Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

3.1           Pharmacodynamic Properties
The bactericidal activity of ceftriaxone results from inhibition of bacterial cell wall synthesis.
Ceftriaxone exerts in-vitro activity against a wide range of gram-negative and gram-positive micro- organisms. Ceftriaxone is highly stable to most ß-lactamases, both penicillinases and cephalosporinases, of gram-positive and gram-negative bacteria. Ceftriaxone is usually active against the following micro-organisms in vitro and in clinical infections (see 2.1 Therapeutic Indication(s)):

Gram-positive aerobes
Staphylococcus aureus (methicillin-sensitive), Staphylococci coagulase-negative, Streptococcus pyogenes (ß-hemolytic, group A), Streptococcus agalactiae (ß-hemolytic, group B), ß-hemolytic Streptococci (non-group A or B), Streptococcus viridans, Streptococcus pneumoniae.
ROCEPHIN®                                                        MoH Approved Prescribing Information Vials 500 mg IV /IM, 1 gr IM                                                               April 2015 
Note: methicillin-resistant Staphylococcus spp. is resistant to cephalosporins, including ceftriaxone.
In general, Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are resistant.

Gram-negative aerobes
Acinetobacter lwoffi, Acinetobacter anitratus (mostly A. baumanii)*, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Alcaligenes-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including C. amalonaticus), Citrobacter freundii*, Escherichia coli, Enterobacter aerogenes*, Enterobacter cloacae*, Enterobacter spp. (other)*, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae**, Moraxella catarrhalis (former Branhamella catarrhalis), Moraxella osloensis, Moraxella spp. (other), Morganella morganii, Neisseria gonorrhea, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri*, Proteus vulgaris*, Pseudomonas fluorescens*, Pseudomonas spp.
(other)*, Providentia rettgeri*, Providentia spp. (other), Salmonella typhi, Salmonella spp. (non- typhoid), Serratia marcescens*, Serratia spp. (other)*, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (other).

* Some isolates of these species are resistant to ceftriaxone, mainly due to the production of the chromosomally encoded ß-lactamase.

** Some isolates of these species are resistant due to production of extended spectrum, plasmid- mediated ß-lactamase.

Note: Many strains of the above micro-organisms that are multiple resistant to other antibiotics, e.g. amino-penicillins and ureido-penicillins, older cephalosporins and aminoglycosides, are susceptible to ceftriaxone. Treponema pallidum is sensitive in vitro and in animal experiments.
Clinical investigations indicate that primary and secondary syphilis respond well to ceftriaxone therapy. With a few exceptions clinical P. aeruginosa isolates are resistant to ceftriaxone.

Anaerobic organisms

Bacteroides spp. (bile-sensitive)*, Clostridium spp. (excluding C. difficile), Fusobacterium nucleatum, Fusobacterium spp. (other), Gaffkia anaerobica (formerly Peptococcus), Peptostreptococcus spp.
* Some isolates of these species are resistant to ceftriaxone due to ß-lactamase-production.
Note: Many strains of ß-lactamase-producing Bacteroides spp. (notably B. fragilis) are resistant.
Clostridium difficile is resistant.
Susceptibility to ceftriaxone can be determined by the disk diffusion test or by the agar or broth dilution test using standardized techniques for susceptibility testing such as those recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCCLS issued the following interpretative breakpoints for ceftriaxone:

Susceptible     Moderately        Resistant susceptible
Dilution test inhibitory concentrationsin mg/l                     =8               16-32        =64 Diffusion test
(disk with 30 µg ceftriaxone),
inhibition zone diameter in mm                 =21             20-14           =13 Micro-organisms should be tested with the ceftriaxone disk since it has been shown by in-vitro tests to be active against certain strains resistant to cephalosporin class disks.


ROCEPHIN®                                                       MoH Approved Prescribing Information Vials 500 mg IV /IM, 1 gr IM                                                              April 2015 
Where NCCLS recommendations are not in daily use, alternative, well standardized, susceptibility- interpretative guidelines such as those issued by DIN, ICS and others may be substituted.

Pharmacokinetic Properties