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. 2004 Nov;48(11):4103–4112. doi: 10.1128/AAC.48.11.4103-4112.2004

TABLE 4.

Results of multistep resistance selection by erythromycin, azithromycin, clarithromycin, telithromycin, clindamycin, GW 708408, and GW 773546a

Straina Selecting agent Initial MIC (μg/ml) Selected resistance
MIC (μg/ml) after 10 antibiotic-free subcultures
Change in sequence
No. of passages MIC (μg/ml) ERY AZI CLARI TELI CLINDA GW 708 GW 773 L4 protein L22 protein 23S rRNA
1 ERY 0.06 38 1.0 0.5 0.25 0.125 0.008 0.03 0.004 0.004 n. chg n. chg n. chg
AZI 0.06 32 0.5 0.5 0.5 0.125 0.008 0.06 0.008 0.004 K68R, A73T n. chg n. chg
TELI 0.004 20 0.03 0.25 0.25 0.125 0.03 0.03 0.03 0.03 n. chg ins 80SEAFAN n. chg
CLINDA 0.016 18 0.25 >64.0 >64.0 >64.0 0.016 0.25 0.03 0.016 n. chg n. chg n. chg
GW 708 0.004 30 0.06 2.0 0.25 0.125 0.06 0.03 0.06 0.03 n. chg R92H, G95D n. chg
GW 773 0.004 26 0.03 0.25 0.25 0.125 0.06 0.06 0.06 0.03 n. chg G95D n. chg
2 ERY 0.06 24 64.0 64.0 64.0 32.0 0.03 0.25 0.06 0.03 E13K n. chg A2059C
AZI 0.125 42 1.0 0.25 0.5 0.06 0.016 0.06 0.008 0.008 G71C n. chg n. chg
CLARI 0.016 32 0.125 1.0 0.25 0.125 0.06 0.03 0.06 0.06 n. chg n. chg n. chg
CLINDA 0.03 18 0.5 0.25 2.0 0.06 0.008 0.5 0.016 0.008 n. chg n. chg n. chg
GW 708 0.008 50 0.06 2.0 0.25 0.125 0.03 0.06 0.03 0.016 n. chg n. chg n. chg
GW 773 0.004 40 0.03 0.5 0.5 0.125 0.03 0.03 0.03 0.016 n. chg n. chg n. chg
3 ERY 0.06 32 0.5 0.5 0.5 0.125 0.016 0.03 0.016 0.008 Q67K, G69E n. chg n. chg
AZI 0.125 22 1.0 0.25 1.0 0.06 0.016 1.0 0.016 0.008 n. chg n. chg n. chg
CLARI 0.016 14 32.0 >64.0 >64.0 32.0 0.25 2.0 2.0 0.25 n. chg n. chg A2058T
TELI 0.008 20 0.06 0.5 0.25 0.25 0.125 0.016 0.125 0.06 n. chg A93T n. chg
CLINDA 0.03 18 0.5 0.125 1.0 0.06 0.008 0.5 0.016 0.004 n. chg n. chg n. chg
GW 708 0.008 26 0.125 2.0 0.25 0.25 0.06 0.016 0.125 0.125 n. chg A93E n. chg
GW 773 0.004 16 0.03 0.25 0.125 0.06 0.03 0.03 0.03 0.03 n. chg A93E n. chg
4 ERY 0.06 24 0.5 0.5 0.5 0.125 0.008 0.125 0.008 0.004 A10T n. chg G2057A
AZI 0.125 26 >64.0 >64.0 >64.0 >64.0 0.125 8.0 0.25 0.125 E13K n. chg A2058G
TELI 0.008 40 0.06 0.25 0.125 0.125 0.06 0.03 0.06 0.06 A10T A93T n. chg
CLINDA 0.03 22 16.0 >64.0 >64.0 >64.0 0.125 16.0 0.25 0.125 A10T n. chg A2058G
GW 708 0.008 34 0.06 >64.0 8.0 64.0 0.06 0.25 0.125 0.06 A10T n. chg n. chg
GW 773 0.004 26 >0.06 >64.0 >64.0 >64.0 0.125 8.0 0.25 0.125 A10T n. chg A2058G
5 ERY 0.06 32 0.5 0.5 0.25 0.125 0.008 0.25 0.004 0.004 n. chg n. chg G2057T
