cefditoren and Pneumococcal-Infections

Cefditoren is a third-generation oral cephalosporin with good activity against respiratory tract pathogens, including penicillin-intermediate and -resistant strains of S. pneumoniae, and beta-lactamase producing strains of H. influenzae and M. catarrhalis. Its bacterial activity, measured by minimum inhibitory concentration (MIC), is similar or superior to that of many other commonly used antibiotics (penicillins, cephalosporins and fluoroquinolones). Considering the target attainment of T > MIC of >or= 40% a more reliable predictor of clinical and microbiologic outcomes, cefditoren covers strains of S. pneumoniae with MIC values

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Acute Disease; Adolescent; Adult; Aged; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Middle Aged; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Topics: Amoxicillin; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Penicillin Resistance; Pharyngitis; Pharynx; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Topics: Acute Disease; Ampicillin Resistance; beta-Lactamases; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae; Treatment Outcome

Topics: Anti-Bacterial Agents; Cephalosporins; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Patient Compliance; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Topics: Adolescent; Adult; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Middle Aged; Otorhinolaryngologic Diseases; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome

Surveillance studies including antibiotic resistance and evolution of pneumococcal serotypes are critical to evaluate the susceptibility of commonly used antibiotics and the contribution of conjugate vaccines against resistant strains.. To determine the susceptibility of clinical isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin to a panel of antibiotics during the period 2004-20 and characterize the impact of pneumococcal conjugate vaccines in the evolution of resistant serotypes.. We selected 3017 clinical isolates in order to determine the minimal inhibitory concentration to penicillin, amoxicillin, cefotaxime, erythromycin, levofloxacin and oral cephalosporins, including cefditoren, cefixime and cefpodoxime.. The antibiotics with the lowest proportion of resistant strains from 2004 to 2020 were cefditoren (<0.4%), followed by cefotaxime (<5%), penicillin (<6.5%) and levofloxacin (<7%). Among oral cephalosporins, cefixime was the cephalosporin with the highest MIC90 (32 mg/L) and MIC50 (8-16 mg/L) throughout the study, followed by cefpodoxime with highest values of MIC90 (4 mg/L) and MIC50 (2 mg/L) for the majority of the study period. In contrast, cefditoren was the cephalosporin with the lowest MIC90 (1 mg/L) and MIC50 (0.25-0.5 mg/L).. Cefditoren was the antibiotic with the highest proportion of susceptible strains. Hence, more than 80% of the clinical strains were susceptible to cefditoren throughout the period 2004-20. The proportion of resistant isolates to cefditoren and cefotaxime was scarce, being less than 0.4% for cefditoren and lower than 5% for cefotaxime, despite the increased rates of serotypes not covered by the 13-valent pneumococcal conjugate vaccine.

Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Pneumococcal Infections; Spain; Streptococcus pneumoniae

Epidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied.. In this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004-20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance.. Serotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC). The increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.. The Spanish Ministry of Science and Innovation and Meiji-Pharma Spain.. For the Spanish translation of the abstract see Supplementary Materials section.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Cephalosporins; COVID-19 Drug Treatment; Drug Resistance, Bacterial; Erythromycin; Humans; Pandemics; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; SARS-CoV-2; Serogroup; Spain; Streptococcus pneumoniae; Vaccines, Conjugate

Morphological changes in penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae (BLNAR) after exposure to oral antibacterial agents could be observed over time under a phase-contrast microscope. Morphological changes in BLNAR were also observed using a scanning electron microscope. The organisms used in this study were ME19F strain identified as genotypic(g) gPRSP (serotype: 19F) and JPH002 strain identified as gBLNAR (serotype: b). The antibacterial agents used were amoxicillin (AMPC), cefditoren (CDTR), tebipenem (TBPM), and tosufloxacin (TFLX). The concentration of each antibacterial agent to which the bacteria were exposed was set at the blood level one hour after Cmax when administered to children at the usual dose. Bacteriolysis of gPRSP cells started after exposure of only 20minutes to TBPM, and 90% of the cells were lysed within 2 hours. A high bactericidal action of TBPM on gPRSP was supported by these findings. When gBLNAR was exposed to AMPC and TBPM, lysis from spheroplasts and cells with vacuoles were sometimes observed. In contrast, after gBLNAR was exposed to CDTR, lysis occurred after marked filamentation in the cells, but after exposure to TFLX, cells deduced to be killed after mild filamentation without lysis. Time-dependent morphological changes that reflect the differences in bactericidal activity and PBP affinity among beta-lactams provide beneficial information to select antibacterial agents.

