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At least 19 recordsLinked to original sources
PubMed1990

Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility.

Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying.

Bile↗
PubMed1990

Concentrative biliary secretion of ceftriaxone. Inhibition of lipid secretion and precipitation of calcium ceftriaxone in bile.

The hepatic transport of ceftriaxone, a third-generation cephalosporin, was characterized in the rat and hamster; its effect on bile flow and bile acid-induced biliary lipid secretion was also measured. In anesthetized rats with biliary fistulae, the Tmax was about 5 mumol.min-1.kg-1, and in the hamster the Tmax was about 1 mumol.min-1.kg-1. The compound was not biotransformed. At high secretion rates, the concentration of cephalosporin in bile increased to 27 mmol/L, a concentration far exceeding the solubility product of its calcium salt [2 x 10(-6) (mol/L)2], which precipitated from bile. In the rat, ceftriaxone induced choleresis (22 microL/mumol ceftriaxone, the expected value for a dianionic compound). In the isolated perfused rat liver, ceftriaxone had a fractional hepatic extraction rate averaging 3%; the compound was concentratively secreted into bile, the bile-perfusate ratio ranging from 35-250. Ceftriaxone inhibited phospholipid and cholesterol secretion induced by endogenous or exogenous bile acids; the rate of inhibition was linearly proportional to the canalicular secretion rate of ceftriaxone. Hepatic transport of ceftriaxone had no influence on hepatic secretion of ursodeoxycholyltaurine. In contrast, the net hepatic transport of ursodeoxycholic acid, ursodeoxycholyltaurine, or cholyltaurine inhibited ceftriaxone transport in a dose-dependent manner. It is concluded that ceftriaxone and bile acids share a common mechanism for hepatic transport in the rat and also interact in the processes involved in biliary lipid secretion. Biliary secretion of unbiotransformed ceftriaxone occurs at high concentrations; secondary Ca2+ entry results in the formation of supersaturated canalicular bile and subsequent precipitation as a calcium salt in the biliary tract. These data explain the formation of biliary sludge that occurs in patients undergoing high-dose ceftriaxone therapy.

Animals↗
PubMed2005

Rifampicin+ceftriaxone versus vancomycin+ceftriaxone in the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis in an experimental rabbit model.

This study was planned to compare the efficacy of ceftriaxone+vancomycin with ceftriaxone+rifampicin in a rabbit model of penicillin and cephalosporin-resistant Streptococcus pneumoniae meningitis. Meningitis was induced by intracisternal inoculation of S. pneumoniae. After 18 h of incubation, Group 1 was given saline solution (control group), whilst Groups 2 and 3 were given ceftriaxone+vancomycin and ceftriaxone+rifampicin, respectively. Cerebrospinal fluid bacterial concentrations were measured at 0, 2, 12, 14 and 24 h after therapy was initiated. In the control group, bacterial growth was present at all time points, whereas no growth was observed in either the ceftriaxone+vancomycin group or the ceftriaxone+rifampicin group after 2 h of therapy. Ceftriaxone+rifampicin was found to be as effective as ceftriaxone+vancomycin in the treatment of penicillin-resistant S. pneumoniae meningitis in experimental rabbit model.

Animals↗
PubMed1989

[Comparative study of intravenous ceftriaxone followed by oral cefixime versus ceftriaxone alone in the treatment of severe upper urinary tract infections].

