ro13-9904 and Otitis-Media

Clinicians in the authors' primary care academic practice have anecdotally perceived an increased use of intramuscular (IM) ceftriaxone, particularly for otitis-conjunctivitis in recent years (pre-pandemic). Increasing rates of ceftriaxone administration for acute otitis media (AOM) may be an important marker of antimicrobial resistance.. We aimed to characterize the population of patients who received ceftriaxone for treatment of AOM, testing our hypothesis that patients with concomitant conjunctivitis would have increased rates of ceftriaxone receipt.. We reviewed cases of AOM at a large U.S. primary care practice from August 2017 to July 2019. We determined the association between each of the following variables and ceftriaxone injection using multivariate analysis: age at AOM diagnosis, provider type, insurance (public vs private), season of year, and presence of conjunctivitis.. There were 6028 AOM episodes in 5195 patients resulting in a total of 7688 patient encounters. Of these episodes, 642 (10.7%) had a concurrent diagnosis of conjunctivitis; 362 (6.0%) ultimately received ceftriaxone. Conjunctivitis was the strongest predictor of treatment with ceftriaxone. The proportion of episodes with conjunctivitis treated with ceftriaxone was 14.5% (93/642) versus 5.0% (269/5386) without conjunctivitis (p < 0.0001). Patients who received ceftriaxone were younger; mean age (SD) for patients receiving ceftriaxone was 14.0 (8.8) months versus 25.0 (23.4) months (p < 0.0001).. There is a strong correlation between the presence of conjunctivitis and receipt of IM ceftriaxone in this large U.S. academic primary care clinic. Younger age was also associated with ceftriaxone treatment. Further study on emerging resistance patterns and implications for management of AOM in young children is warranted.

Topics: Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Conjunctivitis; Humans; Infant; Otitis Media; Primary Health Care

Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics.. To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials.. We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo).. Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted study characteristics and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method.. We included two studies involving 252 children with AOM aged from three months to six years receiving hospital ambulatory care who were treated with intramuscular ceftriaxone, and who were then randomised to the corticosteroid group (corticosteroid and corticosteroid plus antihistamine) or the placebo group (antihistamine and double placebo). In one study, children also had a needle aspiration of middle ear fluid. Both studies were at unclear risk of bias for allocation concealment, and unclear to high risk of bias for selective reporting.One study (N = 179) included pain as an outcome, but we were unable to derive the proportion of children with persistent pain at Day 5 and Day 14. Reduction of overall or specific symptoms was presented as improvement in clinical symptoms and resolution of inflamed tympanic membranes without the need for additional antibiotic treatment: at Day 5 (94% of children in the treatment group (N = 89) versus 89% in the placebo group (N = 90); risk ratio (RR) 1.06, 95% confidence interval (CI) 0.97 to 1.16) and Day 14 (91% versus 87%; RR 1.05, 95% CI 0.95 to 1.17). Low-quality evidence meant that we are uncertain of the effectiveness of corticosteroids for this outcome.The second study (N = 73) reported a reduction of overall or specific symptoms without additional antibiotic treatment during the first two weeks as a favourable outcome. Children in the treatment group had more favourable outcomes (adjusted odds ratio 65.9, 95% CI 1.28 to 1000; P = 0.037), although the numbers were small. We were unable to pool the results with the other study because it did not report the proportion of children with this outcome by treatment group. Only one study reported adverse effects of corticosteroids (e.g. drowsiness, nappy rash), but did not quantify incidence, so we were unable to draw conclusions about adverse effects. Neither study reported a reduction in overall or specific symptom duration.. The evidence for the effect of systemic corticosteroids on AOM is of low to very low quality, meaning the effect of systemic corticosteroids on important clinical outcomes in AOM remains uncertain. Large, high-quality studies are required to resolve the question.

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Histamine Antagonists; Humans; Infant; Otitis Media; Randomized Controlled Trials as Topic

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Failure

To determine the efficacy of a short course of antibiotics (<4 days) in comparison to a longer course (>4 days) for the treatment of acute otitis media in children.. Electronic databases, hand search of reviews, bibliographies of books, abstracts and proceedings of international conferences.. Randomized controlled trials of the empiric treatment of acute otitis media comparing antibiotic regimens of <4 days versus > 4 days in children between four weeks to eighteen years of age were included. The trials were grouped by pharmacokinetic behavior of short-course antibiotics into short-acting antibiotics, parenteral ceftriaxone, and long-acting azithromycin.. We reviewed 35 trials, which provided 38 analytic components. Overall, there was no evidence of an increased risk of treatment failure until one month with a short-course of antibiotics (RR=1.06, 95% CI 0.95 to 1.17, P=0.298). Use of short-acting oral antibiotic in short-course was associated with a significantly increased risk of treatment failure (RR=2.27, 95% CI: 1.04 to 4.99). There was a slightly increased risk of treatment failure with parenteral ceftriaxone (RR=1.13, 95% CI 0.99 to 1.30). The risk of adverse effects was significantly lower with short-course regimens (RR=0.58, 95% CI: 0.48 to 0.70).. There is no evidence of an increased risk of treatment failure with short course of antibiotics for acute otitis media. Among the short course regimens, azithromycin use was associated with a lower risk of treatment failure while short acting oral antibiotics and parenteral ceftriaxone may be associated with a higher risk of treatment failure.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Acute otitis media (AOM) is a common illness during childhood, for which antibiotics are frequently prescribed.. To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a long course of antibiotics (seven days or greater) for the treatment of AOM in children.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL, BIOSIS Previews, OCLC Papers First and Proceedings First, Proquest Dissertations and Theses (inception to November 2009); International Pharmaceutical Abstracts, the NLM Gateway, ClinicalTrials.gov and Current Controlled Trials (inception to August 2008).. Trials were included if they met the following criteria: participants aged one month to 18 years; clinical diagnosis of ear infection; no previous antimicrobial therapy; and randomisation to treatment with less than seven days versus seven days or more of antibiotics.. The primary outcome of treatment failure was defined as the absence of clinical resolution, relapse or recurrence of AOM during one month following initiation of therapy. Treatment outcomes were extracted from individual studies and combined in the form of a summary odds ratio (OR). A summary OR of 1.0 indicates that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of treatment.. This update included 49 trials containing 12,045 participants. Risk of treatment failure was higher with short courses of antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of therapy (21% failure with short-course treatment and 18% with long-course; absolute difference of 3% between groups). There were no differences found when examining treatment with ceftriaxone for less than seven days (30% failure in those receiving ceftriaxone and 27% in short-acting antibiotics administered for seven days or more) or azithromycin for less than seven days (18% failure in both those receiving azithromycin and short-acting antibiotics administered for seven days or more) with respect to risk of treatment failure at one month or less. Significant reductions in gastrointestinal adverse events were observed for treatment with short-acting antibiotics and azithromycin.. Clinicians need to evaluate whether the minimal short-term benefit from longer treatment of antibiotics is worth exposing children to a longer course of antibiotics.

