Oral trimethoprim/sulfamethoxazole for prevention of bacterial infection during the induction phase of cancer chemotherapy in children

We conducted a randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral trimethoprim/sulfamethoxazole (TMP/SMX) in the prevention of bacterial infections in children with cancer. Sixty-three patients with acute leukemia were studied during the induction phase of chemotherapy; 28 patients with solid tumors who were starting intensive chemotherapy were also enrolled and treated for 2 months. There was no significant difference in the frequency of febrile episodes between the 43 children receiving trimethoprim/sulfamethoxazole and the 48 receiving placebo. However, when the group of 74 children who experienced granulocytopenia (absolute granulocyte count less than 500/microL) was analyzed separately, significant reductions in the frequencies of confirmed bacteremia (2.6% v 20.0%, P = .02) and febrile episodes (35.9% v 65.7%, P = .01) were observed in the trimethoprim/sulfamethoxazole group. Furthermore, life table analysis showed that children with leukemia receiving trimethoprim/sulfamethoxazole had significantly more days without fever and without bacteremia. No benefits from prophylaxis were recognized in the subgroup with solid tumors. Although the frequency of oral thrush was greater (P = .02) in the trimethoprim/sulfamethoxazole group (25.6%) than in the placebo group (6.3%), invasive fungal infection did not occur. Although the mean duration of granulocytopenia was greater among those receiving trimethoprim/sulfamethoxazole (13.7 v 9.0 days, P = .05), this did not appear to increase the overall risk for bacterial infection. These data suggest that trimethoprim/sulfamethoxazole reduces the frequency of bacteremia and febrile episodes in granulocytopenic children undergoing induction chemotherapy for acute leukemia.     

Erythromycin-sulfisoxazole vs amoxicillin in the treatment of acute otitis media in children. A double-blind, multiple-dose comparative study

A fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl (erythromycin-sulfa) was compared with amoxicillin for the treatment of acute otitis media (AOM) in children. Of 145 patients studied, 76 boys and 69 girls were compliant and were evaluated for drug efficacy (72 amoxicillin, 73 erythromycin-sulfa). Based on otoscopic and tympanometric results, cure rates at ten to 14 days for AOM due to all organisms were 83% (63/72) for amoxicillin and 89% (65/73) for erythromycin-sulfa; for Haemophilus species (including mixed infections), they were 84% for amoxicillin (26/31) and 83% for erythromycin-sulfa (20/14). Cure rates for ampicillin-resistant Haemophilus were 1/1 for amoxicillin and 7/8 (88%) for erythromycin-sulfa; one patient (12%) had persistent AOM at day 10. Of the patients with AOM due to Streptococcus pneumoniae, 82% (29/35) in the amoxicillin-treated group and 98% (39/40) in the erythromycin-sulfa-treated group were cured. Patients with S pneumoniae as the initial infecting organism who were treated with amoxicillin had significantly more clinical recurrences then their erythromycin-sulfa-treated counterparts, 66% (8/12) vs 33% (3/9). There was no difference between treatment groups in recurrence rates for patients with Haemophilus as the initial infecting organism. On the treatment day indicated, the following number of patients had middle ear effusion: by days 10 to 14, 38% (27/72) amoxicillin-treated patients and 48% (35/73) erythromycin-sulfa-treated patients; by day 28, 10% (7/71) amoxicillin-treated patients and 16% (11/70) erythromycin-sulfa-treated patients. There were no significant differences in adverse reactions. The erythromycin-sulfa combination is safe and effective treatment for AOM, including ampicillin-resistant Haemophilus.     

Acute otitis media in human immunodeficiency virus-infected children

To evaluate the occurrence and outcome of acute otitis media (AOM) in human immunodeficiency virus (HIV)-infected children, a prospective comparative cohort study was performed. Twenty-seven HIV-infected children were individually matched with paired control subjects and followed up for 543 months (mean 19.4 +/- 11). Data collected were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to Centers for Disease Control classification. During the observation period, 46 episodes of AOM were diagnosed in 15 HIV patients and 22 in 16 control children: 11 P1 had 27 AOM episodes vs 17 in 13 control children; 6 P2 had 19 AOM episodes vs 5 in 4 control children. Human immunodeficiency virus infection does not seem to modify the occurrence of AOM. Recurrent AOM (3 or more episodes in 6 months) was, however, significantly more common in P2 children. Amoxicillin, to which the bacteria isolated in P2 children were sensitive in vitro, cured 33 of 46 episodes in HIV-infected children compared with 20 of 22 in control children. Cure rate was similar in P1 children compared with control children but was significantly lower in P2 versus control children (47.3% vs 100%). Reasons for higher occurrence of failures in P2 children remain to be investigated.     

