ro13-9904 and Otitis-Media-with-Effusion

Acute mastoiditis (AM) is a relatively rare complication of acute otitis media (AOM). The most common pathogens include Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Pneumococcal vaccination and changes in antibiotic prescribing recommendations for AOM may change the incidence of AM in the future. Diagnosis of AM can be made based on clinical presentation, but computed tomography of the temporal bone with contrast should be considered if there is concern for complicated AM. Both extracranial and intracranial complications of AM may occur. Previously, routine cortical mastoidectomy was recommended for AM treatment, but new data suggest that a more conservative treatment approach can be considered, including intravenous (IV) antibiotics alone or IV antibiotics with myringotomy. [Pediatr Ann. 2016;45(5):e176-e179.].

Topics: Abscess; Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Infant; Mastoid; Mastoiditis; Otitis Media with Effusion; Periosteum; Periostitis; Pneumococcal Infections; Streptococcus pneumoniae; Tomography, X-Ray Computed

Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM). In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone. A second, non-comparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen. The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate. The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM. In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001). We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children.

Topics: Azithromycin; Ceftriaxone; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Otitis Media with Effusion; Pilot Projects; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; 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

Two potent mediators of acute inflammation, histamine and leukotriene B4 (LTB4), have been shown to play important roles in the pathogenesis and clinical course of acute otitis media (AOM) in children. The purpose of this study was to evaluate the ability of adjuvant drugs, antihistamine and corticosteroid, in reduction of the levels of histamine and LTB4 in the middle ear and their ability to improve outcomes of AOM.. Eighty children with AOM (aged 3 months to 6 years) were enrolled in a prospective, randomized, double-blind, placebo controlled study. All children received one dose of intramuscular ceftriaxone and were randomly assigned to receive either chlorpheniramine maleate (0.35 mg/kg per day) and/or prednisolone (2 mg/kg per day) or placebos three times a day for 5 days. Tympanocentesis was performed at enrollment and after 5 days of adjuvant drug treatment. MEFs were collected for bacterial and viral studies and histamine and LTB4 levels. The subjects were followed for the duration of middle ear effusion or up to 3 months.. Histamine or LTB4 levels in the MEF after 5 days of treatment were not significantly reduced by adjuvant drug treatment. However, subjects receiving corticosteroid had a lower rate of treatment failure during the first 2 weeks and shorter duration of middle ear effusion.. Five day of antihistamine or corticosteroid treatment does not reduce the levels of histamine or leukotriene B4 in the MEF of children with AOM. Positive clinical outcomes of AOM cases associated with corticosteroid treatment needs to be confirmed in a larger clinical trial of children with intact tympanic membranes, who do not receive tympanocentesis.

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Child; Child, Preschool; Chlorpheniramine; Double-Blind Method; Drug Therapy, Combination; Ear, Middle; Female; Histamine; Histamine H1 Antagonists; Humans; Infant; Leukotriene B4; Male; Otitis Media with Effusion; Prednisolone; Prospective Studies

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.. 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.. 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.. 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).. 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.

Topics: Acute Disease; Carrier State; Ceftriaxone; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Follow-Up Studies; Humans; Infant; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Nasopharynx; Otitis Media with Effusion; Pneumococcal Infections; Probability; Prospective Studies; Reference Values; Streptococcus pneumoniae; Treatment Outcome

To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment.. In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14.. Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group.. In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child, Preschool; Drug Administration Schedule; Female; Haemophilus influenzae; Humans; Infant; Male; Moraxella catarrhalis; Nasopharynx; Otitis Media with Effusion; Prospective Studies; Streptococcus pneumoniae; Treatment Outcome

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).. 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.. 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).. A single intramuscular dose of ceftriaxone is comparable in clinical efficacy to 10 days of oral TMP-SMZ for treatment of AOM.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Injections, Intramuscular; Male; Nasopharynx; Otitis Media with Effusion; Prospective Studies; Single-Blind Method; Streptococcus; Sulfamethoxazole; Trimethoprim

Fifty-two children (mean age 23 months) with acute otitis media were treated randomly with either a single intramuscular dose of ceftriaxone (Rocephin) 50 mg/kg (27 patients) or 7 days of amoxicillin 12.5 mg/kg t.i.d. (25 patients). The rate of resolution of acute symptoms and incidence of recurrences and relapses during the first months after commencement of the therapy was similar in the two groups. One week following the start of treatment no difference was observed in the proportion of patients with tympanometric evidence of middle ear effusion (MEE) in either of the two groups. On day 30, however, significantly more patients from the ceftriaxone group had flat tympanograms-83% as compared to 47% in the amoxicillin group. Therefore, single-dose ceftriaxone therapy cannot be suggested at present as routine therapy for acute otitis, although it may be considered a reasonable alternative in noncompliant patients.

