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Ceftriaxone Actions |
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Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.
A nurse or other trained health professional will give you Ceftriaxone. Ceftriaxone is given as a shot into one of your muscles or through a needle placed in one of your veins.
IM: Inject deep IM into large muscle mass; a concentration of 250 mg/mL or 350 mg/mL is recommended for all vial sizes except the 250 mg size (250 mg/mL is suggested); can be diluted with 1:1 water or 1% lidocaine for IM administration only.
IV: Infuse as an intermittent infusion over 30 minutes. IV push administration over 1 to 4 minutes has been reported (concentration: 100 mg/mL), primarily in patients outside the hospital setting (Baumgartner 1983; Garrelts 1988; Poole 1999), although a 2 g dose administered IV push over 5 minutes resulted in tachycardia, restlessness, diaphoresis, and palpitations in one patient (Lossos 1994). Do not coadminister with calcium-containing solutions.
Average plasma concentrations of Ceftriaxone (Ceftriaxone and dextrose injection ) following a single 30-minute intravenous (IV) infusion of a 0.5,1 or 2 g dose in healthy subjects are presented in Table 1.
TABLE 1. Ceftriaxone (Ceftriaxone and dextrose injection ) Plasma Concentrations After Single Dose Administration
Dose/Route | Average Plasma Concentrations (µ/mL) | ||||||||
0.5 hr | 1 hr | 2hr | 4hr | 6hr | 8hr | 12hr | 16 hr | 24 hr | |
0.5 g IV* | 82 | 59 | 48 | 37 | 29 | 23 | 15 | 10 | 5 |
1 g IV* | 151 | 111 | 88 | 67 | 53 | 43 | 28 | 18 | 9 |
2 g IV* | 257 | 192 | 154 | 117 | 89 | 74 | 46 | 31 | 15 |
*IV doses were infused at a constant rate over 30 minutes. |
Multiple IV doses ranging from 0.5 to 2 g at 12- to 24-hour intervals resulted in 15% to 36% accumulation of Ceftriaxone (Ceftriaxone and dextrose injection ) above single dose values.
Ceftriaxone (Ceftriaxone and dextrose injection ) concentrations in urine are high, as shown in Table 2.
TABLE 2. Urinary Concentrations of Ceftriaxone (Ceftriaxone and dextrose injection ) After Single Dose Administration
Dose/Route | Average Urinary Concentrations (µ/mL) | |||||
0-2 hr | 2-4 hr | 4-8 hr | 8-12 hr | 12-24 hr | 24-48 hr | |
0.5 g IV | 526 | 366 | 142 | 87 | 70 | 15 |
1 g IV | 995 | 855 | 293 | 147 | 132 | 32 |
2g lV | 2692 | 1976 | 757 | 274 | 198 | 40 |
Thirty-three percent to 67% of a Ceftriaxone (Ceftriaxone and dextrose injection ) dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 g IV dose, average concentrations of Ceftriaxone (Ceftriaxone and dextrose injection ), determined from 1 to 3 hours after dosing, were 581 µg/mL in the gallbladder bile, 788 µglml in the common duct bile, 898 µg/mL in the cystic duct bile, 78.2 µg/g in the gallbladder wall and 62.1 µg/mL in the concurrent plasma.
Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone (Ceftriaxone and dextrose injection ) is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of < 25 µg/mL to a value of 85% bound at 300 µg/mL. Ceftriaxone (Ceftriaxone and dextrose injection ) crosses the blood placenta barrier.
The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table 3. Ceftriaxone (Ceftriaxone and dextrose injection ) penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table 3.
TABLE 3. Average Pharmacokinetic Parameters of Ceftriaxone (Ceftriaxone and dextrose injection ) in Pediatric Patients With Meningitis
50 mg/kg IV | 75 mg/kq IV | |
Maximum Plasma Concentrations (µg/mL) | 216 | 275 |
Elimination Half-life (hr) | 4.6 | 4.3 |
Plasma Clearance (mL/hr/kg) | 49 | 60 |
Volume of Distribution (mL/kg) | 338 | 373 |
CSF Concentration — inflamed meninges (µg/mL) | 5.6 | 6.4 |
Range (µ/mL) | 1.3-18.5 | 1.3-44 |
Time after dose (hr) | 3.7 (±1.6) | 3.3 (±1.4) |
Compared to that in healthy adult subjects, the pharmacokinetics of Ceftriaxone (Ceftriaxone and dextrose injection ) were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (Table 4); therefore, dosage adjustments are not necessary for these patients with Ceftriaxone (Ceftriaxone and dextrose injection ) dosages up to 2 g per day. Ceftriaxone (Ceftriaxone and dextrose injection ) was not removed to any significant extent from the plasma by hemodialysis. In 6 of 26 dialysis patients, the elimination rate of Ceftriaxone (Ceftriaxone and dextrose injection ) was markedly reduced, suggesting that plasma concentrations of Ceftriaxone (Ceftriaxone and dextrose injection ) should be monitored in these patients to determine if dosage adjustments are necessary.
