sitafloxacin and Urinary-Tract-Infections

The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Fluoroquinolones; Humans; Treatment Outcome; Urinary Tract Infections

Sitafloxacin is one of the newer generation fluoroquinolones with highly active against multidrug-resistant (MDR) bacteria. Our objectives were to identify the sitafloxacin pharmacokinetic/pharmacodynamic (PK/PD) index and breakpoints against MDR isolate in the urinary tract infection model.. Forty-eight MDR isolates underwent sitafloxacin and levofloxacin microdilution susceptibility testing. A 24 h in vitro model was established that simulated the healthy subjects urodynamics of sitafloxacin fumarate injection. Ten MDR isolates (four carbapenem-resistant Escherichia coli, three carbapenem-resistant P. aeruginosa and three vancomycin-resistant E. faecium) were selected. The drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid Emax model was fitted to the killing effect data. Monte Carlo simulations were performed to assess target attainment for the sitafloxacin fumarate doses of 100 and 200 mg q24h.. Analysis indicated that the MICs of sitafloxacin were all significantly lower than that of levofloxacin (P < 0.01). The UAUC0-24h/MIC targets required to achieve stasis, 1-log10 killing and 2-log10 killing were 63.60, 79.49 and 99.45 (carbapenem-resistant E. coli), 60.85, 90.31 and 128.95 (carbapenem-resistant P. aeruginosa), 65.91, 77.81 and 103.11 (vancomycin-resistant E. faecium). Monte Carlo simulation showed the infusion of sitafloxacin fumarate 100 mg q24h was able to achieve 90% probability of target attainment against bacteria with MIC of 8 mg/L for the common complicated urinary tract infections.. Sitafloxacin fumarate injection is an alternative therapeutic agent for the treatment of UTIs caused by MDR isolates.

Topics: Anti-Bacterial Agents; Bacteria; Carbapenems; Escherichia coli; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Urinary Tract Infections; Vancomycin

Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum β-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated.. To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined.. FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections.. The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

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

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased.

Topics: Aged; Aged, 80 and over; Amikacin; Ampicillin; Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Escherichia coli; Female; Fluoroquinolones; Gram-Negative Bacteria; Humans; Imipenem; Japan; Klebsiella oxytoca; Klebsiella pneumoniae; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Population Surveillance; Proteus mirabilis; Pseudomonas aeruginosa; Serratia marcescens; Urinary Tract Infections; Vancomycin

Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.

Topics: Adult; Aged; Anti-Bacterial Agents; Female; Fluoroquinolones; Humans; Male; Middle Aged; Urinary Tract Infections

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

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