Minimal inhibitory concentrations

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.)... 

BLIC, /5-lactamase inhibitor combination BL/BLI, jS-lactamase/jS-lactamase inhibitor FGC, first-generation cephalosporin MIC, minimal inhibitory concentration PRP, penicillinase-resistant penicillin SGC, second-generation cephalosporin TGC, third-generation cephalosporin. Penicillinase-resistant penicillin nafcillin or oxacillin. 

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). 

The H NMR spectram (CDClj, 500 MHz) of 12 showed two singlets (8 0.83 and 8 0.95), each integrating for three protons due to the C-18 and C-19 methyl protons. Three 3H doublets at 8 0.78 (J= 6.5 Hz), 8 0.79 (J= 6.5 Hz) and 8 0.85 (J = 7.0 Hz) were due to the secondary C-26, C-27 and C-21 methyl protons, respechvely. The C-3 methine proton resonated as a one-proton double doublet at 8 3.63 (JJ= 10.5 Hz and J2= 3.5 Hz) and its downfield chemical shift value was indicative of the presence of a geminal hydroxyl funchonality. A one-proton mulhplet at 8 5.21 was ascribed to the C-6 olefinic proton. The C-28 exocyclic methylene protons appeared as two broad singlets at 8 5.40 and 5.58. The C-NMR spectram (CDCl, 125 MHz) showed the resonance of all 28 carbon atoms. The combination of H and C-NMR data suggested that compound 12 has a sterol like structure as most of the H and C-NMR chemical shift values of 12 were similar to those of sterols reported in the literature [19, 20]. The H and C-NMR chemical shift values were assigned with the aid of COSY-45 , HSQC and HMBC spectral data. Compound 12 was found to have modest inhibitory activity against C. xerosis and S. aureus with minimal inhibitory concentration values of 82.35 and 146 pg/ml, respectively. 

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... 

Scheme 7.11). Here the therapeutic index was calculated as the minimal hemolytic concentration/minimal inhibitory concentration of bacteria. 

An effective approach of antimicrobial therapy of an infection is based on the isolation and identification of the infected organism and determining its sensitivity to antimicrobial drngs. In vitro tests, snch as diffnsion in agar and determining the minimally inhibitory concentration in a liqnid medinm are the most widely used tests. 

Triclosan is retained in dental plaque for at least 8 hours, which in addition to its broad antibacterial property could make it suitable for use as an antiplaque agent in oral care preparations. However, the compound is rapidly released from oral tissues, resulting in relatively poor antiplaque properties as assessed in clinical studies of plaque formation. This observation is further corroborated by a poor correlation between minimal inhibitory concentration values generated in vitro and clinical plaque inhibitory properties of triclosan. Improvement of substantivity was accomplished by incorporation of triclosan in a polyvinyl methyl ether maleic acid copolymer (PVM/MA, Gantrez). With the combination of PVM/MA copolymer and triclosan, the substantivity of the triclosan was increased to 12 hours in the oral cavity. 

Moore R, Lietman P, and Smith C. Clinical response to aminoglycosides Importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987 155 93-99. 

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],... 

Fig. 3 Surface-release profile of a biocide loaded into a matrix. MBC minimal biocidal concentration, MIC minimal inhibitory concentration, c concentration of biocide...

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