Journal of Antimicrobial Chemotherapy (2001) 47, 902-903
© 2001 The British Society for Antimicrobial Chemotherapy
Correspondence |
Study of vancomycin tolerance in 120 strains of Streptococcus pneumoniae isolated in 1999 in Madrid, Spain
Servicio de Microbiología, Hospital de Móstoles, 28935 Móstoles, Madrid, Spain
Sir,
Streptococcus pneumoniae is a common cause of bacterial meningitis1 and of respiratory tract infections. Until the beginning of the 1980s the majority of pneumococcal strains were susceptible to penicillin, which was the treatment of choice. However, in recent years there have been reports of strains with structural changes to penicillin binding proteins (PBPs), reducing susceptibility not only to penicillin, but also to all other ß-lactam antibiotics. Some of these strains demonstrate MICs to penicillin of 0.1–1 mg/L (intermediate resistance), which allows the treatment of extrameningeal infections with higher than usual dosages of these antibiotics. However, the increase of strains with MICs 
2 mg/L (considered resistant) raises the need for therapeutic alternatives.
Spain, together with France and Hungary, is one of the European countries where most strains of pneumococci with diminished susceptibility to the penicillins have been isolated. In a study carried out between 1999 and 2000 in 10 of the 11 Health Authority Areas of Madrid with 300 strains of pneumococcus, 40.6% were found to be resistant and 25% intermediately resistant to penicillin.2
As long ago as 1994, 27% of the strains isolated from CSF and blood of children in Atlanta, GA, USA, had diminished sensitivity to penicillin and 13% were resistant to cefotaxime according to the NCCLS criteria.3 At present the American Academy of Pediatrics recommends the use of vancomycin in addition to a third-generation cephalosporin in those cases of meningitis where the agent is suspected to be S. pneumoniae.4 This recommendation has been extended to include the treatment of adults with meningitis.5
Recently, Novak et al.6 reported the existance of strains of S. pneumoniae tolerant to vancomycin, with clinical significance, albeit in an experimental rabbit model of meningitis. The data obtained from the study indicate that if tolerant strains invade the nervous system, they may be responsible for the relapse or persistence of bacterial meningitis. The objective of the present study was to evaluate the existence of this type of strain in clinical isolates in a country like Spain, where the prevalence of pneumococcus strains not susceptible to penicillin is high.
Using a killing curve method, we evaluated vancomycin tolerance in 120 strains of S. pneumoniae isolated from clinical samples in 10 of the 11 Health Authority Areas of Madrid between 1999 and 2000.
The MIC of vancomycin was determined in each strain by the agar dilution method, following NCCLS criteria. Each strain was inoculated in Mueller–Hinton broth and incubated at 37°C to reach an OD of 0.25–0.3 at 620 nm, corresponding with 5 x 107 cfu/mL. Once this concentration was obtained vancomycin was added to each culture to reach 10 x MIC. After 3 h exposure time, 100 µL were serially diluted in Davis medium and inoculated on to plates of Columbia sheep blood agar. The number of viable bacteria was determined at 0, 3 and 6 h in all strains, and at 0, 2, 4 and 8 h in 10 strains. Vancomycin tolerance was considered to exist if death of 2 ± 0.6 log of the initial inoculum occurred at 6 h.
Vancomycin tolerance was not detected in any of the 120 strains studied. The Figure
presents, as an example, the killing curve of one of the strains studied.
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Although there is a high number of pneumococcus strains with diminished susceptibility to penicillin (intermediate or resistant) in Spain, strains tolerant to vancomycin have not yet been found.
Nevertheless, it would be advisable to carry out this type of epidemiological study in order to detect the possible appearance of this type of strain with tolerance to vancomycin.
Notes
J Antimicrob Chemother 2001; 47: 902–903
* Corresponding author. Tel: +34-91-6648695; Fax: +34-91-6471917; E-mail: nachoalos{at}microb.net 
References
1
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Schuchat, A., Robinson, K., Wegener, J. D., Harrison, L. H., Farley, M., Reingold, A. L. et al. (1997). Bacterial meningitis in the United States in 1995. New England Journal of Medicine 337, 970–6.
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Oteo, J., Alós, J. I. & Gómez-Garcés, J. L. (2001). Antimicrobial resistance of Streptococcus pneumoniae isolated in 1999–2000 in Madrid (Spain): multicenter surveillance study. Journal of Antimicrobial Chemotherapy 47, 215–8.
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Hofman, J., Cetron, M. S., Farley, M. M., Baughman, W. S., Facklam, R. R., Elliott, J. A. et al. (1995). The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. New England Journal of Medicine 333, 481–6.
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Quagliarello, V. J. & Scheld, W. M. (1997).Treatment of bacterial meningitis. New England Journal of Medicine 336, 708–16.
6 . Novak, R., Henriques, B., Charpenteir, E., Normak, S. & Tuomanen, E. (1999). Emergence of vancomycin tolerance in Streptococcus pneumoniae. Nature 399, 590–3.[Medline]
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