Synergistic Activity of Colistin and Ceftazidime against Multiantibiotic-Resistant Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

DOI: 10.1128/AAC.47.3.905-909.2003

Article Figures & Data

Open in new tab
Download powerpoint
FIG. 1.
Time-kill curve of P. aeruginosa M29899-1 with colistin with C_maxs of 6 mg/liter (▵) and 18 mg/liter (○), the combination of ceftazidime and colistin as a ceftazidime infusion at 50 mg/liter and colistin with C_maxs of 6 mg/liter (▴) and 18 mg/liter (•), and ceftazidime infusion (C_SS = 50 mg/liter) alone (×). The ceftazidime-alone experiment was conducted for only 24 h.

TABLE 1.

Changes in P. aeruginosa M29899-1 colony counts in initial-inoculum, single- and multiple-dose colistin experiments

Time (h)	Change in colony count (log₁₀ CFU/ml) with C_max (mg/liter) of:^a
Time (h)	0.5	3	6	18	36	72	200	6 (BID)	18 (BID)
0.5	ND	ND	ND	ND	ND	ND	≥−3.52	ND	ND
1	−1.14	−2.30	−2.62	−3.48	ND	≥−3.52	≥−3.52	−2.34	−2.66
2	−1.13	−2.87	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−3.10	≥−3.52
3	−1.33	−3.31	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52
4	−1.43	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52
5.5	−1.34	−3.37	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52
7	−0.69	−2.80	≥−3.52	≥−3.52	≥−3.52	≥−3.52	≥−3.52	ND	ND
12	1.49	−0.97	−2.34	−3.41	−2.70	−2.94	≥−3.52	≥−3.52	≥−3.52
13	ND	ND	ND	ND	ND	ND	ND	−3.42	≥−3.52
14	ND	ND	ND	ND	ND	ND	ND	−3.16	≥−3.52
24	1.68	1.53	0.94	−0.05	−0.64	−0.86	−1.02	−0.79	−2.16

↵a C_max was achieved at time zero only, except where noted otherwise. The time of sampling varied slightly in certain experiments at 5.5, 7, and 12 h, but the variation was within 15 to 90 min of the stated sampling times. BID, twice a day; ND, sample not taken.

TABLE 2.

Changes in P. aeruginosa colony counts in initial-inoculum, single-dose colistin experiments

Time (h)	Change in colony count (log₁₀ CFU/ml) with colistin at indicated C_max (mg/liter) and/or indicated drug^a
Time (h)	6, +CTZ^b	18, +CTZ^b	6, +CTZ^c	18, +CTZ^c	CTZ alone^b	6, +CIP^b^,^d	18, +CIP^b^,^d
1	−2.30	−2.96	≥−3.52	−3.39	0.08	−2.99	−2.76
2	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−0.01	≥−3.52	≥−3.52
3	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−0.63	≥−3.52	≥−3.52
4	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−1.60	−3.41	≥−3.52
5.5	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−1.94	−2.37	≥−3.52
7	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−2.10	−1.90	≥−3.52
12	≥−3.52	≥−3.52	≥−3.52	≥−3.52	−1.92	−1.08	−1.86
24	−2.51	−2.75	−2.77	−2.84	−1.70	1.78	0.08
26	−2.96	≥−3.52	−3.43	≥−3.52
28	−2.90	≥−3.52	−3.45	≥−3.52
30	−3.17	≥−3.52	−3.03	≥−3.52
48	−2.09	−2.79	−2.09	−2.25

↵a Colistin C_max was achieved at time zero only. Ceftazidime (CTZ) concentration was maintained as a constant infusion. The time of sampling varied slightly in certain experiments between 5.5 and 30 h, but the variation was within 15 to 60 min of the stated sampling times. CTZ, ceftazidime.
↵b P. aeruginosa M29899-1.
↵c P. aeruginosa H23259-1.
↵d Ciprofloxacin (CIP) was given to achieve a C_max of 5 mg/liter at 0 and 12 h.