Anti-VRE and Anti-MRSA Activities of New Quinolones and Their Synergism with Commercial Antibiotics. Part 2

YOSHIKAZU SAKAGAMI; SADAO KOMEMUSHI; GORO TSUKAMOTO; HIROSATO KONDO; AKIKO YOSHIKAWA; OSAMU MURAOKA

doi:10.4265/bio.13.103

YOSHIKAZU SAKAGAMI, SADAO KOMEMUSHI, GORO TSUKAMOTO, HIROSATO KONDO, AKIKO YOSHIKAWA, OSAMU MURAOKA

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Keywords: Antibacterial activity, New quinolones, VRE, MRSA, Synergism

JOURNAL FREE ACCESS

2008 Volume 13 Issue 3 Pages 103-110

DOI https://doi.org/10.4265/bio.13.103

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Published: September 10, 2008 Received: May 10, 2008 Available on J-STAGE: June 28, 2010 Accepted: June 23, 2008 Advance online publication: - Revised: -
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Date of correction: June 28, 2010 Reason for correction: - Correction: CITATION Details: Wrong : Burd, M., Humphreys, H., Glynn, G., Mitchell, E., McDonald, P., Johnson, H., McDonnell, B., Doyle, D., and Rossney, A.(2003) Control and the prevention of methicillinresistant Staphylococcus aureus in hospitals in Ireland: North/South Study of MRSA in Ireland 1999. J. Hospital Infection, 53, 297-303.
Calfee, D. P., Giannetta, E. T., Durbin, L. J., Germanson, T. P., and Farr, B. M.(2003) Control of endemic vancomycinresistant Enterococcus among inpatients at a university hospital. Clinical Infectious Disease, 37, 326-332.
Coolson, B.(1995) Aspects of the epidemiology of MRSA in Europe. J. Chemotherapy, 78 (suppl. 3), 93-98.
Cox, R. A., Conquest, C., Mallaghan, C., and Marples, R. R.(1995) A major outbreak of methicillin resistant Staphylococcus aureus caused by a new phage-type (EMRSA). J. Hospital Infection, 29, 87-106.
De Lucas-Villarrubia J. C., Lopez-Franco, M., Granizo, J. J., De Lucas-Garcia, J. C., and Gomez-Barrena, E.(2004) Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery. Internal Orthop., 28, 16-20.
Didry, N., Dubreuil, L., and Pinkas, M.(1993) Microbiological properties of protoanemonin isolated from Ranunculus bulbosus. Phytotherapy Research, 7, 21-24.
Ellis, S. L., Finn, P., Noone, M., and Leaper, D. J.(2003) Eradication of methicillin-resistant Staphylococcus aureus from pressure sores using warming therapy. Surg. Infect., 4, 53-55.
Emori, T. G., and Gaynes, R. P.(1993) An overview of nosocomial infections, including the role of the microbiology laboratory. Clinical Microbiology Review, 6, 428-442.
Garner, J. S.(1996) Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infection Control Hospital Epidemiology, 17, 53-80.
Goto, S., Yo, K., Kawakita, R., Kosakai, N., Mitsuhashi, S., Nishino, T., Ohsawa, N., and Tanami, H.(1981) Rerevision of the method of minimum inhibitory concentration. Chemotherapy, 29, 76-79.
Jarvis, W. R., Schlosser, J., Chinn, R. Y., Tweeten, S., Jackson, M.(2007) National prevalence of methicillinresistant Staphylococcus aureus in inpatients at US health care facilities, 2006. Am. J. Infect. Control, 35, 631-637.
Jinbo, Y., Kondo, H., Inoue, Y., Taguchi, M., Tsujishita, H., Kotera, Y., Sakamoto, F., and Tsukamoto, G.(1993). Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids 1. Journal of Medicinal Chemistry, 36, 2621-2626.
Jinbo, Y., Taguchi, M., Inoue, Y., Kondo, H., Miyasaka, T., Tsujishita, H., Sakamoto, F., and Tsukamoto, G.(1993). Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic Acids 21a. Journal of Medicinal Chemistry, 36, 3148-3153.
Kauffman, C. A.(2003) Therapeutic and preventative options for the management of vancomycin-resistant enterococcal infections. J. Antimicrob. Chemother., 51 (Suppl 3), iii23-30.
Kotilainen, P., Routamaa, M., Peltonen, R., Evesti, P., Eerola, E., Salmenlinna, S., Vuopio-Varkila, J., and Rossi, T.(2001) Eradication of methicillin resistant Staphylococcus aureus from a health center ward and associated nursing home. Archives of Internal Medicine, 161, 859-863.
Kron, C., Revol, M., Felten, A., Marie, O., Cormerais, A., Laffont, I., and Servant, J. M.(2002) Prevalence of nosocomial infections in tetraplegic upper extremity surgery. Prospective study of twenty patients. Annales de Chirurgle Plastique et Esthetique, 47, 12-16.
Kurup, A., Chlebicki, M. P., Ling, M. L., Koh, T. H., Tan, K. Y., Lee, L. C., and Howe, K. B.(2008) Control of a hospitalwide vancomycin-resistant Enterococci outbreak. Am. J. Infect. Control, 36, 206-211.
Leclercq, R., and Courvalin, P.(1997) Resistance to glycopeptides in enterococci. Clinical Infectious Diseases, 24, 545-556.
Linden, P. K.(2002) Treatment options for vancomycinresistant enterococcal infections. Drugs, 62, 425-441.
