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PubMed2003

Clinical isolates of Streptococcus pneumoniae with different susceptibilities to ceftriaxone and cefotaxime.

Ceftriaxone and cefotaxime are extended-spectrum cephalosporins previously demonstrated to possess very similar in vitro activities against Streptococcus pneumoniae. Anecdotal reports of isolates with divergent in vitro susceptibilities to ceftriaxone and cefotaxime have been published. To determine the prevalence of pneumococcal isolates with divergent ceftriaxone and cefotaxime susceptibilities, we tested 1,000 clinical isolates collected by U.S. laboratories in 2001-2002 by broth microdilution and E-test. The percentages of isolates susceptible to ceftriaxone and cefotaxime were significantly different by both broth microdilution (98.6 and 96.6%, respectively; P < 0.05) and E-test (98.3 and 95.8%; P < 0.001). The differences observed were due solely to the activities of the two agents against penicillin-resistant isolates. Twenty-six of 188 penicillin-resistant isolates (13.8%) demonstrated different ceftriaxone and cefotaxime MIC interpretative phenotypes when tested by broth microdilution; 18 isolates were concurrently ceftriaxone susceptible and cefotaxime intermediate, 6 were ceftriaxone intermediate and cefotaxime resistant, and 2 were ceftriaxone susceptible and cefotaxime resistant (1.1% of penicillin-resistant isolates; 0.2% of all isolates tested). Sixteen of the 26 isolates (65%) were from southern U.S. states. The 26 isolates had serogroups and serotypes (6, 9, 14, 19, and 23) commonly associated with penicillin-resistant isolates; SmaI pulsed-field gel electrophoresis identified 18 isolates (69%) dispersed among five subtype groups and 8 isolates that were unrelated to any of the other isolates. We conclude that certain isolates of penicillin-resistant pneumococci are less susceptible to cefotaxime than to ceftriaxone and that these isolates are not the result of the spread of a single clone. Whether such isolates have increased in prevalence over time remains unknown.

Anti-Bacterial Agents↗

PubMed2006

Occurrence of ceftriaxone-resistant commensal bacteria on a dairy farm and a poultry farm.

Approximately 40 samples of animal feces, drinking water, feed, bedding, pine wood shavings, compost, and manure slurry were collected from two animal research farms (one dairy and one poultry) and analyzed for ceftriaxone-resistant bacteria. Our study revealed that the total percentage of aerobic bacteria with reduced susceptibility to ceftriaxone (minimal inhibitory concentration (MIC) > or = 16 micro g/mL) ranged from 0.9% to 10.8% in dairy feces and from 0.05% to 3.93% in chicken feces. The percentages of ceftriaxone-resistant bacteria (MIC > or = 64 micro g/mL) were in the range of 0.01% - 2.3% in dairy feces and 0.01% - 0.79% in chicken feces. Environmental samples contained a wide range of ceftriaxone-resistant bacterial populations. Among those environmental samples, fresh pine wood shavings used as chicken bedding contained the highest percentages (41.5%) of ceftriaxone-resistant bacteria, as determined by a plating method. A total of 105 ceftriaxone-resistant (MIC > or = 128 micro g/mL) bacterial isolates were isolated from the above samples and tested for resistance to nine antibiotics: ampicillin, ceftriaxone, streptomycin, kanamycin, gentamicin, chloramphenicol, tetracycline, ciprofloxacin, and nalidixic acid. The most prevalent resistance pattern (34.3%) among isolates included resistance to all nine antibiotics. Results from this study suggest that ceftriaxone-resistant bacteria exist in farm environments, and the ceftriaxone resistance was frequently associated with resistance to multiple antibiotics. Environmental sources such as pine wood shavings used as bedding can be a potential reservoir for transmitting the multidrug-resistant bacteria.

Agriculture↗

PubMed1998

Protective effect of ceftriaxone against the nephrotoxicity of isepamicin administered once daily in rats.

The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.

