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Ronald N Jones - One of the best experts on this subject based on the ideXlab platform.

  • update of Cefditoren activity tested against community acquired pathogens associated with infections of the respiratory tract and skin and skin structures including recent pharmacodynamic considerations
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Douglas J Biedenbach, Ronald N Jones
    Abstract:

    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), 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).

  • antimicrobial activity of Cefditoren tested against contemporary 2004 2006 isolates of haemophilus influenzae and moraxella catarrhalis responsible for community acquired respiratory tract infections in the united states
    Diagnostic Microbiology and Infectious Disease, 2008
    Co-Authors: Douglas J Biedenbach, Ronald N Jones, Thomas R Fritsche
    Abstract:

    Abstract Among orally administered cephalosporins, aminopenicillins (±clavulanate), and macrolides, Cefditoren was the most potent agent against Haemophilus influenzae (MIC 50/90 , ≤0.008/0.03 μg/mL; 316 isolates including 100 β-lactamase–positive and 10 β-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 μg/mL) was also ≥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 μg/mL), including β-lactamase producers (MIC 50 , 0.12 vs ≤0.008 μg/mL). Cefditoren retains potent activity against respiratory tract isolates in the United States, including those with resistance phenotypes.

  • Cefditoren in vitro activity and spectrum a review of international studies using reference methods
    Diagnostic Microbiology and Infectious Disease, 2001
    Co-Authors: Ronald N Jones, Peter C Appelbaum, Michael R Jacobs, Michael A Pfaller, Peter C Fuchs
    Abstract:

    Abstract Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important β-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, ( Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis ), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other anerobic and anaerobic Gram-positive cocci. The level of Cefditoren activity against S. pneumoniae (MIC 90, 0.5 μg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin ± clavulanate. H. influenzae (MIC 90, 0.016–0.03 μg/mL) and M. catarrhalis (MIC 90, 0.06–0.5 μg/mL) were also very susceptible to Cefditoren. In contrast to cefixime and ceftibuten, Cefditoren was active against oxacillin-susceptible staphylococci (MIC 90, ≤ 1 μg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not Cefditoren-susceptible, but most Enterobacteriaceae, β-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of Cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of β-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) β-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and β-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of Cefditoren in this era of emerging resistant bacterial pathogens.

  • validation of Cefditoren mic quality control ranges by a multi laboratory study 2001
    Diagnostic Microbiology and Infectious Disease, 2001
    Co-Authors: Ronald N Jones, Douglas J Biedenbach
    Abstract:

    Abstract The potency of Cefditoren has been well documented to include broad coverage against both Gram-positive and Gram-negative organisms including species causing community-acquired respiratory tract infections. The accuracy of in vitro test results has been questioned due to debate over inconsistencies in quality control (QC) recommendations published by the National Committee for Clinical Laboratory Standards (NCCLS). Previous studies have recommended conflicting and generally broad MIC dilution ranges for several commonly used QC organisms. This study used NCCLS recommended guidelines to re-evaluate the MIC ranges using a seven laboratory M23-A2 design. The results of this multi-laboratory investigation leads to the proposal of the following QC range recommendations for Cefditoren: Streptococcus pneumoniae ATCC 49619 (0.016–0.06 μg/mL); Haemophilus influenzae ATCC 49247 (0.06–0.25 μg/mL); Escherichia coli ATCC 25922 (0.12–1 μg/mL); and Staphylococcus aureus ATCC 29213 (0.25–1 μg/mL). These proposed ranges validate those suggested previously for E. coli and the problematic H. influenzae, but a three log 2 dilution range may be sufficient for S. aureus and S. pneumoniae .

  • Cefditoren activity against nearly 1000 non fastidious bacterial isolates and the development of in vitro susceptibility test methods
    Diagnostic Microbiology and Infectious Disease, 2000
    Co-Authors: Ronald N Jones, Douglas J Biedenbach, David M Johnson
    Abstract:

