1: Drugs. 2007;67(16):2355-82.

Multidrug-Resistant Streptococcus pneumoniae Infections : Current and Future
Therapeutic Options.

Van Bambeke F, Reinert RR, Appelbaum PC, Tulkens PM, Peetermans WE.

Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de
Louvain, Brussels, Belgium.

Antibacterial resistance in Streptococcus pneumoniae is increasing worldwide,
affecting principally beta-lactams and macrolides (prevalence ranging between
approximately 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 (beta-lactams), provided the dosage is optimised 
to cover less susceptible strains. Macrolides can no longer be used as
monotherapy, but are combined with beta-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.

PMID: 17983256 [PubMed - in process]

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