Animals↗

PubMed2001

Cost-effectiveness of gatifloxacin vs ceftriaxone with a macrolide for the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To determine the cost-effectiveness of sequential IV to oral gatifloxacin therapy vs IV ceftriaxone with or without IV erythromycin to oral clarithromycin therapy to treat community-acquired pneumonia (CAP) patients requiring hospitalization. PATIENTS: Two hundred eighty-three patients enrolled in a randomized, double-blind, clinical trial were eligible for inclusion in the cost-effectiveness analysis. METHODS: Data collected included patient demographics, clinical and microbiological outcomes, length of stay (LOS), and antibiotic-related LOS (LOSAR). Costs evaluated include drug acquisition (level 1); plus costs of preparation, dispensing, and administration, treating adverse events, and clinical failures (level 2); plus hospital per diem costs (level 3). Robustness of economic findings was tested using sensitivity analyses. RESULTS: Two hundred three patients were clinically and economically evaluable (98 receiving gatifloxacin and 105 receiving ceftriaxone). IV erythromycin was administered to 35 patients in the ceftriaxone-treated group. Oral conversion was achieved in 98% of patients in each group. Clinical cure and microbiological eradication rates did not differ statistically (98% and 97% with gatifloxacin vs 92% and 92% with ceftriaxone, respectively). Overall, neither geometric mean LOS nor LOSAR differed significantly (4.2 days and 4.1 days with gatifloxacin vs 4.9 days and 4.9 days with ceftriaxone, respectively). Treatment failures in the ceftriaxone group contributed to a mean incremental increase in LOSAR of 1.09 days and increased mean cost per patient. The geometric mean costs per patient (level 3) were $5,109 for gatifloxacin and $6,164 for ceftriaxone (p = 0.011). The cost-effectiveness ratios (mean cost per expected success) were $5,236:1 and $7,047:1 for gatifloxacin and ceftriaxone, respectively. CONCLUSIONS: Gatifloxacin monotherapy for CAP patients requiring hospitalization is clinically effective and provides an economic advantage compared to the regimen of ceftriaxone with or without erythromycin IV with a switch to oral clarithromycin.

Adolescent↗

PubMed1997

Comparison of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis media. Greater Boston Otitis Media Study Group.

OBJECTIVE: The purpose of this prospective, randomized, single-blind trial was to assess the clinical efficacy of a single intramuscular dose of ceftriaxone compared with 10 days of oral trimethoprim-sulfamethoxazole (TMP-SMZ) in treating acute otitis media (AOM). METHODS: Children aged 3 months through 3 years diagnosed with AOM (signs of acute illness plus evidence of middle-ear effusion) were randomized to treatment with either a single intramuscular dose of ceftriaxone (maximum dose of 50 mg/kg) or 10 days of oral trimethoprim-sulfamethoxazole (8 mg of TMP and 40 mg of SMZ/kg/day in two divided doses). Children were evaluated at scheduled visits on days 3, 14, and 28, and the parents were telephoned on day 5. Children were assessed as cured, improved, or failed on day 3, and as cured or failed on days 14 and 28. Children ill at other times during the study period were, if possible, seen and assessed by the study team. RESULTS: Of 596 children enrolled during the study period, 484 were evaluable. Characteristics of evaluable subjects did not differ significantly by drug. On day 3, 223/241 children in the ceftriaxone group (92.5%) and 231/243 (95.1%) in the TMP-SMZ group were cured or improved. On day 14, 158/197 (80.2%) in the ceftriaxone group and 174/212 (82.1%) in the TMP-SMZ group were cured. On day 28, 108/136 (79.4%) in the ceftriaxone group and 124/155 (80%) in the TMP-SMZ group were cured. Persistence of middle-ear fluid did not differ between groups at day 14 (55% in the ceftriaxone group vs 47% in the TMP-SMZ group; P = .16) or at day 28 (39% vs 43%; P = .48). Pain at the injection site persisting at day 3 occurred in 8.4% of children receiving ceftriaxone. New diarrhea was more common in the ceftriaxone group (23.6% vs 9.2%; P < .001). CONCLUSION: A single intramuscular dose of ceftriaxone is comparable in clinical efficacy to 10 days of oral TMP-SMZ for treatment of AOM.

Anti-Bacterial Agents↗

PubMed2002

Ceftriaxone: an update of its use in the management of community-acquired and nosocomial infections.