Cefixime is a new orally active cephalosporin. Its MICs and beta-lactamase stability are similar to those of the parenteral third generation cephalosporins. This trial was conducted to determine the effectiveness and safety of ceftriaxone as compared with a treatment where oral cefixime was given after a 4-day treatment with ceftriaxone in severe upper urinary tract infections usually requiring parenteral treatment during two weeks. In an open, controlled trial, 95 patients met the inclusion criteria; 48 received IV ceftriaxone 2 g daily during 4 days, followed by IM or IV ceftriaxone 1 g daily for 11 days; 47 patients were treated by IV ceftriaxone 2 g.o.d. during 4 days and then by oral cefixime 200 mg b.i.d. for 11 days. Clinical cure at the end of treatment was achieved in 44 patients in the cefixime group and 47 patients of the ceftriaxone group. Ten to 84 days after the end of treatment, the overall clinical cure and bacteriologic eradication rates for these patients were 74.3 per cent (29/39) for cefixime and 81 per cent (34/42) for ceftriaxone. Treatment failure occurred in two patients in the cefixime arm, one in a patient with renal atrophy and vascular stenosis and the other in an 86-year old diabetic and bed-ridden woman with an infection following the use of a urinary catheter. There were eight relapses or re-infections (about 20 per cent) in each group. Seven minor adverse events were seen in six patients treated with ceftriaxone: pain upon IM injection (3 cases), diarrhea (2 cases) associated in one case with a generalized rash for which treatment was discontinued, and nausea (one case). Laboratory changes in both groups were not noteworthy and without clinical relevance. These results suggest that it seems possible to propose new parenteral cephalosporins with conversion to the oral route on the 5th day using the same class of drugs in the treatment of severe upper urinary tract infections, excluding certain urological or vascular underlying conditions and provided that duration of treatment is adapted to the type of clinical setting. These data define more accurately the use of cefixime with respect to currently available drugs.

Administration, Oral↗
PubMed1991

Ceftriaxone-associated gallbladder sludge. Identification of calcium-ceftriaxone salt as a major component of gallbladder precipitate.

Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of the precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt.

Bile↗
PubMed1998

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.

Adolescent↗
PubMed1996

Effect of gentamicin dosing interval on efficacy of penicillin or ceftriaxone treatment of experimental endocarditis due to penicillin-susceptible, ceftriaxone-tolerant viridans group streptococci.

The efficacy of ceftriaxone or penicillin alone or combined with gentamicin at different dosing intervals was evaluated in experimental endocarditis due to a penicillin-susceptible, ceftriaxone-tolerant strain of Streptococcus sanguis I. The difference between monotherapy with ceftriaxone and procaine penicillin approached statistical significance (P = 0.052). Ceftriaxone combined with gentamicin administered as a single daily dose was less effective than was procaine penicillin combined with gentamicin administered in a single daily dose or in three divided doses.

Animals↗
PubMed1998

Comparative in vitro killing activities of meropenem, imipenem, ceftriaxone, and ceftriaxone plus vancomycin at clinically achievable cerebrospinal fluid concentrations against penicillin-resistant Streptococcus pneumoniae isolates from children with meningitis.

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 microg/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin. However, while the killing activity of imipenem was significantly greater than that of meropenem, no significant difference was observed between the activities of meropenem and ceftriaxone-vancomycin.

Anti-Bacterial Agents↗
PubMed1995

Isepamicin once daily plus ceftriaxone versus amikacin plus ceftriaxone in febrile neutropenic patients.

Isepamicin is a new aminoglycoside with in-vitro activity superior to amikacin. It is a poor substrate for the 6'-aminoacetyltransferase-I enzyme which inactivates amikacin and therefore organisms possessing this enzyme are not resistant to isepamicin. The aim of this study was to compare the efficacy and safety of co-administration of isepamicin once daily plus ceftriaxone to amikacin twice daily plus ceftriaxone to amikacin twice daily plus ceftriaxone in febrile neutropenic cancer patients. Febrile episodes in 235 patients (156 in isepamicin group and 79 in amikacin group) were treated in this study. They occurred in 218 different patients. Fifteen patients were enrolled twice and one three times. Response rates to the two treatment regimens for microbiologically documented episodes, clinically documented episodes and further unexplained fever were similar. Tolerance of the treatment regimens, as measured by serum creatinine levels, hypoaccousia and cutaneous allergy was also similar in both treatment groups. In conclusion, isepamicin given once daily when combined with ceftriaxone in the treatment of febrile episodes in neutropenic cancer patients was as effective and no more toxic than amikacin.

Adolescent↗
PubMedDate not supplied

Comparative study of three antimicrobial drugs protocol (Ceftriaxone, Gentamicin/Amikacin and Metronidazole) versus two antimicrobial drugs protocol (Ceftriaxone and Metronidazole) in cases of intra-abdominal sepsis.

