cefditoren and Respiratory-Tract-Infections

Cefditoren is an oral third-generation cephalosporin with a large spectrum activity against Gram-negative and Gram-positive bacteria which are reported to be responsible for respiratory tract and skin and skin structure infections. In this work we reviewed the pharmacodynamics, pharmacokinetics, and the main clinical indications of cefditoren. Similarly to other beta-lactams, cefditoren is a time-dependent antibiotic, and its "best" PK/PD target is probably 40% dosing interval time > 4- 5-fold MIC and 40-70% dosing interval time > 4- 5-fold MIC for bacteriostatic and bactericidal effect, respectively. In fasting patients oral bioavailability is low and increases when the drug is taken with food. This cephalosporin has significant bactericidal activity against S. pneumoniae (both penicillin-susceptible and penicillin-resistant strains), S. pyogenes, H. Influenzae and M. catarrhalis, as well as methicillin-susceptible S. aureus (MSSA). Regarding Enterobacterales, cefditoren has very low MICs90 against K. pneumoniae andE. coli but is not active against AmpC-, ESBL- and carbapenemase-producer' strains. Licensed indications are treatment of exacerbations of chronic bronchitis,acute rhinosinusitis, otitis media, upper respiratory tract infections (pharyngitis/tonsillitis), lower community-acquired respiratory tract infections (LRTIs), and skin and skin-structure infections (SSTI). Cefditoren might have a role in switching from parenteral to oral therapy in acute pyelonephritis and LRTIs. with a reduction of adverse effects and hospital costs. Eventually, due to its supposed binding to enterococcal penicillin binding proteins (PBPs) cefditoren, in combination with other beta-lactams, might have a role in partial oral enterococcal endocarditis treatment..

Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Monobactams; Respiratory Tract Infections; Staphylococcus aureus

This article reviews and updates published data on cefditoren in the evolving scenario of resistance among the most prevalent isolates from respiratory tract infections in the community (Streptococcus pyogenes, Haemophilus influenzae, and Streptococcus pneumoniae). By relating the in vitro activity of cefditoren (in national and multinational surveillance and against isolates with emerging resistant genotypes/phenotypes) to its pharmacokinetics, the cefditoren pharmacodynamic activity predicting efficacy (in humans, animal models, and in vitro simulations) is analyzed prior to reviewing clinical studies (tonsillopharyngitis, sinusitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia) and the relationship between bacterial eradication and clinical efficacy. The high in vitro activity of cefditoren against the most prevalent respiratory isolates in the community, together with its pharmacokinetics (enabling a twice daily regimen) leading to adequate pharmacodynamic indexes covering all S. pyogenes, H. influenzae, and at least 95% S. pneumoniae isolates, makes cefditoren an antibiotic that will play a significant role in the treatment of respiratory tract infections in the community. In the clinical setting, studies carried out with cefditoren showed that treatments with the 400 mg twice daily regimen were associated with high rates of bacteriological response, even against penicillin-nonsusceptible S. pneumoniae, with good correlation between bacteriological efficacy/response and clinical outcome.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Respiratory Tract Infections