UNLABELLED: Ceftriaxone is a parenteral third-generation cephalosporin with a long elimination half-life which permits once-daily administration. It has good activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci, Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. Although active against Enterobacteriaceae, the recent spread of derepressed mutants which hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases has diminished the activity of all third-generation cephalosporins against these pathogens necessitating careful attention to sensitivity studies. Extensive data from randomised clinical trials confirm the efficacy of ceftriaxone in serious and difficult-to-treat community-acquired infections including meningitis, pneumonia and nonresponsive acute otitis media. Ceftriaxone also has efficacy in other community-acquired infections including uncomplicated gonorrhoea, acute pyelonephritis and various infections in children. In the nosocomial setting, extensive data also confirm the efficacy of ceftriaxone with or without an aminoglycoside in serious Gram-negative infections, pneumonia, spontaneous bacterial peritonitis and as surgical prophylaxis. Outpatient use of ceftriaxone, either as part of a step-down regimen or parenterally, is a distinguishing feature of the data gathered on the agent over the last decade. The review focuses on new applications of the drug and its use in infections in which the causative pathogens or their resistance patterns have changed over the past decade. Ceftriaxone has a good tolerability profile, the most common events being diarrhoea, nausea, vomiting, candidiasis and rash. Ceftriaxone may cause reversible biliary pseudolithiasis, notably at higher dosages of the drug (>/=2 g/day); however, the incidence of true lithiasis is <0.1%. Injection site discomfort or phlebitis can occur after intramuscular or intravenous administration. CONCLUSIONS: As a result of its strong activity against S. pneumoniae, ceftriaxone holds an important place, either alone or as part of a combination regimen, in the treatment of invasive pneumococcal infections, including those with reduced beta-lactam susceptibility. Its once-daily administration schedule allows simplification of otherwise complex regimens in a hospital setting and has also contributed to its popularity as a parenteral agent in an ambulatory setting. These properties, together with a well characterised tolerability profile, mean that ceftriaxone is likely to retain its place as an important third-generation cephalosporin in the treatment of serious community-acquired and nosocomial infections.

Animals↗

PubMed1994

Ceftriaxone. A pharmacoeconomic evaluation of its use in the treatment of serious infections.

Ceftriaxone possesses a broad spectrum of antimicrobial activity that includes the Gram-positive and Gram-negative aerobes commonly associated with serious infections. Its therapeutic efficacy is comparable to that of other third-generation cephalosporins and aminoglycoside-combination regimens. The most commonly reported adverse events with ceftriaxone are similar in incidence and severity to those reported with other third-generation cephalosporins. Notably, the drug has a favourable pharmacokinetic profile which allows once-daily administration. In comparative studies with other parenteral regimens requiring 3 to 6 daily doses, treatment with once-daily ceftriaxone reduced total antimicrobial drug costs (i.e. acquisition, preparation and administration costs) by 17 to 52%. Ceftriaxone was also more cost effective than ceftazidime and a variety of other antimicrobial treatment regimens (penicillins, cephalosporins, combination regimens) in the treatment of patients with community-acquired pneumonia or bronchopneumonia. This reflected lower drug and hospitalisation costs associated with a reduced length of hospital stay in ceftriaxone recipients. In noncomparative studies, ceftriaxone achieved considerable hospitalisation cost savings in patients with serious infections (mostly bone, joint, skin/skin structure infections), who were able to receive all or part of their antimicrobial therapy as outpatients. In one analysis which evaluated all direct and indirect costs (such as training programmes, transportation, time for visits and supplies) and benefits (such as hospitalisation cost savings, return to work or school, increased productivity) of outpatient ceftriaxone therapy, the overall benefit-cost ratio was approximately 5:1. The studies to date confirm that ceftriaxone is effective, well tolerated, convenient to administer and, when utilised appropriately, offers the potential for cost avoidance in patients with serious infections. Although additional well designed pharmacoeconomic analyses are needed to further evaluate its cost effectiveness, ceftriaxone should be considered an essential third-generation cephalosporin formulatory representative in most clinical settings.

Anti-Bacterial Agents↗

PubMed1986

[In vitro study of ceftriaxone binding to blood].