BACKGROUND: Treatment of intra-abdominal sepsis with antibacterial drugs should be initiated as soon as possible diagnosis is made before surgery and continued in the post operative period, unless required to be changed (when there is no satisfactory clinical response). The ideal agent (s) and duration of therapy remains somewhat controversial. However, early experimental and subsequent clinical studies have indicated that the spectrum of chosen antibacterial activity must encompass both colonic aerobes and anaerobes including B. fragilis. There are a number of multi drug protocols that are used to treat intra-abdominal septic conditions. Empiric use of these protocols not only adds toxicity to already ill patient but therapy becomes costly and utilizes human resource, unnecessarily. AIM OF STUDY: To study the clinical efficacy of the treatment of intra-abdominal sepsis with protocol -A (Ceftriaxone, Metronidazole and aminoglycoside) versus protocol -B. (Ceftriaxone and Metronidazole). MATERIAL AND METHODS: This is a prospective randomized study conducted at NGMC, Nepalgunj, Nepal (2003-2004) on the patient attending for the treatment of intra-abdominal sepsis. Patients included in this study were of inflammation, obstruction with or without gangrene and perforation of appendix, small bowel and large bowel with localized or generalized peritonitis. These patients were managed surgically by- appendicectomy, closure of perforation, resection and anastomosis (R & A) and resection and proximal colostomy. Patients of large bowel obstruction without gangrene and small bowel gangrene were managed by R & A. These patients had significant faecal spillage at the surgical site as well as in the peritoneum. At the end of operation peritoneum and surgical site of all cases were washed with saline and povidone-iodine solution. They were put on one of the two protocols for post-operative treatment. A total 59 patients were included in this study. 32 cases were treated with protocol- A and rest 27 cases were treated with protocol- B. These cases were selected randomly for this study. Their outcome was compiled and compared under following headings: postoperative recovery, postoperative pyrexia, wound infection and dehiscence, anastomotic leak, residual abscess and cost of therapy. STATISTICAL ANALYSIS: Statistical analysis was done with the help of Chi square test. RESULT: Of the 59 patients, 32 were randomized to group I, 27 to group II. These groups were comparable in age, weight, sex and duration of therapy. Uneventful recovery was noted in 87.5 % (28/32) in -group I where as in 70.37% (19 /27) in-group II. Complications were observed in 12.5% in-group I where as 29.63 % in-group II. 10 patients in-group I where as 7 patients in -group II had surgical site infections (SSIs). All of these had superficial wound infection with/or without dehiscence of small portion of wound. A single case of residual abscess and anastomotic leak was observed. Postoperative pyrexia was noted in 8 patients in-group I where as in 6 patients in-group II. In pyrexia, temperature ranged from 99-104 0F. Finally except one case, rest of the cases recovered. On follow up after 3weeks, the cases recovered were doing well. CONCLUSION: At least three conclusions can be drawn from this study. Firstly protocol A is equally effective as protocol B. Secondly; it appears that combining aminoglycoside with Ceftriaxone therapeutically has no significant (P = 0.09) benefit over Ceftriaxone alone. Finally protocol A is less expensive in terms of total therapy than protocol B and can be used without fear even in subnormal functioning kidney.

Abdominal Abscess↗
PubMed2001

Comparative study of treatment with penicillin, ceftriaxone, trovafloxacin, quinupristin-dalfopristin and vancomycin in experimental endocarditis due to penicillin- and ceftriaxone-resistant Streptococcus pneumoniae.