Topics: Acute Disease; Age Factors; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Time Factors

Acute otitis media (AOM) is the most frequent bacterial disease and leading cause of antibacterial prescriptions in infants and children. Although AOM resolves spontaneously in most patients, antibacterial treatment is believed to be indicated in most industrial countries, particularly for infants, to prevent severe complications and relieve symptoms more rapidly. The classical duration of oral antibacterial therapy has been 10 days. During the last decade, the efficacy of shortened course antibacterial therapy has been demonstrated in many trials. Advantages of shorter treatment periods include less expense, better compliance, and potentially less impact on the commensal flora. However, short course antibacterial therapy may not be appropriate for children <2 years of age, particularly those attending daycare centers, those with otorrhea or a recent episode (<1 month), and otitis-prone children. Reasons for a poorer efficacy in these groups of children are still not completely understood.

Topics: Acute Disease; Administration, Oral; Anti-Infective Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

To conduct a meta-analysis of randomized controlled trials of antibiotic treatment of acute otitis media in children to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more.. MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations.. Studies were included if they met the following criteria: subjects aged 4 weeks to 18 years, clinical diagnosis of acute otitis media, no antimicrobial therapy at time of diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7 days or more of antibiotic treatment.. Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections.. Included trials were grouped by antibiotic used in the short course: (1) 15 short-acting oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate], cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil), (2) 4 intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The summary odds ratio for treatment outcomes at 8 to 19 days in children treated with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups were comparable (odds ratio, 1.22; 95% CI, 0.98 to 1.54). The risk difference (2.3%; 95% CI,-0.2% to 4.9%) at 20 to 30 days suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. This similarity in later outcomes was observed for up to 3 months following therapy (odds ratio, 1.16; 95% CI, 0.90-1.50). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and at least 7 days of other antibiotics.. This meta-analysis suggests that 5 days of short-acting antibiotic use is effective treatment for uncomplicated acute otitis media in children.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cephalosporins; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Acute Disease; Age Factors; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Humans; Otitis Media

To determine the effect of a clinical practice guideline (CPG) on the use of ceftriaxone for the treatment of refractory acute otitis media (AOM) at a tertiary care pediatric hospital.. Charts of all patients aged 3 to 60 months referred from an emergency department to a day treatment center for management of refractory AOM with ceftriaxone were reviewed. Data were collected during two 18-month periods before and after implementation of a CPG developed by a local group of experts. Ceftriaxone was indicated for children with symptomatic AOM despite 48 hours of treatment with high-dosage amoxicillin or amoxicillin-clavulanate (>75 mg/kg per day) or despite receiving 1 of these 2 antibiotics over the previous month. Overall treatment was considered adequate if patients met these indications for ceftriaxone, if at least 3 daily doses had been prescribed, and if all doses were within the 40- to 60-mg/kg range.. Thirty-two emergency physicians referred 127 patients to the day treatment center (60 preimplementation and 67 postimplementation of the CPG). The mean (SD) patient ages were 16.7 (7.4) and 19.7 (12.4) months in the preimplementation and postimplementation groups, respectively. Indications for prescription of ceftriaxone were adequate in 16.7% of the preguideline and 22.4% of the postguideline groups (P = 0.4). Physicians were twice as likely to use ceftriaxone adequately after the guideline's implementation, but this result was not statistically significant (crude odds ratio, 2.2; 95% confidence interval, 0.5-9.0).. Implementation of a CPG for the treatment of refractory AOM with ceftriaxone did not improve indications for its use.

Topics: Acute Disease; Anti-Bacterial Agents; Canada; Ceftriaxone; Child, Preschool; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Guideline Adherence; Hospitals, Pediatric; Humans; Infant; Injections, Intravenous; Male; Otitis Media; Practice Guidelines as Topic; Retrospective Studies; Treatment Outcome

The use of short-term intramuscular ceftriaxone for pediatric ambulatory conditions raises concerns regarding the promotion of resistance among colonizing enteric bacteria. This study was designed to assess the prevalence of stool colonization with resistant Gram-negative bacilli after single-dose ceftriaxone treatment compared with other regimens for acute otitis media.. Children age 3 months to 7 years and diagnosed with acute otitis media were randomized to receive treatment with single-dose ceftriaxone or with oral cefprozil, amoxicillin or azithromycin. Stool samples were obtained at enrollment and then 3-5 days, 10-14 days, and 28-30 days after therapy was initiated and screened for the presence of facultative Gram-negative bacilli resistant to ceftriaxone, cefprozil, amoxicillin, piperacillin, piperacillin-tazobactam and tobramycin. Mean prevalence of colonization by resistant organisms for each treatment group was compared at each time point.. One thousand nine subjects were enrolled. The prevalence of colonization by a Gram-negative bacillus resistant to at least 1 of the screening antibiotics decreased after receipt of ceftriaxone but returned close to values measured at study entry by 30 days. A qualitatively similar pattern was noted for the 3 other regimens, but a quantitatively greater decrease in the prevalence of colonization by a resistant bacterium was noted at the 3- to 5-day and 10- to 14-day visits among azithromycin recipients (P < 0.001). Colonization by a Gram-negative bacillus resistant specifically to ceftriaxone was unusual at each study visit, regardless of treatment assignment.. A single intramuscular dose of ceftriaxone had a similar effect on the prevalence of antibiotic-resistant Gram-negative facultative bacilli in the stool of healthy children when compared with commonly used oral agents.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefprozil; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance; Feces; Female; Gram-Negative Bacteria; Humans; Infant; Injections, Intramuscular; Male; Otitis Media

In order to evaluate the clinical efficacy and safety profiles of single-dose ceftriaxone (50 mg/kg, not exceeding 1 g) and a 10-day course of amoxicillin-clavulanate (amoxi-clav) [45 mg/kg/day, in 3 divided doses] in children with acute otitis media (AOM), we conducted a prospective, comparative, randomized trial. Between February 2000 and April 2002, 110 children with a mean age of 30.73 +/- 20.79 months were enrolled. 109 patients were evaluated for the safety assessment. The intent-to treat population included 96 patients who completed at least 3 days of treatment. The standard analysis population included 73 patients who completed the 10-day treatment period without any major violation. For the standard analysis population, 57 out of 73 patients experienced treatment success; 31 out of 41 patients in the ceftriaxone group were cured compared with 25 out of 32 patients in the amoxi-clav group. The rate of persistence of middle-ear fluid did not differ between the 2 groups at day 11 or day 28. A higher treatment preference rate was observed in the ceftriaxone group (93.9% vs 58.6%). The most common drug-related adverse effects were found in the digestive system, skin and appendages in both treatment groups. A single dose of ceftriaxone is as safe and effective as amoxi-clav for curing patients with acute otitis media. In addition, a substantially higher proportion of patients receiving single-dose ceftriaxone showed a preference for the study medication compared with those treated with amoxi-clav for 10 days.

