ceftriaxone (Rocephin)

Introduction

Tradename: Rocephin. 3rd generation cephalosporin.

Indications

• treatment of moderate to severe bacterial infections caused by:
  • Streptococcus pneumoniae
  • Klebsiella species
  • Proteus mirabilis
  • Moraxella catarrhalis
• pneumonia
  • community acquired pneumonia
  • ventilator-associated
• Streptococcal endocarditis/sepsis
• CNS infections
  • empiric therapy for meningitis
• acute otitis media
• skin or soft tissue infection
• infectious arthritis
• intra-abdominal infection
• urogenital infection
  • single dose treatment of cervical urethral, rectal or pharyngeal gonorrhea
  • pelvic inflammatory disease
• proctitis
• prophylaxis for perioperative infection
• prophylaxis for bacterial endocarditis
• empiric treatment for fever of unknown origin

Contraindications

• bacterial infections caused by:
  • Enterococcus
  • methicillin-resistant Staphylococcus aureus (MRSA)
  • Pseudomonas aeruginosa
• hyperbilirubinemic neonates, especially prematures

pregnancy category = b

safety in lactation = ?

Dosage

• pneumonia: 1 g IV/IM QD
• meningitis:
  • 2 g IV every 12 hours or 100 mg/kg/day IV (max 4 g)
• endocarditis/sepsis: 2 g IV QD
• gonorrhea: single dose 125 mg IM, 250 mg IM if treating PID
• children:
  • 50-75 mg/kg/day IV (max 2 g) divided every 12-24 hours
• neonates
  • gonococcal prophylaxis: 25-50 mg/kg single dose
  • gonococcal ophthalmia: 25-50 mg/kg QD for 7 days
• dilute in 1% lidocaine for IM use

Powder for injection: 250 & 500 mg, 1 & 2 g

Pharmacokinetics

• widely distributed to body tissues
  • gallbladder, lungs, bone, bile
  • good CSF penetration increased with inflamed meninges
  • crosses placenta
  • appears in breast milk
• peak serum concentrations 1-2 hours after IM administration
• protein binding 85-95%
• 1/2life 5-10 hours
• eliminated by kidneys & via biliary tract
• dosage adjustment with hepatic & renal dysfunction

elimination via kidney

elimination via liver

1/2life = 6-9 hours

protein binding = 94 % <70 ug/mL

protein binding = 84 % 300 ug/mL

protein binding = 58 % 600 ug/mL

elimination by hemodialysis = -

elimination by peritoneal dialysis = -

Antimicrobial activity

Gram positive

• Streptococcus
  • Streptococcus group A
  • Streptococcus group B
  • Streptococcus group C
  • Streptococcus group G
  • Streptococcus pneumonia
  • Streptococcus viridans, milleri
• Staphylococcus aureus (MSSA)
• Staphylococcus epidermidis (+/-)

Gram negative

• Neisseria gonorrhoeae
• Neisseria meningitidis
• Moraxella catarrhalis
• Haemophilus influenzae
• Haemophilus parainfluenzae
• Escherichia coli
• Klebsiella species
• Enterobacter species
• Serratia species
• Salmonella species
• Shigella species
• Proteus mirabilis
• Proteus vulgaris
• Providencia species
• Morganella species
  • Morganella morganii
• Citrobacter species
• Aeromonas species
• Acinetobacter species
• Pseudomonas aeruginosa (+/-)
• Pseudomonas cepacia
• Yersinia enterocolitica
• Yersinia pseudotuberculosis
• Pasteurella multocida
• Haemophilus ducreyi

Anaerobes

• Bacteroides melaninogenicus (+/-)
• Clostridium species
• Peptostreptococcus species

Adverse effects

• not common (1-10%)
  • hypersensitivity: rash, eosinophilia
  • pain at site of injection
  • thrombocytosis
  • leukopenia
  • diarrhea
  • elevation of serum transaminases & BUN
• uncommon (< 1%)
  • phlebitis, pruritus, fever/chills, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia, nausea/ vomiting, dysgeusia, headache, dizziness, moniliasis, vaginitis, diaphoresis, flushing elevation of serum bilirubin, alkaline phosphatase & creatinine, urinary casts
• other
  • cholelithiasis (9%)
  • sludge in gallbadder by US

• drug adverse effects of cephalosporins

Drug interactions

• Ca+2 & Ca+2-containing solutions or products cases of fatal reactions with Ca+2-ceftriaxone precipitates in the lungs & kidneys in both term & premature neonates
• Ca+2-containing solutions or products must not be administered within 48-hours of the last administration of ceftriaxone
• ceftriaxone & Ca+2-containing products may be used concomitantly in patients >28 days of age

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Test interactions

• false positive Coomb's test

Laboratory

• specimen:
  • serum
  • keep specimen on ice-water
  • centrifuge at 4 degrees C
  • remove cells as soon as possible
  • freeze at -70 degrees C until assayed
• methods: HPLC, MB

Mechanism of action

inhibition of bacterial cell wall synthesis

More general terms

• cephalosporin, 3rd generation

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=51800
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2656
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656515
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=59844
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=53056