Minimal inhibitory concentrations antibiotics

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). 

Cell wall agents, such as glycopeptides, have concentration-independent bactericidal activity, and the time over which the antibiotic serum concentration persists over the minimal inhibitory concentration of the pathogen is a main pharmacodynamic determination of the outcome. In a two-way, randomized, open, two-period, crossover study in 10 healthy adults, teicoplanin given in two 200 mg doses intramuscularly produced steady-state trough concentrations even higher than those after once-daily intravenous administration of 400 mg (3). Conversion from intravenous to intramuscular administration may therefore allow better compliance with preserved efficacy. Intramuscular teicoplanin was well tolerated. Adverse effects reported were mild local pain for 2-3 hours, headache, and backache. 

FIGURE 103-7. Killing curve depicting the effect of concentration on antibiotic bactericidal activity. CPU = colony-forming units MIC = minimal Inhibitory concentration. 0.25-64 times the MIC the organism tested was P. aeruginosa ATCC 27853. (From ref 51.)... 

TESTING FOR MICROBIAL SENSITIVITY TO ANTIMICROBIAL AGENTS Bacterial strains, even from the same species, may vary widely in sensitivity to antibiotics. Information about the antibiotic sensitivity of the infecting microorganism is important for appropriate drug selection. Various methods are used to assess susceptibility, including disk-diffusion, dilution test, and automated broth dilution. The results are either reported on a semi-quantitative scale i.e., resistant, intermediate, or susceptible) or in terms of the minimal inhibitory concentration (MIC). 

Fosfomycin is excreted by the kidney, with urinary levels exceeding the minimal inhibitory concentrations (MiCs) for many urinaiy tract pathogens. In a single dose, the drug is less effective than a 7-day course of treatment with fluoroquinolones. With multiple dosing, resistance emerges rapidly and diarrhea is common. Fosfomycin may be synergistic with beta-lactam and quinolone antibiotics in specific infections. 

The minimal inhibitory concentration (MIC) is the concentration of antibiotic which prevents growth of the culture. The minimal bactericidal concentration (MBC) is the concentration that kills 99.9% of the... 

C. beijerinckii is also a producer of clostrubin, an exceptional polyphenolic polyketide antibiotic [26]. Small doses (0.12-0.97 pM minimal inhibitory concentration (MIC)) of clostrubin inhibit growth ofvarious pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and mycobacteria [26]. 

It is found that minimally inhibitoiy concentration of liposomal antibiotic solution with the neutral charge (lecithin liposomes) decreased in three times in comparison with minimally inhibitory concentration of the lincomycin solution concerning Staphylococcus aureus. 

Minimal inhibitory concentrations (MIC, mg/ml) were determined by a broth microdilution method adapted from the tentative reference method (document MJ7-T) recommended hy the Committee on Antifungal Susceptibility Testing (36). Antibiotic medium 3 was used rather than RPMI 1640 medium. The MIC is defined as the lowest concentration of compound chat completely snhihited growth when tested with LY303366, cilofungin, or amphotericin B. 

Table 3 Minimal Inhibitory Concentrations of LY303366 and Amphotericin B that Inhibited 50% (MIC ) and 90% (MlC g) of 107 Clinical Isolates of C. albic

Overall, the shotgun-proteomics findings were consistent with the minimal inhibitory concentration (MIC) determination results because all 20 A. baumannii clinical isolates were foimd resistant to carbapenem, monobactam, cephalosporin, and to a combination treatment of penicillin and P-lactamase inhibitors. The results obtained demonstrate that by augmenting the custom DB with strain-specific unique peptide sequences, it is possible to obtain simultaneously both strain-level identification of. baumannii clinical isolates and their antibiotic resistance mechanism information within 5-6 h. Therefore, the approach developed by Chang et al (2013) could be used for a rapid, sensitive, and specific detection of P-lactam-resistant strains of. baumannii. 

The ability to detect ESBLs has clinical relevance because it will have an impact on antibiotic therapy. Producers of ESBLs are suspected when susceptibility testing indicates resistance to ceftazidime (but may be paradoxically susceptible to ceftriaxone and cefotaxime by the minimal inhibitory concentration [MIC] or disc diffusion) and susceptible to the cephamycins (11). More recently, a breakpoint of 2 ig/mL to cefpodoxime has been suggested as a standard. Another method of detection is the use of the E-test strip with a gradient of ceftazidime on one side and ceftazidime in combination with clavu-lanate on the other. The ESBLs are thought to be present when enhancement of inhibition is demonstrated. Table 2 highlights some of the more common resistance mechanisms for antimicrobial agents used commonly in the treatment of nosocomial pneumonia. 

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