Topics: Acute Disease; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Prospective Studies; Treatment Outcome

The value of tympanometry in detection of middle ear effusion (MEE) has been widely studied in otitis media with effusion. There has been no direct comparison of tympanometric and tympanocentesis (TAP) findings in acute otitis media (AOM). We compared otoscopic, tympanometric and TAP findings in AOM including cases of AOM without effusion.. In a study of AOM treatment of 90 children, a tympanogram was obtained, and TAP was performed before and after 5 days of treatment. Subjects were followed with otoscopy and tympanometry every 2 weeks for 3 months or until the MEE cleared.. In 130 AOM ears, otoscopic, tympanometric and TAP findings were available; MEE was obtained from 110 ears. Of 20 ears with a dry tap, 18 had abnormal tympanogram and otoscopic findings. With TAP findings as the standard, sensitivity and positive predictive value of type B tympanogram were 97 and 87%, respectively. Of 18 AOM ears yielding dry tap, 2 yielded MEE 5 days later, and 8 continued with evidence of MEE 5 days-12 weeks later. Five subjects with 8 AOM ears yielding dry tap were lost to follow-up; all had short duration of clinical symptoms.. Although otoscopic and tympanometric findings suggested the presence of MEE in AOM, MEE was unobtainable by TAP in 14% of cases. Dry tap cases likely represent early AOM before accumulation of detectable MEE. However, technical difficulty in obtaining small amounts of or highly viscous MEE could not be excluded. Sensitivity and positive predictive value of abnormal tympanograms in detection of MEE in AOM cases are comparable with those in otitis media with effusion.

Topics: Acoustic Impedance Tests; Acute Disease; Ceftriaxone; Child; Child, Preschool; Diagnosis, Differential; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Infant; Male; Middle Ear Ventilation; Otitis Media; Otitis Media with Effusion; Otoscopy; Predictive Value of Tests; Prednisolone; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Tympanic Membrane

To determine whether the adjunctive drugs antihistamine and corticosteroid improve immediate and long-term outcomes of acute otitis media (AOM).. Children with AOM (3 mos-6 y) were enrolled in a randomized, double-blind, placebo-controlled trial. All 179 children received one dose of intramuscular ceftriaxone and were assigned to receive either chlorpheniramine maleate (0.35 mg/kg/d) and/or prednisolone (2 mg/kg/day) or placebo for 5 days. Main outcome measures were rate of treatment failure during the first 2 weeks, duration of middle ear effusion, and rate of recurrences of AOM to 6 months.. Clinical outcomes and recurrence rates did not differ significantly with treatment. Children who received antihistamine alone had significantly longer duration of middle ear effusion (median, 73 days) than subjects in other treatment groups (median, 23 to 36 days, P=.04). Temporary normalization of tympanometric findings on day 5 occurred more frequently in the corticosteroid-treated group (P=.04).. Five-day treatment with antihistamine or corticosteroid, in addition to antibiotic, did not improve AOM outcomes. Antihistamine use during an acute episode of OM should be avoided, since the drug may prolong the duration of middle ear effusion. The efficacy of 7- to 10-day treatment of AOM with corticosteroid, in addition to antibiotic, deserves further investigation.

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Child; Child, Preschool; Chlorpheniramine; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Infant; Male; Otitis Media; Prednisolone; Prospective Studies; Recurrence; Time Factors; Treatment Outcome

To compare the efficacy and safety of a single ceftriaxone injection with 10-day oral amoxicillin in the treatment for children's acute otitis media.. This study was a prospective, comparative, open randomized, multicenter trial. In the ceftriaxone group, a single dose sodium ceftriaxone (50 mg/kg, total dose < 1 g) was injected. In the amoxicillin group, the oral amoxicillin [40 mg/(kg.d), tid] was used for 10 days. Totally 236 cases aged from 0.5 to 12 years were enrolled and 212 cases completed the study. These patients were followed up twice and clinical signs and symptoms were recorded, otoscopy, peripheral blood WBC count, hearing test (pure tone test) and tympanography were performed.. In the ceftriaxone group, 103/106 cases were cured or improved (97.17%), while in the amoxicillin group 96/106 cases were cured or improved (90.57%) (P < 0.05). Ceftriaxone was significantly better than amoxicillin in the treatment. Totally 4 cases had side effects such as papular skin rash, urticaria around mouth, skin pigmentation, two cases in the ceftriaxone group and other two cases in the amoxicillin group. There was no significant difference between the 2 groups in side effects.. Ceftriaxone injection was significantly better than ten-day oral amoxicillin for treatment of acute otitis media in children. The single dose regimen with ceftriaxone seems to be a good choice for children, particularly for.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Male; Otitis Media; Prospective Studies; Treatment Outcome

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.. 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.. 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.. 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.. 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.

Topics: Acute Disease; Bacteria; Ceftriaxone; Cephalosporins; Child, Preschool; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Prospective Studies; Recurrence

The increasing prevalence of drug-resistant bacteria is attributed to the extensive use of antibiotics, which causes selective pressure on the nasopharyngeal bacterial flora. Shortened courses of antibiotics have been proposed to decrease the development of resistant strains. We determined the effect of a single intramuscular dose of ceftriaxone (50 mg/kg) on the nasopharyngeal bacterial flora in 167 children (median age 13 mo) with acute otitis media. Nasopharyngeal samples for bacterial culture were obtained before and 5 d after treatment with ceftriaxone. Before treatment, Moraxella catarrhalis was isolated in 99 (59%) children, Streptococcus pneumoniae in 87 (52%), and Haemophilus influenzae in 53 (32%). After treatment, M. catarrhalis was found in 62 (37%) children, which constitutes a 37% decrease in the colonization rate by this pathogen (p < 0.001). S. pneumoniae was isolated in 50 (30%; 43% decrease) and H. influenzae in 17 (10%; 68% decrease) children after treatment (p < 0.001 for both). Before treatment, 60% of pneumococcal isolates were sensitive to penicillin, 26% were of intermediate susceptibility, and 14% were penicillin-resistant. Eradication of S. pneumoniae occurred mainly in children with penicillin-sensitive isolates. As a consequence, only 24% of pneumococcal isolates that remained after treatment were sensitive to penicillin, 59% were penicillin-intermediate, and 16% were penicillin-resistant. A single dose of ceftriaxone resulted in significant changes in the nasopharyngeal bacterial flora, increasing the relative prevalence of pneumococcal strains with decreased susceptibility to penicillin.

