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Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. Methodology/Principal Findings: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. Conclusions/Significance: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections. [ABSTRACT FROM AUTHOR]

This paper reports the effect of soda-lime-glass-nAg coating on the viability of an in vitro biofilm of Streptococcus oralis. Three strains (ATCC 35037 and two clinical isolates from periodontitis patients) were grown on coated with glass, glass containing silver nanoparticles, and uncoated titanium alloy disks. Two different methods were used to quantify biofilm formation abilities: crystal violet staining and determination of viable counts. The influence of the surface morphology on the cell attachment was studied. The surface morphology was characterized by scanning electron microscopy (SEM) and using a profilometer. SEM was also used to study the formation and the development of biofilm on the coated and uncoated disks. At least a >99.7% inocula reduction of biofilm respect to titanium disks and also to glass coated disks was observed in the glass-nAg coated disks for all the studied strains. A quantitative evaluation of the release of silver was conducted in vitro to test whether and to what extend the biocidal agent (silver) could leach from the coating. These findings suggest that the biofilm formation of S. oralis strains is highly inhibited by the glass-nAg and may be useful for materials which require durable antibacterial effect on their surfaces, as it is the case of dental implants. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 μg/ml), Strain 2 (19F, 2 μg/ml) and Strain 3 (23F, 4 μg/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. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics. Methodology/Principal Findings: A computerized two-compartment pharmacodynamic model was used to explore blactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (mg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a β-lactamase positive H. influenzae (BL+; .16, 2 and 0.06) and a b-lactamase positive AMC-resistant H. influenzae (BLPACR, .16, 8 and 0.06). Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of <4×106 cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. β-lactamase production decreased AMX concentrations and fT>MIC against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL+ and S. pneumoniae) was eradicated. Resistance of CDN to TEM β-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT>MIC .58%), and reduced in 94% S. pneumoniae counts (fT>MIC <25%). Conclusions/Significance: Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for β-lactamase resistant cephalosporins with high activity against streptococci. [ABSTRACT FROM AUTHOR]

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 3rd generation cephalosporin, over 24h after an oral 400 mg cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/cefditoren MICs; μg/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 (⩾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 μg/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. [ABSTRACT FROM AUTHOR]

Time-kill studies compared the activities of moxifloxacin with those of levofloxacin, azithromycin and amoxicillin-clavulanate against 10 pneumococcal strains with various drug susceptibilities. Three Streptococcus pneumoniae strains were resistant to moxifloxacin: 6, 7 and 2 strains were resistant to levofloxacin, azithromycin and amoxicillin-clavulanate, respectively. Of these, 1 strain was resistant to all antimicrobial agents studied. Moxifloxacin and amoxicillin-clavulanate were bactericidal after 24 h at serum Cmax levels against 9 and 8 strains, respectively, while levofloxacin and azithromycin were bactericidal against 3 and 2 strains, respectively. A higher activity was only observed for amoxicillin-clavulanate for logarithmic phase cultures at 1, 4 and 8 h compared with stationary phase organisms. Amoxicillin-clavulanate and moxifloxacin were bactericidal at free serum levels (protein unbound) after 24 h against 8 and 3 strains, respectively. Moxifloxacin was bactericidal at epithelial lining fluid levels against all strains at 24 h, including one moxifloxacin, amoxicillin-clavulanate and azithromycin-resistant strain; lower levels of bactericidal activity was observed for levofloxacin, azithromycin and amoxicillin-clavulanate against 7, 2 and 4 strains, respectively. This demonstrated the importance of moxifloxacin tissue levels. [Copyright &y& Elsevier]

Mupirocin and amoxicillin-clavulanate were synergistic against 9 of 49 (18%) strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (CNS). A pattern of enhanced killing was also found using time-kill studies. Time-kill assays were more discriminatory than chequerboard titration assays in demonstrating synergy. These results suggest that combinations of amoxicillin-clavulanate and mupirocin may have therapeutic benefits in prophylaxis against staphylococcal infections. [Copyright &y& Elsevier]