AZI 0.125 42 >64.0 8.0 >64.0 4.0 0.016 1.0 0.016 0.008 n. chg n. chg A2058G
CLARI 0.016 22 >64.0 >64.0 >64.0 >64.0 0.125 4.0 0.25 0.125 n. chg n. chg A2058G
TELI 0.008 32 0.06 1.0 0.5 0.5 0.125 0.03 0.25 0.125 n. chg A93E n. chg
CLINDA 0.03 18 0.25 0.06 0.125 0.03 0.004 0.25 0.004 0.002 E13K n. chg n. chg
GW 773 0.004 16 0.06 1.0 0.5 0.25 0.06 0.03 0.125 0.06 n. chg A93E n. chg
6 ERY 0.06 26 0.5 0.5 1.0 0.125 0.016 0.06 0.016 0.008 ins 66QS n. chg n. chg
AZI 0.125 14 1.0 0.5 1.0 0.125 0.016 0.06 0.016 0.008 ins 66QS n. chg n. chg
CLARI 0.016 14 64.0 >64.0 8.0 64.0 0.125 0.25 0.125 0.125 n. chg n. chg n. chg
CLINDA 0.03 26 0.25 0.06 0.125 0.03 0.008 0.25 0.008 0.004 n. chg n. chg n. chg
GW 773 0.004 40 0.03 0.25 0.25 0.06 0.06 0.06 0.06 0.03 n. chg G95D n. chg
7 TELI 0.03 14 >2.0 >64.0 >64.0 >64.0 0.06 >64.0 0.06 0.06 n. chg S96P n. chg
GW 708 0.03 14 >2.0 >64.0 >64.0 >64.0 16.0 >64.0 64.0 16.0 n. chg R31K n. chg
GW 773 0.016 14 >1.0 >64.0 >64.0 >64.0 0.5 >64.0 2.0 1.0 n. chg n. chg n. chg
8 TELI 0.125 14 >2.0 >64.0 >64.0 >64.0 1.0 >64.0 1.0 0.5 n. chg n. chg n. chg
GW 708 0.03 14 >2.0 >64.0 >64.0 >64.0 16.0 >64.0 64.0 16.0 n. chg n. chg n. chg
GW 773 0.06 14 >1.0 >64.0 >64.0 >64.0 8.0 >64.0 32.0 8.0 n. chg n. chg n. chg
9 TELI 0.06 14 >2.0 >64.0 >64.0 >64.0 0.25 >64.0 1.0 0.5 n. chg n. chg n. chg
GW 708 0.016 14 >2.0 >64.0 >64.0 >64.0 1.0 >64.0 2.0 0.5 n. chg n. chg n. chg
GW 773 0.016 14 >1.0 >64.0 >64.0 >64.0 0.5 >64.0 0.25 0.5 n. chg n. chg n. chg
11 CLARI 4.0 28 32.0 32.0 32.0 16.0 0.5 0.03 0.5 0.125 n. chg n. chg n. chg
TELI 0.125 14 2.0 16.0 16.0 8.0 2.0 0.03 2.0 0.5 n. chg n. chg n. chg
CLINDA 0.016 18 0.25 4.0 8.0 2.0 0.25 0.25 0.25 0.06 n. chg n. chg n. chg
GW 708 0.125 14 2.0 16.0 16.0 8.0 2.0 0.03 2.0 0.5 n. chg n. chg n. chg
GW 773 0.03 14 0.5 8.0 16.0 8.0 1.0 0.03 2.0 0.25 n. chg n. chg n. chg
12 TELI 0.125 14 1.0 16.0 16.0 8.0 1.0 0.06 1.0 0.25 n. chg n. chg n. chg
CLINDA 0.03 37 0.25 4.0 8.0 4.0 0.06 0.25 0.125 0.03 n. chg n. chg n. chg
GW 708 0.25 14 2.0 16.0 16.0 8.0 1.0 0.06 2.0 0.25 n. chg n. chg n. chg
GW 773 0.03 14 0.25 8.0 16.0 8.0 0.5 0.06 1.0 0.125 n. chg S96P, E113K n. chg
a

Strains 1 to 6 are susceptible, strains 7 to 12 are macrolide resistant, 7 to 9 are erm(B) positive, and strains 10 to 12 are mef(E) positive. Strain 10 did not yielded any mutants, so data for this strain are not presented here. Abbreviations: ERY, erythromycin; AZI, azithromycin; CLARI, clarithromycin; TELI, telithromycin; CLINDA, clindamycin; GW 708, GW 708408; GW 773, GW 773546; n. chg, no change in the sequence detected; ins, insertion.