Antimicrobial resistance rates have noticeably increased among commonly isolated species associated with respiratory tract infections and skin and skin structure infections, particularly Streptococcus pneumoniae and Staphylococcus aureus. Cefditoren, an oral 3rd-generation-like cephalosporin, has been shown to be very active against many Gram-positive and Gram-negative species with favorable attributes including bactericidal activity and stability against many beta-lactamase enzymes. Clinical trial data worldwide support the use of cefditoren for infections and species that have been approved by the US Food and Drug Administration (US-FDA). This review and a contemporary study report provide an update of clinical trial and in vitro data for cefditoren especially against pathogens within the spectrum of activity since 2002. A large collection of 7279 clinical isolates collected during 2002 and 2003 from medical centers in North and Latin America and Europe were tested to confirm cefditoren potency and spectrum compared with other oral cephalosporins and other class agents. Isolates were tested at a reference laboratory using reference broth microdilution methods. Cefditoren was shown to be active against nearly all (>99%) isolates of penicillin-susceptible S. pneumoniae isolates (MIC(90), < or = 0.03 microg/mL) and was the most potent orally administered cephalosporin against this organism. Cefditoren was the most active oral cephem tested against Haemophilus influenzae (MIC(90), < or = 0.03 microg/mL) and had >99% activity versus both beta-lactamase-positive and beta-lactamase-negative isolates. The potency of cefditoren (MIC(90), 0.5 microg/mL) was similar to that of amoxicillin/clavulanate and cefdinir (MIC(90), 0.25 microg/mL) when tested against Moraxella catarrhalis. Cefditoren was the most potent cephalosporin tested against oxacillin-susceptible S. aureus with an MIC(90) value of only 1 microg/mL, and it was 100% active against the tested beta-hemolytic streptococci. Using the data generated from the large collection of isolates tested in this global surveillance collection, as well as other summarized supporting studies and clinical trial information, we show that cefditoren has sustained in vitro activity and documented clinical efficacy for indications that have been approved by regulators (US-FDA).

Topics: Anti-Bacterial Agents; Bacteria; Cephalosporins; Clinical Trials as Topic; Drug Resistance, Bacterial; Europe; Humans; Latin America; Microbial Sensitivity Tests; North America; Respiratory Tract Infections; Skin Diseases, Bacterial

A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium.. Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered.. The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p < or = 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively).. This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cephalosporins; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Male; Penicillins; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Superinfection; Vaginitis

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; 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

Biofilm formation by Streptococcus pneumoniae is associated with colonization of the upper respiratory tract, including the carrier state, and with chronic respiratory infections in patients suffering from chronic obstructive pulmonary disease (COPD). The use of antibiotics alone to treat recalcitrant infections caused by biofilms is insufficient in many cases, requiring novel strategies based on a combination of antibiotics with other agents, including antibodies, enzybiotics, and antioxidants. In this work, we demonstrate that the third-generation oral cephalosporin cefditoren (CDN) and the antioxidant

Topics: Acetylcysteine; Animals; Anti-Bacterial Agents; Antioxidants; Biofilms; Cephalosporins; COVID-19; Humans; Mice; Respiratory Tract Infections; SARS-CoV-2; Streptococcus pneumoniae

Lower respiratory tract infections (LRTIs) cause high morbidity and mortality worldwide. Empiric therapy often base the choice of antibiotic treatment on antibacterial spectrum of the agent rather than on its pharmacological properties or the pathogen resistance profile. Inappropriate prescribing leads to therapeutic failure and antibiotic resistance, with increasing direct and indirect health costs. A consensus on appropriate prescribing in LRTI therapy was appraised by this Delphi exercise, based on a panel of 70 pulmonologists, coordinated by a Scientific Committee of nine experts in respiratory medical care. Full or very high consensus was reached on several issues, including the role of oral cephalosporins in first-line treatments of LRTIs and the appropriateness of cefditoren, with balanced spectrum and high intrinsic activity, in LRTI treatment. Evidence-based medicine approach and a comprehensive process of disease management, from diagnosis to therapy and follow-up, should guide antibiotic prescribing.

Topics: Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Bacterial; Evidence-Based Medicine; Humans; Inappropriate Prescribing; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Cephalosporins; China; Community-Acquired Infections; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

