PHARMACOLOGICAL ACTION
Ceftriaxone is a broad-spectrum cephalosporin with a long plasma elimination half-life of approximately 8 hours in normal adults.
Antimicrobial Profile
(In vitro sensitivity does not necessarily imply in vivo efficacy).
The in vitro spectrum of activity of ceftriaxone encompasses:
(a) Gram-positive organisms:
Streptococcus pneumoniae, Streptococcus Group A (including Streptococcus pyogenes), Streptococcus Group B (including Streptococcus agalactiae), Streptococcus viridans, Streptococcus bovis (Group D), Staphylococcus aureus (methicillin sensitive). Peptostreptococcus sp., and Clostridium sp.
Note: Methicillin-resistant Staphylococcus spp. are resistant to ceftriaxone. Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are resistant.
(b) Gram-negative organisms:
Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Neisseria meningitidis, Neisseria gonorrhoeae (including penicillin-resistant strains),Escherichia coli, Klebsiella sp**, Enterobacter sp*, Serratia marcescens, Citrobacter sp., Proteus mirabilis, Indole-positive Proteus (including Morganella morganii),Salmonella sp., Shigella sp., Yersinia pestis and Treponema pallidum (in animal experiments).
*Some isolates of these species are resistant to ceftriaxone, due to the production of the chromosomally encoded beta-lactamases.
**Some isolates of these species are resistant due to production of extended spectrum plasmid mediated beta-lactamase.
(c) Organisms which are only partially sensitive to ceftriaxone in vitro. Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter sp. and Bacteroides sp. Ceftriaxone is stable in relation to the majority of beta-lactamases.
The following organisms are resistant:
Ureaplasma urealyticum, Mycoplasma sp., Mycobacterium sp., Fungi.
It is essential to note that recommended media (free from inhibitory substances especially thymidine and thymine) and methods must be used for satisfactory sensitivity testing.
Pharmacokinetics
The maximum plasma concentration after a single IM dose of 1.0 g is about 81 mg/L and is reached in 2-3 hours after the dose. The area under the plasma concentration-time curve after IM administration is equivalent to that after IV administration of an equivalent dose, indicating 100% bioavailability of intramuscularly administered ceftriaxone.
On intravenous administration, ceftriaxone diffuses into the tissue fluid, where-if it is given in the recommended dosage range-bactericidal concentrations lasting 24 hours may be maintained. Ceftriaxone is reversibly bound to albumin, and the binding decreases with the increase in concentration e.g. from 95% binding at plasma concentrations of <100 mg/L to 85% binding at 300 mg/L. Owing to the lower albumin content, the proportion of free ceftriaxone in interstitial fluid is correspondingly higher than in plasma.
The volume of distribution of ceftriaxone is 7-12 L. After a dose of 1-2 g, concentrations above the minimal inhibitory concentrations of most pathogens responsible for infection are detected for more than 24 hours in the following tissues or body fluids: lung, heart, biliary tract/liver, middle ear and nasal mucosa, bone; and cerebral, pleural, prostatic and synovial fluids.
In healthy, young adult volunteers the total plasma clearance is 10-22 mL/min. The renal clearance is 5-12 mL/min. 50-60% of ceftriaxone is excreted unchanged in the urine, while 40-50% is excreted unchanged in the bile. The elimination half life in adults is about eight hours.
The substance is largely inactivated in the faeces due to metabolism by intestinal flora.
The mean plasma elimination half life is 8 hours in healthy, young adult volunteers. In neonates, urinary recovery accounts for about 70% of the dose. In infants aged less than eight days and in elderly persons aged over 75 years, the average elimination half life is usually 2-3 times that in the young adult group.
In patients with renal or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased; if liver function alone is impaired, renal elimination is increased.
In meningitis patients, administration of 50 mg per kg bodymass leads within 2-24 hours to cerebro spinal fluid concentrations several times as high as the minimum in vitro inhibitory concentrations required for the most common causative organisms of meningitis.
INDICATIONS:
Infections caused by pathogens sensitive to ceftriaxone such as
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sepsis |
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meningitis in neonates and infants |
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perioperative prophylaxis of infections |
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renal and urinary tract infections |
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respiratory tract infections, particularly pneumonia, and ear, nose and throat infections. |
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infections of the bones, joints, soft tissue, skin and of wounds. |
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abdominal infections (peritonitis, infections of the biliary tract). |
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uncomplicated gonorrhoea |
WARNINGS:
Before therapy with Ceftriaxone is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other medicines. About 10% of penicillin-sensitive patients may also be allergic to cephalosporins although the true incidence is uncertain. Great care should be taken if Ceftriaxone is to be given to such patients.
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