Binding of ceftriaxone, a new third generation cephalosporin, to blood was studied in vitro. Steady state dialysis with 14C-ceftriaxone was used. Percentages of ceftriaxone bound to plasma within the range of therapeutic concentrations (10 to 1,000 microM) varied widely (80 to 50%). Indicating that the binding process is saturable, investigations performed with various isolated plasma proteins in physiologic concentrations show that ceftriaxone binds mainly to albumin, and marginally or not at all to alpha-1-acid glycoprotein, gammaglobulins, transferrin, haptoglobin, and lipoproteins. Albumin has a single binding site (n = 0.7) with moderate affinity (Ka = 72,000 M-1) for ceftriaxone. The presence of this site explains why ceftriaxone binds to plasma according to a saturable process. Only a small proportion (5%) of ceftriaxone (75-450 microM) binds to red blood cells in whole blood with a 50% hematocrit. A strongly significant inhibition of ceftriaxone (520 microM) binding to plasma was found with high bilirubin levels (230 microM) (24% decrease; p less than 0.01). A small but significant decrease in ceftriaxone (380 microM) binding to plasma was found with high serum oleic acid (1014 microM) or uric acid (1,800 microM) concentrations (2% decrease; p less than 0.05).

Bilirubin↗

PubMed1990

Lack of probenecid effect on nonrenal excretion of ceftriaxone in anephric patients.

Probenecid has been shown to decrease renal and biliary excretion of organic acids. In a randomized crossover study, the effect of coadministered probenecid on nonrenal excretion of ceftriaxone was studied in six functionally anephric patients in whom ceftriaxone is eliminated exclusively by nonrenal or presumably by biliary excretion. Each patient received 0.5 g IV ceftriaxone without and with probenecid (0.5 g at 10 and 2 hours prior to ceftriaxone and 0.5 g q12h X 3 doses post ceftriaxone). Serial blood samples were collected over 48 hours and plasma analyzed for ceftriaxone by high performance liquid chromatography (HPLC). Pharmacokinetic analysis was based on a model-independent approach. Probenecid did not significantly affect the disposition of ceftriaxone in this study, thus suggesting that nonrenal excretion of ceftriaxone is not inhibited by probenecid.

Adult↗

PubMed1982

Efficacy of ceftriaxone and gentamicin in an abscess model.

The therapeutic efficacy of ceftriaxone and gentamicin was investigated in a foreign body induced abscess model in the rat by implanting a dialysis tube contaminated with Klebsiella pneumoniae into the subcutaneous tissue. Animals were treated for four days with ceftriaxone, gentamicin, and their combination starting immediately following or 48 h after the implantation. Peak free ceftriaxone and gentamicin abscess fluid levels were 4.3 and 2.6 mcg/ml, which were 7.3% and 37.5% of peak blood levels respectively. Both agents persisted longer in abscess fluid than in blood. Ceftriaxone inhibited the development of abscess formation when administered shortly after the implantation of the contaminated foreign body whereas gentamicin alone was without beneficial effect. When administered after 48 h ceftriaxone was less effective than immediately after implantation and gentamicin was again without any therapeutic effect. The effect of the combination of ceftriaxone and gentamicin was slightly better than ceftriaxone alone. Low oxygen tension may be an explanation for the lack of bactericidal effect of gentamicin. Ceftriaxone may be more suitable for the therapy of closed space infections caused by susceptible microorganisms than gentamicin.

Abscess↗

PubMed1994

Increased in vitro activity of ceftriaxone by addition of tazobactam against clinical isolates of anaerobes.

A total of 461 clinical strains of anaerobes were tested using a broth microdilution test to determine the activity of the combination of ceftriaxone and tazobactam and other antimicrobials against these isolates. Ceftriaxone was combined with tazobactam in ratios of 1:1, 2:1, 4:1, and 8:1 and twofold dilutions of ceftriaxone in constant concentrations to tazobactam of 2, 4, 8, 16, and 32 micrograms/ml. Against beta-lactamase-producing strains of the Bacteroides fragilis group, B. capillosus, and Prevotella species all combinations of ceftriaxone and tazobactam showed enhanced in vitro activity and were eight- to 2048-fold more active than ceftriaxone alone. By comparison ceftriaxone and tazobactam showed superior or equal activity to ampicillin and sulbactam, piperacillin and tazobactam, amoxicillin and clavulanate, ticarcillin and clavulanate, and metronidazole against these same strains. Against beta-lactamase nonproducing strains of Porphyromonas, Fusobacterium, Clostridium, Eubacterium, Peptostreptococcus, and Veillonella parvula the addition of tazobactam produced no appreciable enhanced ceftriaxone activity. Fixed concentrations of tazobactam at 2 and 4 micrograms/ml appear to be most suitable for susceptibility testing and are within the pharmacologic profile of this inhibitor. Pharmacologic and toxicity studies will be needed to define the role of ceftriaxone and tazobactam in infectious diseases.

