Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Aug 1995
Comparative StudyPharmacodynamics of ceftazidime administered as continuous infusion or intermittent bolus alone and in combination with single daily-dose amikacin against Pseudomonas aeruginosa in an in vitro infection model.
We compared the pharmacodynamics and killing activity of ceftazidime, administered by continuous infusion and intermittent bolus, against Pseudomonas aeruginosa ATCC 27853 and ceftazidime-resistant P. aeruginosa 27853CR with and without a single daily dose of amikacin in an in vitro infection model over a 48-h period. Resistance to ceftazidime was selected for by serial passage of P. aeruginosa onto agar containing increasing concentrations of ceftazidime. Human pharmacokinetics and dosages were simulated as follows: half-life, 2 h; intermittent-bolus ceftazidime, 2 g every 8 h (q8h) and q12h; continuous infusion, 2-g loading dose and maintenance infusions of 5, 10, and 20 micrograms/ml; amikacin, 15 mg/kg q24h. ⋯ The combination regimens of continuous infusion of 20 micrograms/ml plus amikacin and intermittent bolus q8h or q12h plus amikacin continued to be synergistic. Overall, continuous infusion monotherapy with ceftazidime at concentrations 4 to 5 and 10 to 15 times the MIC was as effective as an intermittent bolus of 2 g q12h (10 to 15 times the MIC) and q8h (25 to 35 times the MIC), respectively, against ceftazidime-susceptible P. aeruginosa. Combination therapy with amikacin plus ceftazidime, either intermittently q8h or by continuous infusion of 20 micrograms/ml, appeared to be effective and exhibited synergism against ceftazidime-resistant P. aeruginosa.