Topics: Acute Disease; Bacteria; Ceftriaxone; Cephalosporins; Chi-Square Distribution; Child; Child, Preschool; Data Interpretation, Statistical; Double-Blind Method; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Infant; Injections, Intramuscular; Microbial Sensitivity Tests; Moraxella catarrhalis; Nasopharynx; Otitis Media; Penicillin Resistance; Penicillins; Placebos; Streptococcus pneumoniae; Time Factors

This multicenter, noncomparative, nonrandomized study evaluated the clinical efficacy and safety of ceftriaxone for treating acute otitis media in children following clinical failure of oral antibiotic therapy. Middle-ear fluid samples were collected on day 0 and on day 3, 4, or 5 (day 3 to 5) and were used to test whether ceftriaxone therapy can eradicate Streptococcus pneumoniae isolates with increased resistance to penicillin (MIC >/= 1 mg/liter). At the first visit, on day 0, middle-ear fluid was sampled for bacteriological testing by tympanocentesis or otorrhea pus suction. Patients were administered 50 mg of ceftriaxone/kg of body weight/day, injected intramuscularly once daily, for 3 days. A second sample was collected by tympanocentesis if a pneumococcus isolate for which the MIC of penicillin was >/=1 mg/liter was detected in the day-0 sample and if the middle-ear effusion persisted on day 3 to 5. This second sample was tested for bacterial eradication. One hundred eighty-six children aged 5 months to 5 years, 10 months, with acute otitis media clinical failure were enrolled and treated in this trial. On day 10 to 12, 145 (83.8%) of the 173 patients evaluable for clinical efficacy were clinically cured. Of the 59 patients infected by pneumococci, 36 had isolates for which the MICs of penicillin were >/=1 mg/liter. Of those patients, on day 10 to 12, 32 (88.9%) were clinically cured. Middle-ear fluid samples collected by day 3 to 5 following the onset of treatment with ceftriaxone were sterile for 24 of the 27 (88.9%) patients who were infected as of day 0 by pneumococci for which the MICs of penicillin were >/=1 mg/liter and who were evaluable for bacteriological eradication. On day 10 to 12, 81.4% of S. pneumoniae-infected children and 87.5% of Haemophilus influenzae-infected children were clinically cured. No discontinuation of treatment due to adverse events, particularly due to local reactions at the injection site, were reported. Only 11 adverse events which had doubtful, probable, or possible links with the study treatment were recorded. Both the bacteriologically assessed eradication of pneumococci for which the MICs of penicillin were >/=1 mg/liter and the clinical cure rates demonstrate that ceftriaxone is of value in the management of acute otitis media unresponsive to previous oral antibiotic therapy.

Topics: Ceftriaxone; Cephalosporins; Child, Preschool; Female; Humans; Infant; Male; Otitis Media; Penicillin Resistance; Streptococcus pneumoniae; Treatment Outcome

To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children.. In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test.. The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse).. A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.

Topics: Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child, Preschool; Drug Administration Schedule; Drug Resistance, Multiple; Female; Follow-Up Studies; Humans; Infant; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Otitis Media; Prospective Studies; Treatment Outcome

Topics: Acute Disease; Anti-Infective Agents; Ceftriaxone; Cephalosporins; Child; Humans; Otitis Media; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Ceftriaxone; Cephalosporins; Child; Costs and Cost Analysis; Humans; Otitis Media

Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012).. Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable.

Topics: Acute Disease; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Statistics, Nonparametric

We conducted a controlled clinical trial to determine the efficacy of single-dose intramuscular ceftriaxone for the treatment of acute otitis media. Fifty-four children aged 18 months to 6 years with clinical and tympanometric evidence of otitis media were randomized to receive either 50 mg/kg ceftriaxone or 10 days of oral cefaclor 40 mg/kg/day. Resolution of symptoms and clinical and tympanometric appearance of the tympanic membrane at follow-up visits were used to determine outcome. Thirty-one children received ceftriaxone and 23 received oral cefaclor. There were no treatment failures. There were no significant differences between groups in persistence of effusion or recurrence of acute otitis media. We conclude that a single intramuscular dose of ceftriaxone compares favorably with 10 days of oral cefaclor for the treatment of acute otitis media.

Topics: Acute Disease; Administration, Oral; Cefaclor; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Treatment Outcome

Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for therapy. Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and culture of blood. Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other. After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H. influenzae type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b), compared with none given ceftriaxone. Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0.52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.94, p = 0.04). Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, prevented significantly more definite focal bacterial complications, and was associated with less persistent fever.

Topics: Administration, Oral; Amoxicillin; Arthritis, Infectious; Bacteremia; Ceftriaxone; Child, Preschool; Fever; Humans; Infant; Injections, Intramuscular; Meningitis, Bacterial; Microbial Sensitivity Tests; Osteomyelitis; Otitis Media; Pneumonia; Prospective Studies

Topics: Acute Disease; Amoxicillin; Ceftriaxone; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Humans; Infant; Injections, Intramuscular; Otitis Media; Treatment Outcome

This study evaluated the efficacy of a single dose of intramuscular ceftriaxone for acute otitis media in children, using amoxicillin as a control. (There is currently no established single-dose treatment for this condition.) In a prospective, randomized, double-blind, clinical trial, 233 children, aged 5 months to 5 years, with uncomplicated acute otitis media were randomly assigned to receive either a single intramuscular injection of ceftriaxone (50 mg/kg) plus placebo oral suspension for 10 days, or a placebo injection plus amoxicillin oral suspension (40 mg/kg per day divided three times per day) for 10 days in a double-blind fashion. Demographic and clinical characteristics were similar in both groups. Treatment was successful in 107 of 117 given amoxicillin (91%, 95% confidence interval 86% to 97%) and 105 of 116 given ceftriaxone (91%, 95% confidence interval 85% to 96%). Rates of improvement, failure, relapse, and reinfection were similar in both groups, as were the otoscopic and tympanometric evaluations at the 14- and 60-day follow-up visits. It is concluded that a single intramuscular injection of ceftriaxone (50 mg/kg) is as effective as 10 days of oral amoxicillin for the treatment of uncomplicated acute otitis media in children.

Topics: Acoustic Impedance Tests; Acute Disease; Amoxicillin; Ceftriaxone; Child; Child, Preschool; Double-Blind Method; Drug Costs; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Prospective Studies; Recurrence; Treatment Failure; Treatment Outcome

This randomized, multicentre prospective study was undertaken to compare the efficacy and tolerance of a one day course of injectable cefotaxime with a five day oral course of co-amoxyclav (amoxycillin plus clavulanic acid) in the treatment of acute otitis media in children. The study was conducted in 116 patients between the ages of three months and 12 years. No significant difference in efficacy was observed between the two treatment groups, but tolerance to the treatments differed significantly. There were no unwanted side-effects in the cefotaxime group whereas 22% of children in the amoxycillin plus clavulanic acid group suffered side-effects (P 0.0007). Short-course antibiotic therapy with cefotaxime appears to be a valuable alternative to conventional treatment regimens for acute otitis media in children.