Topics: Amoxicillin; Ampicillin Resistance; Anti-Bacterial Agents; Bacteriolysis; beta-Lactamases; Carbapenems; Cephalosporins; Child; Dose-Response Relationship, Drug; Fluoroquinolones; Haemophilus Infections; Haemophilus influenzae; Humans; Microscopy, Phase-Contrast; Naphthyridines; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Time Factors

In vitro cefditoren antimicrobial activity was tested against 288 Streptococcus pneumoniae and 220 Haemophilus influenzae clinical strains isolated in our hospital from January 2005 to May 2006 by agar dilution and broth microdilution method, respectively. MICs were also determined for 13 and 10 comparison drugs, respectively. The pneumococci tested comprised 113 (39.2%) penicillin susceptible, 91 (31.6%) penicillin intermediate, and 84 (29.2%) penicillin resistant. Cefditoren was the most active drug on the basis of the MICs (MIC(90)=0.5 microg/mL), followed by ceftriaxone and levofloxacin (MIC(90)=1 microg/mL). Cefditoren MICs ranged from 0.25 to 1 microg/mL for ceftriaxone-resistant isolates, with a modal MIC of 0.5 microg/mL and an MIC(90) of 1.0 microg/mL. No S. pneumoniae isolates evaluated in this study showed MICs to cefditoren higher than 1 microg/mL (MIC range, 4 microg/mL). Against H. influenzae (Hi beta+), the rank order of intrinsic activity (MIC(90), microg/mL) was cefditoren (0.03) < cefixime (0.06)8.0).

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Respiratory Tract Infections; Spain; Streptococcus pneumoniae

Cefditoren is the active form of cefditoren pivoxil, a new, broad-spectrum oral cephalosporin with strong in vitro activity against penicillin-susceptible and resistant Streptococcus pneumoniae. In this study, the minimum inhibitory concentrations (MICs) of cefditoren were determined for a special selection of S. pneumoniae isolates known to be susceptible, moderately susceptible or fully resistant to penicillin; these isolates originated from the lower respiratory tract of adults with pneumonia or the upper respiratory tract of children with or without symptoms of infection. Some of this latter group of isolates exhibited extremely high MICs to penicillin (> or = 32 mg/l), whereas the MICs of cefditoren did not exceed 2 mg/l. The MIC50 and MIC90 of cefditoren proved to be 0.25 and 1.0 mg/l, respectively, with a range of MICs < or = 0.015-2.0 mg/l for all the tested S. pneumoniae isolates. Its good activity suggests that cefditoren is expected to be a potent drug in infections caused by penicillin-resistant and multidrug-resistant S. pneumoniae.

Topics: Adult; Cephalosporins; Child; Drug Resistance, Multiple, Bacterial; Humans; Hungary; In Vitro Techniques; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Respiratory Tract Infections; Streptococcus pneumoniae

The activity of cefditoren and six other cephalosporins was tested against 250 pneumococci, including strains resistant to macrolides and quinolones. Cefditoren gave the lowest MICs, with MIC(50) and MIC(90) values of < or =0.016/0.03, 0.125/0.5 and 0.5/2.0 mg/L for penicillin-susceptible, -intermediate and -resistant pneumococci, respectively. A time-kill study of 12 pneumococcal strains with varying drug susceptibilities showed that cefditoren, at 2 x MIC, gave 99% killing of all strains after 12 h, with 99.9% killing after 24 h. Other cephalosporins gave similar kill kinetics but at higher concentrations. Against 160 Haemophilus influenzae, cefditoren had the lowest MICs (MIC(50) and MIC(90) both < or =0.016 mg/L), irrespective of beta-lactamase production. Time-kill studies of cefditoren compared with five other oral cephalosporins showed that cefditoren, at 8 x MIC, was bactericidal against 8/9 strains and gave 90% killing of all strains at the MIC after 12 h. Activity was bactericidal (99.9% killing) after 24 h with all drugs tested. Multistep studies of four penicillin-susceptible, four penicillin-intermediate and four penicillin-resistant strains showed that cefditoren, co-amoxiclav and cefprozil did not select for resistant mutants after 50 subcultures, compared with cefuroxime and azithromycin, where resistant mutants were selected in two and nine strains, respectively. Single-step mutation studies showed that cefditoren, at the MIC, had the lowest frequency of spontaneous mutants compared with other drugs.

Topics: Cephalosporins; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Mutation; Penicillin Resistance; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae; Structure-Activity Relationship

Topics: Acute Disease; Amoxicillin; Cephalosporins; Child, Preschool; Community-Acquired Infections; Humans; Infant; Middle Ear Ventilation; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Recurrence; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Cephalosporins; Chronic Disease; Clarithromycin; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Lactams; Male; Middle Aged; Ofloxacin; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae; Time Factors

Topics: Acute Disease; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Nasopharynx; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Pulse Therapy, Drug; Retrospective Studies; Severity of Illness Index; Streptococcus pneumoniae; Treatment Outcome

Topics: Acute Disease; Ampicillin Resistance; beta-Lactamases; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

Topics: Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactams; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Respiratory Tract Infections; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

Topics: Cephalosporins; Community-Acquired Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Otitis Media with Effusion; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure; Treatment Outcome

Topics: Age Factors; Cephalosporins; Child Day Care Centers; Community-Acquired Infections; Disease Transmission, Infectious; Humans; Infant; Nasopharynx; Penicillin Resistance; Pneumococcal Infections; Risk Factors; Streptococcus pneumoniae