The efficacy of different antibiotics was compared in an experimental model of aortic valve endocarditis in rabbits, using a serotype 19 strain of Streptococcus pneumoniae resistant to penicillin (MIC 12 mg/L) and ceftriaxone (MIC 12 mg/L). The results were compared with those of a control group, which received no treatment. One hundred and nineteen animals were treated with one of the following antibiotic regimens: im procaine penicillin G at a dosage of 300,000 U/kg weight/12 h (16 animals); iv trovafloxacin, 13.3 mg/kg/12 h (31 animals); iv ceftriaxone, 75 mg/kg/24 h (21 animals); iv vancomycin, 20 mg/kg/12 h (15 animals) and im quinupristin-dalfopristin, 30 mg/kg/8 h (20 animals). All the antibiotics used in this study proved to be efficient in reducing numbers of S. pneumoniae and in increasing the percentage of aortic vegetations that were rendered sterile compared with the control group. Penicillin at the dosage used in our study was capable of achieving serum concentrations two or three times greater than the MIC, thus demonstrating its effectiveness as an antibiotic for this endocarditis model. No significant difference was observed between the effects of vancomycin, quinupristin-dalfopristin and penicillin. Vancomycin proved to be more efficient than trovofloxacin in reducing the bacterial load and increasing the numbers sterilized. There was also a tendency for this antibiotic to be more effective than ceftriaxone in reducing the bacterial load of the vegetations. There was a statistically significant correlation between the weight of the vegetations and their bacterial load. In the light of these results, vancomycin and quinupristin-dalfopristin may be considered suitable alternatives to penicillin for the treatment of penicillin-resistant S. pneumoniae endocarditis.

Animals↗
PubMed1989

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.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1983

Comparative synergistic activity of ceftriaxone-piperacillin versus ceftriaxone-netilmicin.

The effect of combination of ceftriaxone with piperacillin or netilmicin was studied in a total of 119 clinical isolates using the checkerboard titration technique. The isolates included Pseudomonas aeruginosa, Staphylococcus aureus, enterococci and various Enterobacteriaceae. Synergy was observed in all Streptococcus faecalis strains with both combinations. Whereas the ceftriaxone/netilmicin combination showed a higher rate of synergy against Pseudomonas aeruginosa, the rate of synergy against Enterobacteriaceae was the same for the two combinations. In no instance was antagonism encountered.

Cefotaxime↗
PubMed2001

Fractional maximal effect method for in vitro synergy between amoxicillin and ceftriaxone and between vancomycin and ceftriaxone against Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae.

In the present study we assessed the use of a new in vitro testing method and graphical representation of the results to investigate the potential effectiveness of combinations of amoxicillin (AMZ) plus ceftriaxone (CRO) and of CRO plus vancomycin (VAN) against strains of Streptococcus pneumoniae highly resistant to penicillin and cephalosporins (PRP strains). We used the fractional maximal effect (FME) method of time-kill curves to calculate adequate concentrations of the drugs to be tested rather than relying on arbitrary choices. The concentrations obtained, each of which corresponded to a fraction of the maximal effect, were tested alone and in combination with the bacterial strains in a broth medium. Synergy was defined as a ratio of observed effect/theoretical effect, called FME, of greater than 1, additivity was defined as an FME equal to 1, and antagonism was defined as an observed effect lower than the best effect of one of the antibiotics used alone. The area between antagonism and additivity is the indifference zone. The well-known synergy between amoxicillin and gentamicin against a reference strain of Enterococcus faecalis was confirmed, with a best FME equal to 1.07. Two strains of PRP, strains PRP-1 and PRP-2, were studied. The MICs for PRP-1 and PRP-2 were as follows: penicillin, 4 and 16 microg/ml, respectively; AMZ, 2 and 8 microg/ml, respectively, CRO, 1 and 4 microg/ml, respectively; and VAN, 0.5 and 0.25 microg/ml, respectively. For PRP-1 the best FME for the combination AMZ-CRO was 1.22 with drug concentrations of 1.68 mg/liter for AMZ and 0.17 mg/liter for CRO; the best FME for the combination VAN-CRO was 1.75 with VAN at 0.57 mg/liter and CRO at 0.17 mg/liter. For PRP-2 the best FME obtained for the combination AMZ-CRO was 1.05 with drug concentrations of 11.28 mg/liter for AMZ and 0.64 mg/liter for CRO; the best FME obtained for the combination VAN-CRO was 1.35 with VAN at 0.25 mg/liter and CRO at 1.49 mg/liter. These results demonstrated the synergy of both combinations, AMZ-CRO and VAN-CRO, against PRP strains at drug concentrations achievable in humans. Consequently, either of the combinations can be proposed for use for the treatment of PRP infections.

Amoxicillin↗
PubMed2003

Rifampin followed by ceftriaxone for experimental meningitis decreases lipoteichoic acid concentrations in cerebrospinal fluid and reduces neuronal damage in comparison to ceftriaxone alone.

