Preliminary susceptibility testing guidelines for AZD2563, a long-acting oxazolidinone

Rapid expansion of antimicrobial resistance has led to the development of new antimicrobial agents. AZD2563 is a novel oxazolidinone that has activity similar to linezolid and the potential for extended dosing intervals. Recent Gram-positive clinical organisms (1572 strains) were tested including four oxazolidinone-resistant enterococci. Strains processed were: 313 Staphylococcus aureus, 299 coagulase-negative staphylococci, 305 enterococci, 305 Streptococcus pneumoniae, 300 other streptococci (beta-haemolytic and viridans group) and 50 other rarely isolated Gram-positive species. The methods (agar and broth dilution, disk diffusion) of the National Committee for Clinical Laboratory Standards (NCCLS; M7-A6, M2-A8) were followed and linezolid was used as a control agent. A tentative MIC breakppint (less than or equal to2 mg/l) for AZD2563 was based on the manufacturer's recommendation, preliminary pharmacodynamic information and similarity to the current linezolid interpretive criteria. Correlation between AZD2563 MIC values and zone diameters around 30 mug AZD2563 disks indicated a 99.9% categorical agreement and all intermethod errors were minor. Comparison of agar dilution to broth microdilution MIC results for AZD2563 showed 100.0% agreement +/- one log(2), dilution step (89.2% of MIC results were identical). Scattergrams suggest that all Gram-positive organisms could be accurately tested using the same interpretive criteria: susceptible at less than or equal to2 mg/l (greater than or equal to20 mm), intermediate at 4 mg/l (17-19 mm) and resistant at greater than or equal to8 mg/l (less than or equal to 16 mm). These tentative AZD2563 interpretive guidelines should facilitate in vitro susceptibility testing during clinical trials and detect all oxazolidinone-resistant isolates. (C) 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.