    Abstract Cefditoren (formerly ME-1206) is an investigational, orally administered cephalosporin ester with bactericidal activity against many Gram-positive and -negative organisms. Cefditoren potency against nearly 1000 non-fastidious species was determined by National Committee for Clinical Laboratory Standards (NCCLS) reference broth microdilution and standardized disk diffusion methods. Against staphylococci, usable Cefditoren activity was completely correlated with oxacillin with respect to potency and susceptibility interpretation ( mec A -negative strains). Cefditoren was very active against Klebsiella spp., Proteus mirabilis, Salmonella spp., and Escherichia coli (MIC 90 range, 0.12–1 μg/ml; median zone, 23–26 mm). Cefditoren had more limited activity against Citrobacter spp., Enterobacter spp., Serratia marcescens, and indole-positive Proteae (MIC 50 range, 0.12–1 μg/ml; MIC 90 , > 16 μg/ml; median zone, 18–25 mm). Against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp., and other non-fermentors, Cefditoren was inactive (MIC 90 , > 16 μg/ml; zone, 6 mm). Pharmacokinetic analysis of Cefditoren showed that utilized dosages produce a plasma concentration that exceeds 0.5 μg/ml for 5 to 8 h and 1 μg/ml for 4 to 6 hours (T 1/2 ranges from 1.5–2 h). The following interpretive criteria were suggested: ≤ 2 μg/ml or ≥ 15 mm (susceptible) and ≥ 8 μg/ml or ≤ 11 mm (resistance) that yielded an intermethod categorical agreement of 95.8% and very major or major error rates of 0.7% and 0.3%, respectively. Alternatively, ≤ 1 μg/ml or ≥ 18 mm (susceptible) and ≥ 4 μg/ml or ≤ 14 mm (resistant) breakpoints resulted in 96.2% accuracy and combined serious errors of only 1.1%. Cefditoren was observed to be a very active cephalosporin ranking among the most potent available orally active β-lactams for use against a wide variety of pathogens.

Pilar Coronel - One of the best experts on this subject based on the ideXlab platform.

  • comparative in vitro activity of Cefditoren and other antimicrobials against enterobacteriaceae causing community acquired uncomplicated urinary tract infections in women a spanish nationwide multicenter study
    Diagnostic Microbiology and Infectious Disease, 2010
    Co-Authors: Oscar Cuevas, Mercedes Gimeno, Pilar Coronel, Emilia Cercenado, Mercedes Marin, Emilio Bouza
    Abstract:

    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) Cefditoren against Enterobacteriaceae producing community-acquired uncomplicated UTI in women was superior to that of AMP, A/C, FUR, CIP, and SxT and similar to that of FOS.

  • antimicrobial susceptibility of streptococcus pyogenes in central eastern and baltic european countries 2005 to 2006 the Cefditoren surveillance program
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Matilde Gracia, Mercedes Gimeno, Pilar Coronel, C Diaz, Rocio Garciarodas, G Del Prado, Lorena Huelves, Vicente Ruiz, Violeta Rodriguezcerrato, Plinio Naves
    Abstract:

    The in vitro activity of penicillin, ampicillin, Cefditoren, cefotaxime, erythromycin, clarithromycin, and levofloxacin against 763 clinical isolates of Streptococcus pyogenes was determined. Clinically significant isolates collected from November 2005 to December 2006 in the Czech Republic, Slovakia, Hungary, Poland, Romania, Estonia, Latvia, and Lithuania (the latter 3 analyzed as Baltic countries) were studied. No resistance to beta-lactams and levofloxacin was found. The rate of erythromycin resistance in S. pyogenes varied among countries, being low ( 25%) in Hungary and Slovakia. The predominant (75.0%) erythromycin-resistant phenotype among S. pyogenes isolates was MLS(B). The identification of the prevalence of erythromycin resistance mechanism could have impact on the choice of empiric antibiotic therapy for the clinicians in such countries.

  • in vitro activity of Cefditoren and other antimicrobial agents against 288 streptococcus pneumoniae and 220 haemophilus influenzae clinical strains isolated in zaragoza spain
    Diagnostic Microbiology and Infectious Disease, 2008
    Co-Authors: Cristina Seral, Laura Suarez, Carmen Rubiocalvo, R Gomezlus, Mercedes Gimeno, Pilar Coronel, Estrella Duran, Raquel Becerril, Mercedes Oca, Javier F Castillo
    Abstract:

    Abstract 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 μg/mL), followed by ceftriaxone and levofloxacin (MIC 90 = 1 μg/mL). Cefditoren MICs ranged from 0.25 to 1 μg/mL for ceftriaxone-resistant isolates, with a modal MIC of 0.5 μg/mL and an MIC 90 of 1.0 μg/mL. No S. pneumoniae isolates evaluated in this study showed MICs to Cefditoren higher than 1 μg/mL (MIC range, ≤0.015 to 1 μg/mL). Against penicillin-resistant pneumococci, the rank order of intrinsic activity (MIC 90 , μg/mL) was Cefditoren (0.5) H. influenzae , 42 (19.09%) produced a β-lactamase (Hi β+) and 3 (1.1%) were β-lactamase (Hi β-) negative but have reduced susceptibility to ampicillin (BLNAR). The most active drugs on the basis of MICs were Cefditoren and levofloxacin, showing MIC 50 and MIC 90 values of 0.015/0.06 μg/mL. Cefditoren at concentration of 0.06 μg/mL inhibited all 3 BLNAR (ampicillin MICs >4 μg/mL). Against H. influenzae (Hi β+), the rank order of intrinsic activity (MIC 90 , μg/mL) was Cefditoren (0.03) 8.0).