Topics: Acute Disease; Amoxicillin; Cefaclor; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Clavulanic Acid; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Infant; Male; Otitis Media

In order to objectively evaluate the efficacy and the safety of ceftriaxone (CTRX) using once daily administration of 1 g to cases of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media, a group comparison study by the envelope method was conducted using cefotiam (CTM) as the control drug (2 g twice daily). The results obtained are summarized as follows. 1. Clinical efficacies evaluated by the committee were 71% in the CTRX group and 86% in the CTM group for acute suppurative otitis media, and 63% and 60%, respectively, for chronic suppurative otitis media. When all cases were considered both groups evidenced a clinical efficacy of 64%, and no significant difference was observed between the 2 groups. 2. Clinical efficacies evaluated by the physician in charge were 65% in the CTRX group and 86% in the CTM group for acute suppurative otitis media, and 72% and 60%, respectively, for chronic suppurative otitis media. When all cases were considered efficacies were, respectively, 70% and 64%, showing no significant difference between the 2 groups. 3. Bacteriological efficacies were 88% in the CTRX group and 86% in the CTM group for acute suppurative otitis media, and 74% and 62%, respectively, for chronic suppurative otitis media. With all cases bacterial eradication rates were, respectively, 76% and 67%. Bacterial eradication rates were always higher for the CTRX group than for the CTM group, but the difference was not significant between the 2 groups. 4. Against infections caused by Staphylococcus aureus alone, CTRX showed equal clinical and bacteriological efficacies to CTM. 5. As side effects, dermatitis, vomiting, and malaise were observed in 5 cases (4%) of the CTRX group and 3 cases (3%) of the CTM group. As clinical testing abnormalities, elevations of GOT, GPT, and Al-P, and thrombocytopenia were noted only in 3 cases (5%) of the CTRX group. Furthermore, all of these abnormalities were temporary and of moderate degree or mild, thus the safety of either drug was considered high. 6. Clinical utilities were 71% in the CTRX group and 86% in the CTM group for acute suppurative otitis media, and 72% and 62%, respectively, for chronic suppurative otitis media. When all cases were included, they were 72% and 66%, respectively, and there was no significant difference between the 2 groups. It is concluded from the above results that CTRX is a highly useful drug with once daily administration of 1 g in the treatment of suppur

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefotiam; Ceftriaxone; Drug Eruptions; Drug Evaluation; Female; Humans; Japan; Male; Middle Aged; Multicenter Studies as Topic; Otitis Media; Otitis Media, Suppurative; Thrombocytopenia; Vomiting

BACKGROUND We present a case of Group B Streptococcus (Streptococcus agalactiae or GBS) meningitis in a non-pregnant woman that likely originated from acute otitis media. Although invasive Group B Streptococcal infections are increasing in the United States, GBS meningitis is still rare in non-pregnant adults. At the end, we discuss risk factors for this disease and data that suggest that invasive GBS infection is increasing in the adult and elderly populations of the United States. CASE REPORT Our patient was a 55-year-old woman with a history of juvenile rheumatoid arthritis who presented with altered mental status after failure of outpatient treatment of otitis media with oral doxycycline and steroids. Upon admission, she was initially afebrile and hemodynamically stable, but she had a rapid decline and required emergent intubation. Blood cultures grew GBS. CSF PCR analysis performed by BioFire® FilmArray® Meningitis/Encephalitis Panel revealed GBS. Middle-ear fluid and CSF cultures drawn after 1 day of antibiotic therapy did not grow any organisms. Treatment was achieved with high-dose intravenous ceftriaxone for 14 days, and tympanoplasty. At the end of 14 days of antibiotic therapy, the patient had full neurological recovery, without any residual neurological deficits. CONCLUSIONS GBS meningitis is classically associated with neonatal disease, but invasive GBS infection is fairly common in adults and appears to be increasing in incidence secondary to increasing populations living with diabetes, immunosuppressed conditions, and advanced age. Central nervous system infection with this organism is still rare. In this case report we describe a non-pregnant woman who presented with GBS meningitis.

Topics: Adult; Aged; Ceftriaxone; Female; Humans; Infant, Newborn; Meningitis, Bacterial; Middle Aged; Otitis Media; Streptococcal Infections; Streptococcus agalactiae

Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Ceftriaxone; Chinchilla; Disease Models, Animal; Ear, Middle; Humans; Otitis Media; Otitis Media with Effusion; Tomography, Optical Coherence; Tympanic Membrane

The incidence of complications due to acute otitis media (AOM) in childhood has decreased significantly with the use of new antibiotics in recent years. However, acute mastoiditis (AM) is still the most common complication that can lead to further intracranial conditions with high morbidity. Our study aimed to evaluate the clinical characteristics of children with AM and identify possible indicators for further intracranial complications associated with this condition.. Children hospitalized in our clinic with a diagnosis of AM were reviewed. Demographic data, disease-related symptoms, types of complications accompanied by AM, medical/surgical treatments modalities, and culture results were screened. The patients were divided into two groups as those with and without intracranial complications (ICCs). Routine complete blood count tests, biochemical analysis, and C-reactive protein (CRP) level measurement were evaluated and compared between the groups.. Of the 28 AM patients, five (17.9%) had isolated AM. Complications associated with AM included sub-periosteal abscess (28.6%), facial paralysis (25%), meningitis (17.9%), meningitis with sigmoid sinus thrombosis (7.1%), and meningitis with cerebellar abscess (3.6%). Eight patients developed ICCs (28.6%), of whom three had more than one complication. Ceftriaxone was found to be the first-line medical treatment (57.1%). Streptococcus pneumoniae was the most common pathogen isolated from the cultures (42.9%). Three patients (10.7%) were treated non-surgically, eight (28.6%) with myringotomy and ventilation tube (VT) insertion, eight patients (28.6%) with abscess drainage and VT insertion, and nine (32.1%) with cortical mastoidectomy and VT insertion. There was no significant difference between the patients with and without ICCs in terms of complete blood count parameters. The CRP level and the CRP-albumin ratio were significantly higher in patients with ICCs than those without these complications (p < 0.001).. AM remains to be the most common complication of AOM in childhood and can lead to further life-threatening conditions. Additional interventions according to the type of the complication with VT insertion is safe and effective in the management of AM. In patients with AM, it is of great importance to determine whether there is an accompanying ICC. The CRP-albumin ratio is a simple and reliable calculation to detect ICCs in patients with AM.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Blood Cell Count; Brain Abscess; C-Reactive Protein; Ceftriaxone; Child; Child, Preschool; Drainage; Facial Paralysis; Female; Humans; Infant; Male; Mastoidectomy; Mastoiditis; Meningitis; Middle Ear Ventilation; Otitis Media; Serum Albumin; Sinus Thrombosis, Intracranial; Streptococcus pneumoniae

Acute otitis media (AOM) is the main indication for pediatric antibiotic prescriptions, accounting for 25% of prescriptions. While the use of topical drops can minimize the administered dose of antibiotic and adverse systemic effects compared to oral antibiotics, their use has limitations, partially due to low patient compliance, high dosing frequency, and difficulty of administration. Lack of proper treatment can lead to development of chronic OM, which may require invasive interventions. Previous studies have shown that gel-based drug delivery to the ear is possible with intratympanic injection or chemical permeation enhancers (CPEs). However, many patients are reluctant to accept invasive treatments and CPEs have demonstrated toxicity to the tympanic membrane (TM). We developed a novel method of delivering therapeutics to the TM and middle ear using a topical, thermoresponsive gel depot containing antibiotic-loaded poly(lactic-co-glycolic acid) microspheres. Our in vitro and ex vivo results suggest that the sustained presentation can safely allow therapeutically relevant drug concentrations to penetrate the TM to the middle ear for up to 14 days. Animal results indicate sufficient antibiotic released for treatment from topical administration 24h after bacterial inoculation. However, animals treated 72h after inoculation, a more clinically relevant treatment practice, displayed spontaneous clearance of infection as is also often observed in the clinic. Despite this variability in the disease model, data suggest the system can safely treat bacterial infection, with future studies necessary to optimize microsphere formulations for scaled up dosage of antibiotic as well as further investigation of the influence of spontaneous bacterial clearance and of biofilm formation on effectiveness of treatment. To our knowledge, this study represents the first truly topical drug delivery system to the middle ear without the use of CPEs.

