Introduction: Evolving needs in respiratory tract infections

Two issues that have become clinically relevant to the treatment of pneumonia over the past few years are the development of antibiotic resistance among respiratory pathogens and the increasing importance of the atypical respiratory pathogens---Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp. Resistance has become an important issue in Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and Gram-negative rods. The ways by which bacteria become resistant to antibiotics include production of antibiotic-modifying enzymes, reduced access to target sites, efflux of antibiotic, change in the bacterial target site and the bypassing of inhibited pathways. In Streptococcus pneumoniae that are penicillin resistant, the mechanism is through alteration of the target site for penicillins (penicillin-binding proteins) and this may also confer resistance to some cephalosporins. Multidrug resistance has also been reported in some strains of pneumococci. Of particular concern is resistance to macrolides mediated by the ermAM gene, which also confers resistance to lincosamides and streptogramin-B drugs. In Staphylococcus aureus, resistance to virtually all beta-lactam drugs is mediated by acquisition of the mecA gene, which codes for the drug-resistant beta-lactam target PBP2a. Antimicrobials are now needed that have enhanced activity against aerobic Gram-negative rods, atypical respiratory pathogens and Gram-positive cocci.