  • antimicrobial susceptibility of haemophilus influenzae and moraxella catarrhalis isolates in eight central east and baltic european countries in 2005 06 results of the Cefditoren surveillance study
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: Matilde Gracia, Mercedes Gimeno, Pilar Coronel, C Diaz, Rocio Garciarodas, G Del Prado, Lorena Huelves, Vicente Ruiz, Plinio Naves, M C Ponte
    Abstract:

    Sir, Cefditoren pivoxil is an aminothiazolyl oral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative pathogens and is stable to hydrolysis by many common b-lactamases. It has been shown to be active in vitro against many respiratory tract pathogens including Haemophilus influenzae and Moraxella catarrhalis. Resistance of both organisms to b-lactam antibiotics is generally conferred by either the presence of b-lactamase or as a result of alterations in penicillinbinding protein 3. In this study, we compare the in vitro activity of Cefditoren with that of nine other antibiotics against 665 and 133 clinical isolates of H. influenzae and M. catarrhalis strains collected from eight Central, East and Baltic European countries. The isolates were prospectively collected from 1 November 2005 to 31 December 2006, in 25 centres from the Czech Republic, Hungary, Poland, Romania, Slovakia, Estonia, Latvia and Lithuania. Isolates from Estonia, Latvia and Lithuania were analysed all together as ‘Baltic countries’. No isolates of M. catarrhalis were received from Romania. Strain isolates were from patients with upper (ear and sinus exudates) and lower (sputum, bronchial washes and bronchial aspirates) respiratory tract infections and bacteraemia. Duplicate isolates from the same patient were not accepted. The identity of the isolates was confirmed by morphology of the colonies, growth on blood and chocolate agar, and API-NH (bioMerieux, Marcy l’Etoile, France). The following data were collected for each isolate: age group (adults/children), sex, status (outpatients/inpatients) and sample origin (upper respiratory tract/lower respiratory tract/blood). Susceptibility testing was carried out by the CLSI broth microdilution method, using dried commercial plates (Sensititre, Trek Diagnostic Systems Ltd, West Sussex, UK) reconstituted with Haemophilus test medium for H. influenzae and cation-adjusted Mueller–Hinton broth for M. catarrhalis. The antimicrobials tested were ampicillin, amoxicillin, amoxicillin/ clavulanic acid, Cefditoren, cefixime, cefpodoxime, cefuroxime, cefotaxime, clarithromycin and levofloxacin. Breakpoint concentrations published by the CLSI (document M100-S16, 2006) to interpret MIC data qualitatively for H. influenzae were also applied to M. catarrhalis. b-Lactamase production was determined using the chromogenic cephalosporin Cefinase test (bioMerieux). The results of the susceptibility testing of H. influenzae isolates are shown in Table 1. Of the 665 isolates tested, 7 (1.1%) were intermediate and 62 (9.3%) resistant to ampicillin. Among ampicillin-resistant isolates, 95.2% were b-lactamase producers. Susceptibility to ampicillin was higher in isolates from the Czech Republic, Slovakia, Hungary, Poland and Baltic countries and lower in those from Romania, the difference being statistically significant (P 0.005) when compared with any of the other countries. Three (4.8%) ampicillin-resistant isolates were categorized as b-lactamase-negative, ampicillin-resistant (BLNAR); all of them having an MIC of 4 mg/L. No isolate was b-lactamase-positive, amoxicillin/clavulanic-resistant (BLPACR). All isolates were susceptible to amoxicillin/clavulanic acid, cefixime, cefpodoxime, cefuroxime, cefotaxime and levofloxacin. All H. influenzae isolates were inhibited by 0.06 mg/L Cefditoren. More than 98% of the isolates were susceptible to clarithromycin and none was categorized as intermediate. No differences in susceptibility to the antibiotics tested were found comparing source, localization of the patient, age or gender. One hundred and twenty-seven of the 133 (95.5%) M. catarrhalis isolates produced b-lactamase, but only 94 (70.7%) were non-susceptible to ampicillin using CLSI breakpoints. Susceptibility to ampicillin was higher in isolates from Poland than from any other country, but the difference was not statistically significant. All isolates were susceptible to amoxicillin/ clavulanic acid, cefixime, cefpodoxime, cefuroxime, cefotaxime, clarithromycin and levofloxacin. All M. catarrhalis isolates were inhibited by 0.5 mg/L Cefditoren and the MIC50/MIC90 values were 0.12/0.5 mg/L. No differences in susceptibility to the antibiotics tested were found comparing source, localization of the patient, age or gender. The prevalence of H. influenzae isolates producing b-lactamase in Europe varies from low (,6%) in Germany, The Netherlands and Italy to high (.20%) in the UK, Spain and France. – 4 Reports on surveillance studies in our screened countries are scarce but give the following results: 7.9% to 13% in the Czech Republic, 4.8% to 6.5% in Slovakia, 0% to 3.3% in Hungary, 6% to 24% in Poland – 5 and 3.0% in Estonia. Data on the prevalence of BLNAR H. influenzae isolates are variable but prevalence is usually low (,10%), – 4 although some reports have given figures of up to 20% in Poland. No BLPACR isolates were detected in the present study, and the prevalence of such organisms being very low. A high rate (95.5%) of b-lactamase-producing M. catarrhalis isolates was found in our study, with no significant differences Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkn083

