Antipneumococcal Activities of GAR-936 (a New Glycylcycline) Compared to Those of Nine Other Agents against Penicillin-Susceptible and -Resistant Pneumococci

DOI: 10.1128/AAC.44.4.1085-1088.2000

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Fig. 1.
Graphical depiction of GAR-936 kill kinetics versus a tetracycline-resistant (MIC, 64.0 μg/ml) strain of S. pneumoniae.

Table 1.

Agar dilution MICs for 201 pneumococcal isolates

Drug	Penicillin susceptibility of strain^a	MIC (μg/ml)
Drug	Penicillin susceptibility of strain^a	Range	MIC₅₀^b	MIC₉₀^c
Penicillin	S	≤0.008–0.06	≤0.016	0.03
	I	0.125–1.0	0.25	1.0
	R	2.0–>8.0	2.0	4.0
GAR-936	S	≤0.016–0.125	0.03	0.125
	I	≤0.016–0.125	0.03	0.06
	R	≤0.016–0.125	0.06	0.125
Tetracycline	S	≤0.06–64.0	0.25	32.0
	I	≤0.06–64.0	1.0	64.0
	R	≤0.25–128.0	32.0	64.0
Minocycline	S	≤0.06–16.0	0.06	8.0
	I	≤0.06–16.0	0.25	16.0
	R	≤0.06–16.0	4.0	16.0
Doxycycline	S	0.03–16.0	0.125	8.0
	I	≤0.06–32.0	0.5	8.0
	R	0.125–16.0	4.0	8.0
Amoxicillin	S	≤0.008–0.25	0.016	0.03
	I	≤0.016–2.0	0.125	1.0
	R	0.5–4.0	2.0	2.0
Ceftriaxone	S	≤0.008–1.0	0.016	0.03
	I	≤0.016–2.0	0.25	1.0
	R	0.25–8.0	1.0	2.0
Clarithromycin	S	≤0.016–>128.0	0.03	8.0
	I	≤0.016–>128.0	0.06	>128.0
	R	≤0.016–>128.0	1.0	>128.0
Imipenem	S	≤0.008–0.25	≤0.008	0.016
	I	≤0.008–0.25	0.06	0.25
	R	0.03–0.5	0.25	0.5
Meropenem	S	≤0.008–0.5	0.016	0.03
	I	≤0.016–0.5	0.125	0.5
	R	0.125–2.0	0.5	1.0
Vancomycin	S	≤0.06–0.5	0.25	0.25
	I	≤0.06–0.5	0.25	0.25
	R	0.125–0.5	0.25	0.25

↵a S, penicillin susceptible; I, penicillin intermediate; R, penicillin resistant.
↵b MIC₅₀, MIC at which 50% of the isolates tested were inhibited.
↵c MIC₉₀, MIC at which 90% of the isolates tested were inhibited.

Table 2.

Microbroth MICs for 12 strains tested by the time-kill method

↵a S, penicillin susceptible; I, penicillin intermediate; R, penicillin resistant.

Table 3.

Results of time-kill assays of 12 pneumococcal strains

Drug and concn	No. of strains killed by time point, with Δlog₁₀ CFU/ml (from time zero value) of:
	3 h			6 h			12 h			24 h
	−1	−2	−3	−1	−2	−3	−1	−2	−3	−1	−2	−3
GAR-936
8× MIC	7	3	1	12	6	4	12	11	7	12	12	12
4× MIC	6	2	1	12	6	4	12	10	6	12	12	11
2× MIC	5	2	1	11	5	3	12	9	6	12	11	11
MIC	4	1	1	7	5	2	10	8	4	12	11	11
0.5× MIC	0	0	0	3	0	0	3	2	1	5	3	2
Tetracycline^a
8× MIC	3	1	0	5	3	3	5	4	3	6	6	5
4× MIC	2	0	0	4	3	0	5	4	2	6	6	5
2× MIC	2	0	0	3	2	0	5	2	2	6	5	5
MIC	1	0	0	2	0	0	3	2	0	3	3	1
0.5× MIC	0	0	0	0	0	0	1	0	0	0	0	0
Minocycline^a
8× MIC	4	2	1	4	4	2	5	4	4	6	5	5
4× MIC	3	1	1	4	3	2	5	4	3	6	5	5
2× MIC	2	1	0	4	2	2	5	4	3	6	5	4
MIC	2	0	0	3	2	0	5	3	2	6	4	3
0.5× MIC	1	0	0	1	0	0	0	0	0	0	0	0
Doxycycline^a
8× MIC	4	2	0	5	3	3	5	5	3	6	5	5
4× MIC	3	1	0	5	3	0	5	5	3	6	5	5
2× MIC	1	0	0	4	1	0	5	4	1	6	5	4
MIC	1	0	0	2	1	0	2	1	1	2	2	2
0.5× MIC	0	0	0	1	0	0	1	0	0	0	0	0
Amoxicillin
8× MIC	10	4	0	12	10	6	12	12	10	12	12	12
4× MIC	9	2	0	11	9	3	12	12	8	12	12	12
2× MIC	8	3	0	11	8	2	12	12	7	12	12	12
MIC	5	2	0	11	4	2	10	5	3	10	8	8
0.5× MIC	1	0	0	2	1	0	1	1	0	2	1	1
Ceftriaxone
8× MIC	8	0	0	12	10	0	12	12	10	12	12	12
4× MIC	8	1	0	12	9	1	12	11	8	12	12	12
2× MIC	8	0	0	10	7	0	12	10	8	12	12	12
MIC	5	1	0	9	6	0	10	7	1	10	10	8
0.5× MIC	2	0	0	2	0	0	1	1	0	0	0	0
Clarithromycin^b
8× MIC	4	2	0	7	4	0	7	4	4	7	7	6
4× MIC	3	1	0	6	3	0	7	4	4	7	6	6
2× MIC	3	1	0	4	3	1	7	4	4	7	6	6
MIC	2	1	0	4	2	0	6	4	3	7	6	4
0.5× MIC	1	0	0	2	0	0	2	1	0	2	1	1
Imipenem
8× MIC	12	4	0	12	10	2	12	11	10	12	12	12
4× MIC	11	5	0	12	9	2	12	11	10	12	12	12
2× MIC	11	3	0	12	9	4	12	11	10	12	12	12
MIC	10	2	0	12	8	2	12	10	8	11	11	9
0.5× MIC	8	0	0	6	3	0	4	2	0	3	3	2
Meropenem
8× MIC	11	3	1	12	5	2	12	12	9	12	12	12
4× MIC	9	2	0	12	4	2	12	12	7	12	12	11
2× MIC	6	4	0	12	7	3	12	11	8	12	12	11
MIC	6	2	1	11	5	2	11	9	5	10	9	8
0.5× MIC	1	0	0	2	0	0	1	0	0	2	1	1
Vancomycin
8× MIC	7	1	0	12	6	1	12	11	9	12	12	12
4× MIC	7	1	0	12	6	2	12	10	9	12	12	11
2× MIC	7	1	0	12	6	2	12	10	8	12	12	11
MIC	6	1	0	12	4	0	11	9	5	10	9	7
0.5× MIC	0	0	0	2	0	0	2	0	0	2	2	0