Analysis of sequential isolates of Pseudomonas aeruginosa from cystic fibrosis patients, repeatedly treated with ciprofloxacin by mutant prevention concentration, minimal inhibitory concentration and pulsed field gel electrophoresis
Abstract number: 1134_03_194
Blondeau J., Blondeau L., Williams C.
MPC measures the propensity of an antimicrobial (AM) compound to select for AM resistance based on drug concentrations required to block growth of first-step resistant mutants. Cystic fibrosis patients (CFP) are frequently infected with Pseudomonas aeruginosa (PA) and require repeat courses of AM therapy. As AM therapy may precipitate AM resistance, we tested sequential PA isolates from CFP, repeatedly treated with Cpx, by MIC and MPC.
Sequential isolates were collected over a 3-yr period. PA isolates were tested to Cpx and levofloxacin (Lfx) by microbroth dilution in accordance with NCCLS guidelines. For MPC testing, 10 billion organisms were applied to agar plates containing drug and incubated 2448 hr. The lowest concentration preventing growth was the MPC. PA strains were compared by pulsed field gel electrophoresis (PFGE) using Spe I.
Patient 1 (P1) (10 isolates) received 6 courses of Cpx (500750 mg bid) and patient 2 (P2) 5 courses over the period collected (3 yrs). MICs for Cpx and Lfx for P1 and P2 ranged 0.0311 mg/ml and 0.252 mg/ml respectively; MPCs ranged 14 mg/ml (79% <= 2 mg/ml) and 216 mg/ml (64% >= 8 mg/ml) respectively. PFGE profile for P1 isolates were identical while P2 had 3 different strains. Cpx therapy did result in increased MPC values. Lfx MPC values were higher than Cpx in every instance.
This represents first report of MPC testing on sequential PA isolates where AM history was available. MPCs remained constant to Cpx over the duration of organism isolations. MPCs to Lfx were high and beyond achievable and sustainable drug concentrations. As P1, P2 have never received Lfx, yet MPC values were so high, suggests Lfx will more readily select for quinolone resistant PA. MPC can be used to monitor changes in susceptibility and as such guide appropriate selection of AM therapy.
|Session name:||XXIst ISTH Congress|
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