Lowe, IJ. A. II, Drozda, S. E., McLean, S., Bryce, D. K., Crawford, R.T., Snider, R.M., Longo, K.P., Nagahisa, A., and Tsuchiya, M.(1994) Aza-tricyclic substance P antagonists. Journal of Medicinal Chemistry, 37, 2831-2840.
Lucet J. C., Armand-Lefevre, L., Laurichesse, J. J., Macrez, A., Papy, E., Ruimy, R., Deblangy, C., Lozach, A., Lolom, I., Jarlier, V., Andremont, A., and Leport, C.(2007) Rapid control of an outbreak of vancomycin-resistant enterococci in a French university hospital. J. Hospital Infection, 67, 42-48.
Millar, B. C., Prendergast, B. D., and Moore, J. E.(2008) Community-associated MRSA (CA-MRSA): an emerging pathogen in infective endocarditis. J. Antimicrob. Chemother., 61, 1-7.
Moellering, R.C.(1998) Vancomycin-resistant enterococci. Clinical Infectious Diseases, 26, 1196-1199.
Montecalvo, M.A., Jarvis, W. R., Uman, J., Shay, D. V., Petrullo, C., Rodney, K., Gedris, C., Horowitz, H. W., and Wormser, G. P.(1999). Infection-control measures reduce transmission of vancomycin- resistant enterococci in an endemic setting. Annals Internal Medicine, 131, 269-272.
Murry, B. E.(1997) Vancomycin-resistant enterococci. American Journal of Medicine, 102, 284-293.
Muto, C. A., Jernigan, J. A., Ostrowsky, B. E., Richet, H. M., Jarvis, W. R., Boyce, J. M., and Farr, B. M.(2003) SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus. Infection Control Hospital Epidemiology, 24, 362-386
Nourse, C., Byrne, C., Murphy, H., Kaufman, M. E., and Butler, C.A.(2000). Eradication of vancomycin-resistant Enterococcus faecium from a paediatric oncology unit and prevalence of colonization in hospitalized and community-based children. Epidemiology Infection, 124, 53-59.
Peta, M., Carretto, E., Barbarini, D., Zamperoni, A., Carnevale, L., Perversi, L., Pagani, M., Bonora, M. G., Fontana, R., Marone, P., and Langer, M.(2006) Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general intensive care unit. Clin. Microbiol. Infect., 12, 163-169.
Sakagami, Y., and Kajimura, K.(2002) Bactericidal activities of disinfectants against vancomycin-resistant enterococci. J. Hospital Infection, 51, 140-144.
Sakagami, Y., Mimura, M., Kajimura, K., Yokoyama, H., linuma, M., Tanaka, T., and Ohyama, M.(1998). Anti-M RSA activity of sophoraflavanone G and synergism with other antibacterial agents. Letters in Applied Microbiology, 27, 98-100.
Sakagami, Y., Muraoka, M., and Tsukamoto, G.(2003) Anti-VRE, Anti-MRSA Activities and Synergisms of Novel New Quinolone Compounds with Antibiotics. Biocontrol Science, 9, 159-166.
Samad, A., Banerjee, D., Carbarns, N., and Ghosh, S.(2002) Prevalence of methicillin-resistant Staphylococcus aureus colonization in surgical patients, on admission to a Welsh hospital. J. Hospital Infection, 51, 43-46.
Shaikh, Z. H., Osting, C. A., Hanna, H. A., Arbuckle, R. B., Tarr, J. J., and Raad, I. I.(2002) Effectiveness of a multifaceted infection control policy in reducing vancomycin usage and vancomycin-resistant enterococci at a tertiary care cancer centre. J. Hospital Infection, 51, 52-58.
Shetty, N., and Wilson, A. P.(2000) Sitafloxacin in the treatment of patients with infections caused by vancomycinresistant enterococci and methicillin-resistant Staphylococcus aureus. J. Antimicrobial Chemotherapy, 46, 633-638.
Shiojima, T., Ohki, Y., Nako, Y., Morikawa, A., Okubo, T., and lyobe, S.(2003) Immediate control of a methicillinresistant Staphylococcus aureus outbreak in a neonatal intensive care unit. J. Infect. Chemother., 9, 243-247.
Slaughter, S., Hayden, M. K., Nathan, C., Hu, T. C., Rice, T., Van Voorhis, J., Matushek, M., Franklin, C., and Weinstein, R. A.(1996) A comparison of the effect of universal use of gloves and gowns with that of glove use alone on acquisition of vancomycin-resistant enterococci in a medical intensive care unit. Annals Internal Medicine, 125, 448-456.
Timmers, G. J., van der Zwet, W. C., Simoons-Smit, I. M., Savelkoul, P. H., Meester, H. H., Vandenbroucke-Grauls, C. M., and Huijgens, P. C.(2002) Outbreak of vancomycin-resistant Enterococcus faecium in a haematology unit: risk factor assessment and successful control of the epidemic. British J. Hematology, 116, 826-833.
Voss, A., Milatovic, D., Wallrauch-Schwarz, C., Rosdahl, V.T., and Braveny, I.(1994) Methicillin resistant Staphylococcus aureus in Europe. European J. Clin. Microbiol., 13, 50-55.
Working Party Report (1998) Revised guideline for the control of methicillin resistant Staphylococcus aureus infection in hospitals. J. Hospital Infection, 39, 253-255.

