Rn. Jones et al., Development of in vitro susceptibility testing methods for gemifloxacin (formerly LB20304a or SB-265805), an investigational fluoronaphthyridone, DIAG MICR I, 35(3), 1999, pp. 227-234
Potent investigational fluoroquinolones require convenient, but accurate, d
iagnostic tests for initially applied clinical trials. For this purpose, ge
mifloxacin (formerly SB-265805, LB20304a) was tested by the reference dilut
ion tests and standardized disk diffusion methods of the National Committee
for Clinical Laboratory Standards (NCCLS) to establish interpretive criter
ia. For rapid-growing pathogens, 986 organisms were tested by broth microdi
lution MIG, and 5- and 10-mu g disk diffusion tests. Correlation (r) betwee
n 5- and 10-mu g disk zone diameters was 0.99 (y = -0.22 to 0.99x) and the
preferred 5-mu g disk zone/MIC scattergram produced a regression of y = 14.
8 to 0.41x (r = 0.93). At potential pharmacodynamics (C-max = 1.3 mu g/mL f
or 320 mg dose) validated breakpoints Of less than or equal to 0.5 mu g/mL
for susceptible and greater than or equal to 2 mu g/mL for resistant, corre
late zones of greater than or equal to 17 mm and less than or equal to 13 m
m produced rare serious interpretive errors (0.1%) and 96.7% absolute categ
orical agreement. For 304 Streptococcus pneumoniae and 305 strains of other
streptococci, the same breakpoints produced 100 and 99.1% categorical accu
racy even when testing levofloxacin-resistant (MIC, greater than or equal t
o 4 mu g/mL) strains. Interpretive breakpoints were proposed for Hemophilus
influenzae (300 strains tested), with complete correlation between tests.
Etest (AB BIODISK, Solna, Sweden) was compared in all experiments with the
fastidious species and showed a trend toward higher values (twofold). Gemif
loxacin in vitro susceptibility test methods seem to be accurate and with v
ery acceptable intermethod agreement, supported by previously reported func
tional quality control guidelines. (C) 1999 Elsevier Science Inc.