Objectives The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains. Methods Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one β-lactamase-negative (β−; 0.015, 1 and 1), one β-lactamase-positive (β; 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one β− ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one β amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu·h/mL) were calculated and differences between values in antibiotic-free (AUBCK) and in antibiotic simulations determined (ABBC0–24 = AUBCK0–24−AUBC0–24). Results In antibiotic-free medium, total population increased by 1.7 log10 cfu/mL from 0 to 24 h: final composition &ap;90% β−, &ap;6.5% β, &ap;2.5% BLNAR and &ap;1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by β after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC0–24 was higher (P Conclusions Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against β-lactamase‐producing strains and those carrying ftsI gene mutations. [ABSTRACT FROM AUTHOR]

One important feature of the major opportunistic human pathogen Staphylococcus aureus is its extraordinary ability to rapidly acquire resistance to antibiotics. Genomic studies reveal that S. aureus carries many virulence and resistance genes located in mobile genetic elements, suggesting that horizontal gene transfer (HGT) plays a critical role in S. aureus evolution. However, a full and detailed description of the methodology used to study HGT in S. aureus is still lacking, especially regarding natural transformation, which has been recently reported in this bacterium. This work describes three protocols that are useful for the in vitro investigation of HGT in S. aureus: conjugation, phage transduction, and natural transformation. To this aim, the cfr gene (chloramphenicol/florfenicol resistance), which confers the Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A (PhLOPSA)-resistance phenotype, was used. Understanding the mechanisms through which S. aureus transfers genetic materials to other strains is essential to comprehending the rapid acquisition of resistance and helps to clarify the modes of dissemination reported in surveillance programs or to further predict the spreading mode in the future.

Introduction: This study explores effects of pH and inoculum size on imipenem versus tigecycline activity against E. coli, B. fragilis and E. faecalis, both in individual and mixed cultures., Methods: MIC/MBCs (mg/L) of tigecycline and imipenem were 0.12/≥ 16 and 4/4 for E. coli, 0.12/0.5 and ≥ 16/≥ 16 for B. fragilis, and 0.12/≥ 16 and 2/≥ 16 for E. faecalis, respectively. Killing curves in supplemented Brucella broth were performed at pH 7 or 5.8, with two final inocula (≈ 105 or ≈ 107 cfu/ml) of each isolate (individual cultures) and with 1:1:1 mixed inocula. Tubes were 48 h incubated at 37 ºC in anaerobiosis. Final concentrations (estimated concentrations in colon) were 1.50 mg/L for tigecycline and 26.40 mg/L for imipenem, with antibiotic-free curves as controls. Experiments were performed in triplicate., Results: Imipenem showed inoculum effect against E.coli and B. fragilis, with reductions in initial inocula in experiments with standard inocula contrasting with increases in experiments with high inocula (both individual and mixed cultures). Against E. faecalis no inoculum effect for imipenem was observed in individual cultures, with marked reductions in initial inocula regardless inoculum size. However in mixed experiments the indirect protection of E. faecalis by the two gramnegatives resulted in bacterial regrowth. This protection was inoculum-dependant since it occurred with high but not with standard inocula. Tigecycline reduced initial inocula of the three isolates regardless culture type (individual/mixed) or experimental conditions (pH/inocula size), with lower reductions for the tolerant E. faecalis., Conclusion: Carbapenemase activity was inoculum-dependant for self-protection and indirect protection of E. faecalis.

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 10⁷-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 log₁₀ to 4.5 to 5 log₁₀), while the BL⁺ recombined population was maintained in simulations with DNA(BLPACR) and was decreased by ≈2 log₁₀ 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 log₁₀ (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.

