Synergistic Effects Between the Test Compounds and the Commercial
Antibiotics Against VRE and MRSA
Synergistic effects between the test compounds and the commercial antibiotics
against VRE and MRSA are summarized in Table 7.9.
Synergism between sophoraflavanone G and vancomycin hydrochloride or fos-
fomycin against MRSA was observed. Synergism between calozeyloxanthone and
vancomycin hydrochloride against VRE was observed. Synergism between -man-
gostin and gentamicin against VRE, and -mangostin and vancomycin hydrochlo-
ride against MRSA was also observed. The other test compounds possessed partial
synergism except for the case of gnetin E (ampicillin against MRSA, and ampicil-
lin or fosfomycin against VRE).
Synergism between phytoalexins or phytoncides and commercially available
antibiotics could be used to decrease usage of antibiotics, contributing to the de-
crease of nosocomial infectious bacteria such as MRSA and VRE. The use of phy-
toalexins or phytoncides isolated from natural products could also be valuable for
the prevention of infectious bacteria such as VRE and MRSA etc. No reports of bac-
teria resistant to antibacterial compounds isolated from the natural products were
found. The use of antibiotics could also be decreased because of the partial syner-
gism between the antibacterial compounds and the commercial antibiotics, which
means that the detection ratio of the resistant bacteria would become lower.
7.9 Synergism Between the Test Compounds and Commercial Antibiotics 153
Table 7.9 Synergisms between the antibacterial compounds and the commercially
available antibiotics in vitro against VRE or MRSA.
FIC index Ampicillin Gentamicin Minocycline Fosfomycin Vancomycin
(average) hydrochloride
SFG (M) 0.73 0.6 nt 0.48 0.16
CZXT (V) 0.750 0.625 0.563 nt 0.453
-M (VRE) 0.606 0.451 0.969 0.826 0.508
-M (MRSA) 0.779 0.667 0.586 0.504 0.441
Gnemonol B (M) 0.708 0.501 0.833 0.750 0.750
Gnemonol B (V) 0.703 0.550 0.678 0.763 0.624
Genetin E (M) 1.195 0.667 0.913 0.809 0.854
Genetin E (V) 1.030 0.770 1.008 1.091 0.746
M, methicillin-resistant S. aureus; V, vancomycin-resistant enterococci; nt, not tested;
SFG, sophoraflavanone G; CZXT, calozeyloxanthone; -M, -mangostin.
1 Emori, T.G., Gaynes, R.P. Clin. Microb.
Rev. 1993, 6, 428–442.
2 Leclercq, R., Courvalin, P. Clin. Microb.
Rev. 1997, 24, 545–556.
3 Murry, B. Am. J. Med. 1997, 101, 284–293.
4 Moellering, R.C. Clin. Infect. Dis. 1998,
26, 1196–1199.
5 Garner, J.S. Infect. Control Hosp. Epidemiol.
1996, 17, 53–80.
6 Slaughter, S., Hayden, M.K., Nathan, C.,
Hu, T.C., Rice, T., Van Voorhis, J.,
Matushek, M., Franklin, C., Weinstein,
R.A. Ann. Intern. Med. 1996, 125,
448–456.
7 Montecalvo, M.A., Jarvis, W.R., Uman, J.,
Shay, D.V., Petrullo, C., Rodney, K.,
Gedris, C., Horowitz, H.W., Wormser,
G.P. Ann. Intern. Med. 1999, 131, 269–272.
8 Nourse, C., Byrne, C., Murphy, H.,
Kaufman, M.E., Clarke, A., Butler, K.
Epidemiol. Infect. 2000, 124, 53–59.
9 Warren, D.K., Nitin, A., Hill, C., Fraser,
V.J., Kollef, M.H. Infect. Control Hosp.
Epidemiol. 2004, 25, 99–104.
10 Calfee, D.P., Giannetta, E.T., Durbin, L.J.,
Germanson, T.P., Farr, B.M. Clin. Infect.
Dis. 2003, 37, 326–332.
11 Shaikh, Z.H., Osting, C.A., Hanna, H.A.,
Arbuckle, R.B., Tarr, J.J., Raad, I.I. J.
Hosp. Infect. 2002, 51, 52–58.
