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.