  • influence of the β lactam resistance phenotype on the cefuroxime versus Cefditoren susceptibility of streptococcus pneumoniae and haemophilus influenzae recovered from children with acute otitis media
    Journal of Antimicrobial Chemotherapy, 2007
    Co-Authors: Asuncion Fenoll, Mercedes Gimeno, Mariajose Gimenez, L Aguilar, Olga Robledo, David Tarrago, Juanjose Granizo, Pilar Coronel
    Abstract:

    Objectives: To study the influence of resistance phenotypes (based on sentinel antibiotics: penicillin and amoxicillin with/without clavulanate) on the cefuroxime versus Cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media. Methods: Middle ear isolates (193 S. pneumoniae and 114 H. influenzae) received in the Spanish Reference Laboratory (Instituto de Salud Carlos III) were tested. Antimicrobial susceptibility to penicillin, amoxicillin with/without clavulanate, cefuroxime and Cefditoren was determined by agar dilution using Mueller‐Hinton agar supplemented with 5% sheep blood for S. pneumoniae and Haemophilus Test Medium for H. influenzae. Strains were classified according to penicillin susceptibility (S. pneumoniae )o rb-lactamase production (H. influenzae). Results: The decrease in penicillin susceptibility of S. pneumoniae (from the susceptible to the resistant category) decreased amoxicillin and cefuroxime susceptibility rates from 100% to 34% and 0%, respectively. All pneumococcal strains were inhibited by 0.5 mg/L Cefditoren, including those from penicillin-resistant serotypes 14, 23F, 6B and 9V with higher amoxicillin versus penicillin MICs. Susceptibility rates of b-lactamase-positive H. influenzae strains were 93.8% and 85.4% to amoxicillin/ clavulanate and cefuroxime, respectively. Resistance to amoxicillin/clavulanate (MIC � 8/4 mg/L) was 12.1% (8 out of 66) and 6.3% (3 out of 48) in b-lactamase-negative and -positive strains, respectively. All H. influenzae strains were inhibited by � 0.06 mg/L Cefditoren. Conclusions: Susceptibility to sentinel b-lactams cannot predict activity of other members of the group. The addition of clavulanic acid to amoxicillin does not guarantee 100% coverage of H. influenzae, regardless of b-lactamase production.

L Aguilar - One of the best experts on this subject based on the ideXlab platform.

  • Cefditoren and ceftriaxone enhance complement mediated immunity in the presence of specific antibodies against antibiotic resistant pneumococcal strains
    PLOS ONE, 2012
    Co-Authors: Elisa Ramossevillano, Mariajose Gimenez, David Sevillano, L Aguilar, Luis Alou, Fabio Cafini, Cinthya Rodriguezsosa, Ana Navarro, Ernesto Garcia, Jose Yuste
    Abstract:

    This work was supported by grants SAF2009-10824 from Direccion General de Investigacion Cientifica y Tecnica, MPY 1350/10 from ISCIII and an unrestricted educational grant from Tedec-Meiji Farma S. A. (Madrid, Spain). Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES) is an initiative of the ISCIII. E.R-S. was supported by an FPU fellowship from Ministerio de Ciencia e Innovacion and C.R-S was supported by a fellowship from MAEC-AECID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

