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] Related Links [The history of the development and changes of quinolone antibacterial agents] [Yakushigaku Zasshi. 2003] PMID:15143768 Impact of changing pathogens and antimicrobial susceptibility patterns in the treatment of serious infections in hospitalized patients. [Am J Med. 1996] PMID:8678095 Evolving resistance patterns in community-acquired respiratory tract pathogens: first results from the PROTEKT global surveillance study. Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin. [J Infect. 2002] PMID:12150493 Newer treatment options for skin and soft tissue infections. [Drugs. 2004] PMID:15257625 Clinical management of respiratory tract infections in the community: experience with telithromycin. [Infection. 2001] PMID:11785852