12 Montecalvo, M.A., Jarvis, W.R., Uman, J.,
Shay, D.K., Petrullo, C., Horowitz, H.W.,
Wormser, G.P. Control Hosp. Epidemiol.
2001, 22, 437–442.
13 Hanna, H., Umphrey, J., Tarrand, J.,
Mendoza, M., Raad, I. Infect. Control
Hosp. Epidemiol. 2001, 22, 217–219.
14 Ostrowsky, B.E,, Sinkowitz-Cochran, R.Ll,
Quirk, S.B., Jarvis, W.R. Am. J. Infect.
Control. 2001, 29, 53–57.
15 Coolson, B. Eur. J. Chemother. 1995, 78
(suppl. 3), 93–98.
16 Cox, R.A., Conquest, C., Mallaghan, C.,
Marples, R.R. J. Hosp. Infect. 1995, 29,
87–106.
17 Voss, A., Milatovic, D., Wallrauch-
Schwarz, C., Rosdahl, V.T., Braveny, I.
Eur. J. Clin. Microbiol. 1994, 13, 50–55.
18 Working Party Report. J. Hosp. Infect.
1998, 39, 253–255.
19 Kotilainen, P., Routamaa, M., Peltonen,
R., Evesti, P., Eerola, E., Salmenlinna, S.,
Vuopio-Varkila, J., Rossi, T. Arch. Intern.
Med. 2001, 161, 859–863.
20 Hori, S. Nippon Rinsho 2002, 60,
2144–2149 (In Japanese).
21 Sakagami, Y., Mimura, M., Kajimura, K.,
Yokoyama, H., Iinuma, M., Tanaka, T.,
Ohyama, M. Lett. Appl. Microbiol. 1998,
27, 98–100.
22 Sakagami, Y., Kajimura, K., Wijesinghe,
W.M.N.M., Dharmaratne, H.R.W. Planta
Med. 2002, 68, 543–545.
23 Sakagami, Y., Iinuma, M., Piyasena,
K.G.N.P., Dharmaratne, H.R.W.
Phytomedicine 2005, 12, 203–208.
24 Iliya, I. Tanaka, T, Iinuma, M., Ali, A.,
Furusawa, M., Nakaya, K., Shirataki, Y.,
Murata, J, Dornaedi, D. Chem. Pharm.
Bull. 2002, 50, 796–801.
25 Iliya, I., Ali, Z., Tanaka, T., Iinuma, M.,
Furusawa, M., Nakaya, K., Murata, J.,
Dornaedi, D. Helvetica Chim. Acta 2002,
85, 2538–2546.
26 Goto, S, Yo, K., Kawakita, R., Kosakai, N.,
Mitsuhashi, S., Nishino, T., Ohsawa, N.,
Tanami, H. Chemotherapy 1981, 29,
76–79.
27 Sakagami, Y., Kajimura, K. J. Hosp. Infect.
2002, 50, 140–144.
These findings suggest that phytoalexins or phytoncides alone or in combination
with suitable antibiotics against VRE and MRSA might be useful in controlling
VRE and MRSA infections.
Recently, many similar reports about the antibacterial activities of the com-
pounds (phytoalexins and phytoncides etc.) isolated from tropical foods and plants
have been published [30–44]. These research fields would be more progressive, and
would contribute to the prevention of nosocomial infectious bacteria such as VRE
and MRSA etc.
References
154 7 Anti-MRSA and Anti-VRE Activities of Phytoalexins and Phytoncides Isolated from Tropical Plants
References 155
28 Didry, N., Dubreuil, L., Pinkas, M.
Phytother. Res. 1993, 7, 21–24.
29 Williamson, E.M. Phytomedicine 2001, 8,
401–409.
30 Iinuma, M., Tosa, H., Tanaka, T., Asai, F.,
Kobayashi, Y., Shimano, R., Miyauchi, K.
J. Pharm. Pharmacol. 1996, 48, 861–865.
31 Iinuma, M., Tsuchiya, H., Sato, M.,
Yokoyama, J., Ohyama, M., Ohkawa, Y.,
Tanaka, T., Fujiwara, S., Fujii, T. J.
Pharm. Pharmacol. 1994, 46, 892–895.
32 Fukai, T., Oku, Y., Hano, Y., Terada, S.
Planta Med. 2004, 70, 685–687.