  • efficacy of simulated Cefditoren versus amoxicillin clavulanate free concentrations in countering intrastrain ftsi gene diffusion in haemophilus influenzae
    Antimicrobial Agents and Chemotherapy, 2011
    Co-Authors: Natalia Gonzalez, Mariajose Gimenez, P Coronel, David Sevillano, L Aguilar, Luis Alou, M Torrico, Fabio Cafini, Anamaria Lopez, Jose Prieto
    Abstract:

    ABSTRACT This study explores the effects of Cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in β-lactamase-positive (BL + ) and β-lactamase-negative (BL − ) Haemophilus influenzae. DNA from β-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA BLNAR ) and from β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA BLPACR ) isolates was extracted and added to a 10 7 -CFU/ml suspension of one BL + strain (CDN MIC, 0.007 μg/ml; AMC MIC, 1 μg/ml) or one BL − strain (CDN MIC, 0.015 μg/ml; AMC MIC, 0.5 μg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL − and BL + total populations and the BL − recombined population increased (from ≈3 log 10 to 4.5 to 5 log 10 ), while the BL + recombined population was maintained in simulations with DNA BLPACR and was decreased by ≈2 log 10 with DNA BLNAR . CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ ft >MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL − strains ( ft >MIC, 74.0%) in DNA BLNAR and DNA BLPACR simulations, with a small final recombined population (MIC, 4 μg/ml; ft >MIC, 30.7%) in DNA BLPACR simulations. When AMC was used against the BL + strain (in DNA BLNAR or DNA BLPACR simulations), the bacterial load was reduced ≈2 log 10 ( ft >MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 μg/ml; ft >MIC, 0%) in DNA BLNAR and DNA BLPACR simulations, respectively. AMC, but not CDN, unmasked BL + recombined populations obtained by transformation. ft >MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

  • enhanced in vivo activity of Cefditoren in pre immunized mice against penicillin resistant s pneumoniae serotypes 6b 19f and 23f in a sepsis model
    PLOS ONE, 2010
    Co-Authors: Fabio Cafini, Mariajose Gimenez, David Sevillano, L Aguilar, Luis Alou, Natalia Gonzalez, M Torrico, Elisa Ramossevillano, Jose Yuste, Ernesto Garcia
    Abstract:

    Background: Specific antibodies are likely to be present before S. pneumoniae infection. We explored Cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t.MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy. Methodology/Principal Findings: We used three pneumococcal isolates (serotype, MIC of CDN): Strain 1 (6B, 1 mg/ml), Strain 2 (19F, 2 mg/ml) and Strain 3 (23F, 4 mg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heatinactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2–1/16) and CDN (6.25 mg/kg–100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t.MIC values for CDN of <35% (total) and <19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (#20%) or CDN-np alone (#20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t.MIC (total/free) of 22.8%/14.3%, 26.8%/ 16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7. Conclusions/Significance: In mice (CDN protein binding similar to humans) total t.MIC values of <35% (<19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.

  • high protein binding and cidal activity against penicillin resistant s pneumoniae a Cefditoren in vitro pharmacodynamic simulation
    PLOS ONE, 2008
    Co-Authors: David Sevillano, Mariajose Gimenez, P Coronel, L Aguilar, Luis Alou, Natalia Gonzalez, M Torrico, Fabio Cafini, Asuncion Fenoll, Jose Prieto
    Abstract:

    BACKGROUND: Although protein binding is a reversible phenomenon, it is assumed that antibacterial activity is exclusively exerted by the free (unbound) fraction of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: Activity of Cefditoren, a highly protein bound 3(rd) generation cephalosporin, over 24h after an oral 400 mg Cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/Cefditoren MICs; microg/ml): S1 (0.12/0.25), S2 (0.25/0.25), S3 and S4 (0.5/0.5), S5 (1/0.5) and S6 (4/0.5). A computerized pharmacodynamic simulation with media consisting in 75% human serum and 25% broth (mean albumin concentrations = 4.85+/-0.12 g/dL) was performed. Protein binding was measured. The cumulative percentage of a 24h-period that drug concentrations exceeded the MIC for total (T > MIC) and unbound concentrations (fT > MIC), expressed as percentage of the dosing interval, were determined. Protein binding was 87.1%. Bactericidal activity (> or = 99.9% initial inocula reduction) was obtained against strains S1 and S2 at 24h (T > MIC = 77.6%, fT > MIC = 23.7%). With T > MIC of 61.6% (fT > MIC = 1.7%), reductions against S3 and S4 ranged from 90% to 97% at 12h and 24h; against S5, reduction was 45.1% at 12h and up to 85.0% at 24h; and against S6, reduction was 91.8% at 12h, but due to regrowth of 52.9% at 24h. Cefditoren physiological concentrations exerted antibacterial activity against strains exhibiting MICs of 0.25 and 0.5 microg/ml under protein binding conditions similar to those in humans. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that, from the pharmacodynamic perspective, the presence of physiological albumin concentrations may not preclude antipneumococcal activity of highly bound cephalosporins as Cefditoren.