Right : Burd, M., Humphreys, H., Glynn, G., Mitchell, E., McDonald, P., Johnson, H., McDonnell, B., Doyle, D., and Rossney, A.(2003) Control and the prevention of methicillinresistant Staphylococcus aureus in hospitals in Ireland: North/South Study of MRSA in Ireland 1999. J. Hospital Infection, 53, 297-303.
Calfee, D. P., Giannetta, E. T., Durbin, L. J., Germanson, T. P., and Farr, B. M.(2003) Control of endemic vancomycinresistant Enterococcus among inpatients at a university hospital. Clinical Infectious Disease, 37, 326-332.
Coolson, B.(1995) Aspects of the epidemiology of MRSA in Europe. J. Chemotherapy, 78 (suppl. 3), 93-98.
Cox, R. A., Conquest, C., Mallaghan, C., and Marples, R. R.(1995) A major outbreak of methicillin resistant Staphylococcus aureus caused by a new phage-type (EMRSA). J. Hospital Infection, 29, 87-106.
De Lucas-Villarrubia J. C., Lopez-Franco, M., Granizo, J. J., De Lucas-Garcia, J. C., and Gomez-Barrena, E.(2004) Strategy to control methicillin-resistant Staphylococcus aureus post-operative infection in orthopaedic surgery. Internal Orthop., 28, 16-20.
Didry, N., Dubreuil, L., and Pinkas, M.(1993) Microbiological properties of protoanemonin isolated from Ranunculus bulbosus. Phytotherapy Research, 7, 21-24.
Ellis, S. L., Finn, P., Noone, M., and Leaper, D. J.(2003) Eradication of methicillin-resistant Staphylococcus aureus from pressure sores using warming therapy. Surg. Infect., 4, 53-55.
Emori, T. G., and Gaynes, R. P.(1993) An overview of nosocomial infections, including the role of the microbiology laboratory. Clinical Microbiology Review, 6, 428-442.
Garner, J. S.(1996) Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infection Control Hospital Epidemiology, 17, 53-80.
Goto, S., Yo, K., Kawakita, R., Kosakai, N., Mitsuhashi, S., Nishino, T., Ohsawa, N., and Tanami, H.(1981) Rerevision of the method of minimum inhibitory concentration. Chemotherapy, 29, 76-79.
Jarvis, W. R., Schlosser, J., Chinn, R. Y., Tweeten, S., Jackson, M.(2007) National prevalence of methicillinresistant Staphylococcus aureus in inpatients at US health care facilities, 2006. Am. J. Infect. Control, 35, 631-637.
Jinbo, Y., Kondo, H., Inoue, Y., Taguchi, M., Tsujishita, H., Kotera, Y., Sakamoto, F., and Tsukamoto, G.(1993). Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids 1. Journal of Medicinal Chemistry, 36, 2621-2626.
Jinbo, Y., Taguchi, M., Inoue, Y., Kondo, H., Miyasaka, T., Tsujishita, H., Sakamoto, F., and Tsukamoto, G.(1993). Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic Acids 21a. Journal of Medicinal Chemistry, 36, 3148-3153.
Kauffman, C. A.(2003) Therapeutic and preventative options for the management of vancomycin-resistant enterococcal infections. J. Antimicrob. Chemother., 51 (Suppl 3), iii23-30.
Kotilainen, P., Routamaa, M., Peltonen, R., Evesti, P., Eerola, E., Salmenlinna, S., Vuopio-Varkila, J., and Rossi, T.(2001) Eradication of methicillin resistant Staphylococcus aureus from a health center ward and associated nursing home. Archives of Internal Medicine, 161, 859-863.
Kron, C., Revol, M., Felten, A., Marie, O., Cormerais, A., Laffont, I., and Servant, J. M.(2002) Prevalence of nosocomial infections in tetraplegic upper extremity surgery. Prospective study of twenty patients. Annales de Chirurgle Plastique et Esthetique, 47, 12-16.
Kurup, A., Chlebicki, M. P., Ling, M. L., Koh, T. H., Tan, K. Y., Lee, L. C., and Howe, K. B.(2008) Control of a hospitalwide vancomycin-resistant Enterococci outbreak. Am. J. Infect. Control, 36, 206-211.
Leclercq, R., and Courvalin, P.(1997) Resistance to glycopeptides in enterococci. Clinical Infectious Diseases, 24, 545-556.
Linden, P. K.(2002) Treatment options for vancomycinresistant enterococcal infections. Drugs, 62, 425-441.
Lowe, IJ. A. II, Drozda, S. E., McLean, S., Bryce, D. K., Crawford, R.T., Snider, R.M., Longo, K.P., Nagahisa, A., and Tsuchiya, M.(1994) Aza-tricyclic substance P antagonists. Journal of Medicinal Chemistry, 37, 2831-2840.
Lucet J. C., Armand-Lefevre, L., Laurichesse, J. J., Macrez, A., Papy, E., Ruimy, R., Deblangy, C., Lozach, A., Lolom, I., Jarlier, V., Andremont, A., and Leport, C.(2007) Rapid control of an outbreak of vancomycin-resistant enterococci in a French university hospital. J. Hospital Infection, 67, 42-48.