Topics: Administration, Oral; Amoxicillin; Ceftriaxone; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Injections, Intramuscular; Male; Otitis Media with Effusion; Prospective Studies; Random Allocation

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 aim of this study is to examine the internalization of nontypeable Haemophilus influenzae (NTHi) into human epithelial cells.. Bactericidal assay was applied to examine the effects of antibiotics against cell-adherent NTHi using HEp-2 cells. A trans-well chamber assay was applied to examine the internalization and penetration of NTHi using Detroit562 cells.. The adherence of NTHi to HEp-2 cells was noted after 2h of incubation. Azithromycin had a strong bactericidal effect against both cell-associated and non-adherent NTHi, while ceftriaxone did not show bactericidal effects on NTHi adhered to the HEp-2 cells. Three (60.0%) out of five NTHi isolates from the nasopharynx of children with intractable acute otitis media (AOM) internalized into and subsequently penetrated through the epithelial cells at various degrees. Azithromycin had a strong bactericidal effect against the cell-internalized NTHi, while ceftriaxone was bactericidal only against extracellular NTHi.. The potential of NTHi as the intracellular pathogen may contribute to the persistent existence of this pathogen that result in the prolonged and intractable clinical course of AOM. Azithromycin may be a therapeutically significant antibiotic for patients with prolonged respiratory tract infections due to NTHi.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Bacterial Adhesion; Bacterial Physiological Phenomena; Ceftriaxone; Cell Line; Child; Dose-Response Relationship, Drug; Epithelial Cells; Gentamicins; Haemophilus Infections; Haemophilus influenzae; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Microbial Viability; Otitis Media with Effusion

To determine patterns of resistance for isolates of Streptococcus pneumoniae recovered from middle ear fluids of children from eight children's hospitals between September, 1994, and August, 1997.. Data were extracted retrospectively from the medical records of eight children's hospitals. A standardized data form was completed for each episode of pneumococcal infection. Systemic isolates (blood and pleural, synovial and spinal fluids) of S. pneumoniae were collected during the same period. All isolates of S. pneumoniae from each center were sent to a central laboratory. Susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Organisms were considered nonsusceptible to penicillin if the minimum inhibitory concentration was > or = 0.1 microg/ml and nonsusceptible to ceftriaxone if the minimum inhibitory concentration was > or = 1.0 microg/ml.. S. pneumoniae was recovered from the middle ear fluids of 707 children from all centers during the study period. Thirty-nine (5.5%) were infections recorded at 4 centers which evaluated middle ear fluid only sporadically and were not included in this analysis. The remaining 668 infections reported by the 4 remaining participating hospitals reflect the experience of 608 children. There were 54% boys; 440 (73%) were Caucasian, 111 (18%) were African-American, 38 (6%) were Hispanic and for 19 (3%) the race was not recorded. The children ranged in age from 16 days to 13.8 years with a mean (+/-sD) of 26.0 (+/- 26.1) months. Children who received antibiotics in the 30 days before the middle ear isolate was recovered were more likely to harbor a resistant strain of S. pneumoniae than children who had not recently received an antibiotic (P < 0.001). Isolates recovered from children with spontaneous otorrhea were more likely to be susceptible to penicillin than isolates recovered during myringotomy, with or without the insertion of tympanostomy tubes (P < 0.01). There was wide variation in the susceptibility of middle ear isolates to penicillin and ceftriaxone according to geographic location; however, in every locale the middle ear isolates were less likely to be susceptible to penicillin and ceftriaxone than systemic isolates of S. pneumoniae.. The prevalence of penicillin-resistant and cephalosporin-resistant S. pneumoniae in middle ear isolates derived from children cared for at four different children's hospitals was quite variable. In some locations the prevalence of resistance is still increasing, whereas in other areas the rate of resistance was at a plateau during the period of surveillance. The prevalence of isolates of S. pneumoniae susceptible to penicillin and ceftriaxone was always less common among middle ear isolates than among systemic isolates. Previous antibiotic use remains the most predictive factor for the recovery of isolates resistant to penicillin and ceftriaxone.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Otitis Media with Effusion; Penicillin G; Penicillin Resistance; Pneumococcal Infections; Prevalence; Recurrence; Retrospective Studies; Streptococcus pneumoniae; United States

Topics: Area Under Curve; Ceftriaxone; Cephalosporins; Child, Preschool; Exudates and Transudates; Female; Humans; Infant; Male; Otitis Media with Effusion