Randomized, investigator-blinded, multicenter study of gatifloxacin versus amoxicillin/clavulanate treatment of recurrent and nonresponsive otitis media in children

BACKGROUND: Decreased susceptibility of pathogens to currently used agents for recurrent otitis media has provided the impetus for identifying new antimicrobial options. OBJECTIVE: To compare gatifloxacin with amoxicillin/clavulanate in children with recurrent or nonresponsive acute otitis media (AOM). METHODS: Included in this multicenter randomized trial were 413 patients, ranging in age from 6 months to 7 years, who had recurrent AOM (at least 3 episodes in the previous 6 months or 4 episodes in the previous 12 months) and/or had failed antibiotic therapy for AOM within 14 days of enrollment. Diagnosis required evidence of acute inflammation and otoscopic findings of middle ear effusion; baseline tympanocentesis was optional and encouraged. Children were randomly assigned (2:1) to 10 days of oral therapy with gatifloxacin suspension (10 mg/kg of body weight once daily) or amoxicillin/clavulanate suspension (45/6.4 mg/kg/d in 2 divided doses). RESULTS:: Clinical cure was obtained in 90.2% (222 of 246) of patients in the gatifloxacin group and 84.3% (102 of 121) of those in the amoxicillin/clavulanate group (95% confidence interval, -1.9-12.9) 3-10 days after treatment ended. Gatifloxacin was associated with higher clinical cure rates than was amoxicillin/clavulanate in children younger than 2 years of age (92.0% versus 80.0%, respectively). Cure rates by pretreatment pathogen in the gatifloxacin and amoxicillin/clavulanate groups were 92.1% (35 of 38) versus 88.9% (16 of 18) for Streptococcus pneumoniae infections and 88.2% (30 of 34) versus 92.3% (12 of 13) for Haemophilus influenzae infections, respectively. Sustained clinical cures 3-4 weeks after treatment ended were obtained in 74.4% (183 of 246) of patients treated with gatifloxacin and 72.7% (88 of 121) of those treated with amoxicillin/clavulanate. Adverse events considered drug-related occurred with similar frequency in the 2 groups. Six patients (2.2%) in the gatifloxacin group and 2 patients (1.5%) in the amoxicillin/clavulanate group developed transient symptoms of mild or moderate arthralgia. CONCLUSIONS: In this comparative evaluation of fluoroquinolone therapy in children with AOM, gatifloxacin was similar in clinical efficacy to amoxicillin/clavulanate 45/6.4 mg/kg/d for treatment of recurrent/nonresponsive infections.     

Cefaclor v amoxicillin in treatment of acute otitis media

A randomized clinical trial compared cefaclor and amoxicillin for the treatment of acute otitis media (AOM). Twenty-four (77%) of the 31 examined patients treated with cefaclor and 25 (83%) of the 30 examined patients treated with amoxicillin had resolution of signs and symptoms after completing a ten- to 14-day course of the antibiotic. Patients who had bilateral AOM, serous or mucoid middle ear effusion, Hemophilus influenzae cultured from effusion, or more than five previous otitis media episodes, or who were 3 years of age or younger were more likely to fail treatment. Hemophilus influenzae isolated from effusion were significantly less susceptible to cefaclor than amoxicillin, but none of the 12 treatment failures were caused by antibiotic-resistant infections. Eight (36%) of the 22 patients who recovered after treatment and were reexamined one to three weeks later experienced recurrent AOM. Ear-specific, as well as patient-specific, analyses showed no significant differences between cefaclor and amoxicillin.     

Otitis media in children born to human immunodeficiency virus-infected mothers.

Acute otitis media (AOM) is thought to occur frequently in children infected with human immunodeficiency virus (HIV). We compared experience with AOM of 28 HIV-infected children with that of 33 children who seroreverted to HIV antibody negative status by age 18 months. The mean number of episodes/year of AOM for children who seroreverted decreased from 1.33 in the first year of life to 0.13 in the third year, whereas the mean number of episodes/year in HIV-infected children increased from 1.89 to 2.40. By age 3 years, all HIV-infected children had experienced 1 or more episodes of AOM, and 80% had experienced 6 or more, whereas 75% of children who seroreverted had experienced 1 or more episodes, and none had had 6 or more. HIV-infected children with normal T4 lymphocyte counts had a mean of 1.18 episodes of AOM in the first year of life compared with 2.35 episodes in HIV-infected children with decreased counts (P = 0.023). HIV-infected children with low counts had a nearly 3-fold increased risk of recurrent AOM (47% vs. 18%).     

