Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Challenge strains used in this study

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Pharmacodynamics of tebipenem against E. coli ATCC 25922 in a neutropenic thigh infection model. The data are the mean ± standard deviation for 3 mice collected over the course of three independently conducted experiments. The solid squares are the bacterial density at the commencement of therapy, which was at 2 h postinoculation. The mean of these points defines the stasis line, depicted by the broken horizontal line. The open circles are the data points from mice sacrificed after receiving 24 h of antibacterial therapy. The solid line is the fit of an inhibitory sigmoid Emax model.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques: Infection, Standard Deviation

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Pharmacokinetics of tebipenem. The data are the mean ± standard deviation for 3 mice. A destructive design was used. Mice sampled in the period from 16 to 24 h had received drug at 0, 8, and 16 h. The mice were infected with E. coli ATCC 25922.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques: Standard Deviation, Infection

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Pharmacodynamics of tebipenem against E. coli and K. pneumoniae. Data are the mean ± standard deviation for 3 mice. (A) Pharmacodynamics of E. coli versus K. pneumoniae; (B) pharmacodynamics of ESBL-producing Enterobacteriaceae versus the wild type. Data from the strains were comodeled using fAUC0-24/MIC · 1/tau.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques: Standard Deviation

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Histogram of the magnitude of the fAUC0-24/MIC · 1/tau value required to achieve stasis for tebipenem against strains of E. coli (n = 6) and K. pneumoniae (n = 5). The median fAUC0-24/MIC · 1/tau value was 23.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Pharmacodynamics of ertapenem against E. coli. Data are the mean ± standard deviation for 3 mice. (A) Pharmacodynamics determined using fT>MIC, which is the traditional measure of drug exposure for the carbapenems. Stasis was achieved with a fT>MIC of 0.60. (B) The same data from the assay whose results are presented in panel A, but using fAUC0-24/MIC · 1/tau as the pharmacodynamic index. Stasis was achieved with a value of 46.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques: Standard Deviation

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections

doi: 10.1128/AAC.00603-19

Figure Lengend Snippet: Hollow-fiber infection model. The challenge strain (SPT719) used in this experiment is an ESBL-producing E. coli strain (tebipenem MIC, 0.03 mg/liter). Each panel represents the data from an individual fiber. The data represent the total bacterial population (open red triangles), a resistant subpopulation (open blue circles), and the pharmacokinetic profile of tebipenem (open black squares). The outputs from the mathematical model are shown using the same colors. The Bayesian posterior estimates for each fiber are shown. The fAUC0-24/MIC · 1/tau index values associated with the q24h, q12h, q8h, and q6h schedules are 17.3, 34.58, 51.87, and 69.15, respectively. Logarithmic killing was observed with at fAUC0-24/MIC · 1/tau values of 34.58 to 51.87, and suppression of resistance was observed at a value of 69.15. Panel A shows the control. In panels B to E, the same total amount of SPR859 has been administered in different schedules.

Article Snippet: The genotypes of the challenge strains are shown in . table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Species Strain identifier Genotype Modal (range) tebipenem MIC (mg/liter) E. coli NCTC 13462 CTX-M2 0.016 (0.016) E. coli ATCC 35218 TEM-1 ESBL 0.016 (0.008–0.016) E. coli ATCC 25922 Wild type 0.016 (0.008–0.016) E. coli SPT 719 (JMI 742654) SHV-12, TEM-1 0.03 (0.03–0.25) E. coli SPT 720 (JMI 850505) mcr-1 , CMY-2, OXA-1, TEM1 0.5 (0.25–0.5) E. coli SPT 731 (JMI 845741) CTX-M-15, OXA-1/30, TEM-1 ST131 a O25b clade 0.03 (0.015–0.03) K. pneumoniae NCTC 13465 ESBL and CTX-M25 0.03 (0.015–0.03) K. pneumoniae ATCC 27736 Wild type 0.03 (0.03–0.06) K. pneumoniae SPT 725 (JMI 776273) SHV-12 0.125 (0.06–0.25) K. pneumoniae SPT 722 (JMI 934954) CTX-M-15, OXA-1, OXA-9, SHV-28, TEM-1, OmpK35 disrupted, OmpK36 altered 0.25 (0.12–0.5) K. pneumoniae SPT 723 (JMI 632346) CTX-M-15, OXA-1, SHV-12 0.125 (0.12) Open in a separate window a ST131, sequence type 131.

Techniques: Infection