Single Daily Dose Of Ceftriaxone Research Articles

Ceftriaxone prophylaxis in reconstructive esophageal surgery: 5 years of clinical experience

This study presents experience with the administration of intraoperative ceftriaxone prophylaxis in 85 patients who had major resective and reconstructive esophageal surgery. A total of 41 patients in whom the reconstructive procedures did not involve resective surgery received one intraoperative dose of ceftriaxone (250 mg to 1000 mg); another group of 44 patients who underwent resective, and reconstructive surgery received two intraoperative doses of ceftriaxone. In the latter group the doses were administered 30 minutes before transection of the viscera and before completion of the surgery. Because surgery was prolonged (3 to 10 hours) in these patients and was associated with operative blood loss of more than 1000 mL or 20% of the estimated blood volume, the second dose of antibiotic was given after control of active blood loss was achieved. After surgery, patients received a single daily dose of ceftriaxone for 5 or 6 days. The results obtained were satisfactory in each group of patients; one case of anastomotic leak was seen, but no case of wound infection was recorded. Based on these results, we suggest that the prophylactic administration of ceftriaxone be commenced intraoperatively and timed to achieve on optimal circulating concentration of the antibiotic when the clean operative wound inevitably becomes contaminated.

Ceftriaxone/Amikacin vs Ceftazidime/Amikacin as Empirical Therapy for Fever in Patients with Haematological Malignancy and Severe Granulocytopenia

To assess the economic outcomes produced when a conventional antibiotic treatment regimen requiring three administrations per day was replaced with a treatment regimen requiring only one daily administration, the efficacy, tolerability and cost of ceftazidime was compared with that of ceftriaxone (both drugs in combination with amikacin) for the empirical treatment of febrile granulocytopenic patients with haematological malignancy. 102 febrile patient-episodes were randomly assigned to receive ceftazidime (6g in three divided doses) or ceftriaxone (2g as a single daily dose), both in combination with amikacin. The response was evaluable in 94 patients (47 in each group). 75 (80%) patients had an absolute granulocyte count lower than 100/mm(3) at the onset of fever or during the first week of antibiotic therapy. 61 (64.9%) were affected by acute leukaemia. Multiple daily ceftazidime plus amikacin was effective in 33 of 47 (70.2%) patients, and single daily ceftriaxone plus amikacin in 31 of 47 (66%) patients (p > 0.2). Among patients successfully treated, median time to defervescence was 3.3 days (range 1 to 11) for ceftazidime plus amikacin and 4.5 days for ceftriaxone plus amikacin (range 1 to 15) [p = 0.14]; study drugs were continued for 12 (range 7 to 26) and 12.3 days (range 7 to 28), respectively. Our study demonstrated that single daily administration of ceftriaxone was as effective and well tolerated as multiple daily administration of ceftazidime when both were administered in combination with amikacin. Cost analysis showed that compared with the thrice daily regimen, administration of single daily doses of ceftriaxone for a 12-day treatment period would result in a net cost saving of $US392 (626 940 Italian lire).

Ceftriaxone as a Single Agent in Empirical Therapy of Unexplained Fever in Granulocytopenic Children with Solid Tumors

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.

Cost-effectiveness of ceftriaxone and amikacin as single daily dose for the empirical management of febrile granulocytopenic children with cancer.

In children undergoing anticancer chemotherapy, a granulocytopenic febrile episode is a life-threatening condition. Prompt initiation of empirical broad-spectrum antibiotics is essential to limit morbidity and mortality. To evaluate the cost-effectiveness of combination antibiotics consisting of a third generation cephalosporin and an aminoglycoside, a retrospective review of all febrile granulocytopenic patients admitted to our institution was conducted. Between June 1994 and August 1996, 183 febrile episodes in granulocytopenic children with cancer were empirically treated with ceftriaxone and amikacin in a single daily dose. 96/183 (52%) patients had absolute granulocyte count lower than 100/mm3 at the onset; 68 (37%) were affected by acute leukemia or lymphoma, 3 (1%) by chronic leukemia, 94 (51%) by solid tumors, and 21 (11%) patients underwent bone marrow transplantation. Ceftriaxone plus amikacin was effective in 135/183 (74%) patients with a median time to defervescence of 3 days (range 1-11). Economic evaluation (cost minimization analysis) was limited to the cost savings for nonreusable materials, and difference in direct drug costs in comparison with another combination regimen such as ceftazidime and amikacin. This analysis showed that compared to a 3 times daily regimen, administration of single daily doses of ceftriaxone would result in a net cost saving of US$ 11 (17,500 Italian liras) and US$ 65.6 (105,000 Italian liras) for a 1-day and a 6-day treatment period, respectively, for the treatment of a child of 30 kg body weight. Moreover, once daily therapy has the potential to lead to savings in the time of the nursing staff and may well contribute to an improved quality of life for febrile granulocytopenic children. For these reasons, in our department, ceftriaxone plus amikacin still remain the standard regimen for the empirical treatment of febrile granulocytopenic children with cancer.

