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Randomized comparison of ceftriaxone versus ceftriaxone plus amikacin for the empirical treatment of infections in patients with altered host defense: microbiological and clinical evaluation.

Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin. In the ceftriaxone-treated group, 60 out of 143 febrile episodes were microbiologically documented, while in the group receiving the combination therapy, there were 32 out of 140 (p = 0.0007). Gram-positive microorganisms were more common than gram-negative ones, accounting for 59 of the 101 isolated bacteria. The ceftriaxone regimen appeared to have a response rate comparable to the combination regimen (73.91 vs. 78.88%). Superinfections occurred under both regimens.

Adult

Netilmicin plus ceftriaxone versus amikacin plus ceftriaxone in the treatment of infections in granulocytopenic patients.

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Adult

Relationship between ceftriaxone use and resistance of Enterobacter species.

We investigated the relationship between the amount of ceftriaxone used in our hospital and the evolution of the rate of resistance among Enterobacter species isolates. We reviewed all positive microbiological reports for Enterobacter species and the pharmacy records for the ceftriaxone consumption during four semesters over 4 consecutive years. The resistance to ceftriaxone among Enterobacter species rose from 10 to 27% while the amount of ceftriaxone used almost trebled during the study period. In order to investigate the relationship between the use of an antibiotic and the emergence of resistance to it, we studied the development of ceftriaxone resistance in Enterobacter species and the use of this drug at the Centre Hospitalier Universitaire Vaudois (CHUV) each year between 1983 and 1986. The consumption of ceftriaxone more than doubled between 1983 and 1984, and since then has increased only slowly. Within 2 years the rate of Enterobacter species resistance to ceftriaxone has jumped from about 10% between 1983 and 1985 to 27% in 1986. As no particular modification in the preventive methods of hospital hygiene and no epidemics occurred during the period of our study, we conclude that the increase in the prescribing of ceftriaxone probably played a central role in the increased number of resistant strains of Enterobacter species.

Ceftriaxone

In vivo studies of biliary ceftriaxone excretion and solubility in guinea pig hepatic bile.

Ceftriaxone (CFTX), a third-generation cephalosporin, has occasionally been reported to produce biliary sludge composed of its calcium salt. We performed studies in guinea pigs to (1) investigate the hepatic route of CFTX excretion, (2) determine ceftriaione's effects on bile flow and composition, and (3) quantify the solubility and metastability of the calcium salt as a function of administered dose. Our results show that even at high doses ceftriaxone has only minimal effects on bile flow and biliary electrolyte secretion, either alone or in combination with bile salt (taurocholate) infusion. A significant increase in total calcium concentration was observed without change in free Ca2+ concentration, this is compatible with formation of a soluble calcium salt of ceftriaxone, as previously demonstrated in vitro. Ion products of Ca2+ and ceftriaxone as high as 3.5 times the solubility product constant without crystal formation were observed, confirming the presence of a metastable state for the calcium salt of ceftriaxone in the living animal. Biliary excretion of ceftriaxone inhibited excretion of indocyanine green, suggesting that ceftriaxone and indocyanine green share a common anionic excretory pathway in this species.

Animals

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.

Adult

Effects of diclofenac on ceftriaxone pharmacokinetics in humans.

The effects of diclofenac, a nonsteroidal antiinflammatory drug, on the biliary and urinary excretion of ceftriaxone were evaluated in subjects with a T drain in the common bile duct. The kinetic study was carried out on the sixth postoperative day of treatment with ceftriaxone alone (2 g intravenously; group 1) or ceftriaxone combined with diclofenac (50 mg every 12 h orally from postoperative days 3 to 6; group 2). A significant increase in the elimination half-life of ceftriaxone was observed in group 2 patients. Diclofenac caused a significant rise in ceftriaxone biliary excretion. This increase was not sufficient to balance the significant deficit of urinary excretion of ceftriaxone.

Aged

Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

Humans

Cefoperazone versus ceftriaxone monotherapy of nosocomial pneumonia.

