JAC Advance Access originally published online on July 29, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 525
© 2003 The British Society for Antimicrobial Chemotherapy
Correspondence |
Reply
Department of 1 Microbiology and 2 Internal Medicine, University Hospitals Leuven, Department of Microbiology, B-3000 Leuven, Belgium
Keywords: Streptococcus pneumoniae, breakthrough bacteraemia, macrolides, resistance
Sir,
Our study1 is retrospective but not anecdotal. Our starting question was: what is the reason behind the failure of initial therapy in patients with invasive pneumococcal infection? In order to give any therapy a fair chance, our cut-off point was treatment for more than 48 h, which left us with 12 patients remaining out of 136 with proven pneumococcal bacteraemia. The reason for failure after macrolide therapy was resistance, which was not unexpected with regard to the large percentage of high-level resistance (MLSB) in Belgium.2 Whether or not low-level resistance to macrolides inevitably leads to failure is not an issue in our country, or in other European countries with a strong predominance of MLSB-type macrolide resistance. That matter is covered by other investigators.3 Surveillance studies in the USA and Canada show a gradual increase in pneumococcal macrolide resistance, reaching levels up to 40% in certain areas.4 Taking into account a prevalence of MLSB-type resistance of 15%–39%, as cited by the authors, it seems appropriate to survey closely the evolution and type of macrolide resistance among pneumococci in these countries.
The surprising fact was that failures after oral ß-lactam therapy on a twice-daily basis apparently were not as a result of resistance to penicillin. All patients further treated with high doses of ß-lactams recovered quickly, with the exception of three patients (all over 80 years) for whom therapeutic doses were too late. We do not agree with Nuermberger & Bishai5 that the outcomes of the three patients who died may have been preventable with better medical decision making or combination therapy. These patients were very old and died within 3 days of admission, despite treatment with adequate dosages of ß-lactam antibiotics to which the causative organisms were susceptible. A case-fatality rate of three out of 12 patients (25%) is similar to the overall case-fatality rate of 22.8% observed for all patients with pneumococcal bacteraemia, and to case-fatality rates reported in the literature. The advantage of combination treatment of a ß-lactam antibiotic plus a macrolide for treatment of community-acquired pneumonia in hospitalized patients or bacteraemic pneumococcal pneumonia, although widely accepted in the USA and Canada, remains highly controversial in Europe. There are conflicting data regarding the presence and pathogenic role of atypical bacteria in community-acquired pneumonia, and the effect on outcome of omitting treatment for these microbes.6–8
The most likely reason for initial failure of oral ß-lactam therapy is insufficient antibiotic levels (in time/concentration), either because the doses were too low and/or the interval between doses was too long, or because the patients were not taking the drugs. The latter supposition is unlikely in patients whose infection resulted in admission to hospital.
Our conclusions are straightforward: (1) empiric treatment with cephalosporins or co-amoxiclav on a twice-daily basis is not safe for patients at risk for invasive pneumococcal infections; (2) macrolide therapy is not a good alternative in Belgium because of the high-level resistance to this class of antibiotics.
Footnotes
* Corresponding author. Tel: +32-16-347073; Fax: +32-16-347931; E-mail: jan.verhaegen{at}uz.kuleuven.ac.be 
References
1
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Van Kerkhoven, D., Peetermans, W. E., Verbist, L. et al. (2003). Breakthrough pneumococcal bacteraemia in patients treated with clarithromycin or oral ß-lactams. Journal of Antimicrobial Chemotherapy 51, 691–6.
2 . Lagrou, K., Peetermans, W. E., Verhaegen, J. et al. (2002). Macrolide resistance in Belgian Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy 45, 119–21.
3 . Lonks, J. R., Garau, J., Gomez, L. et al (2002). Failure of macrolide antibiotic treatment in patients with bacteraemia due to erythromycin-resistant Streptococcus pneumoniae. Clinical Infectious Diseases 35, 556–64.[CrossRef][ISI][Medline]
4
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Doern, G. V., Heilmann, K. P., Huynh, H. K. et al. (2001). Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000, including a comparison of resistance rates since 1994–1995. Antimicrobial Agents and Chemotherapy 45, 1721–9.
5 . Nuermberger, E. L. & Bishai, W. R. (2003) Significance of macrolide resistance in Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy 52, DOI: 10.1093/jac/dkg349.
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Mundy, L. M., Oldach, D., Auwaerter, P. G. et al. (1998). Implications for macrolide treatment in community-acquired pneumonia. Hopkins CAP Team. Chest 113, 1201–6.
7
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Gleason, P. P., Meehan, T. P., Fine, F. M. et al. (1999). Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Archives of Internal Medicine 159, 2562–72.
8 . File, T. M. & Mandell, L. A. (2003). What is optimal antimicrobial therapy for bacteraemic pneumococcal pneumonia? Clinical Infectious Diseases 36, 396–8.[CrossRef][ISI][Medline]
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