In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying Stenotrophomonas maltophilia

Figures & data

Table 1 Summary of the Pharmacokinetic Parameters and the Experimental Concentrations of the Antimicrobial Agents Used in the Time-Kill Experiments

Antimicrobial Agents	Clinical Dosages	AUC (µg×h/mL)	MSC (ug/mL)	Cmax (ug/mL)	Experimental Concentration (ug/mL)	Reference
Min	200 mg po 24h	48.3^a	2.01	3.5	2	[10]
Tig	50 mg q 12h	3.07^b	0.26	0.63	0.25	[18]
Mox	400 mg q 24h	47.97^a	2.00	4.5	2	[19]
T/K	3 g/0.1 g q 8h	409.6^c	51.2	100	32/2	[20–22]

Notes: ^a0–24 h AUC at steady state for multiple-dose studies; ^b0–12 h AUC at steady state for multiple-dose studies; ^c0–8 h AUC at steady state for multiple-dose studies.

Abbreviations: AUC, area under the curve; MSC, mean steady-state concentration of non-protein-bound drug; C_max, peak concentration; Min, minocycline; Tig, tigecycline; Mox, moxifloxacin; T/K, ticarcillin/clavulanic acid.

Table 2 The Carrying Situation of Dihydropteroate Synthase Genes and the Minimum Inhibitory Concentration of the Six Chosen Stenotrophomonas maltophilia Strains Used in the Time-Kill Experiment

Strain	MIC (ug/mL)
	Sul	SXT	Mox	Min	Tig	T/K
A1	Sul 1	> 152/8	0.25	0.25	0.5	2/2
A2	Sul 2	152/8	0.5	0.5	1	8/2
A3	Sul 1	76/4	1	0.25	1	4/2
A4	Sul 2	> 152/8	1	1	2	16/2
A5	Sul 1	152/8	2	0.5	1	2/2
A6	Sul 1, Sul 2	> 152/8	2	2	2	8/2

Abbreviations: Sul, dihydropteroate synthase; MIC, minimum inhibitory concentration; SXT, sulfamethoxazole-trimethoprim; Mox, moxifloxacin; Min, minocycline; Tig, tigecycline; T/K, ticarcillin/clavulanic acid.

Table 3 Change in Bacterial Concentrations at 24 h of the Six Sul-Carrying Stenotrophomonas maltophilia Strains

Strain	Change in Concentration (log10 CFU/mL) at 24 h
	Min	Mox	Tig	T/K	Min+T/K	Mox+T/K	Tig+T/K	Control
A1	−0.40	−6.18	0.33	0.82	−1.00	−6.18	0.03	3.37
A2	−0.06	−5.90	0.88	1.16	−0.51	−5.90	−0.36	5.03
A3	0.15	−6.00	0.90	2.18	−0.07	−6.00	−0.05	4.28
A4	−0.03	−3.60	0.54	2.94	−0.20	−5.90	0.03	4.18
A5	−0.12	0.12	0.62	2.34	−0.08	−3.12	0.35	3.40
A6	0.09	1.02	0.77	−0.30	0.15	−3.54	−0.37	3.33

Abbreviations: Sul, dihydropteroate synthase; CFU, colony-forming units; Min, minocycline; Mox, moxifloxacin; Tig, tigecycline; T/K, ticarcillin/clavulanic acid.

Figure 1 Time-kill curves for clinical A1 and A6 sul-carrying Stenotrophomonas maltophilia. (A) Time-kill curves for A1 sul-carrying S.maltophilia; (B) Time-kill curves for A6 sul-carrying S.maltophilia.

Abbreviations: Sul, dihydropteroate synthase; CFU, colony-forming units; Min, minocycline; Tig, tigecycline; Mox, moxifloxacin; T/K, ticarcillin/clavulanic acid.

Table 4 The Ability of Antimicrobial Agents to Prevent the Occurrence of Resistance at Clinical Dosage Regimens Against Sul-Carrying S. maltophilia

Antibiotic	MPC Range (ug/mL)	MPC50/MPC90 (ug/mL)	MSC Prevent Resistance (%)	Cmax Prevent Resistance (%)
T/K	> 256/2	> 256/2^a	0	0
Min	4–16	8/16	0	0
Tig	8–16	16/16	0	0
Mox	4–32	16/32	0	10
Min+T/K	4–16	8/16	0	5
Tig+T/K	8–16	16/16	0	0
Mox+T/K	1–8	2/4	70	95

Note: ^aThe MPC₅₀ and MPC₉₀ of T/K are both > 256/2 ug/mL.

Abbreviations: Sul, dihydropteroate synthase; MPC, mutant prevention concentration; MSC, mean steady-state concentrations; C_max, peak concentration; T/K, ticarcillin/clavulanic acid; Min, minocycline; Tig, tigecycline; Mox, moxifloxacin.

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