Minimal inhibitory concentrations MIC

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

The minimal inhibitory concentration (MIC) is the concentration which is able to prevent 105cells/mL from growing up to a visable density ( 108cells/mL) under standardized conditions. 

FIGURE 66-3. Macrotube minimal inhibitory concentration (MIC) determination. The growth control (C), 0.5 mg/dL, and 1 mg/dL tubes are visibly turgid, indicating bacterial growth. The MIC is read as the first clear test tube (2 mg/dL). (Reprinted from Rybak MJ, Aeschlimann JR. Laboratory tests to direct antimicrobial pharmacotherapy. In In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1897.)... 

Most viridans streptococci are exquisitely sensitive to penicillin G with minimal inhibitory concentrations (MICs) less than or equal to 0.12 meg/ mL. The MIC should be determined for all viridans streptococci and the results used to guide therapy. Approximately 10% to 20% are moderately susceptible (MIC 0.12 to 0.5 mcg/mL). 

Wiegand I, Hilpert K, Hancock RE (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3 (2) 163-175... 

The 7-azabenzisoselenazol-3(27/)-ones (169) (Fig. 12), substituted at the 2-position with phenyl or alkyl groups, and the methiodides (170) were found in the antiviral assay to be strong inhibitors of cytopathic activity of herpes simplex type 1 virus (HSV-1) and encephalomyocarditis virus (EMCV), more potent than ebselen. The minimal inhibitory concentration (MIC) values were in the range 0.4-6.0 pg mL 1, substantially lower than those when toxicity was observed. The vesicular stomatis virus (VSV) remained resistant toward tested compounds, except moderately active methiodide (171) [51, 271],... 

In a common type of susceptibility testing, serial dilutions of the antibacterial drug are inoculated with the bacteria to determine a minimal inhibitory concentration (MIC), which is the lowest concentration of the drug that... 

Minimal inhibitory concentrations (MIC) determined in brain-heart infusion broth containing 10 cells/ml. Minimal bactericidal concentrations (MBC) determined by subculture into broth. Figures given are averages of two tubes except that the readings from four tubes were averaged for the E. coli data. 

Based upon pharmacokinetic information and minimal inhibitory concentrations (MIC) for pyrimethamine, an oral daily dose of Img/kg in combination with 22 mg/kg sulfadiazine is recommended in horses. The duration of treatment is controversial and the recommendations range from a minimum of 3 months (least conservative) to the point at which the CSF is seronegative (most conservative). It is clear that the latter course of treatment is least likely to result in relapse of the clinical signs (Fenger 1997), but it is likely that this exceeds what is absolutely necessary in most cases. 

FIGURE 103-3. Macrotube minimal inhibitory concentration (MIC) determination. The growth control (C), 0.5 mg/dL, and 1 mg/dL tubes are visibly turbid, indicating bacterial growth. The MIC is read as the first clear test tube (2 mg/dL). 

FIGURE 103-6. Photograph of E-strip susceptibility test The minimal inhibitory concentration (MiC) is determined from the point where the zone of inhibition intersects with the numerical scale. (Photograph courtesy of the Anti-Infective Research Laboratory, Wayne State University, Detroit, Michigan.)... 

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