Abstract
The objective of this paper was to investigate the in vitro effects of fusidic acid combined with fosfomycin against methicillin-resistant Staphylococcus aureus (MRSA). In all, 196 MRSA strains isolated from three clinical specimens of human infections from hospitals in China were used in this study. The checkerboard method was used to determine whether combinations act synergistically against these strains. The susceptibility results for fusidic acid and fosfomycin were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. The combination of fusidic acid and fosfomycin demonstrated the following interactions: 87.76% (172/196) synergism, 12.24% (24/196) indifference and no antagonism was seen (minimum and maximum fractional inhibitory concentration index 0.14 and 0.75, respectively). Thus, combinations of fusidic acid and fosfomycin show synergism for most of the MRSA isolates tested in this study, and may be a future therapeutic alternative for infections caused by MRSA.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Thornsberry, C. Epidemiology of staphylococcal infections—a USA perspective. J. Chemother. 6 (Suppl 2), 61–65 (1994).
Vandenbroucke-Grauls, C. Epidemiology of staphylococcal infections—a European perspective. J. Chemother. 6 (Suppl 2), 67–70 (1994).
Centers for Disease Control and Prevention (CDC). MRSA among ICU Patients, (1995–2004).
National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October Am. Infect. Control 32, 470–485 (2004).
Ho, P. L., Yuen, K., Yam, W., Sai-yin, W. S. & Luk, W. Changing patterns of susceptibilities of blood, urinary and respiratory pathogens in Hong Kong. J. Hosp. Infect. 31, 305–317 (1995).
Craven, D. E., Kollisch, N. R., Hseih, C. R., Conolly, M. G. & McCabe, W. R. Vancomycin treatment of bacteremia caused by oxacillin-resistant Staphylococcus aureus: comparison with beta-lactam antibiotic treatment of bacteremia caused by oxacillin-sensitive Staphylococcus aureus. J. Infect. Dis. 147, 137–143 (1983).
Sorrell, T. C., Packham, D. R., Shanker, S., Foldes, M. & Munro, R. Vancomycin therapy for methicillin-resistant Staphylococcus aureus. Ann. Intern. Med. 97, 3440–3501 (1982).
Falagas, M. E., Grammatikos, A. P. & Michalopoulos, A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert. Rev. Anti. Infect. Ther. 6, 593–600 (2008).
Brown, E. M. & Thomas, P. Fusidic acid resistance in Staphylococcus aureus isolates. Lancet 359, 803 (2002).
Chang, S. C., Hsieh, S. M., Chen, M. L., Sheng, W. H. & Chen, Y. C. Oral fusidic acid fails to eradicate methicillin-resistant Staphylococcusaureus colonization and results in emergence of fusidic acid-resistant strains. Diagn. Microbiol. Infect. Dis. 36, 131–136 (2000).
Ravenscroft, J. C., Layton, A. & Barnham, M. Observations on high levels of fusidic acid resistant Staphylococcus aureus in Harrogate, North Yorkshire, UK. Clin. Exp. Dermatol. 25, 327–330 (2000).
Grundmann, H., Ires-de-Sousa, M. & Boyce, J. Emergence and resurgence of methicillin-resistant Staphylococcus aureus as a public-health threat. Lancet 368, 874–885 (2006).
Maviglia, R., Nestorini, R. & Pennisi, M. Role of old antibiotics in multidrug resistant bacterial infections. Curr. Drug. Targets 10, 895–905 (2009).
O’Brien, F. G., Botterill, C. I., Endersby, T. G., Lim, R. L. G., Grubb, W. B. & Gustafson, J. E. Heterogeneous expression of fusidic acid resistance in Staphylococcus aureus with plasmid or chromosomally encoded fusidic acid resistance genes. Pathology 30, 299–303 (1998).
Forsgen, A. & Walder, M. Antimicrobial activity of fosfomycin in vitro. J. Antimicrob. Chemother. 11, 467–471 (1983).
Grif, K., Dierich, M. P., Pfaller, K., Miglioli, P. A. & Allerberger, F. In vitro activity of fosfomycin in combination with various antistaphylococcal substances. J. Antimicrob. Chemother. 48, 209–217 (2001).
Morikawa, K., Oseko, F., Morikawa, S. & Sawada, M. Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro. Antimicrob. Agents Chemother. 37, 2684–2687 (1993).
National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial susceptibility testing. Information Supplement M100, S19 (2009).
Moody, J. Synergism testing: broth microdilution checkerboard and broth macrodilution method. in Clinical Microbiology Procedures Handbook (ed. Isenberg, H. D.) 2nd edn, 1–28 (ASM Press: Washington, DC, 2004).
Carmona, P., Romá, E., Monte, E., García, J. & Gobernado, M. Papel de linezolid en terapéutica antimicrobiana. Enferm. Infecc. Microbiol. Clin. 21, 30–41 (2003).
Gobernado, M. Fosfomicina . Rev. Esp. Quimioterap. 16, 15–40 (2003).
Moreno, F., Crisp, C. & Jorgensen, J. H. Methicillin-resistant Staphylococcus aureus as a community organism. Clin. Infect. Dis. 21, 1308–1312 (1995).
Panlilio, A. L., Culver, D. H. & Gaynes, R. P. Methicillin-resistant Staphylococcus aureus in US hospitals, 1975-1991. Infect. Control Hosp. Epidemiol. 13, 582–586 (1992).
Robinson, D. A., Kearns, A. M. & Holmes, A. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired methicillin-resistant clone. Lancet 365, 1256–1258 (2005).
Whitby, M. Fusidic acid in the treatment of methicillin-resistant Staphylococcus aureus. Int. J. Antimicrob. Agents l2, S67–S71 (1999).
Grohs, P., Kitzis, M. D. & Gutmann, L. In vitro bactericidal activities of linezolid in combination with vancomycin, gentamicin, ciprofloxacin, fusidic acid, and rifampin against Staphylococcus aureus. Antimicrob. Agents Chemother. 47, 418–420 (2003).
Acknowledgements
The project was supported by the National Natural Science Foundation of China (no. 30873127).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yu, XH., Song, XJ., Cai, Y. et al. In vitro activity of two old antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiot 63, 657–659 (2010). https://doi.org/10.1038/ja.2010.105
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ja.2010.105
Keywords
This article is cited by
-
The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs
Animal Diseases (2023)
-
The Potential Role of Fosfomycin in Neonatal Sepsis Caused by Multidrug-Resistant Bacteria
Drugs (2017)


