Administration Of Ceftriaxone Research Articles

Short-Chain Fatty Acid and Organic Acid Concentrations in Feces of Healthy Human Volunteers and Their Correlation with Anaerobe Cultural Counts during Systemic Ceftriaxone Administration

Short-chain fatty acid (SCFA) and organic acid concentrations and (an)aerobe cultural counts were determined simultaneously in fresh feces from 10 human volunteers before, during, and after 5 days of single-dose ceftriaxone administration. The changes and the correlation coefficients between these variables were tested to be significant (P less than 0.05). to investigate whether significant changes in the intestinal microflora could be predicted by significant changes in SCFA/organic acid concentrations. Multivariate analysis was used with the same objective. Significant decreases in most SCFA, total SCFA (0.01 less than P less than 0.02), and pyruvic acid (0.02 less than P less than 0.05) concentrations in feces were found on day 3 of treatment and also on day 5, with the exception of the pyruvic acid concentrations. Lactic acid concentrations, however, were significantly increased (0.01 less than P less than 0.02) on day 5. All anaerobic cultural counts were significantly decreased (P less than 0.05) on days 3 and 5 of treatment except those for Clostridium difficile agar, which were only decreased on day 5. Highly significant correlations were found on day 3 between the total anaerobe counts (P less than 0.001), the Bacteroides counts (P less than 0.001), and propionic acid, of which the latter had a predictive value during treatment. The results of multivariate analysis were significant but did not have a predictive value. From this study we can conclude that propionic acid concentrations during ceftriaxone treatment in healthy volunteers have a predictive value for the Bacteroides cultural counts. The results of this study must be confirmed by those from patients treated with ceftriaxone.

Cerebrospinal Fluid Endotoxin Levels in Children with H. influenzae Meningitis before and after Administration of Intravenous Ceftriaxone

Total, cell-free, and cell-bound endotoxin and bacterial density were measured in cerebrospinal fluid (CSF) of 22 children with Hemophilus influenzae meningitis. Also the effect of ceftriaxone on CSF endotoxin levels was investigated in eight patients by reexamining their CSF 2-6 h after the initial dose. Initial CSF bacterial density correlated with initial CSF endotoxin levels (P less than .001). Ceftriaxone induced a marked increase of free endotoxin in CSF, from an initial (mean +/- SE) 0.75 +/- 0.21 to 1.29 +/- 0.23 log10 ng/ml (P less than .01). This increase correlated positively with the number of bacteria killed in the CSF (P less than .01). The increase in free endotoxin was associated with an increase in mean CSF lactate levels from 8.5 to 9.7 units/l (P less than .05) and mean lactate dehydrogenase levels from 102 to 180 mmol/l (P less than .02) and a decrease in mean CSF glucose from 1.17 to 0.46 mmol/l (P less than .05). Initial CSF total endotoxin concentrations correlated both with the Herson-Todd clinical severity score (P less than .001) and with the number of febrile hospital days (P less than .001). These findings suggest that highly bactericidal agents initially lead to release of free endotoxin from gram-negative organisms into CSF, with associated enhanced inflammatory response by the host.

Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis.

By use of an experimental lapin model, the effect of ceftriaxone therapy on inflammation during Hemophilus influenzae type b (Hib) meningitis was evaluated. Meningitis was induced by intracisternal inoculation of 2 x 10(4) to 2 x 10(5) colony-forming units of Hib. Administration of ceftriaxone 6 h after infection provoked rapid bacterial lysis associated with greatly increased concentrations of bacteria-free endotoxin (lipooligosaccharide) and tumor necrosis factor alpha (TNF) in the cerebrospinal fluid (CSF). CSF TNF activity peaked 2 h after initiation of antibiotic therapy (24.4 +/- 2 ng/ml), was significantly higher than that in untreated controls (1.4 +/- 1.1 ng/ml; P less than .05), and was associated with a substantially increased inflammatory response as reflected by higher CSF white blood cell count (24,500 +/- 8,151 vs. 1,920 +/- 644 in untreated controls; P less than .05), lower glucose, and higher protein and lactate concentrations. Simultaneous administration of dexamethasone with antibiotic therapy resulted in a significant reduction in CSF TNF activity that was associated with a substantial reduction in CSF white blood cell count. These data suggest that initiation of ceftriaxone therapy in experimental Hib meningitis exacerbates the meningeal inflammatory response, which can be modulated by concurrent dexamethasone administration.

