Antibiotic Susceptibility of Respiratory Pathogens Recently Isolated in Italy: Focus on Cefditoren

Abstract

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.

Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults

“…S. pyogenes is uniformly susceptible to β-lactams and, among oral cephalosporins, cefditoren exhibits the highest intrinsic activity, with MIC 90 values ≤0.06 mg/l. [ 13 – 15 ] Resistance to erythromycin (implying resistance to clarithromycin and azithromycin) varies from < 10% (USA, Baltic countries, Romania), to 10–20% (Poland, Czech Republic, Spain) and 25–35% (Slovakia, Hungary, Hong Kong), being up to 93.5% in China [ 13 , 16 – 20 ].…”

“…Almost 100% strains of M. catarrhalis are β-lactamase producers [ 21 ]; MIC 90 values of cefditoren (range from 0.25 to 0.5 mg/l) are lower than those of amoxicillin/clavulanic acid (range from 0.25 to 2 mg/l) and cefuroxime (range from 2 to 8 mg/l [ 14 , 15 , 22 , 23 ].…”

“…Studies published in the previous decade (2007–2010) (pre-PCV13 era) showed that among penicillin-susceptible isolates, cefditoren MIC 90 values ranged from ≤0.03 to 0.06 mg/l. [ 14 , 15 , 41 – 48 ] Against penicillin-intermediate strains, values increased to 0.25–0.5 mg/l while among penicillin-resistant strains, they ranged from 0.5 to 1 mg/l. [ 14 , 15 , 41 – 48 ] For amoxicillin and cefuroxime, MIC 90 values for penicillin-susceptible isolates ranged from 0.12 to 0.25 mg/l [ 14 , 15 , 41 – 47 ] for cefuroxime and from 0.03 to 0.25 mg/l for amoxicillin [ 14 , 15 , 42 – 47 ].…”

“…[ 14 , 15 , 41 – 48 ] Against penicillin-intermediate strains, values increased to 0.25–0.5 mg/l while among penicillin-resistant strains, they ranged from 0.5 to 1 mg/l. [ 14 , 15 , 41 – 48 ] For amoxicillin and cefuroxime, MIC 90 values for penicillin-susceptible isolates ranged from 0.12 to 0.25 mg/l [ 14 , 15 , 41 – 47 ] for cefuroxime and from 0.03 to 0.25 mg/l for amoxicillin [ 14 , 15 , 42 – 47 ]. For penicillin-intermediate strains, values ranged from 4 to 8 mg/l [ 14 , 15 , 41 – 47 ] for cefuroxime and from 1 to 4 mg/l for amoxicillin [ 14 , 15 , 42 – 47 ], while for penicillin-resistant strains, they ranged from 8 to 32 mg/l for cefuroxime and from 8 to ≥16 mg/l for amoxicillin [ 14 , 15 , 41 – 47 ].…”

Update on the clinical utility and optimal use of cefditoren

“…Against S. pyogenes and H. influenzae , cefditoren has demonstrated markedly high intrinsic activity, with an MIC 90 of ≤0.06 μg/mL in the studies performed 16,17,32,34,36,41,43–47. In the case of H. influenzae , the high intrinsic activity of cefditoren was maintained against strains exhibiting fts I mutations in contrast to amoxicillin/clavulanate and cefuroxime 43,45,46…”