33 Palombo, E.A., Semple, S.J. J. Basic
Microbiol. 2002, 42, 444–448.
34 Gibbons, S., Leimkugel, J., Oluwatuyi, M.,
Heinrich, M. Phytother. Res. 2003, 17,
274–275.
35 Fukai, T., Oku, Y., Hou, A.J., Yonekawa,
M., Terada, S. Phytomedicine 2005, 12,
510–513.
36 Hur, J.M., Yang, C.H., Han, S.H., Lee,
S.H., You, Y.O., Park, J.C., Kim, K.J.
Fitoterapia 2004, 75, 603–605.
37 Aqil, F., Khan, M.S., Owais, M., Ahmad,
I. J. Basic Microbiol. 2005, 45, 106–114.
38 Tanaka, H., Sato, M., Oh-Uchi, T.,
Yamaguchi, R., Etoh, H., Shimizu, H.,
Sako, M., Takeuchi, H. Phytomedicine
2004, 11, 331–337.
39 Sato, Y., Oketani, H., Yamada, T.,
Singyouchi, K., Ohtsubo, T., Kihara, M.,
Shibata, H., Higuti, T. J. Pharm.
Pharmacol. 1997, 49, 1042–1044.
40 Nostro, A., Cellini, L., Di Bartolomeo, S.,
Di Campli, E., Grande, R., Cannatelli,
M.A., Marzio, L., Alonzo, V. Phytother.
Res. 2005, 19, 198–202.
41 Voravuthikunchai, S.P., Kitpipit, L. Clin.
Microbiol. Infect. 2005, 11, 510–512.
42 Chomnawang, M.T., Surassmo ,S.,
Nukoolkarn, V.S., Gritsanapan, W.
J. Ethnopharmacol. 2005, 101, 330–333.
43 Rukachaisirikul, V., Tadpetch, K.,
Watthanaphanit, A., Saengsanae, N.,
Phongpaichit, S. J. Nat. Prod. 2005, 68,
1218–1221.
44 Sukpondma, Y., Rukachaisirikul, V.,
Phongpaichit, S. Chem. Pharm. Bull.
2005, 53, 850–852.
Antibiotics Against VRE and MRSA
Synergistic effects between the test compounds and the commercial antibiotics
against VRE and MRSA are summarized in Table 7.9.
Synergism between sophoraflavanone G and vancomycin hydrochloride or fos-
fomycin against MRSA was observed. Synergism between calozeyloxanthone and
vancomycin hydrochloride against VRE was observed. Synergism between -man-
gostin and gentamicin against VRE, and -mangostin and vancomycin hydrochlo-
ride against MRSA was also observed. The other test compounds possessed partial
synergism except for the case of gnetin E (ampicillin against MRSA, and ampicil-
lin or fosfomycin against VRE).
Synergism between phytoalexins or phytoncides and commercially available
antibiotics could be used to decrease usage of antibiotics, contributing to the de-
crease of nosocomial infectious bacteria such as MRSA and VRE. The use of phy-
toalexins or phytoncides isolated from natural products could also be valuable for
the prevention of infectious bacteria such as VRE and MRSA etc. No reports of bac-
teria resistant to antibacterial compounds isolated from the natural products were
found. The use of antibiotics could also be decreased because of the partial syner-
gism between the antibacterial compounds and the commercial antibiotics, which
means that the detection ratio of the resistant bacteria would become lower.
7.9 Synergism Between the Test Compounds and Commercial Antibiotics 153
Table 7.9 Synergisms between the antibacterial compounds and the commercially
available antibiotics in vitro against VRE or MRSA.
FIC index Ampicillin Gentamicin Minocycline Fosfomycin Vancomycin
(average) hydrochloride
SFG (M) 0.73 0.6 nt 0.48 0.16
CZXT (V) 0.750 0.625 0.563 nt 0.453
-M (VRE) 0.606 0.451 0.969 0.826 0.508
-M (MRSA) 0.779 0.667 0.586 0.504 0.441
Gnemonol B (M) 0.708 0.501 0.833 0.750 0.750
Gnemonol B (V) 0.703 0.550 0.678 0.763 0.624
Genetin E (M) 1.195 0.667 0.913 0.809 0.854
Genetin E (V) 1.030 0.770 1.008 1.091 0.746
M, methicillin-resistant S. aureus; V, vancomycin-resistant enterococci; nt, not tested;
SFG, sophoraflavanone G; CZXT, calozeyloxanthone; -M, -mangostin.