Millar, B. C., Prendergast, B. D., and Moore, J. E.(2008) Community-associated MRSA (CA-MRSA): an emerging pathogen in infective endocarditis. J. Antimicrob. Chemother., 61, 1-7.
Moellering, R.C.(1998) Vancomycin-resistant enterococci. Clinical Infectious Diseases, 26, 1196-1199.
Montecalvo, M.A., Jarvis, W. R., Uman, J., Shay, D. V., Petrullo, C., Rodney, K., Gedris, C., Horowitz, H. W., and Wormser, G. P.(1999). Infection-control measures reduce transmission of vancomycin- resistant enterococci in an endemic setting. Annals Internal Medicine, 131, 269-272.
Murry, B. E.(1997) Vancomycin-resistant enterococci. American Journal of Medicine, 102, 284-293.
Muto, C. A., Jernigan, J. A., Ostrowsky, B. E., Richet, H. M., Jarvis, W. R., Boyce, J. M., and Farr, B. M.(2003) SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus. Infection Control Hospital Epidemiology, 24, 362-386
Nourse, C., Byrne, C., Murphy, H., Kaufman, M. E., and Butler, C.A.(2000). Eradication of vancomycin-resistant Enterococcus faecium from a paediatric oncology unit and prevalence of colonization in hospitalized and community-based children. Epidemiology Infection, 124, 53-59.
Peta, M., Carretto, E., Barbarini, D., Zamperoni, A., Carnevale, L., Perversi, L., Pagani, M., Bonora, M. G., Fontana, R., Marone, P., and Langer, M.(2006) Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general intensive care unit. Clin. Microbiol. Infect., 12, 163-169.
Sakagami, Y., and Kajimura, K.(2002) Bactericidal activities of disinfectants against vancomycin-resistant enterococci. J. Hospital Infection, 51, 140-144.
Sakagami, Y., Mimura, M., Kajimura, K., Yokoyama, H., linuma, M., Tanaka, T., and Ohyama, M.(1998). Anti-MRSA activity of sophoraflavanone G and synergism with other antibacterial agents. Letters in Applied Microbiology, 27, 98-100.
Sakagami, Y., Muraoka, M., and Tsukamoto, G.(2003) Anti-VRE, Anti-MRSA Activities and Synergisms of Novel New Quinolone Compounds with Antibiotics. Biocontrol Science, 9, 159-166.
Samad, A., Banerjee, D., Carbarns, N., and Ghosh, S.(2002) Prevalence of methicillin-resistant Staphylococcus aureus colonization in surgical patients, on admission to a Welsh hospital. J. Hospital Infection, 51, 43-46.
Shaikh, Z. H., Osting, C. A., Hanna, H. A., Arbuckle, R. B., Tarr, J. J., and Raad, I. I.(2002) Effectiveness of a multifaceted infection control policy in reducing vancomycin usage and vancomycin-resistant enterococci at a tertiary care cancer centre. J. Hospital Infection, 51, 52-58.
Shetty, N., and Wilson, A. P.(2000) Sitafloxacin in the treatment of patients with infections caused by vancomycinresistant enterococci and methicillin-resistant Staphylococcus aureus. J. Antimicrobial Chemotherapy, 46, 633-638.
Shiojima, T., Ohki, Y., Nako, Y., Morikawa, A., Okubo, T., and lyobe, S.(2003) Immediate control of a methicillinresistant Staphylococcus aureus outbreak in a neonatal intensive care unit. J. Infect. Chemother., 9, 243-247.
Slaughter, S., Hayden, M. K., Nathan, C., Hu, T. C., Rice, T., Van Voorhis, J., Matushek, M., Franklin, C., and Weinstein, R. A.(1996) A comparison of the effect of universal use of gloves and gowns with that of glove use alone on acquisition of vancomycin-resistant enterococci in a medical intensive care unit. Annals Internal Medicine, 125, 448-456.
Timmers, G. J., van der Zwet, W. C., Simoons-Smit, I. M., Savelkoul, P. H., Meester, H. H., Vandenbroucke-Grauls, C. M., and Huijgens, P. C.(2002) Outbreak of vancomycin-resistant Enterococcus faecium in a haematology unit: risk factor assessment and successful control of the epidemic. British J. Hematology, 116, 826-833.
Voss, A., Milatovic, D., Wallrauch-Schwarz, C., Rosdahl, V.T., and Braveny, I.(1994) Methicillin resistant Staphylococcus aureus in Europe. European J. Clin. Microbiol., 13, 50-55.
Working Party Report (1998) Revised guideline for the control of methicillin resistant Staphylococcus aureus infection in hospitals. J. Hospital Infection, 39, 253-255.

