Ceftriaxone is a beta-lactam, third-generation cephalosporin antibiotic with bactericidal activity. Ceftriaxone binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. PBPs participate in the terminal stages of assembling the bacterial cell wall, and in reshaping the cell wall during cell division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis. Compared to the second and first-generation cephalosporins, ceftriaxone is more active against gram-negative bacteria and less active against gram-positive bacteria. Ceftriaxone also crosses the blood-brain barrier and reaches therapeutic concentrations in the central nervous system (CNS).
Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis. Compared to the second and first-generation cephalosporins, ceftriaxone is more active against gram-negative bacteria and less active against gram-positive bacteria. Ceftriaxone also crosses the blood-brain barrier and reaches therapeutic concentrations in the central nervous system (CNS).
Mechanism of Action of Ceftriaxone
Ceftriaxone, a beta-lactam antibiotic like the penicillins, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of ceftriaxone, as well as the other cephalosporins and penicillins against a particular organism, depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, ceftriaxone’s ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.
Indications of Ceftriaxone
- Upper/Lower respiratory tract infection (respiratory, skin, soft tissue, UTI, ENT)
- Acute bacterial otitis media
- Skin and skin structure infections
- Urinary tract infections
- Uncomplicated gonorrhea
- Pelvic inflammatory disease
- Bacterial septicemia
- Intra-abdominal infections
- Pelvic Inflammatory Disease
- Meningitis
- Osteomyelitis
- Pelvic Inflammatory Disease
- Surgical prophylaxis
- Community-acquired pneumonia
- Acute otitis media
- Intra-abdominal infections
- Complicated urinary tract infections (including pyelonephritis)
- Infections of bones and joints
- Complicated skin and soft tissue infections
- Gonorrhea
- Syphilis
- Bacterial Endocarditis.
- Meningococcal Meningitis Prophylaxis
- Salmonella Enteric Fever
- Salmonella Gastroenteritis
- Community-acquired pneumonia
- Hospital-acquired pneumonia
- Acute otitis media
- Intra-abdominal infections
- Complicated urinary tract infections (including pyelonephritis)
- Infections of bones and joints
- Complicated skin and soft tissue infections
- For treatment of acute exacerbations of chronic obstructive pulmonary disease in adults
- For treatment of disseminated Lyme borreliosis (early (stage II) and late (stage III)) in adults and children including neonates from 15 days of age.
|For Pre-operative prophylaxis of surgical site infections
Antibacterial Activity
Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in Vitro and in clinical infections.
● Gram-negative bacteria
Acinetobacter calcoaceticus
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis
Morganella morganii
Neisseria gonorrhoeae
Neisseria meningitidis
Proteus mirabilis
Proteus vulgaris
Pseudomonas aeruginosa
Serratia marcescens
● Gram-positive bacteria
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci
● Anaerobic bacteria
Bacteroides fragilis
Clostridium species
Peptostreptococcus species
● Gram-negative bacteria
Citrobacter diversus
Citrobacter freundii
Providencia species (including Providencia rettgeri)
Salmonella species (including Salmonella typhi)
Shigella species
● Gram-positive bacteria:
Streptococcus agalactiae
● Anaerobic bacteria:
Porphyromonas (Bacteroides) melaninogenicus
Prevotella (Bacteroides) bivius
Contra Indications of Ceftriaxone
- History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
- Hemolytic anemia
- Liver problems
- Interstitial nephritis
- Subacute cutaneous lupus erythematosus
- Systemic lupus erythematosus
- Allergies cephalosporins & beta-lactamase
Dosage of Ceftriaxone
Strengths: 250 mg; 500 mg; tablet & 1 g; 2 g; 10 g; I.V ;1 g/50 mL ,2g/50mL suspension
Salmonella Enteric Fever
US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-infected Patients
- 1 g IV every 24 hours
Duration of Salmonellosis Therapy, For gastroenteritis without bacteremia
- If CD4 count at least 200 cells/mm3: 7 to 14 days
- If CD4 count less than 200 cells/mm3: 2 to 6 weeks
For gastroenteritis with bacteremia
- If CD4 count at least 200 cells/mm3: 14 days; longer if persistent bacteremia or complicated infection (e.g., metastatic foci of infection present)
- If CD4 count less than 200 cells/mm3: 2 to 6 weeks
Osteomyelitis
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Salmonella Gastroenteritis
US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-infected Patients
- 1 g IV every 24 hours
Duration of Salmonellosis Therapy, For gastroenteritis without bacteremia
- If CD4 count at least 200 cells/mm3: 7 to 14 days
- If CD4 count less than 200 cells/mm3: 2 to 6 weeks
For gastroenteritis with bacteremia
- If CD4 count at least 200 cells/mm3: 14 days; longer if persistent bacteremia or complicated infection (e.g., metastatic foci of infection present)
- If CD4 count less than 200 cells/mm3: 2 to 6 weeks
Joint Infection
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Bacteremia
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Pneumonia
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
-Complicated infections: Longer therapy may be required.