Anti-Bacterial Agents↗

PubMed2001

A randomized, double-blind comparison of ampicillin/sulbactam and ceftriaxone in the prevention of surgical-site infections after neurosurgery.

BACKGROUND: The use of prophylactic antibiotics has been shown to decrease the rate of surgical-site infections after clean neurosurgical operations, although previous clinical trials have provided no evidence that one antibiotic is superior to another for this purpose. OBJECTIVE: This study was undertaken to compare the rates of postoperative infectious complications of neurosurgery with prophylactic ceftriaxone and ampicillin/sulbactam, a less-expensive antibiotic. METHODS: Consecutive patients undergoing neurosurgery between January and December 1998 were recruited for the study. Those who had an infectious disease for which antibiotics were required, who received antibiotics within 48 hours before surgery, were aged <12 or >85 years, had an indwelling catheter for the monitoring of intracranial pressure, or had a history of allergy to the study drugs were excluded. Before the operation, eligible patients were randomized to either ampicillin/sulbactam 3 g or ceftriaxone 2 g. Surgeons and patients were blinded to treatment assignment. The study drugs were administered by the anesthesiologist as an IV bolus after induction of general anesthesia. All patients were followed for 6 weeks postoperatively. If reoperation was required within 6 weeks of the original operation, the patient received the same antibiotic as during the first surgery, without further randomization. RESULTS: Over the 1-year study period, 180 consecutive patients undergoing neurosurgical operations were recruited. Surgical-site infection occurred in 2 (2.3%) patients in the ampicillin/sulbactam group and 3 (3.3%) in the ceftriaxone group; nonsurgical-site infection occurred in 25 (28.4%) patients in the ampicillin/sulbactam group and 15 (16.3%) in the ceftriaxone group. The between-group differences were not statistically significant, with the exception of surgical implantation of foreign material, which was performed sig- nificantly more frequently in the ceftriaxone group (P = 0.045). In addition, 2 of 3 surgical-site infections in the ceftriaxone group involved foreign-material implantation; however, if these operations are omitted from the analysis, the difference between treatments remains nonsignificant. CONCLUSIONS: The results suggest that ampicillin/sulbactam and ceftriaxone are of similar prophylactic efficacy in clean neurosurgical operations. Because the acquisition cost of 2 g ceftriaxone is approximately 3 times greater than that of 3 g ampicillin/sulbactam, the latter may be more cost-effective than the former for neurosurgical prophylaxis; however, other relevant hospital-related costs were not assessed in this study.

Adolescent↗

PubMed2002

Safety and local tolerability of intramuscularly administered ertapenem diluted in lidocaine: a prospective, randomized, double-blind study versus intramuscular ceftriaxone.

BACKGROUND: Ertapenem is a new, structurally unique, parenteral beta-lactam antimicrobial agent that can be administered once daily. OBJECTIVE: This study compared the local tolerability of ertapenem 1 g once a day administered intramuscularly (IM) versus IM ceftriaxone, with both drugs reconstituted in lidocaine. METHODS: In this prospective, double-blind, multicenter study, adult patients with lower respiratory tract infection, skin infection, or urinary tract infection requiring initial parenteral therapy were randomly assigned in a 3:1 ratio to treatment with IM ertapenem 1 g once daily or IM ceftriaxone 1 g once daily. Although study drugs were administered by unmasked personnel, the patients, investigators, and the sponsor medical reviewer were blinded. Patients who improved clinically could be switched to oral amoxicillin-clavulanate after at least 2 days of IM therapy. Tolerability and safety analyses were carried out for the treated population, and efficacy analyses were performed for the modified intent-to-treat population. RESULTS: A total of 117 patients were randomized. The 87 patients in the ertapenem group and 30 in the ceftriaxone group received IM therapy for a mean duration of 4.1 and 3.8 days, respectively. During treatment, 35.6% (31/87) of patients treated with ertapenem and 43.3% (13/30) of those treated with ceftriaxone experienced > or =1 symptom at the local injection site; the most common symptom was tenderness, followed by pain. Symptoms were moderate to severe in only 1 patient (1.1%) in the ertapenem group and 3 patients (10.0%) in the ceftriaxone group. Clinical drug-related adverse events were reported during IM therapy in 14 patients (16.1%) in the ertapenem group and 5 patients (16.7%) in the ceftriaxone group. Mean +/- SD creatine kinase concentrations, measured in all patients, were 204.8+/-234.8 U/L at the end of IM ertapenem therapy and 382.9+/-721.1 U/L at the end of IM ceftriaxone therapy; at follow-up, values had returned to normal or had decreased in all cases. CONCLUSIONS: Ertapenem 1 g (reconstituted in lidocaine) administered once daily IM was generally well tolerated. The tolerability and safety profiles of IM ertapenem therapy in this study were comparable to those of IM ceftriaxone therapy.