Objectives: The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains., Methods: Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one beta-lactamase-negative (beta(-); 0.015, 1 and 1), one beta-lactamase-positive (beta(+); 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one beta(-) ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one beta(+) amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu.h/mL) were calculated and differences between values in antibiotic-free (AUBC(K)) and in antibiotic simulations determined (ABBC(0-24) = AUBC(K0-24)-AUBC(0-24))., Results: In antibiotic-free medium, total population increased by 1.7 log(10) cfu/mL from 0 to 24 h: final composition approximately 90% beta(-), approximately 6.5% beta(+), approximately 2.5% BLNAR and approximately 1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by beta(+) after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC(0-24) was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus approximately 33), beta(+) (77.8 versus approximately 52), BLNAR (66.1 versus 18.6-30.4) or BLPACR (40.8 versus approximately 0)., Conclusions: Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against beta-lactamase-producing strains and those carrying ftsI gene mutations.

Among 165 Spanish Haemophilus influenzae isolates with mutations in the ftsI gene (ftsI(+)) (2005 to 2007), 73% were beta-lactamase negative and 26.7% were positive. The proportion of beta-lactamase-negative isolates to beta-lactamase-positive isolates was 2:1 to 4:1 in general, versus 1:3 in pediatric hospitals. Among 44 beta-lactamase-positive strains, 8 strains produced ROB-1 (5 from the pediatric hospital). beta-Lactamase-positive ftsI(+) strains were phylogenetically closer than were beta-lactamase-negative strains.

To investigate beta-lactam effects on Streptococcus pneumoniae-mixed cultures, a computerized pharmacodynamic model simulating over 24-hr concentrations obtained after several beta-lactam regimens was used. Strain 1 (no penicillin binding protein [PBP] mutations) and strain 2 (mutation in pbp1a) were penicillin/amoxicillin susceptible. Strain 3 (mutations in pbp1a, pbp2x, and pbp2b) and strain 4 (mutations in pbp1a, pbp2x, and pbp2b [10 changes]) were penicillin/amoxicillin resistant. Initial inoculum was approximately 6 x 10(6) CFU (colony forming units)/ml (with a 1:1:1:1 proportion of each strain). Population analysis profile was performed pre- and post-simulations. Strain 1 exhibited the best fitness (growth over 24 hr) in individual cultures, and strain 2 did so in mixed cultures in antibiotic-free simulations. In antibiotic simulations with the mixed inocula, penicillin/amoxicillin-susceptible strains were eradicated with all study drugs (time that concentrations exceed the minimal inhibitory concentration [T>MIC >or= 43%]). Penicillin-resistant strains showed different evolution depending on the antibiotic: (a) cefditoren produced >2 log(10) reduction of initial inocula at 12-24 hr (T>MIC >or=45%), with a remaining population growing in plates with >or=4 mg/L amoxicillin; (b) cefuroxime, cefixime, and cefaclor did not decrease initial inocula at 12-24 hr (T>MIC=0%), with minor subpopulations growing in plates with 4 mg/L amoxicillin; (c) amoxicillin produced 2.6 log(10) decrease of initial inocula at 12 hr (T>MIC=47.5%), but 1.1 log(10) increase of initial inocula at 24 hr, with a significant population growing in plates with 4 mg/L amoxicillin. Antibiotic activity against mixed inocula (susceptible and resistant strains) depends on intrinsic activity (as well as its subsequent pharmacodynamic activity: T>MIC against resistant strains), and on possible selection of intra-strain-resistant subpopulations.

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.

Background: Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics., Methodology/principal Findings: A computerized two-compartment pharmacodynamic model was used to explore beta-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (microg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a beta-lactamase positive H. influenzae (BL(+); >16, 2 and 0.06) and a beta-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of approximately 4 x 10(6) cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. beta-lactamase production decreased AMX concentrations and fT(>MIC) against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL(+) and S. pneumoniae) was eradicated. Resistance of CDN to TEM beta-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT(>MIC) >58%), and reduced in 94% S. pneumoniae counts (fT(>MIC) approximately 25%)., Conclusions/significance: Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for beta-lactamase resistant cephalosporins with high activity against streptococci.