Ceftriaxone and cefoperazone monotherapy was compared in a multicentered, randomized, nonblinded, prospective study of patients with nosocomial pneumonia. These antibiotics were equally effective, with an overall successful treatment rate of 48 (80%) of 60 for the cefoperazone-treated patients and 35 (70%) of 50 for the ceftriaxone-treated patients. Patients with nursing-home-acquired pneumonia had similar bacterial pathogens and an almost identical cure rate to those patients with hospital-acquired infection. There was no statistical difference in the incidence of side effects of superinfections. The development of secondary pneumonia with resistant bacteria was low, 3% with cefoperazone and 4% with ceftriaxone. When antibiotic, administrative, and laboratory costs were calculated, cefoperazone was slightly less expensive than ceftriaxone. Both cefoperazone and ceftriaxone are effective therapy for the treatment of nosocomial pneumonia.

Adult

Failure of ceftriaxone in the treatment of acute brucellosis.

In an open, multicenter study conducted in Israel in 1989, 18 patients with acute brucellosis were randomized to receive either less than or equal to 2 g of intramuscularly administered ceftriaxone daily for at least 2 weeks or doxycycline for 4 weeks plus streptomycin for 2 weeks. All 10 patients treated with the combination of doxycycline plus streptomycin responded promptly, and their infections did not relapse during 6 months of follow-up. Of eight patients treated with ceftriaxone, six did not respond initially; when ceftriaxone was replaced by the combination of doxycycline and streptomycin, patients responded immediately. No relapses of infection were observed in these patients during follow-up. One patient who received ceftriaxone responded and remained well at the end of 6 months of follow-up, and one patient who initially responded to therapy with this drug experienced relapse of infection within 3 weeks but recovered when the doxycycline/streptomycin regimen was initiated. We conclude that despite encouraging data from in vitro studies and promising clinical studies, 2 g of ceftriaxone administered im daily should not be considered appropriate therapy for brucellosis.

Acute Disease

Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery.

The pharmacokinetics and tissue penetration of ceftriaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied. The patients were scheduled for elective noncardiac thoracic surgery. Adequate levels in serum (higher than or equal to the MIC for 90% of isolates of Staphylococcus aureus, Streptococcus spp., Escherichia coli, Haemophilus influenzae, and Klebsiella pneumoniae) were found for all patients throughout the surgical procedures. Mean maximal (5-min) and final (24-h) ceftriaxone levels in serum were 157 +/- 42 and 8.6 +/- 4.5 mg/liter, respectively. The beta-phase elimination half-life was 8.6 +/- 3 h, the plasma clearance was 18.4 +/- 6.25 ml/min, and the apparent volume of distribution at steady state was 0.21 +/- 0.07 liters/kg. At the time of the thoracotomy, the ceftriaxone concentrations were 13.5 +/- 7.8 micrograms/g in thoracic wall fat and 27 +/- 9 micrograms/g in lung tissue. At the time of closure, the ceftriaxone concentration was 15 +/- 9 micrograms/g in thoracic wall fat. During the different steps of the surgical procedures, 100% of patients had adequate levels in tissue (higher than or equal to the MIC for 90% of isolates of Streptococcus spp., E. coli, H. influenzae, and K. pneumoniae). For S. aureus, 90 to 100% of patients had adequate tissue ceftriaxone levels.

Adult

The "Mannit-Ceftriaxon" preparation for elective colorectal surgery.

Authors report their experiences with evaluating the clinical course of 45 patients undergoing elective colorectal surgery. Patients were divided into three groups, depending on the type and method of preparation to operation. The 140 patients in the first group received according to the "traditional" preparation purgatives, enemas, and mycerine + metronidazole prophylaxis. The preparation of the 160 patients involved in the second group was performed by giving mannit solution (10%) orally 12 hours prior to surgery, and a single dose of 2 g ceftriaxon (Rocephin, Hoffman-La Roche) intravenously 2 hours preoperatively. The preparation for the 150 patients enrolled into the third group was done also by giving mannit solution orally, and for antibiotic prophylaxis 2 g ceftriaxon was given intravenously as in the second group, but an additional 500 mg metronidazole was also given at the same time as the ceftriaxon intravenously. The evaluation of the cases proves, that the mannit + ceftriaxon method warrants satisfactory protection for colorectal surgery, and the necessary time interval is only 12 hours. The rate of septic complications and septic death was higher in the first, traditionally pretreated group, than in the other two. The CTX + metronidazole combination used in the third group was not superior to the administration of ceftriaxon alone.