Aged↗

PubMed1990

A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Adolescent↗

PubMed2000

Bacteriologic and clinical efficacy of one day vs. three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children.

BACKGROUND: One dose of intramuscular ceftriaxone has been recently licensed in the United States for the treatment of acute otitis media. However, data regarding the bacteriologic and clinical efficacy of this regimen in the treatment of nonresponsive acute otitis media are incomplete. OBJECTIVES: To determine the bacteriologic and clinical efficacy of a 1-day 50-mg/kg vs. a 3-day 50-mg/kg/day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media in children. PATIENTS AND METHODS: In an open, prospective study 109 patients ages 3 to 36 months with culture-proved, nonresponsive acute otitis media were randomized to receive 1 (n = 49) or 3 (n = 60) 50-mg/kg/day intramuscular ceftriaxone doses, respectively. Middle ear fluid was aspirated for culture by tympanocentesis on the day of enrollment (Day 1); a second tympanocentesis with middle ear fluid culture was performed on Days 4 to 5. Additional middle ear fluid cultures were obtained if clinical relapse occurred after completion of therapy. Bacteriologic failure was defined by positive cultures on Days 4 to 5. Patients were followed until Day 28 after completion of therapy. Susceptibility of the middle ear pathogens was measured by E-test. RESULTS: Organisms recovered (n = 133) were Streptococcus pneumoniae (30 and 35 isolates for the 1-day and 3-day treatment group, respectively), Haemophilus influenzae (26 and 38, respectively) and Moraxella catarrhalis (n = 4). Of the 30 S. pneumoniae isolated from the 1-day group, 27 (90%) and 6 (20%) were nonsusceptible to penicillin and ceftriaxone, respectively; 9 of 27 (33%) were fully resistant to penicillin. Thirty-four (97%) and 6 (17%) of the 35 S. pneumoniae isolated from the 3-day group were nonsusceptible to penicillin and ceftriaxone, respectively; 16 of 34 (47%) were fully resistant to penicillin. Bacterial eradication of all H. influenzae and penicillin-susceptible S. pneumoniae was achieved in both treatment groups. Bacterial eradication of 14 of 27 (52%) and 33 of 34 (97%) penicillin-nonsusceptible S. pneumoniae was achieved in the 1-day and 3-day group, respectively. Seven (50%) of the 14 patients from the 2 groups who did not achieve bacterial eradication did not improve clinically on Days 4 to 5 and required additional ceftriaxone treatment. CONCLUSION: The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media caused by penicillin-resistant S. pneumoniae.

Acute Disease↗

PubMed2002

Dynamics of pneumococcal nasopharyngeal carriage in children with nonresponsive acute otitis media treated with two regimens of intramuscular ceftriaxone.

