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Table 2 Summary of PK/PD studies carried out with cefditoren (CDN)

From: Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults

Ref. Type of study Strains Comparators Main conclusion
[73] Killing curves in the presence/absence of human albumin (Cmax: 4.1 mg/l) S. pneumoniae
(CDN MICs: 0.12–0.5 mg/l)
_ The activity of cefditoren should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration.
[74] Killing curves in the presence/absence of human albumin or human serum (Cmax: 4.1 mg/l) S. pneumoniae
(CDN MICs: 0.12–0.5 mg/l)
_ The presence of 90% human serum did not limit bactericidal activity as did the use of concentrations similar to free-drug.
[75] In vitro computerized pharmacodynamic simulation in the presence of 75% human serum S. pneumoniae
(CDN MICs: 0.25–0.5 mg/l)
_ Cefditoren physiological concentrations exerted antibacterial activity against strains exhibiting MICs of 0.25 and 0.5 m/l under protein binding conditions similar to those in humans (experimentally measured)
[76] In vitro computerized pharmacodynamic simulation (total vs. free concentrations) H. influenzae (including BLNAR and BLPACR) Co-amoxiclav The experimental bactericidal activity of cefditoren (both total and free concentrations) was maintained over the dosing interval regardless of the presence of mutation in the ftsI gene or β-lactamase production, in contrast to co-amoxiclav.
[77] In vitro computerized pharmacodynamic simulation S. pneumoniae (amoxicillin MIC > penicillin MIC)
(CDN MICs: 0.12–1 mg/l)
Cefuroxime
Co-amoxiclav
Bactericidal activity at 12 and 24 h was obtained against all strains with cefditoren, but not with comparators.
[78] In vitro computerized pharmacodynamic simulation S. pneumoniae (mixed inocula)
(CDN MICs: 0.015, 0.5, 1 mg/l)
Cefuroxime Cefixime
Cefaclor
Amoxicillin
Against penicillin resistant strains, cefditoren (but not comparators) decreased the initial bacterial load all along the simulation, without regrowth and with lower selection of resistant subpopulations
[79] In vitro computerized pharmacodynamic simulation H. influenzae (including BLNAR and BLPACR) Cefuroxime
Co-amoxiclav
Cefditoren exhibited the highest bactericidal activity maintained over time against ampicillin-resistant H. influenzae, regardless of beta-lactamase production and/or BLNAR phenotype.
[80] In vitro computerized pharmacodynamic simulation H. influenzae β
H. influenzae β+
BLNAR
BLPACR
(mixed inocula)
Cefuroxime
Co-amoxiclav
Cefditoren offered higher antibacterial effect than comparators due to its higher activity against beta-lactamase-producing strains and those carrying ftsI gene mutations. BLNAR and BLPACR strains were selected by cefuroxime and co-amoxiclav, respectively.
[81] In vitro computerized pharmacodynamic simulation S. pyogenes
S. pneumoniae
H. influenzae β+
BLPACR
(mixed inocula)
Amoxicillin
Co-amoxclav
Cefditoren (but not comparators) completely countered indirect pathogenicity and eradicated S. pyogenes and both H. influenzae strains.
[82] In vitro computerized pharmacodynamic simulation in media containing ftsI DNA H. influenzae β
H. influenzae β+
Co-amoxiclav Cefditoren (but not co-amoxiclav) was bactericidal and countered intrastrain ftsI gene diffusion
[83] In vitro study assessing by flow cytometry the deposition/binding of components of the complement system to bacterial cells S. pneumoniae Ceftriaxone Increased recognition of S. pneumoniae by the complement system in the presence of sub-inhibitory concentrations of cefditoren
[84] Mice sepsis model (pre-immunized vs. non pre-immunized mice) S. pneumoniae
(CDN MICs: 1, 2, 4 mg/l)
_ In non pre-immunized animals, t > MIC values for CDN of approximately 35% (total) and approximately 19% (free) were associated with 100% survival, with lower values in pre-immunized animals
[85] Monte Carlo simulation _ _ Coverage with total concentrations:
a. criterion of 40% t > MIC: MICs ≤0.5 mg/l
b. criterion of 33% t > MIC: MICs ≤0.5 mg/l
Coverage with extrapolated free concentrations:
a. criterion of 40% t > MIC: MICs ≤0.12 mg/l
b. criterion of 33% t > MIC: MICs ≤0.25 mg/l