Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children.

A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.

Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients.

BACKGROUND: Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment. OBJECTIVES: To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM). METHODS: Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated. RESULTS: A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving. CONCLUSION: A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.

Treatment failures in otitis media--what can we learn?

The role of antibiotics in acute otitis media is to eradicate the causative pathogen from the middle ear. It is therefore important to have antibiotics with good activity which reach the organism in an appropriate concentration at the infection site. Without these parameters successful treatment will not be achieved. The ultimate test of this concept is to demonstrate the eradication of a pathogen from middle ear aspirate post-treatment. Careful analysis of treatment failures show that increasing rate of resistance to existing drugs is associated with a decreased rate of pathogen eradication in acute otitis media and there is a clear correlation between bacteriologic failure and clinical failure.

Bacteriologic response to oral cephalosporins: are established susceptibility breakpoints appropriate in the case of acute otitis media?

Bacteriologic response to cefuroxime axetil and cefaclor administered for 10 days was evaluated in acute otitis media (AOM) in patients aged 6-36 months. Middle ear fluid culture was obtained by tympanocentesis before treatment, on day 4 or 5 after initiation of treatment, and if clinical relapse occurred before day 17. Bacteriologic failure was observed in 32% of patients receiving cefaclor versus 15% of patients receiving cefuroxime axetil (P = .009). Failure rates increased with increasing MIC: For Streptococcus pneumoniae, 0.5 microg/mL (established as cutoff value for cefuroxime by the National Committee for Clinical Laboratory Standards [NCCLS]) discriminated between success and failure. For Haemophilus influenzae, high failure rates were observed for cefaclor, even with low MICs (< or = 1.0 microg/mL), and with both drugs they tended to increase with increasing MIC, even for values below the cutoff suggested by the NCCLS (8.0 and 4.0 microg/mL for cefaclor and cefuroxime, respectively). Thus, for AOM caused by H. influenzae, lower susceptibility cutoff levels for MICs should be established.

Impaired bacteriologic response to oral cephalosporins in acute otitis media caused by pneumococci with intermediate resistance to penicillin.

BACKGROUND: Penicillin resistance of Streptococcus pneumoniae, one of the most common causes of acute otitis media, has recently increased and is now highly prevalent in many regions. However, its contribution to clinical failure still must be proved. Because the role of antibiotics in acute otitis media is to eradicate the pathogens present in the middle ear fluid, we conducted a randomized controlled study to determine bacterial eradication of pathogens in acute otitis media by two commonly used oral cephalosporins, cefuroxime axetil (30 mg/kg/day) and cefaclor (40 mg/kg/day). METHODS: Patients 6 to 36 months old with pneumococcal otitis media seen in the Pediatrics Emergency Room were studied. An initial middle ear fluid culture was obtained at enrollment, and a second culture was obtained on Day 4 or 5 during treatment. Follow-up was done also on Days 10, 17 and 42 after initiation of treatment. In cases of clinical relapse a third culture was obtained. RESULTS: In total 78 patients were enrolled, 41 in the cefuroxime axetil group and 37 in the cefaclor group. Of the 78 S. pneumoniae isolates 31 (40%) were intermediately penicillin-resistant (MIC 0.125 to 1.0 microgram/ml). Of the 47 patients with penicillin-susceptible organisms 3 (6%) had bacteriologic failure vs. 4 of 19 (21%) and 7 of 11 (64%) of those with MIC of 0.125 to 0.25 microgram/ml and 0.38 to 1.0 microgram/ml, respectively (P < 0.001). For intermediately resistant pneumococci, in 7 of 12 (58%) of those receiving cefaclor the isolate was not eradicated vs. only 4 of 19 (21%) of those receiving cefuroxime axetil (P = 0.084). MIC to the administered cephalosporin of > 0.5 microgram/ml was associated with bacteriologic failure. Clinical failure was observed in 9 of 14 (64%) patients with bacteriologic failure vs. 10 of 52 (19%) patients with bacteriologic eradication (P = 0.003). CONCLUSION: Intermediately penicillin-resistant S. pneumoniae is associated with an impaired bacteriologic and clinical response of acute otitis media to cefaclor and cefuroxime axetil. This effect was more pronounced with cefaclor than with cefuroxime axetil.

Medical treatment of chronic suppurative otitis media without cholesteatoma in children--a two-year follow-up.

A prospective long-term study was carried out in 48 infants and children with chronic suppurative otitis media without cholesteatoma treated initially with wide spectrum intravenous antibiotics and suction and debridement. Patients were followed for a period of two years. All children were cured after completion of therapy. At 3 and 6 months follow-up 75% of the children were still free of discharge and at 12, 18 and 24 months the proportion of dry ears dropped to 71%, 66% and 52%, respectively. Eighty percent of all recurrences developed already during the first 6 months of follow-up. Pseudomonas aeruginosa was the most common pathogen isolated, both in the initial and recurrent bouts of the disease, and was commonly associated with other pathogens. Children with early reappearance of ear discharge were less likely to benefit from further antimicrobial or surgical treatment. The recurrence rate was not affected by the antibiotic regimen, age, duration of drainage before treatment or the presence of granulation tissue. No intracranial or intratemporal complications were observed during the follow-up period.