1 Emori, T.G., Gaynes, R.P. Clin. Microb.
Rev. 1993, 6, 428–442.
2 Leclercq, R., Courvalin, P. Clin. Microb.
Rev. 1997, 24, 545–556.
3 Murry, B. Am. J. Med. 1997, 101, 284–293.
4 Moellering, R.C. Clin. Infect. Dis. 1998,
26, 1196–1199.
5 Garner, J.S. Infect. Control Hosp. Epidemiol.
1996, 17, 53–80.
6 Slaughter, S., Hayden, M.K., Nathan, C.,
Hu, T.C., Rice, T., Van Voorhis, J.,
Matushek, M., Franklin, C., Weinstein,
R.A. Ann. Intern. Med. 1996, 125,
448–456.
7 Montecalvo, M.A., Jarvis, W.R., Uman, J.,
Shay, D.V., Petrullo, C., Rodney, K.,
Gedris, C., Horowitz, H.W., Wormser,
G.P. Ann. Intern. Med. 1999, 131, 269–272.
8 Nourse, C., Byrne, C., Murphy, H.,
Kaufman, M.E., Clarke, A., Butler, K.
Epidemiol. Infect. 2000, 124, 53–59.
9 Warren, D.K., Nitin, A., Hill, C., Fraser,
V.J., Kollef, M.H. Infect. Control Hosp.
Epidemiol. 2004, 25, 99–104.
10 Calfee, D.P., Giannetta, E.T., Durbin, L.J.,
Germanson, T.P., Farr, B.M. Clin. Infect.
Dis. 2003, 37, 326–332.
11 Shaikh, Z.H., Osting, C.A., Hanna, H.A.,
Arbuckle, R.B., Tarr, J.J., Raad, I.I. J.
Hosp. Infect. 2002, 51, 52–58.
12 Montecalvo, M.A., Jarvis, W.R., Uman, J.,
Shay, D.K., Petrullo, C., Horowitz, H.W.,
Wormser, G.P. Control Hosp. Epidemiol.
2001, 22, 437–442.
13 Hanna, H., Umphrey, J., Tarrand, J.,
Mendoza, M., Raad, I. Infect. Control
Hosp. Epidemiol. 2001, 22, 217–219.
14 Ostrowsky, B.E,, Sinkowitz-Cochran, R.Ll,
Quirk, S.B., Jarvis, W.R. Am. J. Infect.
Control. 2001, 29, 53–57.
15 Coolson, B. Eur. J. Chemother. 1995, 78
(suppl. 3), 93–98.
16 Cox, R.A., Conquest, C., Mallaghan, C.,
Marples, R.R. J. Hosp. Infect. 1995, 29,
87–106.
17 Voss, A., Milatovic, D., Wallrauch-
Schwarz, C., Rosdahl, V.T., Braveny, I.
Eur. J. Clin. Microbiol. 1994, 13, 50–55.
18 Working Party Report. J. Hosp. Infect.
1998, 39, 253–255.
19 Kotilainen, P., Routamaa, M., Peltonen,
R., Evesti, P., Eerola, E., Salmenlinna, S.,
Vuopio-Varkila, J., Rossi, T. Arch. Intern.
Med. 2001, 161, 859–863.
20 Hori, S. Nippon Rinsho 2002, 60,
2144–2149 (In Japanese).
21 Sakagami, Y., Mimura, M., Kajimura, K.,
Yokoyama, H., Iinuma, M., Tanaka, T.,
Ohyama, M. Lett. Appl. Microbiol. 1998,
27, 98–100.
22 Sakagami, Y., Kajimura, K., Wijesinghe,
W.M.N.M., Dharmaratne, H.R.W. Planta
Med. 2002, 68, 543–545.
23 Sakagami, Y., Iinuma, M., Piyasena,
K.G.N.P., Dharmaratne, H.R.W.
Phytomedicine 2005, 12, 203–208.
24 Iliya, I. Tanaka, T, Iinuma, M., Ali, A.,
Furusawa, M., Nakaya, K., Shirataki, Y.,
Murata, J, Dornaedi, D. Chem. Pharm.