TABLE 4. Average Pharmacokinetic Parameters of Ceftriaxone (Ceftriaxone and dextrose injection ) in Humans
Subject Group | Elimination Half-Life (hr) | Plasma Clearance (L/hr) | Volume of Distribution (L) |
Healthy Subjects | 5.8-8.7 | 0.58-1.45 | 5.8-13.5 |
Elderly Subjects (mean age, 70.5 yr) | 8.9 | 0.83 | 10.7 |
Patients with Renal Impairment | |||
Hemodialysis Patients (0-5 mL/min)* | 14.7 | 0.65 | 13.7 |
Severe (5-15 mL/min) | 15.7 | 0.56 | 12.5 |
Moderate (16-30 mL/min) | 11.4 | 0.72 | 11.8 |
Mild (31-60 mL/min) | 12.4 | 0.70 | 13.3 |
Patients With Liver Disease | 8.8 | 1.1 | 13.6 |
*Creatinine clearance. |
The bactericidal activity of Ceftriaxone (Ceftriaxone and dextrose injection ) results from inhibition of cell wall synthesis. Ceftriaxone (Ceftriaxone and dextrose injection ) has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.
Ceftriaxone (Ceftriaxone and dextrose injection ) has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections described in the INDICATIONS AND USAGE section.
Aerobic gram-negative microorganisms
Acinetobacter calcoaceticus
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae (including ampicillin-resistant and beta-lactamase producing strains)
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis (including beta-lactamase producing strains)
Morganella morganii
Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase-producing strains)
Neisseria meningitidis
Proteus mirabilis
Proteus vulgaris
Serratia marcescens
Ceftriaxone (Ceftriaxone and dextrose injection ) is also active against many strains of Pseudomonas aeruginosa.
NOTE: Many strains of the above organisms that are multiply resistant to other antibiotics, e.g., penicillins, cephalosporins, and aminoglycosides, are susceptible to Ceftriaxone (Ceftriaxone and dextrose injection ).
Aerobic gram-positive microorganisms
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci
NOTE: Methicillin-resistant staphylococci are resistant to cephalosporins, including Ceftriaxone (Ceftriaxone and dextrose injection ). Most strains of Group D streptococci and enterococci, e.g., Enterococcus (Streptococcus) faecalis, are resistant.
Anaerobic microorganisms
Bacteroides fragilis
Clostridium species
Peptostreptococcus species
NOTE: Most strains of Clostridium difficile are resistant.
The following in vitro data are available, but their clinical significance is unknown. Ceftriaxone (Ceftriaxone and dextrose injection ) exhibits in vitro minimal inhibitory concentrations (MICs) of ≤ 8 µg/mL or less against most strains of the following microorganisms, however, the safety and effectiveness of Ceftriaxone (Ceftriaxone and dextrose injection ) in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-negative microorganisms
Citrobacter diversus
Citrobacterfreundii
Providencia species (including Providencia rertgeri)
Salmonella species (including Salmonella typhi)
Shigella species
Aerobic gram-positive microorganisms
Streptococcus agalactiae
Anaerobic microorganisms
Prevotella (Bacteroides) bivius
Porphyromonas (Bacteroides) melaninogenicus
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. testing method:
Method | Microoraanism | ATCC®# | MIC (µq/mL) |
Agar | Bacteroides fragilis | 25285 | 32-128 |
Bacteroides thetaiotaomicron | 29741 | 64-256 | |
Broth | Bacteroides thetaiotaomicron | 29741 | 32-128 |
REFERENCES
1. National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Fifth Edition. NCCLS document M7-A5 (ISBN 1-56238-309-9). NCCLS, Wayne, PA 19087-1898,2000.
2. National Committee for Clinical Laboratory Standards, Supplemental Tables. NCCLS document M100-S10(M7) (ISBN 1-56238-309-9). NCCLS, Wayne, PA 19087-1898,2000.
3. National Committee fof'Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Teste; Approved Standard-Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898,2000.
4. National Committee for Clinical Laboratory Standards, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacterial; Approved Standard-Fourth Edition. NCCLS document M11-A4 (ISBN 1-56238-210-1). NCCLS, Wayne, PA 19087-1898,1997.
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Information checked by Dr. Sachin Kumar, MD Pharmacology
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