In the 58 years since penicillin was clinically introduced, 238 antibacterial agents have been used in Japan. Through the alternation of generation and selection, 154 are available today. The majority of current agents are 65β-lactams and 24 synthetic chemotherapeutics including fluoroquinolones.
Taking a general view of approval of antibacterial agents during the last 2 decades, 46 of different classes were approved in the first decade but only 19 of limited classes in the second. Such low activity suggests the need to develop novel antibacterial agents with potential for coping with the alteration of infectious diseases within 5-10 years.
Current development of medicinal products including antibacterial agents is conducted globally, simultaneously, and cooperatively. Novel agents created in Japan are often evaluated simultaneously in clinics in Japan, the US and Europe. Unlike Japan, however, the approval of agents in the US in last 10 years is recognized to be preferred to those possessing activity against defined resistant bacteria and being applied to a narrow spectrum of infectious diseases. Philosophies on development of antibacterial agents differ in Japan and the west, i.e., carbapenems and fluoroquinolones dominate over those under development in Japan, while glycopeptide, rifamycin, and others are extensively developed in the US and Europe.
Industries involved in the development of antibacterial agents also differ, i.e., are limited to megapharma firms in Japan but, in the US, small industries called biopharma are creating novel agents with novel mechanism of action under unique approaches. The US megapharm firms may take them to clinical development when they have completed their preliminary evaluation. Such novel agents have been evaluated at ICAAC annual meetings sponsored by the American Society for Microbiology, and a great deal of information the trends in development of antibacterial agents is available at the conference.

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In order to examine the activity of fluoroquinolone antibiotics against fresh clinical isolates, we conducted a survey on the susceptibility of 2, 228 strains of four gram-positive bacteria and eight gram-negative bacteria to 11 antimicrobials including gatifloxacin (GFLX), during the period from November 2002 to March 2003. These were isolated from sputum, urine, sinus discharge, otorrhea, and middle ear discharge obtained from 15 facilities in Japan. All the isolates were tested in accordance with the National Committee for Clinical Laboratory Standards. The MIC₉₀ of GFLX against penicillin-resistant Streptococcus pneumoniae (PRSP) was 0.5μg/mL and its sensitivity rate was also satisfactory at 100%. As in the penicillin-susceptible strains, GFLX exhibited strong antimicrobial activity and good sensitivity against PRSP. MIC₉₀ of GFLX against Haemophilus influenzae was as low as 0.03μg/mL and its sensitivity was 99%. The MIC₉₀ of GFLX against Escherichia coli stood at 8μg/mL. The MIC₉₀ values of fluoroquinolone antimicrobials against Neisseria gonorrhoeae ranged from 2μg/mL to 16μg/mL and their sensitivity rates surpassed 90%. On an average, this survey found that fluoroquinolone antimicrobials were very active against Klebsiella pneumoniae, including S. pneumoniae, H. influenzae, and Moraxella catarrhalis. Additionally, GFLX, among others, demonstrated particularly strong bactericidal activity against S. pneumoniae without suffering a decline in drug sensitivity.
Consequently, GFLX could be one of the clinically useful drugs for respiratory infections. On the other hand, it is now evident that E. coli, Enterococci, Pseudomonas aeruginosa, and N. gonorrhoeae have developed more resistance to fluoroquinolone antimicrobials as compared to their previous susceptibility.

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A 77 year old man with sepsis caused by MRSA, that could not be treated by VCM, TEIC or ABK suffered severe renal failure and required immediate hemodialysis. He also suffered DIC and liver dysfunction. The administration of LZD 600mg/day by intravenous injection ameliorated sepsis and DIC, and renal and liver function improved. LZD is thus effective in patients with sepsis caused by MRSA for whom other are ineffective drugs or who suffer severe organ dysfunction.

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We studied the efficacy and safety of levofloxacin (LVFX) at 200 mg b.i.d. for 7 days, and the correlation between efficacy and the AUC/MIC ratio in patients with suspected pneumococcal pneumonia. Subjects were suspected of having mild to moderate pneumococcal pneumonia because pneumococcal antigen was detected in the urine or Gram staining of sputum was positive before the start of treatment. We measured blood LVFX twice in each patient and used the Bayesian method with population parameters to calculate AUC.
Of the 71 subjects enrolled, 57 were analyzed for clinical efficacy, and efficacy was 93.0%(53/57). Of these, 46 had pneumococcal pneumonia, diagnosed as positive for Streptococcus pneumoniae by culture or urinary antigen. Efficacy was 93.5%(43/46). Of the 30 in whom S. pneumoniae was isolated and identified, bacterial eradication was 96.7%(29/30).
Side effects occurred in 17 of 70 patients, i.e., 15 mild, and LVFX administration was continued. Two had moderate side effects and recovered quickly after LVFX administration was discontinued.
The AUC/MIC ratio calculated for 22 patients in whom the MIC of LVFX for S. pneumoniae could be measured was 68.5±31.9 (mean±S.D.). Of these, only 1 patient was AUC/MIC < 25.
Considering from above results, it was suggested that 200 mg LVFX administered twice a day could achieve an adequate AUC/MIC ratio and high clinical efficacy in patients with suspected pneumococcal pneumonia.

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