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Multidrug-Resistant Streptococcus pneumoniae Infections

Current and Future Therapeutic Options

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Abstract

Antibacterial resistance in Streptococcus pneumoniae is increasing worldwide, affecting principally β-lactams and macrolides (prevalence ranging between ≈1% and 90% depending on the geographical area). Fluoroquinolone resistance has also started to emerge in countries with high level of antibacterial resistance and consumption. Of more concern, 40% of pneumococci display multi-drug resistant phenotypes, again with highly variable prevalence among countries.

Infections caused by resistant pneumococci can still be treated using first-line antibacterials (β-lactams), provided the dosage is optimised to cover less susceptible strains. Macrolides can no longer be used as monotherapy, but are combined with β-lactams to cover intracellular bacteria. Ketolides could be an alternative, but toxicity issues have recently restricted the use of telithromycin in the US. The so-called respiratory fluoroquinolones offer the advantages of easy administration and a spectrum covering extracellular and intracellular pathogens. However, their broad spectrum raises questions regarding the global risk of resistance selection and their safety profile is far from optimal for wide use in the community. For multi-drug resistant pneumococci, ketolides and fluoroquinolones could be considered. A large number of drugs with activity against these multi-drug resistant strains (cephalosporins, carbapenems, glycopeptides, lipopeptides, ketolides, lincosamides, oxazolidinones, glycylcyclines, quinolones, deformylase inhibitors) are currently in development. Most of them are only new derivatives in existing classes, with improved intrinsic activity or lower susceptibility to resistance mechanisms. Except for the new fluoroquinolones, these agents are also primarily targeted towards methicillin-resistant Staphylococcus aureus infections; therefore, demonstration of their clinical efficacy in the management of pneumococcal infections is still awaited.

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Notes

  1. The website of this network (http://www.sph.emory.edu/PMEN/index.html) presents the criteria for inclusion of clones in the database and depicts the main characteristics of the 43 epidemic clones described so far.

  2. The issue of quinolone toxicity is so topical that a website (http://www.fqresearch.org/index.htm) is devoted to the follow-up of adverse events and changes brought to package inserts as a consequence of pharmacovigilance studies.

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Acknowledgements

Dr Van Bambeke is Maître de Recherches of the Belgian Fonds de la Recherche Scientifique - Fonds National de la Recherche Scientifique. Dr Van Bambeke has acted as a consultant to Targanta, Dr Reinert has received honoraria for consultancies from Wyeth and GSK, and a research grant from Wyeth. Drs Appelbaum, Tulkens and Peetermans have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

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  1. Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL7370 avenue Mounier 73, Brussels, 1200, Belgium

    Françoise Van Bambeke & Paul M. Tulkens

  2. Institute for Medical Microbiology, National Reference Center for Streptococci, University Hospital (RWTH), Aachen, Germany

    René R. Reinert

  3. Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania, USA

    Peter C. Appelbaum

  4. Department of Internal Medicine-Infectious Diseases, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium

    Willy E. Peetermans

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Van Bambeke, F., Reinert, R.R., Appelbaum, P.C. et al. Multidrug-Resistant Streptococcus pneumoniae Infections. Drugs 67, 2355–2382 (2007). https://doi.org/10.2165/00003495-200767160-00005

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  • DOI: https://doi.org/10.2165/00003495-200767160-00005

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