Sulfisoxazole prophylaxis of middle ear effusion and recurrent acute otitis media

The efficacy of sulfisoxazole prophylaxis was evaluated in 32 otitis-prone children in a double-blind cross-over clinical trial. During the sulfisoxazole therapy, seven patients (22%) had nine episodes of acute otitis media (AOM) while 20 patients (63%) receiving placebo had 36 episodes of AOM (P = .001). Although sulfisoxazole appeared to be beneficial in patients aged 2 to 5 years, statistically significant efficacy was noted only in children under 2 years of age. Otitis media with effusion persisting for more than five weeks was observed in ten children (31%) during sulfisoxazole therapy and in 14 children (44%) during the placebo period (P greater than .975). Sulfisoxazole therefore appears effective in preventing recurrent symptomatic AOM but not in reducing the frequency of persistent otitis media with effusion. The importance of careful follow-up of children receiving long-term sulfisoxazole therapy for prevention of recurrent AOM is stressed.     

Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial

A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy. Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively). In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than those assigned to placebo treatment (36.0% vs 44.4%, P = .004), but recurrence rates of acute otitis media in the two groups were similar. In the 2-year-and-older age group, severe episodes resulted in more initial treatment failures in subjects assigned to receive myringotomy alone than in subjects assigned to receive amoxicillin with, or without, myringotomy (23.5% vs 3.1% vs 4.1%, P = .006). In the study population as a whole, severe episodes in subjects assigned to receive amoxicillin alone, and amoxicillin with myringotomy, had comparable outcomes. It is concluded that children with acute otitis media should routinely be treated with amoxicillin (or an equivalent antimicrobial drug). The data provide no support for the routine use of myringotomy either alone or adjunctively.     

Otitis media-related antibiotic prescribing patterns, outcomes, and expenditures in a pediatric medicaid population

BACKGROUND: Treatment of otitis media is the most frequent reason for administering antibiotics to children in the United States. However, only limited data are available on medical effectiveness of antibiotic prescribing patterns for otitis media and their associated expenditures or the factors that influence antibiotic prescribing. METHODS: The study population consisted of 131 169 children during 1991 and 157 065 children during 1992 who were 相似文献   

Disappearance of middle ear effusion in acute otitis media monitored daily with tympanometry

BACKGROUND: Disappearance of middle ear effusion is one of the most important outcomes in the treatment of acute otitis media (AOM). AIM: To evaluate the duration of effusion in AOM treated by antimicrobials and to find factors influencing it. METHODS: Parents of 90 children with AOM monitored daily the disappearance of effusion with tympanometry. The children were randomly allocated to be treated with either oral amoxicillin or cefuroxime-axetil for 10 d. Daily monitoring lasted for 14 d or until the tympanogram was normal (curve A or C) in both ears. Pneumatic otoscopy was carried out every 2 wk. RESULTS: Normal tympanograms were obtained after a median time of 7.5 d (range 1-58 d) among 75 successfully monitored patients. In two-thirds (69%) of them, effusion resolved in 14 d. The median duration of effusion did not differ significantly between the two treatment groups (8 vs 7 days, p=0.7). The children who had unilateral AOM cured more rapidly than those with bilateral AOM (5 vs 19 d, p<0.001). In logistic regression analysis adjusted for age, bilaterality explained treatment failure at 2 wk with an odds ratio of 28.1 (95% CI 4.6-169.5, p<0.001). CONCLUSION: The choice of antimicrobials did not influence the duration of middle ear effusion, which was much shorter than had been thought previously. Children with unilateral AOM were cured much more quickly than those with bilateral AOM.     

A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media

BACKGROUND: High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM. OBJECTIVE: To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM. METHODS: This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study). RESULTS: The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001). CONCLUSIONS: In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.     

Effectiveness of inactivated influenza vaccine for prevention of otitis media in children

OBJECTIVE: The objective of this study was to evaluate the effectiveness of inactivated influenza vaccine in preventing acute otitis media (AOM) and otitis media with effusion (OME) in children aged 6 to 60 months who attend day care. STUDY DESIGN: This prospective, single-blind study was conducted in 8 day care centers in Ankara, Turkey. One hundred nineteen (61 vaccinated and 58 unvaccinated against influenza) healthy children were examined at study entry and at 6-week intervals for 6 months by the same 2 otorhinolaryngologists who were blinded about the vaccination status of the children. The frequency of AOM and OME is compared between the 2 groups and the effect of influenza season on frequency of episodes was evaluated. Based on national influenza laboratory data, the influenza season was determined to be the period between December 15, 2003, and January 31, 2004. RESULT: The frequencies of AOM, OME and total otitis media episodes in vaccinated children were 2.3%, 22.8% and 25.2%, respectively, and these frequencies were 5.2%, 31.1% and 36.3% in the unvaccinated group. The difference was statistically significant (P < 0.01). This difference was especially prominent in the influenza season (P < 0.05). CONCLUSION: Influenza vaccine is effective in reducing AOM and OME episodes in 6- to 60-month-old day care children, especially during influenza season.     

Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children

BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited. OBJECTIVES: To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM. METHODS: In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2. Susceptibility to penicillin and amoxicillin was measured by E-test. RESULTS: Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S. pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1 beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days 4 to 6. CONCLUSIONS: The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.     

Microbiology of acute otitis media recently treated with aminopenicillins.

INTRODUCTION: Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). METHODS: Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. RESULTS: Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). CONCLUSIONS: The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.     

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.     

Sulphamethoxazole prophylaxis in the otitis-prone child.

A bedtime dose of sulphamethoxazole was effective in preventing ear infections in otitis-prone young children. Thirty-three such children were studied by means of a random, double-blind, placebo-controlled, cross-over protocol. Nine (27%) of 33 children treated with sulphamethoxazole experienced 10 episodes of acute suppurative otitis media or otitis media with effusion while 19 (58%) of 33 children given a placebo experienced 27 episodes of acute otitis media or otitis media with effusion. No new episode of otitis media was observed in 11 children in whom serial urine samples uniformly had a positive response to Micrococcus lutea bioinhibition test, the method we chose to monitor compliance. Otitis media with effusion (secretory otitis media) was detected less often in the children who were given sulphamethoxazole; this fact suggests that prophylaxis with sulphamethoxazole may prevent persistent middle ear effusion in otitis-prone young children.     

The dynamics of bacteria in the middle ear during the course of acute otitis media with tympanostomy tube otorrhea

BACKGROUND: Dynamics of bacteria during acute otitis media (AOM) has not been thoroughly studied because it requires repeated tympanocentesis. AOM with tympanostomy tube otorrhea provides a unique opportunity to study the appearance and disappearance of pathogens during the course of the disease without stressing the child. METHODS: Middle ear fluid (MEF) samples were taken before treatment (amoxicillin clavulanate or placebo) and then daily during follow-up from 75 children having AOM with otorrhea through a tympanostomy tube. Bacteria were identified by culture, and typical AOM pathogens also by polymerase chain reaction. RESULTS: Bacteria were initially shown in 67 (89%) children. New bacteria appeared in MEF more often in placebo than in amoxicillin clavulanate recipients [9 of 38 (24%) versus 2 of 37 (5%); P = 0.032]. During the follow-up, new occurrences of Moraxella catarrhalis were detected in MEF more frequently than those of Streptococcus pneumoniae or Haemophilus influenzae. Of the 28 patients with bilateral otorrhea, 11 (39%) had disparate bacteria at study entry and/or during the follow-up. CONCLUSIONS: Changes in bacterial findings during the course of AOM are common in patients not receiving treatment, and even possible despite adequate treatment. In bilateral otorrhea, disparate bacterial findings are common.     

Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children

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). Conclusion 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. Received: 17 January 1997 / Accepted: 22 May 1997     

A multicenter, open label, double tympanocentesis study of high dose cefdinir in children with acute otitis media at high risk of persistent or recurrent infection

BACKGROUND: Given the relatively high prevalence of recurrent and persistent acute otitis media (AOM) and the prominent etiologic role of Streptococcus pneumoniae, especially penicillin-nonsusceptible strains in children with these conditions, new alternative treatments are desirable. METHODS: Children 6 months-4 years of age with AOM considered to be at risk for recurrent or persistent infection received large dosage cefdinir 25 mg/kg oral suspension once daily for 10 days. Children were evaluated pretreatment (day 1), on therapy (days 4-6), end of therapy (days 12-14) and at follow-up (days 25-28). All children had tympanocentesis at enrollment. In culture-positive children, tympanocentesis was repeated after 3-5 days (days 4-6) unless evidence of absence of middle ear effusion was documented. RESULTS: Of 447 children enrolled, 230 were clinically and bacteriologically evaluable (74% 2 years old or younger; 57% treated for AOM in previous 3 months). Bacteriologic eradication, based on repeat tympanocentesis on days 4-6, was achieved in 74% (170 of 230) of children; 76% (201 of 266) of AOM pathogens were eradicated. Eradication of penicillin-susceptible, -intermediate and -resistant S. pneumoniae was 91% (50 of 55), 67% (18 of 27) and 43% (10 of 23), respectively (P < 0.001); eradication of H. influenzae was 72% (90 of 125). Overall clinical response at days 12-14 was 83% (76 and 82% for children with S. pneumoniae and Haemophilus influenzae, respectively). Sustained clinical response at days 25-28 was 85%. Clinical response was 83% for culture-positive children versus 96% for culture-negative children at baseline tympanocentesis (P < 0.001). CONCLUSIONS: In this study of AOM among children at risk for persistent or recurrent infection, large dose cefdinir resulted in an overall successful clinical response at end of treatment of 83%. This regimen was efficacious against penicillin-susceptible S. pneumoniae, but effectiveness was markedly decreased against nonsusceptible strains and was moderate for H. influenzae strains.