Inhibition of staphylococcal growth by fusidic acid prevents production of volatile metabolites

Nico Caggiano and Ian Chopra*

Antimicrobial Research Centre and Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK

Sir,

Microorganisms produce a range of volatile compounds that provide a basis for the identification of microbial species.1 This approach has been extended to the presumptive identification of infections in humans. For instance, Chandiok et al.2 demonstrated a correlation between the volatiles present in vaginal swabs and clinical symptoms of bacterial vaginosis. Changes in the production of volatile compounds by microorganisms could also indicate whether an infection has resolved following application of chemotherapeutic agents. Thus, the pattern of volatiles detected in biopsy samples from patients with infected venous ulcers shifted when antibiotic therapy started and assumed a different profile by the end of the regimen, following healing of the ulcer.3 These findings probably reflect inhibition of bacterial growth in vivo, followed by suppression of volatile microbial metabolite production and a shift in the pattern of volatiles detected in biopsy materials. Nevertheless, the changes could represent a host-related, rather than microbial, response. In view of the potential importance of equipment that detects volatile microbial products for use as an adjunct to the diagnosis and treatment of infectious diseases,2,3 we sought evidence that inhibition of bacterial growth by antibiotics does indeed result directly in suppression of volatile product formation. For this purpose we examined the effects of fusidic acid on Staphylococcus aureus.

Aliquots (1 mL) of cultures containing 108 cfu in nutrient broth (Oxoid Ltd., nutrient broth number 2; Basingstoke, UK) were absorbed on to sterile cotton wool swabs which were then placed into individual sterile glass vials (22 mL). The vials were sealed and loaded into the carousel of an Osmetech Microbial Analyser (Osmetech plc, Crewe, UK) within the incubator compartment. Cultures, containing varying concentrations of fusidic acid, were incubated statically (37°C) and the headspace volatiles produced were sampled automatically for each vial on one occasion to provide progressive monitoring from early (30 min) to later periods (up to 18 h).

Addition of fusidic acid to cultures of S. aureus caused a dose-dependent inhibition of the appearance of volatile products (Table). This was measured by determining the time required for a 100% increase (doubling) in the production of volatile components in relation to the concentration of antibiotic. Furthermore, using strains with different susceptibilities to the drug we demonstrated that the dose dependency for suppression of volatile production was related to the sensitivity of the individual strain to fusidic acid. However, an exact correlation between the MIC determined by agar dilution and the concentration of drug required to prevent the production of volatile components was not observed. For instance, even in the presence of fusidic acid at 256 mg/L, production of volatiles was not completely suppressed in cultures of strain UB4005 (MIC 256 mg/L). The variance in the apparent susceptibilities of the organisms to fusidic acid is likely to reflect differences in the physiological status of bacteria grown in agar, compared with the environment of the cotton wool swabs within the vials of the Microbial Analyser.

Although an exact correlation between MIC and inhibition of the production of volatiles by S. aureus was not observed, the data presented here demonstrate that exposure of staphylococci to fusidic acid in vitro results in suppression of volatile component production. Consequently, the shift in the pattern of volatiles, previously detected in infected patients following the onset of antibiotic treatment,3 probably reflects direct inhibition of bacterial growth in vivo. Our results therefore support a role for the use of instruments such as the Osmetech Microbial Analyser in the clinical setting to determine whether an infection has resolved following the application of chemotherapeutic agents.


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Table Susceptibility of S. aureus strains to fusidic acid and inhibition of volatile product formation
 
Acknowledgments

We thank Mr John Plant of Osmetech plc for technical advice. This work was supported by a grant to I.C. from Osmetech plc.

Notes

J Antimicrob Chemother 2000; 46: 335–336

* Corresponding author. Tel: +44-113-233-5604; Fax: +44-113-233-5638, E-mail: i.chopra{at}leeds.ac.uk Back

References

1 . Gibson, T. D., Prosser, O., Hulbert, J. N., Marshall, R. W., Corcoran, P., Lowery, P. et al. (1997). Detection and simultaneous identification of micro-organisms from headspace samples using an electronic nose. Sensors and Actuators B44, 413–22.[ISI]

2 . Chandiok, S., Crawley, B. A., Oppenheim, B. A., Chadwick, P. R., Higgins, S. & Persaud, K. C. (1997). Screening for bacterial vaginosis: a novel application of artificial nose technology. Journal of Clinical Pathology 50, 790–1.[Abstract]

3 . Greenwood, J., Crawley, B. & Dunn, K. (1997). Something smells good in Manchester. European Hospital Management Journal 4, 58–60.

4 . Novick, R. (1967). Properties of a cryptic high frequency transducing phage in Staphylococcus aureus. Virology 33, 155–66.[ISI][Medline]

5 . Chopra, I. (1976). Mechanisms of resistance to fusidic acid in Staphylococcus aureus. Journal of General Microbiology 96, 229–38.[ISI][Medline]





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