A single daily dose of ceftriaxone for bacterial meningitis in adults: experience with 84 patients and review of the literature.

Although the pharmacokinetics of ceftriaxone allows its administration in a single daily dose, this practice is not standard in the treatment of bacterial meningitis. Herein, we review our experience and that of other investigators with this mode of therapy. We used a single daily dose of ceftriaxone (50 mg/[kg.d]; maximum, 4 g/d) for the treatment of bacterial meningitis in 84 adult patients. Meningitis was due to Neisseria meningitidis in 34 cases, to Streptococcus pneumoniae in 25, to Escherichia coli in three, to Klebsiella pneumoniae in two, to Haemophilus influenzae in two, to viridans streptococci in two, and to an unknown agent in 16. Eleven patients died, for an overall mortality of 13%; therapy failed in three additional cases. The mean trough levels of ceftriaxone in cerebrospinal fluid was 3.5 micrograms/mL; the median trough bactericidal titer at this site was 1:128. Both our experience and that in the literature suggest that a single daily dose is optimal when ceftriaxone is used for the treatment of bacterial meningitis.

Einmal tägliche Ceftriaxon-Kurzzeittherapie der akuten bakteriellen Meningitis bei Kindern: Resultate einer Schweizerischen Multizenterstudie. Teil I: Klinische Resultate

In a prospective Swiss multicenter study, 119 children (aged three weeks to 15.5 years) with acute bacterial meningitis were treated with single daily doses of ceftriaxone (100 mg/kg on days one and two and 60 mg/kg thereafter). All patients were randomly assigned to either short course (four, six, seven days) or full course (eight, 12, 14 days) therapy depending on whether they had contracted meningococcal, Haemophilus influenzae type b or pneumococcal meningitis. Bacteriological cure was obtained in 92 children who fully completed the study and in all the 20 culture-positive of the 27 children secondarily excluded from the study for failure to meet all bacteriological and initial safety criteria for continuation in protocol (secondary exclusions). Complete clinical recovery was noted in 105 of 119 patients (88%) and was as frequent in the short course (91%) as in the full course (89%), and as in the secondary exclusion (81%) group. All patients survived. At follow-up examination three to six months after hospital discharge only seven infants and seven children (11.8%), mostly those with poor presentation on admission (p = 0.0012), showed residual neurological sequelae. Side effects of antibiotic therapy were minor but more frequent, albeit not statistically significant (p = 0.065), in children receiving the full course therapy. The results of this study suggest that short course treatment of acute bacterial meningitis in children with single daily ceftriaxone monotherapy is as efficacious as full course therapy and at least as well tolerated.

Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: Results of a Swiss multicenter study. Part II: Bacteriological results

The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b.

Ceftriaxone Monotherapy for Bacterial Meningitis in Children

A total of 33 patients with bacterial meningitis were treated with single daily doses of ceftriaxone (CTR 100 mg/kg/day i.v.) for a median duration of 13 days. Pathogens isolated by culture and/or determined by latex agglutination were 15 Haemophilus influenzae b, 7 Neisseria meningitidis, 2 Streptococcus pneumoniae, 1 group B streptococcus, 2 Streptococcus viridans and 2 Staphylococcus epidermidis. In 4 cases a diagnosis of purulent meningitis could only be made by means of the inflammatory liquor parameters. All cerebrospinal fluid (CSF) drug levels even at the end of the dosing interval were at least 10-fold higher than the MICs of the respective bacterial isolates. The average penetration of CTR into the CSF was 6.6%. Within 12-46 h after the first dose, control spinal taps were performed. Cultures were sterile in all cases. Side effects encountered were diarrhea, exanthema, neutropenia and transient elevation of glutamic oxaloacetic transaminase, but none caused a change of therapy. One patient developed a biliary concrement. No patient died; 5 patients had prolonged fever (greater than 5 days), and 2 were left with persistent hearing deficiencies. CTR can be recommended as a safe and effective antibiotic agent for once daily treatment of bacterial meningitis in children.

