Ceftriaxone, Indications/Uses, Dosage, Side Effects, Pregnancy

Ceftriaxone, Indications/Uses, Dosage, Side Effects, Pregnancy

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
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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.
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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
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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

More common

Rare

Drug Interactions of Ceftriaxone

Ceftriaxone may interact with following drugs, supplements, & may change the efficacy of drugs

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

Ceftriaxone

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