BACKGROUND: A 3-day intramuscular ceftriaxone regimen was superior to a 1-day regimen in the treatment of nonresponsive acute otitis media caused by resistant Streptococcus pneumoniae. However, the effect of various regimens of intramuscular cefriaxone on the nasopharyngeal carriage of S. pneumoniae and especially that of resistant strains during and after therapy has not been thoughtfully studied. OBJECTIVES: To compare the effect of one dose and three dose intramuscular ceftriaxone regimens on the nasopharyngeal carriage of S. pneumoniae in patients with nonresponsive acute otitis media treated with these two regimens and to document the dynamics of nasopharyngeal colonization with S. pneumoniae during and after completion of these two therapeutic regimens. PATIENTS AND METHODS: In a prospective study performed during January, 1998, through September, 1999, 170 evaluable patients ages 3 to 36 months with nonresponsive acute otitis media were randomized to receive the 1 (n = 83)- or 3 (n = 87)-day intramuscular ceftriaxone regimen (50 mg/kg/day), respectively. Nasopharyngeal cultures for S. pneumoniae were obtained on Days 1, 4 to 5, 11 to 14 and 28 to 30. Susceptibility of S. pneumoniae to penicillin and ceftriaxone was determined by E-test. RESULTS: On Day 1 nasopharyngeal S. pneumoniae carriage was found in 108 (64%) patients, 54 in each treatment group. Forty-seven of 54 (87%) and 9 of 54 (17%) S. pneumoniae isolates from the one dose group were nonsusceptible to penicillin and ceftriaxone, respectively; the respective values in the three dose group were 49 of 54 (91%) and 8 of 54 (15%). On Days 4 and 5 negative nasopharyngeal cultures were achieved in 43 of 83 (52%) and 70 of 87 (80%) cases from the one dose and three dose group, respectively (P < 0.001). Eradication of penicillin-nonsusceptible S. pneumoniae was achieved on Day 4 to 5 in 18 of 49 (37%) and 39 of 49 (80%) organisms isolated from the one dose and three dose groups, respectively (P < 0.001). Nasopharyngeal S. pneumoniae carriage among evaluable patients on Days 11 to 14 and Days 28 to 30 was 43 of 69 (62%) and 31 of 45 (69%) for the one dose group and 42 of 73 (58%) and 31 of 50 (62%) for the three dose group, respectively (P not significant). A decrease was observed during the study period in the proportion of highly penicillin-resistant S. pneumoniae isolated in the three dose group compared with the one dose group (30, 24, 17 and 13% vs. 30, 27, 19 and 26% at Days 1, 4 to 5, 11 to 14 and 28 to 30, respectively; P = 0.05). CONCLUSIONS: A marked reduction in the carriage of penicillin-nonsusceptible S. pneumoniae (including highly penicillin-resistant organisms) was achieved on Days 4 to 5 of therapy with both ceftriaxone regimens. The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day regimen in the reduction of carriage during the treatment period. The reduction of overall S. pneumoniae nasopharyngeal carriage by both ceftriaxone regimens was a short-lived phenomenon followed by rapid recolonization of the nasopharynx.

Acute Disease↗

PubMed1992

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↗

PubMed1985

Effect of caffeine on the plasma protein binding and the disposition of ceftriaxone.

The effects of caffeine on the in-vitro protein binding and the pharmacokinetics of ceftriaxone (a highly protein bound cephalosporin) were investigated. Caffeine failed to decrease in-vitro protein binding of ceftriaxone. Rabbit plasma concentrations of ceftriaxone (30 mg kg-1 i.v.) were elevated significantly (P less than 0.05 at 0.3, 0.6 and 1 h after injection) when caffeine 5 or 10 mg kg-1 i.v. was co-administered compared with ceftriaxone given alone. Caffeine increased the volume of distribution of the central compartment (V1) for ceftriaxone significantly from 49 +/- 38 ml kg-1 (mean +/- s.d., n = 6) to 97 +/- 33 ml kg-1 (caffeine 5 mg kg-1, P less than 0.05), and 94 +/- 8 ml kg-1 (caffeine 10 mg kg-1, P less than 0.05) and decreased the volume of distribution of the peripheral compartment (V2) from 145 +/- 106 ml kg-1 (mean +/- s.d., n = 6) to 31 +/- 18 ml kg-1 (caffeine 5 mg kg-1, P less than 0.5) and 36 +/- 31 ml kg-1 (caffeine 10 mg kg-1, P less than 0.1). The rate of transfer of ceftriaxone to the peripheral compartment (k12) was also decreased significantly (P less than 0.05) after caffeine. The elevated plasma concentration of ceftriaxone, increased V1 value and the decreased V2 and k12 values are probably the result of caffeine altering the distribution of ceftriaxone to the central and the peripheral compartments.

Animals↗