  • urine bactericidal activity against escherichia coli isolates exhibiting different resistance phenotypes genotypes in an in vitro pharmacodynamic model simulating urine concentrations obtained after oral administration of a 400 milligram single dose
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: David Sevillano, Mariajose Gimenez, P Coronel, L Aguilar, Luis Alou, Natalia Gonzalez, M Torrico, Fabio Cafini, Mariateresa Relano, Jose Prieto
    Abstract:

    Activity of simulated Cefditoren urinary concentrations was determined against seven Escherichia coli isolates. Bactericidal activity was obtained from 4 to 24 h against TEM-1 (penicillinase production/hyperproduction), TEM-34 (IRT-6), and TEM-116 (extended-spectrum beta-lactamase [ESBL]) and from 6 to 8 h against SHV/TEM-116 (ESBL) but never against SHV/TEM-1 (ESBL). Extension of bactericidal activity depended on the resistance genotype/phenotype tested.

Mariajose Gimenez - One of the best experts on this subject based on the ideXlab platform.

  • Cefditoren and ceftriaxone enhance complement mediated immunity in the presence of specific antibodies against antibiotic resistant pneumococcal strains
    PLOS ONE, 2012
    Co-Authors: Elisa Ramossevillano, Mariajose Gimenez, David Sevillano, L Aguilar, Luis Alou, Fabio Cafini, Cinthya Rodriguezsosa, Ana Navarro, Ernesto Garcia, Jose Yuste
    Abstract:

    This work was supported by grants SAF2009-10824 from Direccion General de Investigacion Cientifica y Tecnica, MPY 1350/10 from ISCIII and an unrestricted educational grant from Tedec-Meiji Farma S. A. (Madrid, Spain). Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES) is an initiative of the ISCIII. E.R-S. was supported by an FPU fellowship from Ministerio de Ciencia e Innovacion and C.R-S was supported by a fellowship from MAEC-AECID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

  • efficacy of simulated Cefditoren versus amoxicillin clavulanate free concentrations in countering intrastrain ftsi gene diffusion in haemophilus influenzae
    Antimicrobial Agents and Chemotherapy, 2011
    Co-Authors: Natalia Gonzalez, Mariajose Gimenez, P Coronel, David Sevillano, L Aguilar, Luis Alou, M Torrico, Fabio Cafini, Anamaria Lopez, Jose Prieto
    Abstract:

    ABSTRACT This study explores the effects of Cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in β-lactamase-positive (BL + ) and β-lactamase-negative (BL − ) Haemophilus influenzae. DNA from β-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA BLNAR ) and from β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA BLPACR ) isolates was extracted and added to a 10 7 -CFU/ml suspension of one BL + strain (CDN MIC, 0.007 μg/ml; AMC MIC, 1 μg/ml) or one BL − strain (CDN MIC, 0.015 μg/ml; AMC MIC, 0.5 μg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL − and BL + total populations and the BL − recombined population increased (from ≈3 log 10 to 4.5 to 5 log 10 ), while the BL + recombined population was maintained in simulations with DNA BLPACR and was decreased by ≈2 log 10 with DNA BLNAR . CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ ft >MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL − strains ( ft >MIC, 74.0%) in DNA BLNAR and DNA BLPACR simulations, with a small final recombined population (MIC, 4 μg/ml; ft >MIC, 30.7%) in DNA BLPACR simulations. When AMC was used against the BL + strain (in DNA BLNAR or DNA BLPACR simulations), the bacterial load was reduced ≈2 log 10 ( ft >MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 μg/ml; ft >MIC, 0%) in DNA BLNAR and DNA BLPACR simulations, respectively. AMC, but not CDN, unmasked BL + recombined populations obtained by transformation. ft >MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

  • Cefditoren in upper and lower community acquired respiratory tract infections
    Drug Design Development and Therapy, 2011
    Co-Authors: F Soriano, Mariajose Gimenez, Lorenzo Aguilar
    Abstract:

    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.