The aim of this study was to evaluate the in vitro activity of cefditoren and comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections (CARTIs). A total of 391 Streptococcus pneumoniae, 266 H. influenzae, and 76 M. catarrhalis were isolated from 10 centers located at 6 cities in China from January 2009 to May 2010. The microdilution method was used to determine minimum inhibitory concentrations (MICs). The pneumococci comprised 189 (48.3%) penicillin susceptible, 129 (33.0%) penicillin intermediate, and 73 (18.7%) penicillin resistant. Moxifloxacin and levofloxacin showed the highest activity (99.2% and 97.7%, respectively) against Streptococcus pneumoniae, followed by parenteral penicillin G (95.7%), cefditoren (83.1%) and amoxicillin-clavulanic acid (79.3%). Among the 266 H. influenzae isolates, 26 (9.8%) were ampicillin-resistant β-lactamase-producing strains and 24 (9.0%) were ampicillin-resistant β-lactamase-nonproducing strains (BLNAR). Most of antimicrobial agents demonstrated good activity (>97% susceptibility) against H. influenzae except ampicillin, cefuroxime, and cefaclor, which showed relatively lower activity (81.2%, 88.7%, and 88%, respectively). Cefditoren showed excellent activity with the lowest MIC(50) and MIC(90) (≤0.016/0.064 μg/mL) among all tested drugs, which is independent of β-lactamase production or ampicillin resistance. Cefditoren at a concentration of 0.5 μg/mL inhibited all BLNAR strains. Seventy of 76 isolates of M. catarrhalis produced β-lactamase. Cefditoren also showed excellent activity with MIC(90) of 0.064 μg/mL against β-lactamase-nonproducing strains and 0.5 μg/mL against β-lactamase-producing strains. In conclusion, the excellent intrinsic activity of cefditoren suggests that it may be a good choice for the treatment of CARTIs caused by Streptococcus pneumoniae, H. influenzae, and M. catarrhalis in China, while the activity should be closely monitored.

Topics: Anti-Bacterial Agents; Cephalosporins; China; Community-Acquired Infections; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae

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.

Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Italy; Microbial Sensitivity Tests; Respiratory Tract Infections

The antibacterial susceptibility to frequently prescribed antibiotics of Streptococcus pneumoniae isolated from the pediatric patients with acute respiratory infectious diseases was investigated in a study of three medical institutions in Korea. Total 143 clinical isolates of S. pneumoniae were available for susceptibility tests between May 2003 and July 2007. Antimicrobial susceptibility data for S. pneumoniae were analyzed by using agents of amoxicillin, cefaclor, cefuroxime, cefdinir, and cefditoren as the test antibiotics. The prevalence of each resistance class, penicillin-resistant S. pneumoniae (PRSP) were high with the proportion of MIC range (susceptible = 8.4%, intermediate resistance = 18.2%, resistance = 73.4%). MIC90 and susceptible (S) rate of antimicrobial agents to the strains tested were amoxicillin (MIC90 = 4 microg/ml, S = 76.2%), cefaclor (MIC90 = 128 microg/ml, S=8.4%), cefuroxime (MIC90 = 16 microg/ml, S = 24.5%), cefdinir (MIC90 = 16 microg/ml, S = 21.8%), and cefditoren (MIC90 = 0.5 microg/ml, S=90.2%) respectively. Against clinical isolates including PRSP, cefditoren demonstrated the strongest antibacterial activity intrinsically among the antibiotics tested. Conclusively, the antimicrobial activity of cefditoren to S. pneumoniae strains isolated from pediatric patients with acute respiratory infection is very high. In South Korea, where the antibiotic resistance ofS. pneumoniae is issued, cefditoren is expected to be used as a primary or secondary antibiotic. Moreover, cefditoren may serve as a useful option for secondary antibiotics after failure of amoxicillin treatment, which is most primarily used for acute respiratory S. pneumoniae infection in children.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cefdinir; Cefuroxime; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Korea; Respiratory Tract Infections; Streptococcus pneumoniae

The time-kill method was used to determine the bactericidal activity of cefditoren compared with oral cephalosporins, amoxicillin, amoxicillin/clavulanate and levofloxacin against a randomly selected group of strains isolated from community-acquired respiratory tract infections (CARTIs). Cefditoren was the only agent showing significant bactericidal activity (>or=3 log(10 )reduction of viable cells) within 4 h against all Streptococcus pneumoniae strains, both penicillin-susceptible (PEN S) or -resistant (PEN R), as well as against Streptococcus pyogenes, and Moraxella catarrhalis. Against beta-lactamase positive strains of Haemophilus influenzae, cefditoren was comparable to the quinolone and more active than other cephalosporins at 24 h. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.

