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- Moraxella spp. - morganella morganii (= proteus morganii). - Neisseria gonorrhoeae (including penicillinase-producing strains), N.meningitidis. - Pasteurella multocida. - plesimonas shigelloides - Proteus mirabilis, P.vugaris. - providencia spp. - Salmonella spp. (including S.typhi). - Serratia spp. (including S.marcescens). - Shigella spp. - vibrio spp. (including V.cholera). - Yersina spp. (including y.enterocolitica). Anaerobic organisms: - Clostridium spp. (except C.difficile) - Fusobacterium spp. (except F.mortiferum and F.varium) - Peptococcus spp. Peptostreptococcus spp. Therapeutic indications: Treatment of pneumonia, septicemia, bacterial meningitis, abdominal infections (peritonitis, infections of the biliary and gastrointestinal tract) ,gonorrhea, bone and joints infections, skin and soft tissue infections, renal and urinary tract infections. Treatment of infections in patients with impaired defense mechanisms. Prophylaxis of pre-and post-operative infections. Pharmacokinetic properties: Ceftriaxone displays non-linear concentration-dependent protein binding, mainly binding to albumin. The plasma free (unbound) fraction of the drug increased from 4 to 17% over the concentration range of 500µg to 300mg/ml. Plasma Concentrations: Intravenous injection (bolus): A dosage of mg and 1.5 gm, administered intravenously as a bolus injection, results in a mean peak plasma concentration of 150 and 285µ g/ml respectively. Intravenous infusion over 30minutes: after a 30-minute intravenous infusion of 500mg , 1gm or 2gm a mean peak plasma concentration of 80, 150, or 200µg/ml. respectively, was achieved.
Intramuscular injection: After 1 hour the mean peak plasma concentration after intramuscular administration was half that after intravenous administration of and equivalent dose. The AUC after 24 hours were not significantly different, therefore bioavailability after intramuscular injection is 100%. Excretion: ceftriaxone is eliminated unchanged by the kidney and the liver, with 45-60 % of an intravenous dose of 500mg to 3g excreted in the urine (almost exclusively by glomerular filtration) within 24 hours. The remainder is metabolized in the intestinal tract after biliary excretion. The total plasma clearance is 0.8- 1.2 L/h, and increases with dose. The renal clearance is 9.5L/h. The elimination half- life in adults is approximately 6-9 hours. The half life dose not significantly with route of administration ,dose or after single or multiple doses. Pharmacokinetics in special clinical situations: The average elimination half-life is usually longer in patients over 75 year of age and in neonates, compared to the young adult group. As with all cephaosporins, a decrease in renal function in the elderly may lead to a small but significant increase in half-life . Dosage adjustment should not be necessary in elderly patients. The elimination half –life of ceftriaxone is only slightly to moderately affected in patients with decreased renal function, increased Biliary clearance compensates for loss of renal clearance, Patients with decreased hepatic function show an increase proportion of the drug excreted renally. Only in patients with simultaneous renal and hepatic dysfunction should the plasma concentration be monitored and the dose adjusted accordingly. Cerebrospinal fluid: Ceftriaxone can cross the meninges, a higher flux is observed across inflamed meanings compared to non-inflamed . Concentrations attained are approximately 5% of the simultaneous plasmas concentration.
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