Rifampin (RIF) releases smaller quantities of lipoteichoic acids (LTAs) from Streptococcus pneumoniae than ceftriaxone (CRO). Due to the rapid development of resistance, RIF cannot be used as a single agent for therapy of bacterial meningitis. For this reason, we compared the effect of treatment with RIF followed by treatment with CRO (RIF-CRO) or the effect of treatment with clindamycin (CLI) followed by treatment with CRO (CLI-CRO) to that of CRO alone on the concentrations of LTAs and teichoic acids in vitro. The effects of RIF-CRO on LTA concentrations in cerebrospinal fluid (CSF) and on neuronal injury were investigated in a rabbit model of S. pneumoniae meningitis. In vitro, bacterial titers were effectively reduced by CRO, RIF-CRO, and CLI-CRO when each drug was used at 10 micro g/ml. The levels of release of LTAs after the initiation of therapy were lower in RIF-CRO- and CLI-CRO-treated cultures than in cultures treated with CRO alone (P < 0.05 from 3 to 12 h after initiation of treatment). Similarly, in rabbits, the increase in the amount of LTAs in CSF was lower in RIF-CRO-treated animals than in CRO-treated animals (P = 0.02). The density of dentate apoptotic granular cells was lower after RIF-CRO therapy than after CRO therapy (medians, 58.4 and 145.6/mm(2), respectively; 25th quartiles, 36.3 and 81.7/mm(2), respectively; 75th quartiles, 100.7 and 152.3/mm(2), respectively; P = 0.03). Therefore, initiation of therapy with a protein synthesis-inhibiting antibacterial and continuation of therapy with a combination that includes a beta-lactam may be a strategy to decrease neuronal injury in bacterial meningitis.

Animals↗
PubMed1986

[Bacteriological, pharmacokinetic and clinical evaluations of ceftriaxone in the pediatric field. Pediatric study group of ceftriaxone].

UNLABELLED: Ceftriaxone (CTRX), a new injectable cephem antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in the pediatric field by a study group organized with pediatricians from all over the country. The following are a summary of the results of the evaluation. Antibacterial effects: The inhibition of growth was attained for over 90% of strains of K. pneumoniae, H. influenzae and Salmonella spp. at the concentration of 0.10 micrograms/ml and of strains of S. pneumoniae and E. coli at the concentration of 2.0 micrograms/ml. The CTRX was proved to have excellent antibacterial effects. Absorption and excretion: Thirty minutes after one shot intravenous administration with 10, 20, 40 and 50 mg/kg of CTRX, its serum levels were 73, 124, 169 and 190 micrograms/ml, respectively, a clear tendency of dose-response relationship being noticed. The serum levels decreased only gradually and stayed as high as 10 to 20 micrograms/ml even after 12 hours. The half-lives of the drug were 5.5, 6.3, 6.0 and 4.7 hours for the 4 different dose levels, respectively. Following the intravenous injection with 10, 20 and 40 mg/kg, the urinary excretion rates were 55, 52 and 54%, respectively. Following the one shot intravenous administration or by the drip infusion for 30 minutes with about 50 mg/kg, CTRX levels in the cerebrospinal fluid ranged from 1 to 20.3 micrograms/ml in case of purulent meningitis (5 to 10 micrograms/ml in most cases). CLINICAL RESULTS: A total of 322 cases was enrolled. The efficacy of CTRX was evaluated in 295 cases out of the 322, excluding drop-outs and the cases which did not meet the protocols. The clinical efficacy rate was 94% of 191 cases where the causative bacteria were identified, CTRX being "excellent" in 108 cases and "effective" in 72. In the remaining 104 cases where the causative bacteria were not identified, the efficacy rate was 92%, CTRX being "excellent" in 42 cases and "effective" in 54. Furthermore, the efficacy rate was 89% of 18 cases infected with more than one kind of bacteria. The drug showed "excellent" or better effectiveness in 88% of 75 cases which had not responded to other antibiotics. Bacteriologically, 174 out of 216 strains (93%) which were judged to be causative bacteria disappeared with the use of CTRX. Eighty-five percent of 53 strains which had not responded to other antibiotics disappeared by the CTRX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