  • enhanced in vivo activity of Cefditoren in pre immunized mice against penicillin resistant s pneumoniae serotypes 6b 19f and 23f in a sepsis model
    PLOS ONE, 2010
    Co-Authors: Fabio Cafini, Mariajose Gimenez, David Sevillano, L Aguilar, Luis Alou, Natalia Gonzalez, M Torrico, Elisa Ramossevillano, Jose Yuste, Ernesto Garcia
    Abstract:

    Background: Specific antibodies are likely to be present before S. pneumoniae infection. We explored Cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t.MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy. Methodology/Principal Findings: We used three pneumococcal isolates (serotype, MIC of CDN): Strain 1 (6B, 1 mg/ml), Strain 2 (19F, 2 mg/ml) and Strain 3 (23F, 4 mg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heatinactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2–1/16) and CDN (6.25 mg/kg–100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t.MIC values for CDN of <35% (total) and <19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (#20%) or CDN-np alone (#20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t.MIC (total/free) of 22.8%/14.3%, 26.8%/ 16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7. Conclusions/Significance: In mice (CDN protein binding similar to humans) total t.MIC values of <35% (<19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.

  • breakthrough in penicillin resistance streptococcus pneumoniae isolates with penicillin cefotaxime mics of 16 mg l and their genotypic and geographical relatedness
    Journal of Antimicrobial Chemotherapy, 2008
    Co-Authors: F Soriano, Mariajose Gimenez, Lorenzo Aguilar, Luis Alou, Fabio Cafini, David Tarrago, Matilde Gracia, M C Ponte, Denisa Leu, Marina Pana
    Abstract:

    Received 17 July 2008; returned 11 August 2008; revised 18 August 2008; accepted 22 August 2008Objectives: To phenotypically and genotypically characterize 11 strains (isolated in four differentcentres) exhibiting penicillin MIC of 8–32 mg/L among isolates of the SPICE project. Nine isolates werefrom Romania (9/162; 5.56%) and two from Poland (2/305; 0.66%).Methods: In vitro susceptibility was determined in triplicate by microdilution (CLSI guidelines), andadditionally, MICs of penicillin, cefotaxime and amoxicillin were confirmed in triplicate by agar dilution.Multilocus sequence typing (MLST), PFGE and gene amplification and sequencing were performed.Results: For the nine Romanian isolates, MICs were 16 mg/L for penicillin, cefotaxime and amoxicillin, 32 mg/L for cefuroxime and cefpodoxime, 4–8 mg/L for Cefditoren and 128 mg/L for erythromycinand gentamicin. All isolates were non-susceptible to imipenem (MIC 5 0.5–1 mg/L) and susceptible tolevofloxacin (MIC 5 0.5–1 mg/L) and vancomycin (MIC 5 0.25–0.5 mg/L). These Romanian strains pre-sented a new cluster in the 595–600 region of PBP2X (YSGIQL !LSTPWF) conferring 98% homology withStreptococcus mitis PBP2X, with a new MurM allele (seven strains) with eight amino acid changes versusR6. PBP nucleotide sequences were highly conserved suggesting a common origin. Allelic profiles of twostrains gave sequence type 321, three strains exhibited a single- and four a double-locus variance. MLST-predicted serotype was 23F in all but one strain (19F), but three strains were 19A by Quellung.Conclusions : The multidrug high resistance (precluding adequate oral therapy in children), its origin, theprevalence found in Romania and the presence of non-vaccine (7-valent) serotypes should worry themedical community because of a possible clonal diffusion that would limit therapeutic alternatives.Keywords: MurM, multidrug resistance, serotype 23F, serotype 19A

Douglas J Biedenbach - One of the best experts on this subject based on the ideXlab platform.

  • update of Cefditoren activity tested against community acquired pathogens associated with infections of the respiratory tract and skin and skin structures including recent pharmacodynamic considerations
    Diagnostic Microbiology and Infectious Disease, 2009
    Co-Authors: Douglas J Biedenbach, Ronald N Jones
    Abstract:

    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), 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).

