Ceftriaxone - An update of its use in the management of community-acquired and nosocomial infections

Ceftriaxone is a parenteral third-generation cephalosporin with a long elimination half-life which permits once-daily administration. It has good activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci, Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. Although active against Enterobacteriaceae, the recent spread of derepressed mutants which hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases has diminished the activity of all third-generation cephalosporins against these pathogens necessitating careful attention to sensitivity studies. Extensive data from randomised clinical trials confirm the efficacy of ceftriaxone in serious and difficult-to-treat community-acquired infections including meningitis, pneumonia and nonresponsive acute otitis media. Ceftriaxone also has efficacy in other community-acquired infections including uncomplicated gonorrhoea, acute pyelonephritis and various infections in children. In the nosocomial setting, extensive data also confirm the efficacy of ceftriaxone with or without an aminoglycoside in serious Gram-negative infections, pneumonia, spontaneous bacterial peritonitis and as surgical prophylaxis. Outpatient use of ceftriaxone, either as part of a step-down regimen or parenterally, is a distinguishing feature of the data gathered on the agent over the last decade. The review focuses on new applications of the drug and its use in infections in which the causative pathogens or their resistance patterns have changed over the past decade. Ceftriaxone has a good tolerability profile, the most common events being diarrhoea, nausea, vomiting, candidiasis and rash. Ceftriaxone may cause reversible biliary pseudolithiasis, notably at higher dosages of the drug (greater than or equal to2 g/day); however, the incidence of true lithiasis is <0.1%. Injection site discomfort or phlebitis can occur after intramuscular or intravenous administration. Conclusions: As a result of its strong activity against S. pneumoniae, ceftriaxone holds an important place, either alone or as part of a combination regimen, in the treatment of invasive pneumococcal infections, including those with reduced beta-lactam susceptibility. Its once-daily administration schedule allows simplification of otherwise complex regimens in a hospital setting and has also contributed to its popularity as a parenteral agent in an ambulatory setting. These properties, together with a well characterised tolerability profile, mean that ceftriaxone is likely to retain its place as an important third-generation cephalosporin in the treatment of serious community-acquired and nosocomial infections.