The era of antimicrobial resistance - implications for the clinical laboratory

The emergence of resistance to antimicrobial drugs in a range of bacterial pathogens of the respiratory tract creates a challenge for the clinical diagnostic laboratory. Resistance to macrolides among strains of Streptococcus pneumoniae has reached high levels in many countries. There are two main types of resistance mechanisms, one (MLSB phenotype) leading to high-level resistance and the other (M phenotype) resulting in a lower level of resistance. As there are indications that high-level resistance may have clinical relevance, it is important to be able to detect such strains. This is now possible with the erythromycin/clindamycin double disc diffusion test. Although resistance to beta-lactams has also increased, there is now evidence that some beta-lactams are still effective against isolates that have low-level resistance. In response to these observations, new breakpoints have now been introduced by the National Committee for Clinical Laboratory Standards (NCCLS) for amoxicillin, cefotaxime and ceftriaxone, which increase the percentage of pneumococcal isolates that can still be treated effectively with these agents. As a consequence of the increasing use of fluoroquinolones, resistance has now emerged to this group of compounds and this has been associated with clinical failures. Although standard minimum inhibitory concentration tests can detect strains with high levels of resistance (double step mutants) they are not reliable in detecting strains with a single mutation. This is important as there is increasing evidence that strains with a single mutation in the target topoisomerase are even more likely to develop a second mutation, leading to higher levels of resistance and thus probably, therapeutic failure. Because resistance to fluoroquinolones is currently low in the US, the NCCLS does not recommend that susceptibility testing with the newer respiratory fluoroquinolones be carried out routinely. However, since the respiratory fluoroquinolones have in fact become the first line of therapy for the treatment of community-acquired pneumonia, it may now be time to institute routine testing of clinical isolates of pneumococci to these agents. Simple techniques for the clinical diagnostic laboratory to enable these first-step mutants to be detected are urgently required.