Ceftriaxone monotherapy for severe bacteremic infections. Spanish Ceftriaxone Study Group.

We tested the efficacy of a single daily dose of ceftriaxone (active ingredient of Rocephin) for the treatment of severe bacteremic infections in 125 non-neutropenic adult patients. A single daily dose of ceftriaxone ranging from 1 to 4 g was given. Surgical procedures were performed if needed. Seventy-six (60.8%) were males and bacteremia was nosocomially acquired in 45 (36%). Microbiologically proven bacteremia was demonstrated in all patients. The most common microorganisms isolated were Escherichia coli (46 episodes), Streptococcus pneumoniae (17 episodes), Klebsiella pneumoniae, and Haemophilus influenzae, Serratia marcescens, Salmonella sp., and Staphylococcus aureus (9, 7, 6, 6, respectively). The urinary tract was the source of the bacteremia in 45 cases (36%), and the lower respiratory tract in 33 (26.4%). Mean duration of treatment was 10.8 days (range 3-21 days). One hundred and six patients (84.8%) recovered completely, 11 (8.8%) improved, but needed an alternative antibiotic treatment. An alternative treatment was also given to a patient whose condition had initially deteriorated. Seven patients (5.6%) died. Death was directly related to the infection in 2 cases. Three patients (2.4%) developed a superinfection, and 5 (4%) a severe (1 case) or mild (4 cases) adverse effect. In summary, a single daily dose of ceftriaxone proved to be useful for the treatment of selected severe bacteremic infections.

Ceftriaxone in chemoprophylaxis and therapy of urinary tract infections.

We analysed eight prospective randomized trials describing the use of ceftriaxone (Rocephin) in short-term prophylaxis in patients undergoing urologic surgery. The results of these trials show that chemoprophylaxis with ceftriaxone is effective. In the therapy of postoperative infections in urologic surgery the single daily dose of ceftriaxone represents a considerable advantage both regarding patients' compliance and clinical convenience. From March 1987 to January 1988, 25 patients with postoperative infections after urologic surgery were treated with ceftriaxone 1 g i.m. once daily. Quick resolution of signs and symptoms of infection occurred in all cases.

ONCE-DAILY CEFTRIAXONE FOR SERIOUS BACTERIAL INFECTIONS.

Investigators compared the efficacy of a single daily dose of ceftriaxone with therapy combining cefuroxime and gentamicin in 105 patients believed to

Once-daily administration of ceftriaxone in the treatment of meningitis and other serious infections in children.

Forty-three children (ten neonates, 15 infants and 18 older children) were treated with single daily doses of ceftriaxone (50 to 100 mg/kg) intravenously or intramuscularly for serious bacterial infections. The infections included meningitis (31 patients), brain abscesses (four patients), septicaemia (three patients), pleuro-pneumonia (two patients), septic arthritis and soft tissue phlegmona (three patients). No other antibacterial agents were used except in four patients with brain abscesses, in whom ceftriaxone was combined with ornidazole. The overall bacteriological cure rate was 98%, and sterilisation of the cerebrospinal fluid occurred in 27 of 28 patients (96%) with proven bacterial meningitis. Two patients died, three survived with severe neurological sequelae; one neonate required partial gut resection. A complete clinical cure was achieved in the remaining 37 patients. Only one treatment failure was directly related to the drug therapy. The only side effect noted were sterilisation of the gut with overgrowth of Candida albicans in 35% of neonates and infants, an prolonged fever in 13% of all patients. Ceftriaxone given in a 24-hourly regimen is convenient and highly effective in serious bacterial infections in children and is without significant toxicity.