In vitro activity of 21 antimicrobials against vancomycin-resistant Staphylococcus aureus (VRSA) and heteroVRSA (hVRSA)

M. Wootton1,*, R. A. Howe1, T. R. Walsh2, P. M. Bennett2 and A. P. MacGowan1

1 Bristol Centre for Antimicrobial Research and Evaluation (BCARE), North Bristol NHS Trust, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB; 2 Department of Microbiology and Pathology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK

Sir,

The emergence of vancomycin resistance and hetero-resistance in Staphylococcus aureus has wide-reaching implications for the clinician. It is therefore important to know which antimicrobials may be expected to have useful activity against vancomycin-resistant S. aureus (VRSA) and heteroVRSA (hVRSA) strains.

Sixty S. aureus strains were used from the collection at Southmead: 54 hVRSA and six VRSA. The isolates were collected between 1995 and 2000 and originated from France, Sweden, the USA, the UK and Japan. These include strains from Liverpool that were isolated from an outbreak of hVRSA in the same hospital and were later reduced to five separate clonal variations. The strains from Sweden were obtained from different sites in Europe and displayed clonal variation. Their vancomycin resistance status was determined by the originating laboratory and confirmed by MIC testing and population analysis profile in Bristol.1 Agar dilution MICs were performed according to the BSAC.2 The 21 antimicrobials used were incorporated into the medium in a log 2 dilution series from 0.008 to 128 mg/L, except in the case of fosfomycin, which ranged from 0.25 to 1024 mg/L. Inocula were prepared using direct colony suspension in 0.9% saline, to achieve a suspension equivalent to 0.5 McFarland standard, which results in ~104 cfu/spot when applied by multipoint inoculator (Denley Instruments, Billinghurst, UK). Plates were incubated at 35–37°C in air for 18 h. The MIC was defined as the lowest concentration of drug to inhibit macroscopically visible colonies. The breakpoints used to define resistance are those of the BSAC,2 with the exception of fosfomycin: susceptible <=16 mg/L, resistant >=32 mg/L (Ferrara et al.3).

Of the four quinolones tested, moxifloxacin and gemifloxacin appeared to be the most potent (see Table 1). Nevertheless, almost all the isolates were resistant to all quinolones. In a previous study, methicillin-resistant S. aureus (MRSA)4 (n = 101) strains displayed MIC90s of 2, 8, 16 and 128 mg/L of moxifloxacin, levofloxacin, gemifloxacin and ciprofloxacin, respectively. Both fusidic acid and co-trimoxazole are relatively effective against hVRSA and VRSA strains, but have limited clinical use due to suspected toxicity issues. The MICs of quinupristin/dalfopristin and linezolid for hVRSA seem to be similar to those for MRSA, essentially being susceptible to these newer agents.5 However, two hVRSA strains had quinupristin/dalfopristin MICs of 8 mg/L. These MICs would therefore be considered resistant by BSAC criteria. Rybak et al.6 studied three isolates of VRSA, which were tested against quinupristin/dalfopristin, and had MICs of 0.25 mg/L. These results compared favourably with the six VRSAs studied in this report, which had an MIC range of 0.5–1 mg/L. Rybak et al.6 also tested linezolid; the three VRSAs had an MIC range of 1–2 mg/L and MRSAs a range of 1–8 mg/L, whereas all of our strains had linezolid MICs < 1 mg/L.


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Table 1.  In vitro potency of a range of anti-staphylococcal antimicrobials against strains of VRSA and hVRSA
 
The rarity of VRSA strains makes it difficult to compare these isolates, but if, as hypothesized, hVRSA are predecessors of VRSA, then their resistance patterns should indeed be similar. Overall, hVRSA and VRSA are generally resistant to a wide range of different antibacterial agents, but retain susceptibility to quinupristin/dalfopristin and linezolid.

Footnotes

* Corresponding author. Tel: +44-117-928-7541; Fax: +44-117-959-3217; E-mail: Mandy.Wootton{at}bristol.ac.uk Back

References

1 . Wootton, M., Howe, R. A., Hillman, R., Walsh, T. R., Bennett, P. M. & MacGowan, A. P. (2000). A modified population analysis profile (PAP) method to detect Staphylococcus aureus with decreased susceptibility to vancomycin in a UK hospital. Journal of Antimicrobial Chemotherapy 47, 399–403.[Abstract/Free Full Text]

2 . Andrews, J. M. for the British Society for Antimicrobial Chemotherapy. (2001). Determination of minimum inhibitory concentrations. British Society for Antimicrobial Chemotherapy Working Party Report on Antimicrobial Susceptibility Testing. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, 29–42.[Abstract/Free Full Text]

3 . Ferrara, A., Dos Santos, C., Cimbro, M. & Gialdroni Grassi, G. (1997). Effect of different combinations of sparfloxacin, oxacillin and fosfomycin against methicillin-resistant staphylococci. European Journal of Clinical Microbiology and Infectious Diseases 16, 535–7.[ISI][Medline]

4 . Wootton, M., Noel, A. R., MacGowan, A. P., Howe, R. A., Walsh, T. R. & Bennett, P. M. (2001). In-vitro activity of BMS2847576 against Staphylococcus aureus strains with various vancomycin susceptibilities. In Program and Abstracts of the Forty-first Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, USA, 2001. Abstract E715, p. 177. American Society for Microbiology, Washington, DC, USA.

5 . Low, D. E. & Nadler, H. L. (1997). A review of in-vitro antibacterial activity of quinuprstin/dalfopristin against methicillin-susceptible and -resistant Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 39, Suppl. A, 53–8.[Abstract]

6 . Rybak, M. J., Hershberger, E., Moldovan, T. & Grucz, R. G. (2000). In vitro activities of daptomycin, linezolid and quinupristin–dalfopristin against staphylococci and enterococci including vancomycin-intermediate and -resistant strains. Antimicrobial Agents and Chemotherapy 44, 1062–6.[Abstract/Free Full Text]