Diagnosis and antibiotic treatment of community-acquired pneumonia.

Only a few pathogens cause most community-acquired pneumonias. In outpatients, treatment is empiric, based on the results of chest films, leukocyte counts, and Gram''s stains (if available). Antibiotics must always cover pneumococci and should cover Mycoplasma pneumoniae in young adults and during epidemic periods. A follow-up chest film in smokers and those older than 40 years is strongly recommended. In inpatients, the evaluation and treatment are tailored to individual cases. A search for a wider range of causes, using invasive tests if necessary, is undertaken, and all likely pathogens should be covered with the initial antibiotic therapy.     

Bacterial evolution and the cost of antibiotic resistance.

Bacteria clearly benefit from the possession of an antibiotic resistance gene when the corresponding antibiotic is present. But do resistant bacteria suffer a cost of resistance (i.e., a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put resistance genes into naive bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments (in vitro and in vivo) show that the cost of antibiotic resistance can be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics.     

The biological cost of antibiotic resistance.

The frequency and rates of ascent and dissemination of antibiotic resistance in bacterial populations are anticipated to be directly related to the volume of antibiotic use and inversely related to the cost that resistance imposes on the fitness of bacteria. The data available from recent laboratory studies suggest that most, but not all, resistance-determining mutations and accessory elements engender some fitness cost, but those costs are likely to be ameliorated by subsequent evolution.     

What's new in the antibiotic pipeline.

Many advances have recently been made in the development of chemotherapeutic agents for bacterial infections. As a consequence of problematic antimicrobial-resistant bacteria, research is now directed towards narrow-spectrum agents rather than broad-spectrum agents. Further, orally active agents have always been desirable, but today's cost-saving environment, in line with a desire to minimize treatment costs, values reduced administration costs and keeping patients out of the hospital. There has been a recent increase in research into orally active antibacterial agents, such as carbapenems and cephalosporins, and non-glycopeptide natural products.