Aged

Evaluation of treatment with single-dose ampicillin/sulbactam with probenecid or ceftriaxone in patients with uncomplicated gonorrhea.

This study compared ampicillin/sulbactam plus probenecid with ceftriaxone for treatment of uncomplicated gonorrhea. Of the 297 men and women who were enrolled and randomized to receive either ampicillin/sulbactam (1.0 g/0.5 g) with probenecid (1 g) or ceftriaxone (0.25 g), 274 patients were evaluable. Both ampicillin/sulbactam and ceftriaxone were administered by intramuscular injections. Patients were gonococcal contacts, had positive culture results for Neisseria gonorrhoeae, or had clinical evidence of gonorrhea. Specimens for gonococcal cultures were collected from the cervix (female patients), urethra, rectum, and pharynx at pretreatment and test-of-cure visits. The presence of N. gonorrhoeae and a test-of-cure visit were required for drug efficacy analysis. Of the 274 evaluable patients, 195 (71.2%) had positive culture results for N. gonorrhoeae. Cure was achieved in 93 (94.9%) of 98 patients receiving ampicillin/sulbactam with probenecid and in 96 (99.0%) of 97 patients receiving ceftriaxone. Penicillinase-producing N. gonorrhoeae strains were found in 21 (10.8%) patients; these were eradicated by either ampicillin/sulbactam with probenecid (N = 9) or ceftriaxone (N = 12). Overall, the two drug regimens were very well tolerated and no serious adverse effects were noted. Ampicillin/sulbactam with probenecid may be useful as single-dose therapy in patients with uncomplicated genitorectal gonorrhea.

Adolescent

Oral cefixime versus intramuscular ceftriaxone in patients with uncomplicated gonococcal infections.

A randomized trial was conducted to compare cefixime (400 mg or 800 mg single oral dose) with ceftriaxone (250 mg single intramuscular dose) in terms of efficacy and safety for the treatment of uncomplicated Neisseria gonorrhoeae urethritis or cervicitis. Of 75 men and 150 women screened, 187 had positive culture results for N. gonorrhoeae. The course of treatment was evaluable in 155 cases (59 men, 96 women). Bacteriologic eradication was evident in 97% (105 out of 108) of the patients treated with cefixime and in 100% (47 out of 47) of the patients treated with ceftriaxone. N. gonorrhoeae was eliminated at 98% (143 out of 146) and 100% (72 out of 72) of the infection sites in the respective treatment groups. Of the 187 isolates, 8 were penicillinase-producing (PPNG) and 20 had high-level tetracycline resistance (TRNG). The cefixime and ceftriaxone MIC90 for all 187 study isolates was 0.008 micrograms/ml. The adverse clinical experiences reported by the patients treated with cefixime (10%) were self-limiting; no adverse experiences occurred in the patients treated with ceftriaxone. Cefixime was as well tolerated and efficacious as ceftriaxone in the treatment of the patients with uncomplicated N. gonorrhoeae urethritis or cervicitis reported here.

Administration, Oral

Single-dose oral temafloxacin versus parenteral ceftriaxone in the treatment of gonococcal urethritis/cervicitis.

Temafloxacin is an oral fluoroquinolone with potent in vitro activity against Neisseria gonorrhoeae. The efficacy and safety of a single dose of temafloxacin were compared with ceftriaxone, the current treatment of choice for gonorrhea, in a randomized, multicenter study. A total of 421 patients with uncomplicated gonococcal urethritis or cervicitis were randomly assigned to receive a single oral dose of temafloxacin 200 mg (n = 63) or 400 mg (n = 175), or a single intramuscular injection of ceftriaxone 250 mg (n = 183). In evaluable patients, bacteriologic cure rates were greater than 99% for both temafloxacin and ceftriaxone recipients. Corresponding clinical cure rates were 93.6% and 94.6%, respectively. Both regimens were well tolerated. A single oral dose of temafloxacin appears to be as safe and effective as injectable ceftriaxone in the treatment of uncomplicated gonococcal urethritis or cervicitis.

