Effective evaluations of antimicrobial susceptibility tests (ASTs) require robust study design. The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing has recognized that many published studies reporting the performance of commercial ASTs (cASTs) suffer from major design and/or analysis flaws, rendering the results difficult or impossible to interpret. This minireview outlines the current consensus of the Methods Development and Standardization Working Group of the CLSI Subcommittee on Antimicrobial Susceptibility Testing regarding best practices for systematic evaluation of the performance of an AST, including the analysis and presentation of essential data intended for publication.

We analyzed the emergence of daptomycin nonsusceptibility in a patient with persistent vancomycin-intermediate Staphylococcus aureus (VISA) bacteremia. The daptomycin-nonsusceptible VISA's cell wall demonstrated a reduction in muramic acid O-acetylation, a phenotypic parameter not previously reported for VISA; some isolates also contained a single point mutation in the mprF gene.

The development of new therapies to treat methicillin-resistant Staphylococcus aureus (MRSA) is needed to counteract the significant threat that MRSA presents to human health. Novel inhibitors of DNA gyrase and topoisomerase IV (TopoIV) constitute one highly promising approach, but continued optimization is required to realize the full potential of this class of antibiotics. Herein, we report further studies on a series of dioxane-linked derivatives, demonstrating improved antistaphylococcal activity and reduced hERG inhibition. A subseries of analogues also possesses enhanced inhibition of the secondary target, TopoIV.

Penicillin-binding proteins (PBPs) of 15 selected penicillin-and amoxicillin-resistant Streptococcus pneumoniae isolates (MICs of 2 to 8 and 8 to 16 g/ml, respectively) were studied. In addition to typical changes in PBPs 1A and 2X, these strains had 10 unique changes in PBP 2B, including a 618 A-G substitution, which may be the key alteration associated with amoxicillin resistance.

In vitro susceptibility data were collected for co-amoxiclav and other antimicrobial agents against 1297 recent anaerobe isolates collected in Europe and the USA. The co-amoxiclav (amoxicillin/clavulanic acid) MIC(50/90)s (amoxicillin/clavulanic acid concentration in a ratio of 2:1, expressed in terms of amoxicillin concentration in mg/L) were 0.5/4 for Bacteroides fragilis, 96% susceptible) except E. corrodens (MIC(50/90) of >32/>64 mg/L), which is a capnophilic organism. Imipenem was also highly active against all species (>98% susceptible). Levofloxacin and clindamycin were the least potent agents tested, particularly against Bacteroides, Prevotella and Peptostreptococcus (levofloxacin susceptibility rates: Bacteroides 72.7%, Prevotella 71.5%, F. magna 72.4%; clindamycin susceptibility rates: Bacteroides 79.5%, Prevotella 92.1%, F. magna 84.7%).