Institute of Development, Aging and Cancer, Tohoku University

About

Div. Anti-Infective Agents

Professor Akira Watanabe, MD
Visiting professor Shigeru Fujimura, MD
Technical assistant Tomoko Ito
Technical assistant Tomomi Nakano


This research department places the primary focus more on the appropriate implementation of clinical studies than on preclinical studies among the various stages of anti-infective drug development, attaching weight especially to secure clinical development in a short period. Our purpose is to actively and voluntarily undertake the development of not only antibiotics and antimicrobials but antifungals, tuberculostatics, antivirals, and various vaccines. We experienced the advent of emerging infections such as AIDS and the resurgence of reemerging infections such as intractable tuberculosis caused by multidrug-resistant organism in the 1980s and spread of MRSA and multidrug-resistant Streptococcus pneumoniae in the 1990s. In the 2000s, the increase in fatalities from AIDS (³3 millions per year) and the emergence of drug-resistant bacteria such as multidrug-resistant Pseudomonas aeruginosa and super-resistant strain of Mycobacterium tuberculosis have attracted social attention. As for infections and resistant bacteria, it is necessary not only to stop the spread from the outbreak location but also to control the outbreak itself. We place more emphasis on the prevention of the outbreak itself than on the containment of the infections and resistant bacteria, and aim to foster human resources involved in the development of drugs for treatment and prevention of infections as well as anti-infectives based on the themes listed below.

  1. Leading-edge drug discovery and development in medical and pharmaceutical sciences, promotion of researches on pharmaceutical agent, and development of human resources.
  2. Promotion of clinical studies on novel anti-infectives, improvement of post-marketing clinical studies, and promotion of international standardization.
  3. Establishment of proper usage of anti-infectives based on the drug characteristics, and promotion of clinical researches.
  4. Prevention of in-hospital infection, promotion of researches on drug-resistant bacteria control, and dissemination and promotion of the achievements.
  5. Promotion of researches on zoonotic infections and anti-bioterrorism measures.
  6. Promotion of development and practical application of bird flu anti-viral drugs.
  7. Basic and clinical researches on drug-resistant bacteria and promotion of the control.
  8. Epidemiological measures for the prevention of chronic infections such as tuberculosis and promotion of the prospective treatment and prevention.

References

  1. Watanabe A, Yates PJ, Murayama M, Soutome T and Furukawa H: Evaluation of safety and efficacy of intravenous zanamivir in the treatment of hospitalized Japanese patients with influenza: an open-label, single arm study. Antiviral Ther (Epub a head print 2014)
  2. Fujimura S, NakanoY, Watanabe A. A correlation between reduced susceptibilities to vancomycin and daptomycin among the MRSA isolates selected in mutant selection window of both vancomycin and daptomycin. J Infect Chemother 20(12): 752-756, 2014.
  3. Izumikawa K, Watanabe A, Miyashita N, Ishida T and Kohno S: Efficacy and safety of garenoxacin tablets on bacterial pneumonia: postmarketing surveillance in Japan. J Infect Chemother 20(9):549-557, 2014.
  4. Izumikawa K, Watanabe A, Miyashita N, Ishida T and Kohno S: Efficacy and safety of garenoxacin tablets on clinically diagnosed atypical pneumonia: postmarketing surveillance in Japan. J Infect Chemother 20(9):541-548, 2014.
  5. Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Eguchi K, Watanabe A, Origasa H, Shoji T, Miyasaka N and Koike T: Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of J-RAPID study. Mod Rheumatol 24(5):734-743, 2014.
  6. Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Eguchi K, Watanabe A, Origasa H, Shoji T, Miyasaka N and Koike T: Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of HIKARI study. Mod Rheumatol 24(5):725-733, 2014.
  7. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka N, Eguchi K, Watanabe A, Origasa H, Shoji T, Sakamaki Y, van der Heijde D, Miyasaka N and Koike T. Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: the J-RAPID randomized, placebo-controlled trial. Mod Rheumatol 24(5):715-724, 2014.
