Bacteriologic Response in Otitis MediaAre We Hearing Impaired?
ABSTRACT & COMMENTARY
Synopsis: Cefuroxime axetil was superior to cefaclor in the treatment of acute otitis media. Current NCCLS susceptibility criteria may need adjustment.
Source: Dagan R, et al. Bacteriologic response to oral cephalosporins: Are established susceptibility breakpoints appropriate in the case of acute otitis media? J Infect Dis 1997;176:1253-1259.
Dagan and associates in israel were able to find 266 children (ages 3-36 months) with otitis media and parents who were willing to have tympanocenteses performed before and four or five days after initiation of antimicrobial therapy. Children were randomized to receive either cefaclor (Ceclor; 30 mg/kg in 2 doses) or cefuroxime axetil (Ceftin; 40 mg/kg in 3 doses). One quarter of the cases were eliminated when the initial tap grew no bacteria. The organisms recovered were primarily non-typeable Hemophilus influenzae (53%) and Streptococcus pneumoniae (41%). Moraxella catarrhalis accounted for another 3%. Most of the culture-positive cases could be evaluated, although 16% of the cefuroxime patients were unable to complete the 10-day course of treatment due to gastrointestinal intolerance.
Bacteriologic failure was determined by repeat aspirates on day four or five of therapy. The investigators found statistically significant differences after the 10-day courses of therapy. Cefaclor had a 32% (33/103 cases) failure rate compared to cefuroxime, which had a 15% (14/93) failure rate (P = 0.009).
In addition, Dagan et al performed quantitative susceptibility testing using an E-test methodology and found a clear relationship with bacteriologic outcome. Using the standard NCCLS (National Committee for Clinical Laboratory Standards) MIC cutoff of 0.5 mcg/mL for Streptococcus pneumoniae, there was a clear correlation with bacteriologic outcome. For cefaclor, the failure rate was 0% below and 57% above the MIC. For cefuroxime, it was 9% below and 50% above the MIC. There was also an interesting correlation between outcomes and MIC of the organisms to penicillin, with failure rates of 80% and 50% above an MIC of 0.38 for penicillin and 4% and 9% below an MIC of 0.1 for the cefaclor and cefuroxime isolates, respectively.
For the Hemophilus influenzae strains, the bacteriologic failure rate was clearly higher with cefaclor at 39% (22/57) compared to cefuroxime at 15% (7/46) (P = 0.016). In addition, there was a clear correlation of outcomes with MICs but at much lower concentrations than expected for the NCCLS cutoffs of 8 mcg/mL for cefaclor and 4 mcg/mL for cefuroxime. Their testing showed a 30% bacteriologic failure rate with an MIC of 1.0 mcg/mL or less for cefaclor, compared to a 50% failure rate with an MIC of greater than 2 mcg/mL. For cefuroxime, the failure rate was 11% for MICs less than 1.0 mcg/mL and 100% with MICs over 2.0 mcg/mL.
The authors point out the value of tympanocenteses for the evaluation and management of otitis media. In addition, they suggest the NCCLS change their recommendations for testing and cutoff levels for susceptibility and resistance for Hemophilus influenza in the case of otitis media to reflect the efficacy of cefaclor and cefuroxime demonstrated here.
COMMENT BY ALAN D. TICE, MD, FACP
Acute otitis media is the number one cause of antibiotic use in infants and young children. The primary etiologic pathogens recovered are Hemophilus influenzae, Streptococcus pneumoniae, and Moraxella, as indicated by this study.
The study is a large one with good methodology. It is not easy to gather so many cases of children with initial and follow-up tympanic membrane aspirates. The value of the microbiology information from the taps is clear, however, and suggests that they should be done more, even outside the research setting. They are not difficult to do with experience and may even provide some relief from pain with drainage.
The findings of the study are also interesting. For the standard doses used over 10 days, the tolerance to cefuroxime was not as good as to cefaclor, but the bacteriologic outcomes were betterespecially with the untypeable Hemophilus strains. This was likely in part related to the greater activity of cefuroxime vs. cefaclor against S. pneumoniae (MIC 90 of 1.5 vs MIC 90 of 8.0 mcg/mL) as well as against H. influenzae (MIC 90 of 1.0 vs 4.0 mcg/mL).
The authors’ insight into the poor correlation between the standard cutoffs for susceptibility testing and patient results is important. It is unusual to see this type of comparison between the in vivo and in vitro results, yet the need is great. An E-test methodology was used, but it usually correlates well with tube dilution or agar dilution results and may be preferred in some situations. The present reporting of "resistant" and "susceptible" is not adequate for the present standard MIC cutoffs. Reporting of quantitative results may be helpfulor changing the standards.
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