In vitro bactericidal activity of imipenem in combination with amikacin or ciprofloxacin against Klebsiella pneumoniae producing extended-spectrum b-lactamases

In vitro bactericidal activity of imipenem in combination with amikacin or ciprofloxacin against Klebsiella pneumoniae producing extended-spectrum b-lactamases

Sutthiporn Pattharachayakul, D. of Clinical Pharmacy, F. of Pharmaceutical Sci., PSU
Melinda M. Neuhauser, D. of Clinical Sci. and Ad., U. of Houston, USA
Susan Pendland, Assoc. Prof., D. of Pharmacy Practice, U. of Illinois at Chicago, USA
Jenifer L. Prause, D. of Pharmacy Practice, U. of Illinois at Chicago, USA
Corresponding e-mail : spatth1@hotmail.com

Presented : American College of Clinical Pharmacy 2000 Annual Meeting, Los Angeles, California, USA, November 5-8, 2000
Key words : ESBL, Klebsiella pneumoniae, imipenem, time- kill

Purpose : Carbapenems are the drug of choice for ESBL-producing microorganisms. Combination therapy may produce greater killing and potentially better clinical outcomes. The purpose of this study was to examine the bactericidal activity of imipenem alone and in combination with amikacin or ciprofloxacin.

Methods : Bactericidal activity (ł 3 log10 decrease in CFU/mL) was determined using the NCCLS time-kill method. Four clinical isolates of ESBL-producing K. pneumoniae were studied. The concentration of each antibiotic tested was 2X MIC. Viable counts were determined at 0, 1, 1.5, 2, 6, 12, and 24 hours.

Results : All isolates were sensitive to imipenem (MICs : 0.06-1 mg/mL) and amikacin (MICs: 1-2 mg/mL); 3 isolates were intermediate to ciprofloxacin (MICs : 1-2mg/mL). The killing rates were: imipenem/amikacin = amikacin (bactericidal at 1-2 hours) > imipenem/ciprofloxacin (bactericidal at 1.5-6 hours) > ciprofloxacin (bactericidal at 6 hours) = imipenem (bactericidal at 6 hours). One strain demonstrated synergy (ł 2 log₁₀ decrease in CFU/mL) with imipenem/ciprofloxacin. Additivity (ł 1 log₁₀ decrease) was seen with imipenem/amikacin in 2 strains and with imipenem/ciprofloxacin in 1 strain. No antagonism (> 2 log10 increase) was observed.

Conclusion : The bactericidal activity of imipenem in combination with amikacin or cipro-floxacin was greater than that of imipenem alone. This was primarily due to the excellent in vitro activity of amikacin and ciprofloxacin. However, the ciprofloxacin concentrations tested may not be clinically achievable throughout the dosing interval. Based on the in vitro data, combination therapy may provide better clinical outcomes than imipenem alone in patients with serious infections due to ESBL-producing organisms.

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