Topics: Amoxicillin; Anti-Bacterial Agents; Bacteria; Cephalosporins; Colony Count, Microbial; Community-Acquired Infections; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Time Factors; Treatment Outcome

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

In this study we evaluated the in vitro activities of cefditoren--a broad-spectrum oral cephalosporin--and other comparator agents against 2,396 fresh isolates from community-acquired respiratory tract infections, collected from 6 clinical Italian microbiology laboratories. On penicillin-susceptible pneumococci and Streptococcus pyogenes, cefditoren demonstrated to be the most active antibiotic (MIC(90)values of 0.03 and 0.06 mg/L respectively), showing only a slight decrease in potency on penicillin-intermediate and resistant pneumococci (MIC(90)value 0.5 mg/L, 1.0 mg/L respectively). All the other comparators displayed MIC(90 )values of 4 - 8 mg/L for penicillins and of 4 to >64 mg/L for the oral cephalosporins. Cefditoren and levofloxacin were the most active against MSSA (MIC(90)0.5 mg/mL). Cefditoren displayed a uniformly potent inhibitory activity (MIC(90)of 0.03 mg/L) against all strains of Haemophilus influenzae, regardless of their ampicillin resistance (mediated or not by beta-lactamase production), while against Moraxella catarrhalis MIC(90)values were higher against beta-lactamase-positive (0.25 mg/L). Cefditoren was active also against Klebsiella pneumoniae and Escherichia coli : in this case its activity was comparable with that of levofloxacin. In conclusion, cefditoren, due to its potent activity, is a new effective therapeutic option for the treatment of respiratory tract infections.

Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Haemophilus influenzae; Humans; Italy; Klebsiella pneumoniae; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Among orally administered cephalosporins, aminopenicillins (+/- clavulanate), and macrolides, cefditoren was the most potent agent against Haemophilus influenzae (MIC(50/90), < or =0.008/0.03 microg/mL; 316 isolates including 100 beta-lactamase-positive and 10 beta-lactamase-negative ampicillin-resistant [BLNAR]) and was 32-, 64-, and 512-fold more potent than cefdinir, cefuroxime, and cefprozil, respectively. Cefditoren (MIC(50), 0.03 microg/mL) was also > or =32-fold more active against BLNAR phenotypes, although newer macrolides provided complete coverage against these strains. All Moraxella catarrhalis isolates were inhibited by cefditoren (0.5 microg/mL), including beta-lactamase producers (MIC(50), 0.12 vs < or =0.008 microg/mL). Cefditoren retains potent activity against respiratory tract isolates in the United States, including those with resistance phenotypes.

Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; United States

A pooled analysis of all upper respiratory tract infection studies performed with cefditoren (CDN) was performed.. Studies were prospective, comparative, multicentre and randomised. Comparators were penicillin V (pharyngitis) and cefuroxime or amoxicillin/clavulanate (sinusitis). A total of 1,322 patients were randomized, 1,241 included in intention-to-treat (ITT) and 1,010 in per-protocol populations (PP) in pharyngotonsillitis studies, and 1,819 randomized, 1,726 included in ITT and 1,589 in PP in acute sinusitis studies.. No significant differences in pharyngitis clinical response were found (success rates: 89.4 % to 95.3 %). S. pyogenes eradication was higher with cefditoren at end of therapy (EOT) (90.4% vs. 82.7%; p=0.002) and follow-up (84.7% vs. 76.7%; p=0.008), although no statistically significant (p<0.001). In both groups, clinical failures were significantly higher (p<0.001) in patients showing S. pyogenes persistence than in those showing eradication (> or =98.5% vs. 51.4 %). No differences in sinusitis clinical response were found between CDN and comparators both at EOT (80.2% vs. 84.8%) and at end of follow-up (71.2% vs. 77.4%).. Cefditoren had similar point estimates of clinical efficacy to comparators in pharyngotonsillitis and sinusitis, and a tendency to higher S. pyogenes eradication in pharyngotonsillitis.

Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome

Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC(50), 0.015 mg/L), including against penicillin-intermediate strains (MIC(50), 0.12 mg/L), and was two-, four- and eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin-resistant strains were largely resistant to all tested ss-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.

Topics: Anti-Bacterial Agents; beta-Lactams; Cephalosporins; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections; Streptococcus pneumoniae

Haemophilus influenzae (H. influenzae) is the most frequent bacterial pathogen of respiratory tract infections in children. Detection of antimicrobial susceptibility of H. influenzae is necessary for institution of appropriate antibiotic treatments.. A total of 281 strains of H. influenzae isolated from sputum samples of 281 pediatric patients with respiratory tract infections were recruited for study. Antibiotic susceptibility was determined by assessing minimum inhibitory concentrations (MIC) of antimicrobial agents. MIC were measured by utility of Agar dilution susceptibility test.. Of the total, 38 (13.5%) strains produced beta-lactamase (BLP), 56 (19.9%) strains were beta-lactamase non-producing, ampicillin resistant (BLNAR). The overall resistant proportion to ampicillin was 33.4%. The data indicated that sulbactam/ampicillin, cefotaxime, ceftriaxone and cefditoren are effective against BLP strains. In addition, a high prevalence of BLNAR H. influenzae strains was identified, with an overall isolation rate of 19.9%. Those strains mainly demonstrated intermediate level to ampicillin (ampicillin-MIC

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Respiratory Tract Infections

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; 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; 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

This study investigates the susceptibility to cefditoren of penicillin-susceptible strains of invasive Streptococcus pneumoniae (n = 312) and of penicillin-intermediate strains of S. pneumoniae (n = 30) isolated mainly from patients with respiratory tract infections. The MIC(90)s of penicillin-susceptible and -intermediate isolates were as follows: cefditoren, < or =0.06 and 1 mg/L; penicillin G, < or =0.06 and 0.5 mg/L. Cefditoren showed the highest activity against the penicillin-intermediate strains investigated compared with the other beta-lactam antibiotics and is therefore considered to be a promising agent for the treatment of infections caused by pneumococci with reduced penicillin susceptibility.

Topics: Cephalosporins; Germany; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillins; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae

The in vitro post-antibiotic effect (PAE) and batericidal activity of cefditoren was compared to that of cefixime, cefuroxime, loracarbef, cefaclor, amoxicillin, amoxicillin/clavulanate, clarithromycin, azithromycin, erythromycin, and ciprofloxacin against ATCC culture strains and clinical respiratory isolates. A PAE > 1 h was observed for cefditoren and generally for the macrolides against Streptococcus pneumoniae, beta-lactamase-negative Moraxella catarrhalis, and Streptococcus pyogenes, whereas the other beta-lactams showed mixed results. Cefditoren was the only beta-lactam showing significant bactericidal activity (>3 log reduction of viable cells) within 4 h against penicillin-resistant S. pneumoniae. Only cefditoren and ciprofloxacin showed significant bactericidal activity against beta-lactamase-negative (after 24 h) and beta-lactamase-positive strains of H. influenzae (after 12 h). Against beta-lactamase-positive strains of M. catarrhalis, cefditoren was the only agent to show significant bactericidal activity at 6 h (versus cefuroxime and ciprofloxacin at 12 h).