Use of -Lactamase-Producing Anaerobes to Prevent Ceftriaxone from Degrading Intestinal Resistance to Colonization

Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and beta-lactamase activities were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae, and fungi were counted. In two volunteers, no fecal beta-lactamase activity was detected, but ceftriaxone was present during treatment at concentrations of 1.8-2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped from 10.5 to less than 8 log10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, beta-lactamase activity was high during ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident beta-lactamase-producing anaerobes. In gnotobiotic mice associated with a human fecal flora containing no beta-lactamase-producing anaerobes, it was possible to prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four beta-lactamase-producing anaerobic strains.

Ceftriaxone versus clavulanate-potentiated amoxycillin for prophylaxis against post-operative sepsis in biliary surgery: A prospective randomized study in 200 patients

A prospective study was carried out in 200 consecutive patients undergoing biliary surgery to compare the prophylactic effectiveness of ceftriaxone and clavulanate-potentiated (CP-) amoxycillin. Patients were assigned in a randomized fashion to two groups and received ceftriaxone (2 g intravenously pre-operatively), or CP-amoxycillin (1200 mg, to be repeated for 2 more doses in the case of patients undergoing procedures other than elective cholecystectomy). Post-operative wound infection occurred in 4% of patients in each group. Administration of ceftriaxone was associated with a lower incidence of post-operative pyrexia and chest infection as well as with a shorter hospital stay.

Once-Daily Administration of Ceftriaxone for the Treatment of Selected Serious Bacterial Infections in Children

Ceftriaxone treatment (50 to 80 mg/kg once daily) was given to 201 children between 1 month and 18 years of age. There were 201 serious bacterial infections, including epiglottitis, pneumonia, cellulitis, osteomyelitis, septic arthritis, pyelonephritis, sepsis, and meningitis. The common pathogens responsible for pediatric infections isolated from these patients included Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Escherichia coli. The overall clinic cure rate was 94%. Ten patients were clinically improved but not cured. There were two clinical failures. Bacteriologic failure occurred in six patients. The overall bacteriologic cure rate was 97%. Twenty patients (10%) experienced adverse effects; none required discontinuation of therapy. The efficacy, safety, spectrum, and convenience of ceftriaxone monotherapy make this antimicrobial agent a candidate for the treatment of choice of selected serious pediatric infections.

Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers.

In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone. The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats. Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained. Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route. Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing. In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit. In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio.

Clinical consequences of development of resistance to third generation cephalosporins.

Eighteen patients are described in whom initially sensitive microorganisms were replaced by resistant isolates during administration of ceftriaxone (n = 8), cefoperazone (n = 5), moxalactam (n = 4), cefotaxime (n = 2) or ceftazidime (n = 1), despite combination with aminoglycosides. All patients had documented gram-negative infections; in 12 patients underlying haematological diseases were present. Resistant strains of Enterobacter cloacae (14), Serratia marcescens (4), Klebsiella oxytoca (3), Pseudomonas aeruginosa (2) and Citrobacter freundii (2) emerged within 2 to 19 (mean 9) days after the beginning of treatment. In 12 patients relapse or secondary infections occurred. Seven of the patients with haematological disorders died. Resistance development was seen in 8 of 29 patients on ceftriaxone and 4 of 10 patients on moxalactam during prospective evaluations; the other drugs were used sporadically. Thus, selection of resistant bacteria is relatively frequent and may have serious clinical consequences in patients with impaired host-defense mechanisms.

Outpatient treatment of serious infections in infants and children with ceftriaxone

Pediatric patients hospitalized at Strong Memorial Hospital, Rochester, New York, between April 1, 1985, and November 7, 1986, who received ceftriaxone were identified by daily examination of pharmacy records. Hospital records were retrospectively reviewed, and patients who completed antibiotic therapy with ceftriaxone as outpatients were identified. Primary physicians were contacted by telephone to verify duration of therapy, determine office versus home administration of ceftriaxone, and identify complications or problems. Parents were also contacted by telephone, and a questionnaire used to obtain information about drug-related complications, relapse or recurrence, impact of home versus hospital treatment, and their acceptance of outpatient therapy. Costs related to antibiotic therapy were based on 1986 pharmacy charges, which include a fixed dispensing fee of $3.40 per dose. As an estimate of minimum daily hospital costs, the $250 room fee for a standard semiprivate room at SMH was used. The cost for home therapy was based on the $51 visiting nurse service fee for basic evaluation and administration of medication in Monroe County, New York.

Ceftriaxone: a beta-lactamase-stable, broad-spectrum cephalosporin with an extended half-life.

