The classical term “pneumonia” was first noted by Hippocrates in the 4^th century BC, as a seriousillness in the thorax. In 1819, Laennec recorded the physical findings of chest abnormalities obtained by percussion and auscultation with the stethoscope he invented, and compared them with the post mortemfindings. Then, the pneumonia and pneumonic consolidation, were differentiated from pleural effusion, and the criteria for pneumonia were classified anatomically into lobar and lobular pneumonia.
The causative bacteria of infectious diseases, including pneumonia, were discovered inlate the19^th.century. This fact induced at least three important things, (1) evidence that pneumonia is clearly caused by invasion of microorganisms into lung through airway or bloodstream.(2) analysis of serotyping of bacterial capsules of pneumococci led to development of type specific serotherapy and (3) synthesis of chemotherapeutic agents based on the idea that dyestuffs enter bacterial bodies.
In the1920s-1930s, along with increasing popularity of type specific serotherapy, an accurate determination of the causative organisms was attached importance to diagnosis of pneumonia, because the Type specific serotherapy was only the way to get a favorable prognosis of the patients withpneumococcal pneumonia At the sametime, bacteriology-baseddiagnosis, such as “pneumococcal pneumonia”, became more popular than anatomy-based diagnosis. Such an active observation toward the bacteriologic examination, on the other hand, led to postulation of the existence of a different type ofpneumonia, “atypicalpneumonia”, whosecausative organisms were speculated to be viruses or transfilterable agents.Mycoplasma pneumoniae (1962), Legionella pneumophila (1976), Chlamydia pneumoniae (1980s) and SARS-Co-V (2002) were later discovered.
In the late20^th century, the incidence of opportunistic pneumonia increased in association with the aging of society and the increased longevity of immunodeficient patients. Also, the incidenceofPneumocystis carinii pneumonia re-emerged, parallel with the spread ofHIV infection, and pneumonia caused by antibacterial agent resistant strains, for instance MRSA or PRSP emerged. In this situation, a new concept of the community acquiredpneumonia (CAP) and the hospital acquiredpneumonia (HAP) was populariged (1980s). Since the point of this criteria was well reflected the correlation between preference for the causativeorganisms and thepatients background, this classification was convenient for the choice of antimicrobial agent based on empirical evidence. Recently, however, the close relationship between pathogens and patient background has sometimes became unclear, because patients with immunodeficiency diseases, patients withchronic intractable diseases and elderly patients are increasingly living in community. It indicates that the terminology of CAP or HAP has to reconsider to go back the starting point.
Although the purulent exacerbation of chronic bronchitis was postulated by the infection with numerous microorganisms, the bacterial analysis of chronic bronchitis remained incomplete until 1940s. In the 1950s, asignificant role of Haemophilus influenza, e wasprevailed.

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To use fluoroquinolones effectively and safely, pharmacokinetic/pharmacodynamic (PK/PD) analysis is strongly recommended. The plasma concentration of fluoroquinolones in the patients is necessary for PK/PD analysis. We established new HPLC system with a fluorescent detector enabling us to determine the concentration of 9 fluoroquinolones-ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, pazufloxacin, tosufloxacin-only by changing excitation and emission wave length. We suggest that this is useful for the determination of plasma concentrations of fluoroquinolones in patients and essential for PK/PD analysis.

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Between 1998 and 2004, we studied the minimal inhibitory concentration (MICs) of 11 strains of Gramnegative bacilli isolated from blood in patients with late-onset neonatal bacteremia in a neonatal intensive care unit. Pathogenic organisms were 3 in Acinetobacter spp., 2 in Enterobacter cloacae, 2 in Ralstonia pidcettii, and 1 each in Klebsiella pneumoniae, Burkhokleria cepacia, Pseudomonas aeruginosa, and Proteus mirabilis.
The susceptibility of ciprofloxacin, imipenem, and meropenem to these organisms exceeded 80%. Ciprofloxacin was not susceptible to P. aeruginosa, and imipenem and meropenem were not susceptible to R pickettii.

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In order to continually examine the susceptibility of clinical isolates against gatifloxacin (GFLX), we conducted a surveillance measuring that of 2, 508 strains of four gram positive and seven gram-negative pathogens to 12 antimicrobials including GFLX, during the period from November 2004 to March 2005 following previous surveillance conducted in 2002. Tested pathogens were isolated from sputum, urine and sinus discharge obtained from 15 facilities throughout Japan. GFLX exhibited superior antibacterial activity against Streptococcus pneumoniae, comparison to other fluoroquinolones, by showing same MIC₅₀ and MIC₉₀ values of 0.25 μg/ml, and a satisfactory susceptible rate at 96. 5%. Antibacterial activity of GFLX was not influenced by the development of penicillin-resistance in S. pneumoniae. The MIC₉₀ values of fluoroquinolones against Haemophilus influenzae and Moraxella catarrhalis were commonly as low as 0.015 μg/ml to 0.03 μg/ml. The MIC₅₀ and MIC₉₀ values of GFLX against Escherichia coll. and Enterococcus faecalis were 0.06 μg/mL-0.5 μg/mL and 8μg /ml-16 μg/mL, respectively. The susceptible rate for fluoroquinolones were 83-67%. On an average, this surveillance indicated that fluoroquinolones kept strong antibacterial activities against H. influenzae and M. catarrhalis. Among others, GFLX has maintained strong antibacterial activity against S. pneurnartiae as the MIC₉₀ value of 0.25 μg/mL was identical to that observed at the launch. It was thought that GFLX was the clinically useful drugs for empiric therapy against main pathogens of respiratory tract, otorhinolaryngology and urinary tract infections. While antibacterial activities of fluoroquinolones against E. coli and E. faecalis did not almost change from 2002 surveillance, it was thought the susceptibility needed to be examined continually in future.

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