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The number of infants with acute otitis media insusceptible to conservative therapy, such as tympanostomy with antibiotic medication, has been increasing. It has been well known that Haemophilus influenzae or Streptococcus pneumoniae (or both) are isolated from more than 75% of young patients with acute otitis media. In intractable acute otitis media, which cannot improve by oral antibiotics, one should consider reduced drug sensitivity or drug resistance of those two pathogens against common oral antibiotics [1]. In this report, we investigated drug susceptibility of H. influenzae and S. pneumoniae isolated from ear and nasal discharge.

The samples, including H. influenzae or S. pneumoniae were isolated from ear and nasal discharge in 1991, 1996 and 2001, and all samples such as sputum and meningeal fluid from 2001 were used for this study. Susceptibility of the bacteria to antibiotics was investigated according to the broth microdilution method, and MIC was measured to evaluate drug resistance. Insusceptibility of S. pneumoniae was classified according to NCCLS (The National Committee for Clinical Laboratory Standards, USA) criteria; penicillin-resistant S. pneumoniae was classified under three types; PSSP (penicillin sensitive S. pneumoniae) with the MIC of PCG less than 0.1 µg/ml, PISP (penicillin intermediate S. pneumoniae) with the MIC between 0.1 and 1 µg/ml and PRSP (penicillin resistant S. pneumoniae with the MIC more than 2 µg/ml.

Based on the MIC of ABPC against H. influenzae and whether the microbe produces b-lactamase, the antibiotic-resistant H. influenzae was classified as three types: BLPAR (b-lactamase positive ampicillin resistant), BLNAR (b-lactamase negative ampicillin resistant) and BLPACR (b-lactamase positive clavulanic acid resistant). When the MIC of ABPC against H. influenzae was more than 4 µg/ml, the microbe was defined as BLNAR.

Twenty-five H. influenzae samples obtained from ear discharge included 18 samples of BLNAS, two of BLPAR and five of BLNAR. The total number of H. influenzae samples was 324 (Fig. 1).

Seventeen S. pneumoniae samples obtained from ear discharge included two samples of PSSP, 12 of PISP and three of PRSP. The total number of S. pneumoniae samples was 242 (Fig. 2).

Fig. 3 shows the pattern of distribution of H. influenzae MICs to ampicillin(ABPC), amoxicillin-clavulanate (AMPC/ACV), cefditoren pivoxil (CDTR/PI), and ceftriaxone(CTRX) in 2001.

Fig. 4 shows the distribution of MICS of S. pneumoniae to penicillin G, ABPC, CDTR/PI, clindamycin (CLDM) and PAPM/BP in 2001.

BLPAR has been well known as a representative of ABPC-resistant H. influenzae. The isolation rate of BLPAR, however, has fluctuated around 10% for these 20 years and has not been increasing. BLPAR infection can be treated by b-lactamase inhibitors such as SBP/ABPC and ACV/AMPC. Besides, the isolation rate of the new pathogen termed as BLNAR has been increasing [2]. BLNAR, like PRSP, has acquired antibiotic-resistance by altering biochemical properties of the penicillin-binding protein.

Therapy for the multi-drug resistant microbe as well as PRSP has been more difficult. S. pneumoniae has acquired stronger resistance against penicillin year by year [3, 4]. Compared with data obtained in 1996 and 2001, the isolation rate of PISP and PRSP increased from 40% to 59.9% and from 10% to 26.5%, respectively.

Therapy for otitis media has been quite difficult because of the multi-drug resistance or multi-antibiotic insusceptibility of the microbe [5].

The increasing generation of the multi-drug resistant bacteria appears to result from an increase in use of the third generation of cephems, and some social factors such as nursery for younger children than previously. Appropriate choice of antibiotics for otitis media should be necessary to prevent the increasing generation of drug-resistant pathogens.

1. Although the isolation rate of BLPAR has not been increasing, that of BLNAR has been dramatically increasing.
2. The isolation rate of PRSP has been increasing. S. pneumoniae has acquired much stronger drug-resistance than ever.
3. Therapy for otitis media has been difficult, because PRSP and PISP as well as BLNAR have acquired multi-drug resistance.
4. The stronger resistance of the pathogens appears to result from excessive use of the third generation of cephems, and some social factors such as nursery for younger children than previously.