Ceftriaxone• 3rd generation cephalosporins-have enchanced activity against gram-negatice bacili• Must be used with caution as they are associated with collateral damage that means induction and

spread of antimicrobial resistance• Effective and safe agent used for all types of osteomyelitis• active against most of the causative organisms• once-daily dosing has made outpatient therapy feasible for most patients• Has longest half-life of any cephalosporin which permits once a day dosing• High level of the drug can be achieved in blood and CSF• Effective against genital, anal and pharyngeal penicillin-resistant Nisseria gonorrhoeae• This drug is excreted in bile and may be used in patients with renal insufficiency• Has good penetration into bone• third-generation cephalosporin ceftriaxone may not be as effective against Staphylococcus aureus as

other agents, its long half-life allows for once-daily administration, which would be advantageous in at-home therapy

• the minimal inhibitory concentration for ceftriaxone is more than that for cefazolin (1st generation). Despite this difference, it concluded that ceftriaxone is effective in the treatment of S. aureus osteomyelitis.

Contraindications- 1.should not be used in those with an allergy2.should not be used in hyperbilirubinemic neonates, particularly those who are premature(displaces bilirubin from albumin binding sites)3.concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days)

Mechanism of Action-• inhibits bacterial cell wall synthesis by means of binding to the penicillin-binding proteins (PBPs)• inhibition of PBPs would in turn inhibit the transpeptidation step in peptidoglycan synthesis which is

required for bacterial cell walls (bacteriocidal)

ADR - 1.may precipitate in bile, causing biliary sludge and gallstones, especially in children2.may cause allergic reactions3. local irritation at the injections site, rash4.diarrhea5. Hypoprothombinaemia and bleeding are specific side-effects.6.Haemolysis 7.post renal failure in children

Goals of treatment & which antibiotic useful• Antibiotic treatment should be based on the identification of pathogens from bone

cultures at the time of bone biopsy or debridement• Prophylactic treatment with the bead pouch technique has been suggested in open

fractures to reduce the risk of infection, with systemic antibiotics supplemented with antibiotic beads compared to using systemic antibiotics alone

• Oral antibiotics that have been proven to be effective include clindamycin, rifampin, trimethoprim-sulfamethoxazole, and fluoroquinolones

• Empirical therapy is necessary when it is not possible to isolate organisms from the infection site. Hospital-acquired infections are usually derived from methicillin-resistant staphylococci. Infections contracted outside the hospital are often polymicrobial with the presence of gram-negative bacteria

• Parenteral antibiotics should be administered for several weeks, often requiring patients to remain in the hospital for an extended duration

• Rifampin must always be used in combination with other antibiotics for prosthesis infections because it acts on the biofilm and avoids recurrence. Infection may recur if rifampin is not used within a few weeks to a month of treatment

• Suppressive antibiotic therapy should also be directed by bone culture and is given orally when surgery is contraindicated. Good bioavailability, low toxicity, and adequate bone penetration are important factors in treatment. If the infection recurs after 6 months of suppressive antibiotic treatment, a new, lifelong regimen of suppressive therapy may be tried

Aduts dose- 1-2 g/day IV/IM in single daily dose or divided q12hr for 4-14 days, depending on type and severity of infection

Pediatric dose- <12 years: 50-75 mg/kg/day IV/IM in single daily dose or divided q12hr >12 years: 1-2 g/day IV/IM in single daily dose or divided q12hr for 4-14 days, depending on type and severity of infection

References

• http://www.ncbi.nlm.nih.gov/pubmed/1918220

• http://www.aafp.org/afp/2000/0415/p2474.html

• Lippincotts Illustrated Pharmacology 5th edition