  8. Yamamoto Y, Ohmichi M, Watanabe A, Niki Y, Aoki N, Kawai S, Chida K, Mikasa K, Seki M, Ishida T, Kadota J, Matsuse A, Fujita J and Kohno S. A study on the management of acute respiratory tract infection in adults. Jpn J Antibiotics 67(4):223-232, 2014.
  9. Naito T, Matsuda N, Tanei M, Watanabe Y and Watanabe A: Relationship between public subsidies and vaccination rates with the 23-valent pneumococcal vaccine in elderly persons, including the influence of the free vaccination campaign after the great East Japan earthquake. J Infect Chemother 20(7):450-453, 2014.
  10. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka N, Eguchi K, Watanabe A, Origasa H, Iwai K, Sakamaki Y, D van der Heijde, Miyasaka N and Koike T. Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: The HIKARI randomised, placebo-controlled trial. Mod Rheumatol 24(4):552-560, 2014.
  11. Takeuchi T, Yamamoto K, Yamanaka H, Ishiguro M, Tanaka Y, Eguchi K, Watanabe A, Origasa H, Shoji T, Miyasaka N, and Koike T: Early response to certolizumab pegol predicts long-term outcomes in patients with active rheumatoid arthritis: results from the Japanese studies. Mod Rheumatol 20:1-10, 2014.
  12. Kohno S, Tateda K, Kadota J, Fujita J, Niki Y, Watanabe A and Nagashima M: Contradiction between in vitro and clinical outcome: Intravenous followed by oral azithromycin therapy demonstrated clinical efficacy in macrolide-resistant pneumococcal pneumonia. J Infect Chemothr 20(3):199-207, 2014.
  13. Kikuchi T, Kobashi Y, Hirano T, Tode N, Santoso A, Tamada T, Fujimura S, Mitsuhashi Y, Honda Y, Nukiwa T, Kaku M, Watanabe A and Ichinose M. Mycobacterium avium genotype is associated with the therapeutic response to lung infection. Clinical Microbiology and Infection 20:256-262, 2014.
  14. Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Eguchi K, Watanabe A, Origasa H, Shoji T, Miyasaka N and Koike T: Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of HIKARI study. Modern Rheumatology, 2013.
  15. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka N, Eguchi K, Watanabe A, Origasa H, Shoji T, Sakamaki Y, van der Heijde D, Miyasaka N and Koike T. Efficacy and safety of certolizumab pegol plus methotrexate in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: the J-RAPID randomized, placebo-controlled trial. Modern Rheumatology, 2013.
  16. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka N, Eguchi K, Watanabe A, Origasa H, Iwai K, Sakamaki Y, D van der Heijde, Miyasaka N and Koike T. Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: The HIKARI randomised, placebo-controlled trial. Modern Rheumatology, 2013.
  17. Hamasuna R, Yasuda M, Ishikawa K, Uehara S, Takahashi S, Hayami H, Yamamoto S, Matsumoto T, Minamitani S, Watanabe A, Iwamoto A, Totsuka K, Kadota J, Sunakawa K, Sato J, Hanaki H, Tsukamoto T, Kiyota H, Egawa S, Tanaka K, Arakawa S, Fujisawa M, Kumon H, Kobayashi K, Matsubara A, Naito S, Tatsugami K, Ito S, Narita H, Kanokogi M, Sumii T, Ito K, Hosobe T, Kawai S, Kawano H, Takayama K, Yamaguchi T, Endo K, Yamauchi T, Maeda S, Yoh M, Horie M, Ito M, Chokyu H, Ihara H, Akiyama K, Uno S, Monden K, Kaji S, Nishimura H, Kawahara M, Sato T, Koniishi T, Nishi S, Ishihara S and Yoshioka M: Nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan. J Infect Chemother 19:571-578, 2013.
  18. Kashiwagi S, Watanabe A, Ikematsu H, Awamura S, Okamoto T, Uemori M and Ishida K: Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomidouble blind placebo controlled trial. J Infect Chemother 19:740-749, 2013.
  19. Kohno S, Niki Y, Kadota J, Yanagihara K, Kaku M, Watanabe A, Aoki N, Hori S, Fujita J, and Tanigawara Y: Clinical dose findings of sitafloxacin treatment: Pharmacokinetic- pharmacodynamic analysis of two clinical trial results for community-acquiured respiratory tract infections. J Infect Chemother 19:486-494, 2013.
