Pharmacodynamic effects of subinhibitory concentrations of imipenem on Pseudomonas aeruginosa in an in vitro dynamic model

Abstract

The postantibiotic effect (PAE), sub-MIC effect (SME), and postantibiotic sub-MIC effect (PASME) of imipenem on Pseudomonas aeruginosa were investigated with an in vitro dynamic model reproducing in vivo elimination kinetics of the antibiotic. The PASMEs were constantly longer than the corresponding SMEs, but differences between them were not statistically significant. Both PASMEs and SMEs were initially bactericidal and were significantly longer than PAEs. The mean values of both PASMEs and SMEs were over 12 h. SMEs appear to be more relevant for the bacterial growth kinetics than PAEs.Dosage schedules for antibiotic therapy are generally based on the assumption that drug concentrations must be maintained above the MIC. However, it has been shown that discontinuous therapy is as effective as continuous therapy, even if the concentrations in serum fall below the MIC (24). A lag phase before the regrowth of bacteria previously challenged with antibiotics has been demonstrated and named the postantibiotic effect (PAE) (2,14). This phenomenon is thought to be a possible explanation for the success of intermittent-dosing regimens (2).The PAE has been demonstrated for various antibioticbacterium combinations (1,8,9,22). However, the PAE is a highly artificial parameter, as in vivo, a suprainhibitory concentration of a drug will always be followed by subinhibitory concentrations (sub-MICs).Subinhibitory antibiotic concentrations may have different effects on bacteria previously exposed to suprainhibitory concentrations and on unexposed bacteria (18)(19)(20). In most of the investigated combinations with I8-lactam antibiotics, the postantibiotic sub-MIC effect (PASME) was significantly longer than the sub-MIC effect (SME).The aim of this study was to investigate the occurrence of the PASME and SME of imipenem on The bacteria, in the exponential growth phase, were then exposed to five times the MIC of the antibiotic for 1.5 h at 37°C. The exposed strains were washed three times for 5 min each time at 1,400 x g to eliminate the antibiotic and were then resuspended in fresh medium. Controls, unexposed to the antibiotic, were treated similarly. Exposed cultures and controls were either diluted or left undiluted and inoculated into the dynamic model (see below) to obtain a final concentration of approximately 5 x 105 CFU/ml.Samples were withdrawn at 0 (before and after dilution), 1, 2, 4, 7, 10, 13, 16, and 20 h and, if necessary, diluted with phosphate-buffered saline. Samples were seeded on Iso-Sensitest agar plates and incubated for 20 h, and CFU were counted. CFU were counted only for plates with 10 to 500 colonies. All experiments were performed in triplicate.The PAE was defined according to the previously described formula (2) PAE = T -C, where T is the time required for the viable counts of the antibiotic-exposed cultures to increase by 1 log1o above the counts observed immediately after the seeding of the system and C is the corresponding time for the unexposed cultures.Determination of the effects of sub-MICs. Th...

Cinnamon Oil Inhibits Shiga Toxin Type 2 Phage Induction and Shiga Toxin Type 2 Production in Escherichia coli O157:H7

“…The lowest concentration of cinnamon oil without visible bacterial growth is considered to be the MIC, while the concentration that eliminated bacterial growth is regarded as the MBC detected by plating onto LB agar plates. A cinnamon oil concentration lower than the MIC is defined as a subinhibitory concentration (29)(30)(31). Six replicates were used for each treatment in the MIC and MBC assay.…”