Quality control guidelines for BAL9141 (Ro 63-9141), an investigational cephalosporin, when reference MIC and standardized disk diffusion susceptibility test methods are used.

BAL9141 is a novel cephalosporin with a broad spectrum of activity, including activity against methicillin-resistant staphylococci. This multicenter study was performed to establish quality control (QC) guidelines for susceptibility testing of BAL9141 in phase 3 clinical trials and after U.S. Food and Drug Administration approval. The proposed 3 or 4 log(2) dilution MIC ranges encompass 97.8 to 100.0% of reported results, while the proposed 7- to 9-mm-zone-diameter QC ranges included 95.2 to 99.4% of the participant-reported disk diffusion results.

Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone.

The MIC results using a dry-form broth microdilution panel (TREK Diagnostic/Sensititre, Westlake, OH, USA) were validated for AZD2563, a novel oxazolidinone compound. In comparision studies against reference frozen-form panels, the commercial MIC results were the same as the reference calue for 82.7% of organisms and all results were within +/- one log2 dilution. Using 462 organisms, most from three genus groups (enterococci, staphylococci, streptococci), test results indicate that Sensititre MIC values were comparable to the reference test and can be utilized in clinical trials of for routine laboratory use when testing AZD2563 and linezolid, the drug class comparator.

Re-evaluation of quality control guidelines for gatifloxacin and garenoxacin (BMS284756) when susceptibility testing Haemophilus influenzae and Streptococcus pneumoniae.

An eight laboratory M23-A2 quality control (QC) study was performed for the re-evaluation of gatifloxacin, a new fluoroquinolone, using disk diffusion tests against Streptococcus pneumoniae ATCC 49619. The study also re-evaluated garenoxacin, a novel investigational des-F(6)-quinolone, using disk diffusion tests against S. pneumoniae ATCC 49619 and broth MIC for Hemophilus influenzae ATCC 49247. The gatifloxacin zone diameter results for S. pneumoniae did not indicate a need for QC range modification (26-34 mm; 98.3% of results); however, the garenoxacin zone diameters did demonstrate a need for a minor modification (1 mm; 26-34 mm; 96.3% of reported results). The broth MIC results for H. influenzae showed that 83.1% of the results were at the upper limit of the current range (0.008 microg/ml) published by the National Committee for Clinical Laboratory Standards (NCCLS). The proposed correction could either be 0.002-0.015 microg/mlor 0.004-0.015 microg/ml, each encompassing 100.0% of reported results (prior and current studies). All MIC results for control drugs, levofloxacin and moxifloxacin (disks) or gatifloxacin and clarithromycin (MIC), were within published NCCLS ranges.

AZD2563, a new oxazolidinone: bactericidal activity and synergy studies combined with gentamicin or vancomycin against staphylococci and streptococcal strains.

AZD2563, a novel oxazolidinone, was tested against 10 well characterized multiple-resistant strains of staphylococci and viridans group or beta-hemolytic streptococci using kill curve kinetic methods. Generally, AZD2563 demonstrated bacteriostatic action and modest concentration-dependent cidal activity against a minority of strains of both genera. When combined with gentamicin (MIC/4 concentration), rapid bactericidal action was observed against all streptococci tested, but not against the staphylococci. No enhanced activity was noted when AZD2563 was added to subinhibitory concentrations of vancomycin. Linezolid used as a control, showed the same characteristics, confirming that AZD2563 possesses activity comparable to other agents in the oxazolidinone class. AZD2563 remained active (MIC, < or = 1 microg/ml) against all 10 strains tested.