  20. Fujita J, Niki Y, Kadota J, Yanagihara K, Kaku M, Watanabe A, Aoki N, Hori S, Tanigawara Y, Cash HL and Kohno S: Clinical and bacteriological efficacies of sitafloxacin against community-acquired pneumonia caused by Streptococcus pneumoniae: nested cohort within a multicenter clinical trial. J Infect Chemotherpy 19:472-479, 2013.
  21. Hayami H, Takahashi S, Ishikawa K, Yasuda M, Yamamoto S, Uehara S, Hamasuna R, Matsumoto T, Minamitani S, Watanabe A, Iwamoto A, Totsuka K, Kadota J, Sunakawa K, Sato J, Hanaki H, Tsukamoto T, Kiyota H, Egawa S, Tanaka K, Arakawa S, Fujisawa M, Kumon H, Kobayashi K, Matsubara A, Naito S, Tatsugami K, Yamaguchi T, Ito S, Kanokogi M, Narita H, Kawano H, Hosobe T, Takayama K, Sumii T, Fujii A, Sato T, Yamauchi T, Izumitani M, Chokyu H, Hara H, Akiyama K, Yoshida M, Uno S, Monden K, Kano M, Kaji S, Kawai S, Ito K, Inatomi H, Nishimura H, Ikuyama T, Nishi S, Takahashi K, Kwano Y, Ishihara S, Tsuneyoshi K, Matsushita S, Yamane T, Hirose T, Fujihiro S, Endo K, Oka Y, Takeyama K, Kimura T and Uemura T: Nationwide surveillance of bacterial pathogens from patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2009 and 2010: antimicrobial susceptibility of Escherichia coli and Staphylococcus saprophyticus. J Infect Chemother 19:393-403, 2013.
  22. Kohno S, Imamura Y, Shindo Y, Seki M, Ishida T, Teramoto S, Kadota J, Tomono K and Watanabe A: Clinical practice guidelines for nursing- and healthcare-associated pneumonia (NHCAP). Respiratory Investigation 51:103-126, 2013.
  23. Fujita J, Niki Y, Kadota J, Yanagihara K, Kaku M, Watanabe A, Aoki N, Hori S, Tanigawara Y, Cash HL and Kohno S: Clinical and bacteriological efficacies of sitafloxacin against community-acquired pneumonia caused by Streptococcus pneumoniae: nested cohort within a multicenter clinical trial. J Infect Chemotherpy 19:472-479, 2013.
  24. Watanabe A: A randomized double-blind controlled study of laninamivir comparing with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases. J Infect Chemother 19:89-97, 2013.
  25. Fuse K, Fujimura S, Kikuchi T, Gomi K, Iida Y, Nukiwa T, Watanabe A: Reduction of virulence factor pyocianin production in multidrug-resistant Pseudomonas aeruginosa. J Infect Chemother 19:82-88, 2013.
  26. Takesue Y, Watanabe A, Hanaki H, Kusachi S, Matsumoto T, Iwamoto A, Totsuka K, Sunakawa K, Yagisawa M, Sato J, Oguri T, Makanishi K, Sumiyama Y, Kitagawa Y, Wakabayashi G, Koyama I, Yanaga K, Konishi T, Fukushima R, Seki S, Imai S, Shintani T, Tsukada H, Tsukada K, Omura K, Mikamo H, Takeyama H, Kusunoki M, Kubo S, Shimizu J, Hirai T, Ohge H, Kadowaki A, Okamoto K and Yanagihara K: Nationwide surveillance of antimicrobial susceptibility patterns of pathogens isolated from surgical site infections (SSI) in Japan. J Infect Chemother 18:816-826, 2012.
  27. Takahashi H, Fujimura S, Ubukata S, Sato E, Shoji M, Utagawa M, Kikuchi T and Watanabe A: Pneumonia after earthquake, Japan, 2011. Emerg Infect Dis 18: 1909-1911, 2012.