Abstract

Anti-VRE and anti-MRSA activities of new quinolone derivatives [The two quinolone derivatives are 8- [3- [(ethylamino) methyl] -1-pyrrodinyl] -7-fluoro-9, 1- [(N-methylimino) methano] -5-oxo-5H-thiazolo [3, 2-a] quinolone-4-carboxylic acid (compound A) and 7-fluoro-8-morpholino - 9, 1- [(N-methylimino) methano] - 5 - oxo - 5H - thiazolo [3, 2-a] quinolone-4-carboxylic acid (compound B)] and their synergism with commercial antibiotics were investigated. Compound A exhibited potent antibacterial activity against VRE and MRSA among the five new quinolone compounds tested, and showed superior activity to pefloxacin, ofloxacin and levofloxacin, which are clinically in use these days. With respect to the anti-VRE activity, compound A showed synergism with fosfomycin (FOM), and partial synergism with ampicillin (ABPC), gentaicin (GM), minocycline (MINO) and vancomycin hydrochloride (VCM). Partial synergism in anti-VRE activity was also observed between compound B and GM, MINO, FOM and VCM. Compound A also showed synergism with MINO and FOM in anti-MASA activity. Partial synergism was observed with ABPC, GM and VCM. Synergism with ABPC was not detected in anti-MRSA activity. On the other hand, the synergism of compound B with FOM, and the partial synergisms with ABPC, GM and MINO were also found against MRSA. No synergism with ABPC was found against MRSA. These results suggested that compound A and B could possibly reduce the daily administration dose of these antibiotics in the treatment of nosocomial infections, and also reduce the possibility of the occurrence of nosocomial infections caused by VRE and/or MRSA.

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