  • antimicrobial activity of Cefditoren tested against contemporary 2004 2006 isolates of haemophilus influenzae and moraxella catarrhalis responsible for community acquired respiratory tract infections in the united states
    Diagnostic Microbiology and Infectious Disease, 2008
    Co-Authors: Douglas J Biedenbach, Ronald N Jones, Thomas R Fritsche
    Abstract:

    Abstract Among orally administered cephalosporins, aminopenicillins (±clavulanate), and macrolides, Cefditoren was the most potent agent against Haemophilus influenzae (MIC 50/90 , ≤0.008/0.03 μg/mL; 316 isolates including 100 β-lactamase–positive and 10 β-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 μg/mL) was also ≥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 μg/mL), including β-lactamase producers (MIC 50 , 0.12 vs ≤0.008 μg/mL). Cefditoren retains potent activity against respiratory tract isolates in the United States, including those with resistance phenotypes.

  • validation of Cefditoren mic quality control ranges by a multi laboratory study 2001
    Diagnostic Microbiology and Infectious Disease, 2001
    Co-Authors: Ronald N Jones, Douglas J Biedenbach
    Abstract:

    Abstract The potency of Cefditoren has been well documented to include broad coverage against both Gram-positive and Gram-negative organisms including species causing community-acquired respiratory tract infections. The accuracy of in vitro test results has been questioned due to debate over inconsistencies in quality control (QC) recommendations published by the National Committee for Clinical Laboratory Standards (NCCLS). Previous studies have recommended conflicting and generally broad MIC dilution ranges for several commonly used QC organisms. This study used NCCLS recommended guidelines to re-evaluate the MIC ranges using a seven laboratory M23-A2 design. The results of this multi-laboratory investigation leads to the proposal of the following QC range recommendations for Cefditoren: Streptococcus pneumoniae ATCC 49619 (0.016–0.06 μg/mL); Haemophilus influenzae ATCC 49247 (0.06–0.25 μg/mL); Escherichia coli ATCC 25922 (0.12–1 μg/mL); and Staphylococcus aureus ATCC 29213 (0.25–1 μg/mL). These proposed ranges validate those suggested previously for E. coli and the problematic H. influenzae, but a three log 2 dilution range may be sufficient for S. aureus and S. pneumoniae .

  • Cefditoren activity against nearly 1000 non fastidious bacterial isolates and the development of in vitro susceptibility test methods
    Diagnostic Microbiology and Infectious Disease, 2000
    Co-Authors: Ronald N Jones, Douglas J Biedenbach, David M Johnson
    Abstract:

    Abstract Cefditoren (formerly ME-1206) is an investigational, orally administered cephalosporin ester with bactericidal activity against many Gram-positive and -negative organisms. Cefditoren potency against nearly 1000 non-fastidious species was determined by National Committee for Clinical Laboratory Standards (NCCLS) reference broth microdilution and standardized disk diffusion methods. Against staphylococci, usable Cefditoren activity was completely correlated with oxacillin with respect to potency and susceptibility interpretation ( mec A -negative strains). Cefditoren was very active against Klebsiella spp., Proteus mirabilis, Salmonella spp., and Escherichia coli (MIC 90 range, 0.12–1 μg/ml; median zone, 23–26 mm). Cefditoren had more limited activity against Citrobacter spp., Enterobacter spp., Serratia marcescens, and indole-positive Proteae (MIC 50 range, 0.12–1 μg/ml; MIC 90 , > 16 μg/ml; median zone, 18–25 mm). Against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp., and other non-fermentors, Cefditoren was inactive (MIC 90 , > 16 μg/ml; zone, 6 mm). Pharmacokinetic analysis of Cefditoren showed that utilized dosages produce a plasma concentration that exceeds 0.5 μg/ml for 5 to 8 h and 1 μg/ml for 4 to 6 hours (T 1/2 ranges from 1.5–2 h). The following interpretive criteria were suggested: ≤ 2 μg/ml or ≥ 15 mm (susceptible) and ≥ 8 μg/ml or ≤ 11 mm (resistance) that yielded an intermethod categorical agreement of 95.8% and very major or major error rates of 0.7% and 0.3%, respectively. Alternatively, ≤ 1 μg/ml or ≥ 18 mm (susceptible) and ≥ 4 μg/ml or ≤ 14 mm (resistant) breakpoints resulted in 96.2% accuracy and combined serious errors of only 1.1%. Cefditoren was observed to be a very active cephalosporin ranking among the most potent available orally active β-lactams for use against a wide variety of pathogens.

  • antimicrobial activity and in vitro susceptibility test development for Cefditoren against haemophilus influenzae moraxella catarrhalis and streptococcus species
    Diagnostic Microbiology and Infectious Disease, 2000
    Co-Authors: David M Johnson, Douglas J Biedenbach, Michael A Pfaller, Mondell L Beach, Ronald N Jones
    Abstract:

    Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of Cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of /= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at