Ceftriaxone is an aminothiazolyl-oxyimino cephalosporin. It possesses the typical in vitro activity of a third-generation cephalosporin with excellent activity against many gram-negative aerobic bacilli: Escherichia coli; species of Proteus, Klebsiella, Morganella, Providencia and Citrobacter; and Enterobacter agglomerans. Ceftriaxone also has outstanding bactericidal action against pneumococci, group B streptococci, meningococci, gonococci and Hemophilus influenzae. In healthy volunteers, it has an exceptionally long serum half-life of 5.8-8.7 (mean 6.5) hours. It distributes well throughout all body spaces, including cerebrospinal fluid in the presence of inflammation. Dosage modification is necessary only when there is combined hepatic and renal dysfunction. Adverse reactions characteristic of cephalosporins have been observed with the administration of ceftriaxone. No unique toxicities have been identified, and hypoprothrombinemic bleeding is not part of the adverse reaction profile. Ceftriaxone has been used to treat serious bacterial infections in neonates, infants, children and adults. Bacteriologic and clinical success rates have consistently exceeded 90%. The drug has also been used as single-dose chemoprophylaxis in coronary artery bypass, biliary tract, vaginal hysterectomy and prostatic surgery. Efficacy and safety were similar to multiple-dose cefazolin. Ceftriaxone warrants special consideration because its extended half-life allows for less frequent dosing than other antimicrobials. Significant cost savings can be realized with proper use of this antibiotic.

The influence of third-generation cephalosporins on the aerobic intestinal flora.

The influence of three third-generation cephalosporins with varying degrees of biliary excretion on the aerobic flora was investigated. The faecal flora prior to therapy with one of these substances consisted mainly of anaerobic bacilli. Escherichia coli was present in concentrations of 10(9) organisms/g stool. Candida albicans and enterococci were observed in concentrations of 10(5) - 10(6) organisms/g stool. Within 24 hours after the administration of ceftriaxone and cefoperazone, the gram-negative aerobic flora was completely eradicated. C. albicans and enterococci increased to 10(9) organisms/g stool. Between the third and tenth days (mean 6.7 days) of therapy Pseudomonas aeruginosa, Enterobacter and Citrobacter in this order of frequency reappeared in the faecal flora with complete resistance to all betalactam antibiotics. C. albicans and enterococci decreased to 10(7) organisms/g stool. The anaerobic flora was largely unaltered. In contrast, cefotaxime had only a moderate influence on the aerobic faecal flora. Concentrations of gram-negative organisms decreased to 5 X 10(7) organisms/g stool during the first five days of therapy; the concomitant increase in C. albicans and enterococci was approximately 1 log 10. No alterations in the susceptibility pattern were observed. We would like to emphasize that substantial alterations of the faecal flora and the susceptibility pattern of antibiotics may accompany the use of antimicrobial agents, particularly those with a high degree of biliary elimination.

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

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

Effect of Broad-Spectrum Cephalosporins on the Microbial Flora of Recipients

The flora in the throat and the stools of 10 patients receiving chemotherapy for malignant diseases in a laminar air-flow room was studied during the prophylactic administration of ceftazidime. Ten percent of aerobic gram-negative bacilli, 41% of aerobic gram-positive organisms, 59% of anaerobes, and 70% of fungi persisted in stool specimens during ceftazidime administration. This drug had a less pronounced effect on the throat flora; 66% of organisms persisted during antibiotic administration. The throat and fecal flora of another eight patients were studied during the prophylactic administration of ceftriaxone. This antibiotic had a profound effect on the fecal flora; none of the gram-negative bacilli, only 24% of aerobic gram-positive organisms, and only 10% of anaerobes persisted during ceftriaxone administration. Like ceftazidime, ceftriaxone had a less marked effect on the throat flora; 59% of organisms persisted during antibiotic administration. The results show that new, expanded-spectrum cephalosporins can have a major suppressive effect on patients' endogenous microbial flora.

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.

Ceftriaxone therapy of bone and soft tissue infections in hospital and outpatient settings

Ceftriaxone, a broad-spectrum cephalosporin with a markedly extended half-life, was administered to 100 patients with 56 bone and 44 soft tissue infections. Sixty-eight received 1 g twice daily, and 32 received 2 g once daily intravenously. Overall, 91% had a satisfactory clinical response, with similar efficacies in both treatment regimens. In six patients, failure to achieve a cure correlated well with the development of resistance to ceftriaxone during therapy in Enterobacter and Pseudomonas species (two cases) and with superinfection with Bacteroides fragilis (four cases). In 41 patients, intravenous drug therapy was continued after discharge from the hospital. In this group, 1,093 patient-days of hospitalization were saved, amounting to $150,020 in cost savings. The prolonged half-life facilitated the administration of ceftriaxone in this setting.