Ceftriaxone (Ro 13-9904) therapy of serious infection

Abstract

Ceftriaxone (Ro 13-9904), a newly developed cephalosporin with a long halflife, was evaluated for efficacy and safety in 19 patients with serious infections. Underlying illnesses were present in 16 patients. Ceftriaxone was given intravenously every 12 h. Infections treated included gram-negative bacillary pneumonias (two cases), staphylococcal and streptococcal soft tissue-skeletal infections (six cases), spontaneous peritonitis (two cases), and complicated urinary tract infections (nine cases). Bacteremia was present in three patients. Microbiological and clinical cures were achieved in all but one case, although three patients with urinary infection had recurrences 6 weeks posttherapy. The only failure occurred in a patient with pneumonia who had a Pseudomonas aeruginosa isolated from sputum with an initial minimal inhibitory concentration of 4 ,uglml, but after 9 days of therapy, a repeat isolate had a minimal inhibitory concentration of 32 ,ug/ml. The minimal inhibitory concentrations for the other isolates ranged from <0.6 to 8.0 ,ug/ml. The mean peak plasma level of ceftriaxone was 99.9 ,ug/ml, whereas ceftriaxone levels obtained 12 h after a dose had a mean of 37.3 ,ug/ml. The only side effects noted were drug fever in one patient, phlebitis in two patients, and thrombocytosis in four patients.Cephalosporin antibiotics are widely used to treat serious infections because of the spectrum of activity and the relative safety compared with other types of antibiotics. Several newly developed cephalosporins have increased potency against Enterobacteriaceae while maintaining activity against streptococci and staphylococci. Ceftriaxone (Ro 13-9904) is a 2-aminothiazolyl methoxyimino cephalosporin which inhibits most gram-negative enteric bacilli and streptococci at concentrations of less than 1 ,ug/ml (3,5,12). It has a potential advantage over other recently discovered P-lactam antibiotics because of a contrast in pharmacokinetics. Ceftriaxone has a serum half-life of 8 h compared with 1 to 3 h for cefotaxime, cefoperazone, moxalactam, and other investigative third-generation cephalosporins (10). This prolonged serum half-life apparently is related to a high degree of protein binding and a different excretion pattern for ceftriaxone compared with the cephalosporins listed above (11,16). In an open trial, the safety and clinical and bacteriological efficacy of ceftriaxone therapy of serious bacterial infection at a dosage of 1.0 g twice a day were evaluated.(

Pharmacokinetics of Ceftriaxone in Pediatric Patients With Meningitis

“…2 Preliminary studies for the treatment of bacterial meningitis in neonates, infants, and children have been published (4). Clinical efficacy and tolerance studies in adults with serious bacterial infections have recently been published and have established ceftriaxone as an agent with a high degree of efficacy and a low incidence of toxicity (3,7). These reports support its selection as single drug therapy for a variety of clinical presentations.…”

Management of Infections Due to Antibiotic-Resistant Streptococcus pneumoniae

“…Since a variety of antimicrobial regimens were used in these patients, it is very difficult to draw any conclusions regarding single-agent therapy. However, most of the antibiotics administered to these patients were shown to achieve concentrations in synovial fluid, peritoneal fluid, or bone in excess of their MICs for penicillin-resistant isolates (21,26,72,98,104,123). In synovial fluid, ceftriaxone reaches a level of up to 66 to 100% of the concomitant levels in serum.…”

Intravitreal Ceftriaxone in a Rabbit Model

“…Groups of at least three rabbits were killed as described 0, 4,8,24, and 72 hours after injection. Groups of at least three rabbits were killed as described 0, 4,8,24, and 72 hours after injection.…”