Bull. 2002, 50, 796–801.
25 Iliya, I., Ali, Z., Tanaka, T., Iinuma, M.,
Furusawa, M., Nakaya, K., Murata, J.,
Dornaedi, D. Helvetica Chim. Acta 2002,
85, 2538–2546.
26 Goto, S, Yo, K., Kawakita, R., Kosakai, N.,
Mitsuhashi, S., Nishino, T., Ohsawa, N.,
Tanami, H. Chemotherapy 1981, 29,
76–79.
27 Sakagami, Y., Kajimura, K. J. Hosp. Infect.
2002, 50, 140–144.
These findings suggest that phytoalexins or phytoncides alone or in combination
with suitable antibiotics against VRE and MRSA might be useful in controlling
VRE and MRSA infections.
Recently, many similar reports about the antibacterial activities of the com-
pounds (phytoalexins and phytoncides etc.) isolated from tropical foods and plants
have been published [30–44]. These research fields would be more progressive, and
would contribute to the prevention of nosocomial infectious bacteria such as VRE
and MRSA etc.
References
154 7 Anti-MRSA and Anti-VRE Activities of Phytoalexins and Phytoncides Isolated from Tropical Plants
References 155
28 Didry, N., Dubreuil, L., Pinkas, M.
Phytother. Res. 1993, 7, 21–24.
29 Williamson, E.M. Phytomedicine 2001, 8,
401–409.
30 Iinuma, M., Tosa, H., Tanaka, T., Asai, F.,
Kobayashi, Y., Shimano, R., Miyauchi, K.
J. Pharm. Pharmacol. 1996, 48, 861–865.
31 Iinuma, M., Tsuchiya, H., Sato, M.,
Yokoyama, J., Ohyama, M., Ohkawa, Y.,
Tanaka, T., Fujiwara, S., Fujii, T. J.
Pharm. Pharmacol. 1994, 46, 892–895.
32 Fukai, T., Oku, Y., Hano, Y., Terada, S.
Planta Med. 2004, 70, 685–687.
33 Palombo, E.A., Semple, S.J. J. Basic
Microbiol. 2002, 42, 444–448.
34 Gibbons, S., Leimkugel, J., Oluwatuyi, M.,
Heinrich, M. Phytother. Res. 2003, 17,
274–275.
35 Fukai, T., Oku, Y., Hou, A.J., Yonekawa,
M., Terada, S. Phytomedicine 2005, 12,
510–513.
36 Hur, J.M., Yang, C.H., Han, S.H., Lee,
S.H., You, Y.O., Park, J.C., Kim, K.J.
Fitoterapia 2004, 75, 603–605.
37 Aqil, F., Khan, M.S., Owais, M., Ahmad,
I. J. Basic Microbiol. 2005, 45, 106–114.
38 Tanaka, H., Sato, M., Oh-Uchi, T.,
Yamaguchi, R., Etoh, H., Shimizu, H.,
Sako, M., Takeuchi, H. Phytomedicine
2004, 11, 331–337.
39 Sato, Y., Oketani, H., Yamada, T.,
Singyouchi, K., Ohtsubo, T., Kihara, M.,
Shibata, H., Higuti, T. J. Pharm.
Pharmacol. 1997, 49, 1042–1044.
40 Nostro, A., Cellini, L., Di Bartolomeo, S.,
Di Campli, E., Grande, R., Cannatelli,
M.A., Marzio, L., Alonzo, V. Phytother.
Res. 2005, 19, 198–202.
41 Voravuthikunchai, S.P., Kitpipit, L. Clin.
Microbiol. Infect. 2005, 11, 510–512.
42 Chomnawang, M.T., Surassmo ,S.,
Nukoolkarn, V.S., Gritsanapan, W.
J. Ethnopharmacol. 2005, 101, 330–333.
43 Rukachaisirikul, V., Tadpetch, K.,
Watthanaphanit, A., Saengsanae, N.,
Phongpaichit, S. J. Nat. Prod. 2005, 68,
1218–1221.
44 Sukpondma, Y., Rukachaisirikul, V.,
Phongpaichit, S. Chem. Pharm. Bull.
2005, 53, 850–852.
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