-Infections due to Streptococcus pyogenes: At least 10 days
Septicemia
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Urinary Tract Infection
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Bronchitis
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to Streptococcus pyogenes: At least 10 days
Intraabdominal Infection
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
Meningitis
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
IDSA Recommendations
- Bacterial meningitis: 4 g IV every 24 hours (or in equally divided doses every 12 hours) for 7 to at least 21 days
US CDC Recommendations
- Gonococcal meningitis: 1 to 2 g IV every 12 to 24 hours for 10 to 14 days
Pelvic Inflammatory Disease
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day)
- Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
US CDC Recommendations
- 250 mg IM as a single dose
Skin or Soft Tissue Infection
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day) -Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to S pyogenes: At least 10 days
IDSA Recommendations
- Incisional surgical site infection: 1 g IV every 24 hours
- Aeromonas hydrophila necrotizing infection: 1 to 2 g IV every 24 hours
- Vibrio vulnificus necrotizing infection: 1 g IV once a day
- Infection after the animal bite: 1 g IV every 12 hours
Skin and Structure Infection
- 1 to 2 g IV or IM once a day (or in equally divided doses twice a day) – Duration of therapy: 4 to 14 days
- Complicated infections: Longer therapy may be required.
- Infections due to S pyogenes: At least 10 days
IDSA Recommendations
- Incisional surgical site infection: 1 g IV every 24 hours
- Aeromonas hydrophila necrotizing infection: 1 to 2 g IV every 24 hours
- Vibrio vulnificus necrotizing infection: 1 g IV once a day
- Infection after animal bite: 1 g IV every 12 hours
Pediatric Dose for Bacteremia
- 1 month or older: 50 to 75 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 g/day
American Academy of Pediatrics (AAP) Recommendations
- Neonates: 50 mg/kg IV or IM every 24 hours
1 month or older
- Mild to moderate infections: 50 to 75 mg/kg IV or IM once a day
- Maximum dose: 1 g/day
- Severe infections: 100 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 to 4 g/day
Pediatric, Osteomyelitis
- 1 month or older: 50 to 75 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 g/day
American Academy of Pediatrics (AAP) Recommendations
- Neonates: 50 mg/kg IV or IM every 24 hours
1 month or older
- Mild to moderate infections: 50 to 75 mg/kg IV or IM once a day
- Maximum dose: 1 g/day
- Severe infections: 100 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 to 4 g/day
Pediatric, Urinary Tract Infection
- 1 month or older: 50 to 75 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 g/day
American Academy of Pediatrics (AAP) Recommendations
- Neonates: 50 mg/kg IV or IM every 24 hours
1 month or older
- Mild to moderate infections: 50 to 75 mg/kg IV or IM once a day
- Maximum dose: 1 g/day
- Severe infections: 100 mg/kg IV or IM once a day (or in equally divided doses twice a day)
- Maximum dose: 2 to 4 g/day
Meningitis
1 month or older
- Initial dose: 100 mg/kg IV or IM at the start of therapy
- Maximum dose: 4 g/dose
- Maintenance dose: 100 mg/kg IV or IM once a day (or in equally divided doses every 12 hours)
- Maximum dose: 4 g/day
- Duration of therapy: 7 to 14 days
IDSA Recommendations
- Infants and children with bacterial meningitis: 80 to 100 mg/kg IV every 24 hours (or in equally divided doses every 12 hours) for 7 to at least 21 days
- Maximum dose: 4 g/day
US CDC Recommendations
- Neonates with DGI and documented meningitis: 25 to 50 mg/kg IV or IM every 24 hours for 10 to 14 days
- Adolescents with gonococcal meningitis: 1 to 2 g IV every 12 to 24 hours for 10 to 14 days
Intraabdominal Infection
- 1 month or older: 50 to 75 mg/kg/day IV or IM in divided doses every 12 hours
- Maximum dose: 2 g/day
IDSA and SIS Recommendations
- 50 to 75 mg/kg IV once a day (or in equally divided doses twice a day)
- Maximum dose: 2 g/day
Side Effects of Ceftriaxone
Most common
- allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
- leukopenia/leukemia
- hemolytic anemia
- serum sickness
- agranulocytosis
- pain, swelling, irritation where injected
- stomach upset
- sweating
- skin color change, mild diarrhea
- mild nausea
- loss of appetite
- vaginal discharge and itching
- swelling of feet or legs
- chest pain
- constipation
- a cough
- diarrhea or loose stools
- difficulty with breathing
- dizziness
- heartburn
Pregnancy Catagory of Ceftriaxone
FDA Pregnancy Category B
Pregnancy:
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
Ceftriaxone passes into breast milk in small amounts. If you are a breastfeeding mother and are taking ceftriaxone, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. Newborn and premature infants (up to the age of 10 weeks) should not receive calcium-containing solutions within 5 days of receiving ceftriaxone.
References
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