  28. Fujimura S, Watanabe A: Generic antibiotics in Japan. J Infect Chemother 18: 421-427, 2012.
  29. Watanabe A, Yanagihara K, Matsumoto T, Kohno S, Aoki N, Oguri T, Sato J, Muratani T, Yagisawa M, Ogasawara K, Koashi N, Kozuki T,Kooto A, Takahashi Y, Tsuji T, Terada M, Nakanishi K, Hattori R, Hirako Y, Maruo A, Minamitani S, Morita K, Wakamura T, Sunakawa K, Hanaki H, Ohsaki Y, Honda Y, Sasaoka S, Takeda H, Ikeda H, Sugai A, Miki M, Nakanowatari S, Takahashi H, Utagawa M,Kobayashi N, Takasaki J, Konosaki H, Aoki Y, Shoji M, Goto H, Saraya T, Kurai D, Okazaki M, Kobayashi Y, Katano Y, Kawana A, Saionji K, Miyazawa N, Sato Y, Watanuki Y, Kudo M, Ehara S, Tsukada H, Imai Y, Watabe N, Aso S, Honma Y, Mikamo H, Yamagishi Y, Takesue Y, Wada Y, Nakamura T, Mitsuno N, Mikasa K, Kasahara K, Uno K, Miyashita N, Kurokawa Y, Takaya M, Kuwabara M, Watanabe Y, Doi M, Shimizu S, Negayama K, Kadota J, Hiramatsu K, Motirinaga Y, Honda J, Fujita M, Iwata S, Iwamoto A, Ezaki T, Onodera S, Kusachi S, Tateda K, Tanaka M, Totsuka K, Niki Y and Matsumoto T: Nationwide surveillance of bacterial respiratory pathogens conducted by the Surveillance Committee of Japanese Society of Chemotherapy,Japanese Association for Infectious Diseases, and Japanese Society for Clnical Microbiology in 2009: general view of the pathogens' antibacterial susceptibility. J Infect Chemother 18: 609-620, 2012.
  30. Yamamoto Y, Watanabe A, Goto H, Matsushima T, Abe S, Aoki N, Shimokata K, Mikasa K, Niki Y, Kohno S: Nationwide, multicenter survey on the efficacy and safety of piperacillin for adult community-acquired pneumonia in Japan. J Infect Chemother 18: 544-551, 2012.
  31. Watanabe A, Goto H, Soma K, Kikuchi T, Gomi K, Miki H, Maemondo M, Ikeda H, Kuroki J, Wada H, Yokoyama T, Izumi S, Mitsutake K, Ueda Y: Usefulness of linezolid in the treatment of hospital-acquired pneumonia caused by MRSA: a prospective observational study. J Infect Chemother 18: 160-168, 2012.
  32. Watanabe A, Goto H, Kohno S, Matsushima T, Abe S, Aoki N, Shimokata K, Mikasa K, and Niki Y: Nationwide survey on the 2005 guidelines for the management of community-acquired pneumonia: Validation of differenciation between bacterial pneumonia and atypical pneumonia. Resp Invest 50: 23-32, 2012.
  33. Watanabe A, Goto H, Kohno S, Matsushima T, Abe S, Aoki N, Shimokata K, Mikasa K, and Niki Y: Nationwide survey on the 2005 guidelines for the management of community-acquired pneumonia: Validation of severity assessment. Resp Invest 50: 14-22, 2012.
  34. Fujimura S, Kimura K, Kaji M, and Watanabe A: Probiotics mechanism of Lactobacillus gasseri OLL2716 strain against Helicobacter pylori. J Clin Microbiol 50:1134-1136, 2012.
  35. Yamamoto Y, Kadota J, Watanabe A, Yamanaka N, Tateda K, Mikamo H, Tomono K, Niki Y, Aoki N, Sunakawa K, and Kohno S: Compliance with oral antibiotic regimens and associated factors in Japan: compliance survey of multiple oral antibiotics (COSMOS). Scand J Infect Dis 44: 93-99, 2012.
  36. Watanabe A, Tokue Y, Aoki N, Matsumoto T, Yanagihara K, Higa F, Tsuge H, Nagashima M, Matsuoka H, Sasagawa Y, Matsumoto M, Fujimaki K, Taguchi K, Ariyasu M, YamamotoN, Kunii O, Shiba K: Criteria for safety evaluation of antimicrobial agents. J Infect Chemother 17:139-147, 2011.
