cefditoren and Enterobacteriaceae-Infections

To investigate a possible role of Cefditoren, a recently marketed in Greece third-generation oral cephalosporin in urinary infections of outpatients.. During a multicenter survey of Enterobacteriaceae causing UTIs in outpatients during 2005-2007, Cefditoren MICs were determined by agar dilution method in a randomly selected sample of uropathogens. Susceptibility against 18 other oral/parenteral antimicrobials was determined according to Clinical and Laboratory Standards Institute methodology.. A total of 563 isolates (330 Escherichia coli, 142 Proteus mirabilis and 91 Klebsiella spp) was studied; MIC50/MIC90 of Cefditoren was 0.25/0.5 mg/L respectively, with 97.1% of the isolates being inhibited at 1 mg/L. All 12 strains producing ESBLs or AmpC enzymes were resistant to cefditoren. Susceptibility rates (%) for amoxicillin/clavulanic acid, cefuroxime axetil, cefotaxime, ciprofloxacin, trimethoprim/sulfamethoxazole and fosfomycin were 93.1- 94.1- 96.8-93.1-71.9 and 92.8% respectively. Cefditoren MIC was significantly higher in nalidixic/ciprofloxacin non-susceptible strains; resistance to cefditoren was not associated with resistance to mecillinam, fosfomycin nitrofurantoin and aminoglycosides. Multivariate analysis demonstrated history of urinary infection in the last two weeks or three months as risk factors for cefditoren resistance.. Cefditoren exhibited enhanced in vitro activity against the most common uropathogens in the outpatient setting, representing an alternative oral treatment option in patients with risk factors for resistance to first-line antibiotics.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Greece; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Outpatients; Pregnancy; Risk Factors; Treatment Outcome; Urinary Tract Infections; Young Adult

Cefditoren is a third-generation orally administered cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacterial species. After an oral 400-mg single dose, the mean concentrations in urine are 186.5 mg/L at 2 to 4 h and 12.7 mg/L at 8 to 12 h, and it is a potential drug to be used in the treatment of urinary tract infection (UTI). We performed a multicenter nationwide study in Spain in order to determine the in vitro activity of cefditoren and other comparative agents against Enterobacteriaceae causing community-acquired uncomplicated UTI in women. From June 2008 to March 2009, 89 institutions participated in the study. A total of 2152 Enterobacteriaceae were collected and sent to a coordinating laboratory where identification and antimicrobial susceptibility testing was performed against 20 antimicrobials using an automated microdilution method (MicroScan; Siemens, Sacramento, CA). Cefditoren MICs were determined by the broth microdilution method (Clinical and Laboratory Standards Institute guidelines) using the same inoculum. Microorganisms isolated were Escherichia coli (81.8%), Klebsiella pneumoniae (7.9%), Proteus mirabilis (5.2%), and others (5.1%). A total of 51 isolates (2.4%) were extended-spectrum beta-lactamase (ESBL) producers, 3 (0.1%) produced plasmidic AmpC enzymes, and 64 (2.9%) produced chromosomal AmpC. The MIC(50)/MIC(90) (mg/L) of cefditoren against all isolates was 0.12/0.5. Cefditoren inhibited 96.5% of isolates at 1 mg/L and was uniformly active against all isolates with the exception of strains producing ESBLs or AmpC enzymes. The MIC(50)/MIC(90) of other antimicrobials were ampicillin (AMP) >16/>16, amoxicillin/clavulanic acid (A/C) 2, trimethoprim/sulfamethoxazole (SxT) 4/76, and fosfomycin (FOS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Automation; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Spain; Urinary Tract Infections; Young Adult