Topics: Acute Disease; Administration, Topical; Animals; Anti-Bacterial Agents; Ceftriaxone; Chinchilla; Ciprofloxacin; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Gels; Guinea Pigs; Microspheres; Otitis Media

Gradenigo's syndrome is defined by the classic clinical triad of ear discharge, trigeminal pain, and abducens nerve palsy. It has become a very rare nosological entity after the introduction of antibiotics, so that has been defined as the "forgotten syndrome." However, the underlying pathological process (apical petrositis) still represents a life-threatening condition that shall be immediately recognized in order to address the patient to the proper therapy. The therapy itself may be an argument of discussion: on a historical background ruled by surgery, reports of successful conservative antibiotic treatment have risen in recent years.. We reported a case of Gradenigo's syndrome in a child with an abscess of the left petrous apex and initial involvement of the carotid artery. After multidisciplinary evaluation, we decided to encourage conservative treatment, until complete regression was observed.. The available literature of the last 10 years was reviewed, with particular attention to the presence of an apical abscess and the therapeutic approach. The principles of management with regard to conservative therapy versus surgical indications are therefore examined and discussed.

Topics: Abscess; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Child; Drug Therapy, Combination; Humans; Male; Methylprednisolone; Metronidazole; Otitis Media; Petrositis; Petrous Bone; Teicoplanin

Acute otitis media (AOM) nonresponsive to antibiotics is most commonly caused by antibiotic-resistant Streptococcus pneumoniae and Haemophilus influenzae. A strategy for treating these infections with parenteral ceftriaxone was adopted at the Children's Hospital Iceland. The 10-valent pneumococcal H. influenzae protein D-conjugate vaccine was introduced into the vaccination program in Iceland in 2011. The aim was to study its effect on the incidence of AOM with treatment failure.. This retrospective observational study included children who visited the Children's Hospital Iceland because of AOM or received ceftriaxone, regardless of indication from 2008-2015. Incidence rate was calculated for prevaccine (2008-2011) and postvaccine (2012-2015) periods using person-years at risk within the hospital's referral region. Incidence rate ratio of ceftriaxone treatment episodes of AOM was calculated using the Mantel-Haenzel method adjusting for age. Incidence risk ratio of ceftriaxone treatment if presenting to the hospital with AOM was calculated to adjust for rate of AOM visits.. Visits for AOM decreased from 47.5 to 33.9 visits per 1000 person-years, incidence rate ratio (IRR) 0.86 (95% confidence interval [CI]: 0.81-0.91), P < 0.001. Fewer AOM episodes were treated with ceftriaxone, decreasing from 6.49 to 2.96 treatment episodes per 1000 person-years, with an overall Mantel-Haenzel adjusted IRR 0.45 (95% CI: 0.37-0.54; P < 0.001). This remained significant after adjusting for the decrease in AOM visits, IRR 0.53 (95% CI: 0.44-0.63; P < 0.001).. Visits for AOM and ceftriaxone use decreased significantly after H. influenzae protein D-conjugate vaccine introduction. The observed decrease in ceftriaxone use is presumed to represent a decline in AOM with treatment failure, secondary to a decrease in resistant infections.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Ceftriaxone; Child; Child, Preschool; Haemophilus Infections; Haemophilus Vaccines; Humans; Iceland; Immunoglobulin D; Incidence; Infant; Infant, Newborn; Lipoproteins; Otitis Media; Pneumococcal Infections; Pneumococcal Vaccines; Retrospective Studies; Treatment Failure

Topics: Adult; Anti-Bacterial Agents; Brain Edema; Ceftriaxone; Humans; Magnetic Resonance Imaging; Male; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections

Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae.. Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance.. CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%.. High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; beta-Lactam Resistance; Ceftriaxone; Child; Computer Simulation; Dose-Response Relationship, Drug; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

A case of Haemophilus parainfluenzae meningitis in a woman with a 3-day history of acute otitis media is reported. Her medical history included bladder cancer surgery. Unequivocal identification of the isolate was obtained by using molecular techniques such as 16S rRNA sequencing besides to conventional culture methods. To investigate bacterial virulent traits possibly related to invasive properties, in vitro serum resistance of our isolate was analyzed, but it was found serum susceptible. Our study demonstrates that H. parainfluenzae can be considered an opportunistic pathogen able to cause life-threatening infections not only in children but also in patients with underlying conditions.

Topics: Acute Disease; Adult; Ampicillin; Anti-Bacterial Agents; Ceftriaxone; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infusions, Intravenous; Meningitis, Haemophilus; Otitis Media; RNA, Bacterial; RNA, Ribosomal, 16S; Virulence

We present the clinical, radiological and pathological features of a case of a cranial hypertrophic pachymeningitis that developed in the course of mastoiditis and petrous apex inflammation and responded to immunosuppressive therapy only. Documented by the development of clinical findings, magnetic resonance imaging, cerebrospinal fluid changes, histopathology findings, by otosurgical intervention and finally by the insertion of a ventriculo-peritoneal shunt, the case illustrates a gradual development of pachymeningitis with consequent hydrocephalus and intracranial hypertension. We consider this disease development an example of immune-induced proliferative fibrotic changes in meninges.

Topics: Abducens Nerve Diseases; Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid; Chloramphenicol; Drug Therapy, Combination; Humans; Hydrocephalus; Hypertrophy; Immunoglobulin G; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Mastoiditis; Meninges; Meningitis; Methotrexate; Methylprednisolone; Middle Aged; Otitis Media; Petrous Bone; Syndrome; Trigeminal Nerve Diseases

To examine the incidence of acute otitis media (AOM) and mastoiditis in children after cochlear implantation (CI) and to evaluate the role of mastoidectomy in decreasing the rate of AOM in implanted children by comparing two surgical techniques: the Posterior tympanotomy approach (MPTA, with mastoidectomy) and the Suprameatal approach (SMA, without mastoidectomy).. A retrospective study was conducted on 234 children up to 16 years of age who underwent CI between 1993 and 2003 in our department. The children were divided into two groups according to the surgical technique that had been used for the implantation: the MPTA group and the SMA group.. Part of the children with a history of pre-implantation AOM (22 of 29 in MPTA group and 26 of 38 in SMA group) did not suffer from AOM post-CI (p=0.59), and an incidence of AOM after CI in children who did not have history of AOM prior to implantation (13 patients of MPTA group and 15 patients of SMA group) was unrelated to surgical approach (p=0.65). The incidence of pre-implantation AOM was similar for the two groups and declined after CI unrelated to performing of mastoidectomy in surgical technique. Overall, 47 children (20.1%) had post-CI AOM compared to 67 children (28.6%) who had pre-CI AOM. Mastoiditis developed in 11 children (4.7%), all 11 in the MPTA group. A subperiosteal abscess was incised and drained with the retroauricular approach in three of these children and the others were managed with intravenously administered ceftriaxone 50mg/kg/day for 3-5 consecutive days, followed by a course of oral cephalexin until there is complete clinical resolution of the effusion in the middle ear. The implants were preserved in all cases. Seven out of 11 children with mastoiditis had no history of AOM prior to implantation.. AOM and mastoiditis represent common complications of CI that can be successfully treated with the prompt use of antibiotics. However, the subperiosteal abscess could require surgical drainage. In our opinion, the decrease of incidence of AOM in implanted children is the result of natural history of otitis media and is unrelated to the surgical approach.