  37. Fujimura S, Nakano Y, Takane H, Kikuchi T, and Watanabe A: Risk factors for health care-associated pneumonia: Transmission of multidrug-resistant Pseudomonas aeruginosa isolates from general hospitals to nursing homes. Am J Infect Control 59:173-175, 2011.
  38. Fujimura S, Fuse K, Takane H, Nakano Y, Gomi K, Kikuchi T, Watanabe A. Antibacterial effects of brand-name teicoplanin and generic products against clinical isolates of methicillin-resistant Staphylococcus aureus. J Infect Chemother 17: 30-33, 2011.
  39. Gomi K, Fujimura S, Fuse K, Takane H, Nakano Y, Kariya Y, Kikuchi T, Kurokawa I, Tokue Y, Watanabe A. Antibacterial activity of carbapanems against clinical isolates of respiratory bacterial pathogens in the Northeastern region of Japan in 2007. J Infect Chemother 17: 200-206, 2011.
  40. Kohno S, Seki M, Watanabe A and the CAP Study Group: Evaluation of an Assessment System for the JRS 2005:A-DROP for the Management of CAP in Adults. Internal Medicine 50:1183-1191, 2011.
  41. Niki Y, Hanaki H, Matsumoto T, Yagisawa M, Kohno S, Aoki N, Watanabe A, Sato J, Hattori R, Koashi N, Terada M, Kozuki T, Maruo A, Morita K, Ogasawara K, Takahashi Y, Matsuda K, Nakanishi K, Takeuchi K, Fujimura S, Takeda H, Ikeda H, Sato N, Niitsuma K, Saito M, Koshiba S, Kaneko M, Miki M, Nakanowatari S, Takahashi H, Utagawa M,Nishiya H, Kawakami S, Aoki Y, Chonabayashi N, Ueda H, Sugiura H, Ichioka M, Goto H, Kurai D, Okazaki M, Yoshida T, Yoshida T, Tsukada H, Imai Y, Honma Y, Yamamoto T, Kawai A, Mikamo H, Takesue Y, Takesue Y, Wada Y, Miyara T, Sato K, Mitsuno N, Nakajima H, Kubo S, Mikasa K, Kasahara K, Nakagaki E, Sano R, Yagi S, Takaya M, Kuorokawa Y, Kusano N, Mihara E, Kuwabara M, Fujiue Y, Ishimaru T, Matsubara N, Kawasaki Y, Tokuyasu H, Masui K, Kido M, Ohta T, Honda J, Kadota J, Hiramatsu K, Aoki Y, Nagasawa Z, Yanagihara K, Fujita J, Tateyama M, and Totsuka K: Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2008: A general view on antibacterial susceptibility. J Infect Chemother 17:510-523, 2011.
  42. Daito H, Kikuchi T, Sakakibara T, Gomi K, Damayanti T, Zaini J, Tode N,Kanehira M, Koyama S, Fujimura S, Ebina M, Ishii KJ, Akira S, Takai T, Watanabe A, Nukiwa T.  Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+CD11c+ cells. Eur Respir J 38: 688-701, 2011.
  43. Suzuki K, Nishimaki K, Okuyama K, Katoh T, Yasujima M, Chihara J, Suwabe A, Shibata Y, Takahashi C, Takeda H, Ida S, Kaku M, Watanabe A, Nukiwa T, Niitsuma K, Kanemitsu K, Takayanagi M, Ohno I: Trends in antimicrobial susceptibility of Streptococcus pneumonia in the Tohoku district of Japan: A longitudinal analysis from 1998 to 2007. Tohoku J Exp Med 220:47-57, 2010.
  44. Kato S, Fujimura S. Primary antimicrobial resistance of Helicobacter pylori in children during the past 9 years. Pediatric Int 52: 187-90, 2010.
  45. Fujimura S, Watanabe A. National survey on antimicrobial therapy compliance in Japan. Scand J Infect Dis 42:637-638, 2010.
  46. Watanabe A, Chang SC, Kim MJ, Wai-sing Chu D and Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: a double-blind, randomized, noninferiority clinical trial. Clin Infect Dis 51: 1167-1175, 2010.

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