Administration, Oral

Comparison of cefotaxime with ceftriaxone given intramuscularly 12-hourly for community-acquired pneumonia.

Cefotaxime 1 g intramuscularly (i.m.) 12-hourly was compared with ceftriaxone 1 g i.m. 12-hourly in adult patients requiring hospitalization with uncomplicated community-acquired pneumonia. Fifty-two patients were enrolled and two were subsequently withdrawn, leaving 50 patients who completed the study; 23 received cefotaxime and 27 received ceftriaxone. Clinical cure was achieved in 49 of the 50 patients (98%). One treatment failure occurred in a patient who received ceftriaxone. The only significant pathogen isolated from the pretreatment sputum cultures was Streptococcus pneumoniae (50%). All isolates were sensitive to both drugs. Cefotaxime 1 g i.m. 12-hourly was as effective as ceftriaxone in the treatment of patients with uncomplicated community-acquired pneumonia requiring hospital admission.

Adult

Comparison of the efficacy and adverse effect profile of cefotaxime and ceftriaxone in ICU patients with susceptible infections.

In a prospective randomized double-blind trial, the efficacy and safety of cefotaxime and ceftriaxone were compared in intensive care unit (ICU) patients with serious infections requiring systemic antimicrobial therapy. Patients were randomly assigned to receive either cefotaxime 1 g i.v. t.i.d. or ceftriaxone 2 g every 24 hr. Clinical and bacteriologic assessments were made before treatment, at 48 hr and 5 days during treatment, and 48 hr after treatment. At the time of reporting, a total of 34 patients had been entered into the trial, 27 of whom were evaluable; 23 patients (85%) completed a minimum of 5 days antibiotic treatment. At the end of treatment, using current statistics 67% of cefotaxime and ceftriaxone patients demonstrated clinical cure or improvement. Bacteriologic responses appeared greater in the cefotaxime group (55% vs 42%). The incidence of adverse effects, which were usually minor, was similar in each group. From these preliminary results, it would appear that at the doses used in this study, cefotaxime and ceftriaxone are equally effective in the treatment of infections in the ICU.

Adolescent

Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone.

STUDY OBJECTIVE: To determine the outcome of outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. DESIGN: Prospective consecutive cohort study. SETTING: Urban emergency department. PATIENTS: Five hundred three infants 28 to 89 days of age with temperatures greater than or equal to 38 degrees C who did not appear ill, had no source of fever detected on physical examination, had a peripheral leukocyte count less than 20 x 10(9) cells/L, had a cerebrospinal fluid leukocyte count less than 10 x 10(6)/L, did not have measurable urinary leukocyte esterase, and had a caretaker available by telephone. Follow-up was obtained for all but one patient (99.8%). INTERVENTION: After blood, urine, and cerebrospinal fluid cultures had been obtained, the infants received 50 mg/kg intramuscularly administered ceftriaxone and were discharged home. The infants returned for evaluation and further intramuscular administration of ceftriaxone 24 hours later; telephone follow-up was conducted 2 and 7 days later. RESULTS: Twenty-seven patients (5.4%) had a serious bacterial infection identified during follow-up; 476 (94.6%) did not. Of the 27 infants with serious bacterial infections, 9 (1.8%) had bacteremia (8 of these had occult bacteremia and 1 had bacteremia with a urinary tract infection), 8 (1.6%) had urinary tract infections without bacteremia, and 10 (2.0%) had bacterial gastroenteritis without bacteremia. Clinical screening criteria did not enable discrimination between infants with and those without serious bacterial infections. All infants with serious bacterial infections received an appropriate course of antimicrobial therapy and were well at follow-up. One infant had osteomyelitis diagnosed 1 week after entry into the study, received an appropriate course of intravenous antimicrobial therapy, and recovered fully. CONCLUSIONS: After a full evaluation for sepsis, outpatient treatment of febrile infants with intramuscular administration of ceftriaxone pending culture results and adherence to a strict follow-up protocol is a successful alternative to hospital admission.

Ambulatory Care