Topics: Anti-Bacterial Agents; Bacteria; Cephalosporins; Colony Count, Microbial; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Streptococcus pneumoniae; Streptococcus pyogenes

One hundred and thirteen strains of Streptococcus pneumoniae (S. pneumoniae) were isolated from the clinical specimens of patients with respiratory tract infections between January and December 1998 in three hospitals in Hokusetsu area of Osaka. We investigated susceptibility of 113 strains of S. pneumoniae to benzylpenicillin (PCG) and other antimicrobial agents and their serotypes. 1) Of the 113 strains of S. pneumoniae isolated, 25.7% were susceptible (PSSP), 51.3% were intermediate (PISP) and 23% were resistant to benzylpenicillin (PRSP). 2) The MICs of cefaclor, cefditoren, cefpodoxime, cefdinir, erythromycin, clindamycin and minocycline were elevated, but the MIC values of cefditoren ranged from < or = 0.03 to 1.0 microgram/ml. The susceptibility of 113 strains to cefditoren was comparatively high. 3) The MIC values of imipenem, meropenem and vancomycin for 81 strains of PISP and PRSP ranged from < or = 0.015 to 1.0 microgram/ml, from < or = 0.015 to 2.0 micrograms/ml and from 0.13 to 0.5 microgram/ml, respectively. The susceptibility of these strains to three antimicrobial agents was superior to that to the other antimicrobial agents examined. 4) Of the 60 strains examined, 19, 6, and 23 serotypes were 30, 25 and 18.3%, respectively. The three serotypes were observed in PISP and PRSP with a high frequency. 5) Isolates of S. pneumoniae were 37.2% for children under 2 years of age and 30.9% for children from 2 to 6 years of age. Most of the strains isolated from these children were resistant.

Topics: Anti-Bacterial Agents; Cefdinir; Cefpodoxime; Ceftizoxime; Cephalosporins; Child; Child, Preschool; Clindamycin; Erythromycin; Humans; Minocycline; Penicillin G; Penicillins; Respiratory Tract Infections; Serotyping; Streptococcus pneumoniae

In the present study we developed a new sensitive and selective HPLC-assay for the determination of cefditoren (ME 1206) in the plasma. The column switching technique was used to regenerate the pre-column and the analytical column separately. This method is suitable for pharmacokinetic studies and for drug monitoring. Thus, we measured plasma samples of 15 elderly patients (age range: 67-88 years), receiving cefditoren-pivoxil therapy because of infections of the respiratory tract. In addition, these patients were treated with several co-medications because of further diseases. With our HPLC-method no interfering peaks could be detected at the retention time of cefditoren (10.67 min) or of the internal standard (16.62 min). The lowest plasma concentration of cefditoren to be quantified was 25 ng/ml (R.S.D.= 15.5%, n = 5).

Topics: Aged; Aged, 80 and over; Calibration; Cephalosporins; Chromatography, High Pressure Liquid; Drug Monitoring; Drug Therapy, Combination; Equipment Design; Humans; Reference Standards; Reproducibility of Results; Respiratory Tract Infections; Sensitivity and Specificity

Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was evaluated in vitro against 1249 recently isolated strains of Streptococcus pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus influenzae (499 strains). Reference National Committee for Clinical Laboratory Standards methods were used and the strains were representative for the current rates of beta-lactamase production or penicillin resistance. Cefditoren had MIC50/MIC90 results for Moraxella catarrhalis and Haemophilus influenzae of 0.12/0.5 and < or = 0.008/0.015 microgram/mL, respectively. The pneumococci were consistently twofold to eightfold more susceptible to cefditoren than other oral cephalosporins or penicillins. The MIC90 for penicillin-resistant S. pneumoniae was only 2 micrograms cefditoren/mL, and the highest recorded MIC was 4 micrograms/mL. Cefditoren appears to be a very promising beta-lactam possessing the greatest potency and potential spectrum versus contemporary (1997) respiratory tract pathogens.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Community-Acquired Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Penicillin Resistance; Penicillins; Respiratory Tract Infections; Streptococcus pneumoniae