Topics: Abscess; Acute Disease; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Cephalexin; Child; Child, Preschool; Cochlear Implantation; Drainage; Female; Humans; Infant; Israel; Male; Mastoiditis; Otitis Media; Retrospective Studies

A 10-kg 9-month-old infant with recurrent, unresponsive otitis media presented with bilateral acute otitis media caused by Streptococcus pneumoniae type 19A, resistant to all oral agents and intermediately susceptible to ceftriaxone. Treatment with myringotomies and intramuscular ceftriaxone, 50 mg/kg/d for 5 days, was unsuccessful. The patient responded to pressure equalization tubes and local ciprofloxacin with dexamethasone drops.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Ear, Middle; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

Rheumatoid arthritis is a severe deforming chronic disease which has major implications for mortality and quality of life. Agents with anti-tumour necrosis factor alpha (TNFalpha) activity are a new modality of therapy, which can significantly reduce the acute inflammation in this condition. However, TNFalpha is a cytokine involved in initiating the protective immune response; consequently, patients receiving this therapy are at increased risk of infection. Etanercept is a recombinant form of the p75 TNF receptor (TNF-RII) dimerised by fusion with a portion of the human IgG1 Fc tail with anti-TNFalpha activity. We report the first case of a patient with rheumatoid arthritis who developed pneumococcal meningitis whilst on etanercept, suggesting a possible association between etanercept and this severe life threatening infection.

Topics: Antirheumatic Agents; Ceftriaxone; Ciprofloxacin; Disease Susceptibility; Etanercept; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Infusions, Intravenous; Meningitis, Pneumococcal; Middle Aged; Otitis Media; Receptors, Tumor Necrosis Factor; Streptococcus pneumoniae; Treatment Outcome

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefprozil; Ceftriaxone; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Otitis Media; Risk Assessment; Sensitivity and Specificity; Streptococcus pneumoniae

A 65-year-old woman with diabetes mellitus and chronic otitis media developed headache, fever, and hoarseness, all of which did not responded to the oral antibiotics. As stiff neck and lower cranial nerve palsies appeared, bacterial meningitis was suspected. Neurological examination revealed the right hearing disturbance, right recurrent laryngeal nerve palsy, left sternocleidomastoid muscle atrophy and bilateral tongue atrophy. The CSF examination revealed mild pleocytosis and elevated protein, but no bacterial organism was cultured from the CSF. CT scans showed bilateral mastoiditis, and the right mastoid process and a posterior part of the petrous bone were eroded, indicating the exposed bony structures to the posterior fossa. MRI scans demonstrated the thickening of the dura mater of the posterior fossa and the right cerebellar tentorium. This is a rare example of bacterial pachymeningitis of the posterior fossa, the clinical symptoms and MRI findings of which resolved solely by antimicrobial agents without corticosteroid.

Topics: Aged; Ceftriaxone; Female; Humans; Hypertrophy; Mastoiditis; Meningitis; Otitis Media

(1) The best-assessed antibacterial agents in otitis are penicillin V and amoxicillin. No other antibacterial agents are any more effective in clinical trials. (2) In France, amoxicillin seems the best choice because it is still active against pneumococci with diminished sensitivity to penicillin. Also, amoxicillin causes very few serious adverse effects. (3) There is no firm evidence that clavulanic acid makes amoxicillin any more effective. In fact the combination of amoxicillin + clavulanic acid causes more gastrointestinal adverse effects (including potentially severe diarrhoea) than any other antibacterial agent. (4) For patients who are allergic to penicillin, a macrolide such as erythromycin, or cotrimoxazole, appear to be acceptable first-line alternatives. (5) According to a reliable randomised trial, delaying the decision about antibacterial treatment by 72 hours in children with acute otitis media does no harm. If the decision is delayed, three quarters of children avoid antibacterial therapy altogether. (6) Patients get no extra benefit from extending treatment beyond 5 to 7 days. (7) Prolonged treatment, and the use of low doses are risk factors for subsequent carriage of resistant bacteria. (8) There are no comparative trials of antibacterial agents in children at high risk of severe or complicated disease including infants under 3 months old, children with immunosuppression, and those with high fever.

Topics: Amoxicillin; Ceftriaxone; Child; Clavulanic Acid; Clinical Trials as Topic; Drug Resistance, Bacterial; France; Haemophilus influenzae; Humans; Moraxella catarrhalis; Otitis Media; Penicillin V; Randomized Controlled Trials as Topic; Streptococcus pneumoniae

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Clarithromycin; Female; Humans; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae

(1) Ceftriaxone, a third-generation cephalosporin antibiotic, is now licensed in France for (intramuscular) treatment of acute otitis media in children, both as first-line therapy in children under 30 months, and after failure of a first antibiotic regimen. (2) The clinical file on first-line ceftriaxone treatment is relatively bulky. In contrast, only two non comparative trials of ceftriaxone after failure of initial treatment are available. (3) According to trials of first-line treatment, the efficacy of a single intramuscular dose of ceftriaxone is equivalent to that of the sulfamethoxazole + trimethoprim combination and the amoxicillin + clavulanic acid combination, and similar to that of amoxicillin (when all these reference antibiotics are given orally for 10 days). (4) Pain at the injection site is the main adverse effect of ceftriaxone, despite the local anaesthetic (lidocaine) contained in the solvent.

Topics: Ceftriaxone; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Drug Approval; Drug Resistance, Microbial; France; Humans; Infant; Otitis Media; Treatment Outcome

The case of a 72-year-old woman suffering from chronic otitis media is presented. This insulin dependent diabetic patient was under steroid therapy for collagenosis and suffered from chronic polysinusitis. After two preceding drainages of the mastoid (antrotomy and mastoidectomy), the patient developed putrid mastoiditis followed by Bezold's abscess, an epidural abscess and thrombosis of the sigmoid sinus. Lateral petrosectomy and drainage of the neck were performed, but the patient again developed an abscess with extension to the lateral skull base, the foramen magnum and the upper cervical spine. After a further operation with extensive drainage and a three-month course of antibiotic treatment with ceftriaxon, the infection finally healed. A germ of the Streptococcus milleri group was identified.

