According to the Good Clinical Practice (GCP) ordinance enacted in April 1998, an important responsibility of pharmaceutical institutions is to monitor new drugs based on di rect access to sourced ocuments. Too few pharmaceutical companies and institutions currently have coordinators stationed for clinical trials, however, and the monitors are not sufficiently qualified to proces s clinical trials as defined by the GCP ordinance, essentially rendering monitoring in effective. To make extensively improve clinical trials and obtain reliable results, monitoring must be accurate.

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Clinical and bacteriological studies were done in infants and children with acute purulent otitis media caused by Haemophilus influenzae between December 1998 and July 2000. A total of 309 strains were isolated from 282 patients aged 3 months to 15 years old (average: 3.8 years). Ampicillin-sensitive H.influenzae comprised 57.9%, β-lactamase produced H.influenzae 14.9%, and β-lactamasenegative ampicillin-resistant H. influenzae 27.2%. By age group, each strain showed 2 peaks; Ampicillin-sensitive H. influenzae peaked in the 1- and 5-year-olds, β-lactamase produced H.influenzae in 1- and 7-year-olds and β-lactamase-negative ampicillin-resistant H.influenzae occurred in 1-and 4-year-olds. MIC₈₀ of oral β-lactam antibiotics showed that cefditoren pivoxil had the strongest effect (MIC₈₀: 0.06μg/mL) against H.influenzae. MIC₉₀ of oral β-lactam antibiotics showed the same results. Cefpodoxime proxietil had a strong effect, but a few strains resisted this antibiotic. Effective clinical treatment was achieved in 88.0% of patients with a combination of oral antibiotics and surgical treatment (myringotomy), but further surgical treatment (insertion of a tympanotomy tube) was necessary or ear discharge persisted in 12.0% of patients. We therefore wish to emphasize the importance of preparing guidelines for antimicrobiological treatment of H.influenzae.

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We clinically evaluated 42 patients with lower respiratory infection due to Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae, who were orally administered azithromycin (AZM) at 10mg/kg once daily for 3 days, between September 2000 and March 2001. Patients ranged from 6 months to 9 years. Clinical efficacy was 76.2%. Clinical efficacy by pathogenic organism was 100% in M.pneumoniae, 50.0% in penicillin resistant S.pneumoniae (PRSP), 62.5% in H.influenzae, and 78.6% in H. influenzae and S. pneumoniae. Bacteriological efficacy was 31.8% in H. influenzae and 4.5% in S. pneumoniae. No adverse reactions were seen.

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We verified in the special investigation on the pathological relation to penicillin-resistant Streptococcus pneumoniae (PRSP) and β-lactamase negative ampicillin-resistant (BLNAR) Haemohilus influenzae in clinical practice after introduction of cefditren pivoxil (CDTR-PI; brand names: Meiact^® Tablets 100, Meiact^® Fine Granules). We also studied shedding of the 2 bacterial strains and the distribution of their susceptibilities to various antibacterial agents before and after treatment with CDTR-PI and judgment of the clinical response made medical doctor. The significance of S. pneumoniae and H.influenzae isolated from the epipharynx was examined. We found that S. pneumoniae and H. influenzae isolated in this investigation resided mainly in the epipharynx of infants less than 1 year old to 2 or 3 years, and that they were associated with acute respiratory infection and acute otitis media. These bacterial strains, including PRSP and BLNAR, were eliminated or decreased in the epipharynx shortly after the start of CDTR-PI. They easily invaded the epipharynx again, however settled down, and proliferated there when the plasma drug concentration decreased to a trough level. Bacterial strains repeated this cycle, and some cases are likely to lead to persistent or repeated upper respiratory tract infection or otitis media. Infants nursery or nursery school and their siblings are likely to be of high risk, as suggested by a number of medical experts. The susceptibilities of S. pneumoniae and H.influenzae isolated before and after treatment with CDTR-PI to antibacterial agents were measured. In comparison of the distribution of MICs, the MICs of a variety of β-lactam antibiotics shifted slightly to higher resistance depending on their affinity for PBPs of bacterial strains. Bacteriological testing for the epipharynx is necessary to identify causative bacteria for acute respiratory tract infection in children and following acute otitis media. It is essential to know the type of resistant bacteria for selection of appropriate antibacterial agents considering persistent and repeated infection caused by PRSP and BLNAR H.influenzae. The investigation on drug-resistant genes by polymerase chain reaction has provided very useful information. It also suggested the importance of microscopical examination by gram staining for the shedding of bacteria in the epipharynx at least 2 to 3 days and 10 days after the start of treatment with antibacterial agents in infection associated with flora in the epipharynx. In the judgment of clinical response medical dictor, clinical findings in the pharynx, tonsil, or tympanic membrane, and the characteristics of nasal or middle ear discharge were focused on. The relationship between these findings and microscopic findings of the epipharynx and the number of bacteria detected there was analyzed by multivariate analysis, and a significant relationship detected.

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Imipenem/cilastatin (IPM/CS) and arbekacin sulfate (ABK) combination therapy was conducted in 39 patients on clinical isolates with severe methicillin-resistant Staphylococcus aureus (MRSA) and/or other aerobic gram-nagative bacilli containing mainly Pseudomonas aeruginosa infection between April 1995 and December 1999. Clinical efficiency was 69%-27 good and 12 poor-in 27 patients with pneumonia, 7 with secondary infection with respiratory disease, 2 with decubitus, 2 with sepsis, and 1 with urinary tract infection. MRSA was eradicated in 31%-12 of 39 cases. No side effects or abnormal laboratory findings were detected in any cases. To determine whether ABK serum concentration was appropriate, 9 blood samples were drawn from each patient just before and after infusions and ABK concentration was determined by bioassay. The mean serum concentration of ABK ranged between 9 troughs just before 9 infusion was 0.52μg/mL and 9 peaks just after was 8.81μg/mL. High plasma peaks of ABK are commonly considered useful in treating MRSA infection. We therefore recommend IPM/CS and ABK combination therapy for patients with severe MRSA and gram-negative bacilli infections both for the enhanced effect and serum concentration.

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From January 1999 to December 2000, 156 women at between 5 and 19 weeks gestation underwent induced abotion at Kyoto First Red Cross Hospital. Subjects were divided into 2 groups based on antimirobials administered postoperatively. Group 1 consisted of 109 women given cephems for 4 or 5 days (cefotiam hexetil (CTM-HE) 600mg/day in 8 cases, cefoteram pivoxil (CFTM-PI) 600mg/day in 93 cases, and cefcapene pivoxil (CFPN-PI) 300mg/day in 8 cases). Group 2 consisted of 47 women given fluoroquinolones for 4 or 5 days (tosufloxacin (TFLX) 450mg/day). Eight cases (7.3%) from group 1 and 2 (4.3%) from group 2 developed postabortion infection requiring additional antimicrobials and recurettage. Chlamydia trachomatis was sampled from the uterine cervix in 28 of the 156 and isolated from 5 (17.9%), all included in 10 cases of postabortion infection. C. trachomatis was sampled in 11 of 85 married women but not isolated and in 17 of 71 single women and isolated from 5 (29.4%). We concluded that fluoroquinolones are more desirable than cephems for prophylactic antimicrobials against postabortion infection and that women, especially single, requesting abortion should be examined and treated for infection with C. trachomatis either before or, at the latest, in conjunction with abortion.

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