EUCAST expert rules have been developed to assist clinical microbiologists and describe actions to be taken in response to specific antimicrobial susceptibility test results. They include recommendations on reporting, such as inferring susceptibility to other agents from results with one, suppression of results that may be inappropriate, and editing of results from susceptible to intermediate or resistant or from intermediate to resistant on the basis of an inferred resistance mechanism. They are based on current clinical and/or microbiological evidence. EUCAST expert rules also include intrinsic resistance phenotypes and exceptional resistance phenotypes, which have not yet been reported or are very rare. The applicability of EUCAST expert rules depends on the MIC breakpoints used to define the rules. Setting appropriate clinical breakpoints, based on treating patients and not on the detection of resistance mechanisms, may lead to modification of some expert rules in the future.

Clinical breakpoints are used in clinical microbiology laboratories to categorize microorganisms as clinically susceptible (S), intermediate (I) or resistant (R) dependent on the quantitative antimicrobial susceptibility as indicated by the MIC value determined in a well-defined standard test system. The laboratory report, with the designations of S, I or R for each antimicrobial agent, provides guidance to clinicians with respect to the potential use of agents in the treatment of patients, and clinical breakpoints should therefore distinguish between patients that are likely or unlikely to respond to antimicrobial treatment. In Europe, clinical breakpoints are set by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), following a defined procedure. This includes evaluation of efficacy in experimental settings and clinical studies to derive pharmacodynamic targets such as the fAUC/MIC ratio or %fT > MIC required for efficacy, the pharmacokinetic properties of the agent, Monte Carlo simulations to estimate exposures of the antimicrobial agent in the target patient population and commonly used dosing regimens. The probability of target attainment is subsequently determined for a range of pharmacodynamic targets and the results from the Monte Carlo simulations. The breakpoints derived are subsequently evaluated with respect to the wild-type population of the target microorganisms, specific resistance mechanisms and other relevant data. In this paper, we provide an overview of the EUCAST process and considerations for setting pharmacokinetic/pharmacodynamic breakpoints. These are the breakpoints that in the EUCAST breakpoint tables are referred to as 'non-species-related breakpoints'.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

During the second quarter each of 1988, 1989, and 1990, a French collaborative study group, including 12 university hospital laboratories, surveyed the resistance to 13-lactams of clinical isolates from hospitalized patients: consecutively, 10,641, 10,692, and 9,382 isolates were tested. The distribution of bacterial species over time was similar in each laboratory. The susceptibilities of microorganisms to amoxicillin, ticarcillin, cephalothin, cefoxitin, cefotaxime (CTX), ceftazidime (CAZ), aztreonam (ATM), and imipenem (IPM) were measured by the disk diffusion method in accordance with the recommendations of the Antibiogram Committee of the French Society for Microbiology. Five reference strains were included for quality control. Extendedspectrum 13-lactamases were detected by the synergistic effect of the combination of clavulanic acid-amoxicillin with CTX, CAZ, and ATM in the double-diffusion test. A synergistic effect with CTX, CAZ, and ATM was detected for 1.5% of all strains, mainly those of KlebsieUla pneumoniae (13.3%). For this species, the synergy test enabled the detection of roughly 50% of the resistant strains misclassified as susceptible on the basis of interpretative standards. Extended-spectrum 13-lactamases disseminated in 1990 in most enterobacterial species but at a low frequency. Important variations in the percentages of resistant strains were observed in terms of bacterial species, hospitals, and wards. However, when the total number of strains was considered,

The antimicrobial activity of cefepime, a new broad-spectrum parenteral cephalosporin, was evaluated in vitro against 1757 recent clinical Gram-positive and Gram-negative isolates. Cefepime was active at low concentrations (MIC50 values < or = 0.06 mg/L and MIC90 values < or = 0.12 mg/L) against non-cephalosporinase-producing Enterobacteriaceae (Escherichia coli, Proteus mirabilis, Salmonella spp. and Shigella spp.). For Klebsiella pneumoniae, MICs were between 0.016 and 16 mg/L; the highest MIC values were observed for extended-spectrum beta-lactamase-producing strains. Against Enterobacteriaceae, such as cephalosporinase producing Enterobacter cloacae, MICs were < or = 0.5 mg/L, but MICs against cephalosporinase hyperproducing strains were generally higher. Ticarcillin-sensitive strains of Pseudomonas aeruginosa were inhibited by cefepime concentrations of 0.5-16 mg/L, while cefepime MICs were 8-64 mg/L for strains resistant to ticarcillin. The cefepime MIC50 value for Haemophilus spp. including many resistant to amoxycillin, was 0.03 mg/L. Against methicillin-sensitive strains of Staphylococcus aureus, cefepime MICs were 0.5-16 mg/L; MICs against methicillin-resistant staphylococci were 16- > 128 mg/L). Against methicillin-sensitive coagulase-negative staphylococci, cefepime MIC values were 0.03-16 mg/L; corresponding values for methicillin-resistant strains were 2-128 mg/L. Streptococci (Groups A, C and G) were sensitive to cefepime with MICs ranging from < or = 0.008-2 mg/L (MIC50, 0.03 mg/L; MIC90, 0.25 mg/L). The activity of cefepime against Group B streptococci and pneumococci were comparable, with MIC50 values of 0.12 and 0.25 mg/L, respectively, and MIC90 values of 0.03 and 0.25 mg/L, respectively. Most enterococci and all Listeria monocytogenes strains had MICs > or = 32 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)