Topics: Aged; Ceftriaxone; Cephalosporins; Chronic Disease; Diabetes Mellitus, Type 1; Epidural Abscess; Female; Humans; Mastoiditis; Neck; Otitis Media; Sinusitis; Skull Base; Streptococcal Infections

Ceftriaxone was approved in 1997 for the treatment of otitis media despite previous studies that documented an association of ceftriaxone with elevated hepato-biliary enzymes and transient biliary stasis. The case cited here highlights the need for continued awareness education for physicians who may use ceftriaxone to treat common illnesses such as acute exudative tonsillitis and otitis media in children. Specifically, for children with a family history of gallbladder, biliary tract, liver or pancreas dysfunction, ceftriaxone may not be the drug of choice since the likelihood of complications is increased in this population. Additionally, ceftriaxone may cause problems in either adults or children with preexisting disease, who may not be well-nourished, or who may be dehydrated.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bile Duct Diseases; Ceftriaxone; Cephalosporins; Chemical and Drug Induced Liver Injury; Humans; Infant; Male; Otitis Media

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Otitis Media; Practice Patterns, Physicians'; Streptococcus pneumoniae

To assess the clinical outcome and risk of failure after oral vs. intravenous treatment in otitis media caused by penicillin-resistant pneumococci. To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome.. Retrospective study of 156 cases collected between 1993 and 1995. Mean follow-up: 5 months. Setting. Two tertiary academic medical centers in Paris, France.. Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156. Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed. For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed. Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure.. Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins. Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate). Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy. Acute mastoiditis occurred in 4 infants resulting in mastoidectomy. Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively. Mean duration of therapy was 10.7 days. Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred. No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence. A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome.. Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media. Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Cefotaxime; Ceftriaxone; Cephalosporins; Humans; Infant; Injections, Intravenous; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Penicillins; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Treatment Failure

Selection of appropriate antibiotic treatment for children with acute otitis media (AOM) is challenging. Although the diagnosis is relatively easy for experienced clinicians, the distinction between AOM and otitis media with effusion is often more subtle. In general therapy is empiric and the pathogen causing disease in a given patient remains unknown. However, this situation is made even more difficult by the dynamic nature of the pathogenesis of AOM. Both the proportion of patients infected with one of the three primary pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and the antimicrobial susceptibility patterns of these pathogens are changing. Currently there are 16 antibiotics labeled for use in AOM. Only 2 are reliably effective against penicillin-resistant pneumococcus: high dose amoxicillin (80 to 100 mg/kg/day) and im ceftriaxone. Among the others all are beta-lactamase-stable and have proven clinical effectiveness in AOM patients infected with H. influenzae or M. catarrhalis. Even with the high spontaneous resolution rate reported for AOM, antimicrobial therapy remains the standard of care in the United States. Recognition of the fundamental determinants of effective therapy should permit rational antibiotic selection for each patient.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Decision Making; Drug Resistance, Microbial; Humans; Infant; Otitis Media

The gram negative bacteria, nontypable Haemophilus influenzae (NTHi) was used to induce otitis media in a total of 18 chinchillas. Three days post-inoculation, three cohorts of 6 chinchillas each were treated daily for four days with either ceftriaxone, chloramphenicol, or diluent without antibiotics. Middle ear fluid (MEF) was obtained daily, assayed for endotoxin content by means of the chromogenic limulus amebocyte lysate assay, and concentration of the NTHi/mL MEF determined by standard plate count. The endotoxin concentration per mL MEF from both the antibiotic treated cohorts decreased during the observation period, but increased in the MEF of the untreated control group. The data indicate that, unlike the dramatic increase in endotoxin concentration, after antibiotic treatment in the cerebrospinal fluid (CSF) during experimental Haemophilus influenzae-induced meningitis, there is no demonstrable sustained release of endotoxin in the middle ear subsequent to antibiotic treatment during experimental otitis media.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Chinchilla; Chloramphenicol; Disease Models, Animal; Endotoxins; Haemophilus influenzae; In Vitro Techniques; Otitis Media; Protein Synthesis Inhibitors

Nontypeable Haemophilus influenzae strain INT1 was isolated from the blood of a young child with clinical signs of meningitis following acute otitis media. No immunologic or anatomic predisposition of this child for invasive bacterial infection with an unusual organism was documented. Sensitive ELISA proved the absence of intra- or extracellular capsular polysaccharide production by INT1 and Southern blot analysis confirmed the lack of an intact capsulation (cap) gene locus within the chromosome. Nevertheless, INT1 established bacteremia and meningitis in infant and weanling rat models of invasive H. influenzae infection. High-molecular-weight DNA isolated from INT1 was shown to confer an invasive phenotype on transformation of a nonencapsulated, avirulent laboratory strain of H. influenzae. Together these findings imply the presence of one or more as-yet-undiscovered, noncapsular virulence factors of H. influenzae that are capable of mediating invasive disease and resistance to immunologic clearance.

Topics: Amoxicillin; Animals; Bacteremia; Bacterial Capsules; Blotting, Southern; Ceftriaxone; Cephalosporins; Child, Preschool; DNA, Bacterial; Enzyme-Linked Immunosorbent Assay; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Meningitis, Bacterial; Otitis Media; Penicillins; Phenotype; Polysaccharides, Bacterial; Rats; Rats, Sprague-Dawley; Virulence

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.

Topics: Animals; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Chromatography, High Pressure Liquid; Female; Gerbillinae; Half-Life; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Acute Disease; Body Weight; Ceftriaxone; Cephalosporins; Child; Humans; Injections, Intramuscular; Otitis Media

Topics: Acute Disease; Ceftriaxone; Cephalosporins; Child; Drug Resistance, Microbial; Drug Utilization; Humans; Otitis Media

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ceftriaxone; Cephalosporins; Child; Clavulanic Acids; Drug Therapy, Combination; Humans; Otitis Media; Parents; Treatment Failure

A case of sepsis and meningitis caused by Neisseria meningitidis with relative resistance to penicillin occurred in North Carolina in August 1992. This isolate was relatively resistant due to decreased affinity of its penicillin-binding protein 2 for penicillin. Such isolates have been reported in Spain, elsewhere in Europe, in South Africa, and in Canada, but invasive disease caused by meningococcal isolates relatively resistant to penicillin was not recognized in the United States before a preliminary report of this case in October 1992. The Centers for Disease Control and Prevention recently retrospectively identified 3 additional cases from 1991. A fifth case occurred in Kentucky in 1993. Surveillance studies of penicillin susceptibility of N. meningitidis isolates suggest such meningococci have existed sporadically in the past. Increases in prevalence and magnitude of penicillin resistance among strains of N. meningitidis would require reconsideration of current clinical practice with regard to treatment of meningococcal disease.

Topics: Amoxicillin; Bacteremia; Bacterial Proteins; Carrier Proteins; Ceftriaxone; Drug Therapy, Combination; Female; Hexosyltransferases; Humans; Infant; Meningitis, Meningococcal; Meningococcal Infections; Multienzyme Complexes; Muramoylpentapeptide Carboxypeptidase; Neisseria meningitidis; North Carolina; Otitis Media; Penicillin G; Penicillin Resistance; Penicillin-Binding Proteins; Peptidyl Transferases; Rifampin

Topics: Acute Disease; Amoxicillin; Ceftriaxone; Child; Humans; Otitis Media

Topics: Acute Disease; Amoxicillin; Ceftriaxone; Child; Humans; Otitis Media