Study of nasopharyngeal bacterial flora. Variations in nasopharyngeal bacterial flora in schoolchildren and adults when administered antimicrobial agents.

Changes in nasopharyngeal bacterial flora in adults with acute upper respiratory tract infection on administration of antimicrobial agents were investigated, and how these changes contrasted with those in children. Many patients with acute sinusitis due to allergies, and patients with malignancy and diabetes mellitus were included in the investigation. The detection rates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the major bacteria of acute otitis media (AOM), were 22%, 10%, and 7% respectively, which were significantly lower than those for children. Gram stain examination of nasopharyngeal swab samples showed a significant relation between leukocyte infiltration and the detection amount of S. pneumoniae (P = 0.0086). A significant relation (P = 0.0134) was also observed when H. influenzae was simultaneously detected. No significant change in the three major AOM bacteria present in nasopharyngeal bacterial flora after administration of antimicrobial agents was observed. However, all S. pneumoniae and H. influenzae detected after antimicrobial agent administration had the beta-lactam-resistance gene. It was observed that a significant improvement in leukocyte infiltration occurred 6 to 10 days after antimicrobial agent administration. In contrast, a significant improvement in children was observed at 2 to 5 days. In the adult subjects, this improvement was probably due to spontaneous remission rather than the effect of the antimicrobial agents. Although investigation of the long-term administration of antimicrobial agents was also conducted, its benefits for the patients were not elucidated.

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 1.

In our first report, we investigated nasopharyngeal bacterial flora related to penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR) and their relation to acute upper respiratory tract infection (AURTI). This report analyzes the results of a study of nasopharyngeal bacterial flora before the administration of antimicrobial agents in 172 AURTI patients aged 6 years or younger. In addition to Gram staining, microscopic observation, and culturing, a polymerase chain reaction (PCR) method was used to identify PRSP (gPRSP) and BLNAR (gBLNAR) drug-resistant genes. Of the patients analyzed, 90% had acute otitis media (AOM) and were aged 2 years or younger. The antimicrobial agents administered were amoxicillin (34%), clavulanic acid/amoxicillin (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). This was particularly true for patients administered CDTR-PI, among whom there were many who had already suffered one or more episodes of AOM by the age of 1 year or younger, and many in which gPRSP were detected (P < 0.01). There was a significant relation between the degree of nasopharyngeal inflammation indicated by leukocyte infiltration images and the amount of S. pneumoniae and H. influenzae detected, which are the main pathogenic bacteria causing AOM (P < 0.01). In addition to leukocyte infiltration images, there were cases in which shedding of ciliated cells was observed and/or giant monocytic cells. Both nasopharyngeal leukocyte infiltration images and/or shed cell findings observed in infant AURTI cases are important indices for the prompt detection of gPRSP and/or gBLNAR and appropriate doses of antimicrobial agents.

Study of nasopharyngeal bacterial flora. Second report. Variations in nasopharyngeal bacterial flora in children aged 6 years or younger when administered antimicrobial agents. Part 2.

This report focuses on changes in the nasopharyngeal bacterial flora before and after administration of antimicrobial agents in 172 cases of acute upper respiratory infection in patients aged 6 years or younger. The antimicrobial agents administered were amoxicillin (AMPC) (34%), clavulanic acid/amoxicillin compound (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). Changes in nasopharyngeal bacterial flora were investigated with reexaminations conducted after 2-5 days (day 2-5 subgroup), 6-10 days (day 6-10 subgroup), and 11 days and thereafter. There was a significant reduction in the Streptococcus pneumoniae detected in the group administered AMPC (AMPC group) in the day 2-5 subgroup and the day 6-10 subgroup. There was also a significant decrease in H. influenzae in the group administered CDTR-PI (CDTR-PI group) in the day 2-5 subgroup. From this it was inferred that for the most part significant changes in infectious nasopharyngeal bacteria occurred in the day 2-5 subgroups. However, a significant improvement in the degree of inflammation, as indicated by leukocyte infiltration images for the AMPC group, was observed in the day 2-5 subgroup, and for the CDTR-PI group in the day 6-10 subgroup. On the other hand, in both the antimicrobial agent groups, S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were newly detected at reexamination. Furthermore, a difference in the incidence of these bacteria was observed between the 2 antimicrobial agent groups. It was suggested that such phenomena related to the survival of resistant strains or a recurrence otitis media.

Pharmacokinetics of beclomethasone dipropionate in an hydrofluoroalkane-134a propellant system in Japanese children with bronchial asthma.

BACKGROUND: Hydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma. METHODS: Plasma concentrations of beclomethasone 17-monopropionate (17-BMP),a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 microg as four inhalations from 50 microg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters. RESULTS: The area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t)) was 1659 +/- 850 pg x h/mL (arithmetic mean +/- standard deviation (SD)), the maximum concentration observed (C(max)) was 825 +/- 453 pg/mL and the apparent elimination half-life (t(1/2)) was 2.1 +/- 0.7 hours. The time to reach Cmax Tmax was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC(0-t), 1.04 for Cmax and 1.4 for t(1/2). The median of Tmax was 0.5 hours in American patients as well as Japanese patients. CONCLUSIONS: The pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested.

Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.