total, 3558 case cards were collected from 287 medical institutions and 3331 cases were subjected to a safety evaluation and 3225 were subjected to an efficacy evaluation. Incidence of adverse drug reactions (ADRs) was 4.44% (148/3331 cases). Major ADRs were diarrhea (55 cases) and hepatic function disorders (39 cases), and the incidences were 1.65% and 1.17%, respectively. Serious ADRs were observed in 5 cases (7 episodes); gastrointestinal haemorrhage, hepatic function abnormal, white blood cell count decreased, drug eruption, hypoglycemia, pneumonia, and superinfection in one case each. Efficacy rate was 92.9% (2997/3225 patients) in total with a range of 91.4 to 97.8% by type of infection such as respiratory tract and urinary tract. Eradication rate of indicated strains was 91.5% (808/883 strains) including Gram-positive bacteria at 92.3% (310/336 strains), Gram-negative bacteria at 90.7% (458/505 strains), anaerobes at 100.0% (28/28 strains) and atypical bacteria at 85.7% (12/14 strains). In conclusion, this use-results survey confirmed that STFX is a useful antibacterial agent with no serious problems in its safety profile and efficacy rates of over 90% against all infections.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Drug-Related Side Effects and Adverse Reactions; Female; Fluoroquinolones; Humans; Incidence; Male; Middle Aged; Product Surveillance, Postmarketing; Respiratory Tract Infections; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Otorhinolaryngologic Diseases; Outpatients; Respiratory Tract Infections; Urinary Tract Infections