Subinhibitory concentration

The selection of rifaximin-resistant strains was also investigated on five different isolates of H. pylori. None of the strains exhibited primary resistance to rifaximin, but, after exposure to subinhibitory concentrations of the antibiotic, all five strains became resistant. The mutation frequency was similar to that observed with macrolides and quinolones, but was less frequent than that observed with metronidazole [52, 53],... 

Three studies have addressed the possibility of inducing cross-resistance to Mycobacterium tuberculosis during the use of rifaximin. In an experimental guinea pig model of M. tuberculosis, rifaximin was administered in an effort to induce resistance among M. tuberculosis strains of human origin. Not only did no resistance develop, crossresistance to rifampin also did not occur [17, 18]. In another approach, M. tuberculosis strains were subjected to subinhibitory concentrations of rifaximin. No induction of resistance or cross-resistance to rifampin occurred... 

Breines, D., Burnham, J. Modulation of Escherichia coli type 1 fimbrial expression and adherence to uroepithelial cells following exposure of logarithmic phase cells to quinolones at subinhibitory concentrations. J Antimicrob Chemother 1994 34 205-21. 

Sawker et al. reported that IV-nonyl-DNJ (97) is a potent inhibitor of lysosomal /3-glucosidase, with an IC50 value of 1 pM, and the addition of subinhibitory concentration (10 pM) of this compound to a fibroblast culture medium leads to a 2-fold increase in the mutant (N370S) enzyme activity [135]. Very recently, examination of a series of DNJ analogues on the resid-... 

Resistance to EM is encountered intrinsically in such Gm- organisms as E. coli, where a single amino acid mutation of the L-4 protein of the 50S subunit is responsible. Induction of resistance to S. aureus has also been demonstrated in subinhibitory concentrations. Once induced the resistance is to all macrolides. Induction of resistance has not been demonstrated in 16-membered macrolides such as spiramycin. 

In contrast to many other, primarily bacteriostatic drugs, both colistin and polymyxin rarely induce resistance during repeated passage of normally sensitive strains in subinhibitory concentrations. 

Molinari, G., Guzman, C. A., Pesce, A., and Schito, G. C. (1993). Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics. J. Antimicrob. Chemother. 31, 681-688. 

Table 2 Susceptibility of P. aeruginosa to antimicrobial drugs after ten passages through subinhibitory concentrations ...

Since the coumarin compounds show phosphodiesterase inhibitory activity, the observed change in the morphology of Candida albicans could be partly due to this property. Each Candida yeast cell can normally have a budding scar or the daughter cell still attached to it [319]. The possible cause of multibudding phenomenon could be PD inhibition. A similar observation was done in treatment with caffeine, which at the subinhibitory concentrations caused an increase in unusual modes of proliferation with signs of multiple budding in Candida albicans [320]. 

After the MIC has been determined, it is necessary to decide whether the results suggest whether the organisms are susceptible to the tested antimicrobial in vivo. This decision requires an understanding of the PK of the dmg (see Chapter 2 for discussion) and other factors. For example, in vitro assessments of activity may underestimate the in vivo activity because of a post-antibiotic effect and post-antibiotic leukocyte enhancement. The post-antibiotic ejfect (PAE) refers to a persistent antibacterial effect at subinhibitory concentrations, whereas the term post-antibiotic leukocyte enhancement term (PALE) refers to the increased susceptibility to phagocytosis and intracellular killing demonstrated by bacteria following exposure to an antimicrobial agent. ... 

Barchietto, T., Saindrenan, P., Bompeix, G. Physiological responses of Phytophthora citrophthora to a subinhibitory concentration of phosphonate. Pestic. Biochem. Physiol. (1992) 42, 151-166. 

Carter, G., Young, L.S., Bermudez, L.E., 2004. A subinhibitory concentration of clarithromycin inhibits mycobacterium avium biofilm formation. Antimicrob. Agents Chemother. 48 (12), 4907—4910. Available from http //dx.doi.org/10.1128/... 

The coadministration of 22a-25b and a subinhibitory concentration of ciprofloxacin led to an observed synergistic effect with a number of silver compounds, with the most pronounced effects in 22c, 25a, and 25b. Compound 25a demonstrated the largest reduction in MIC value, with an eightfold decrease (64 to 8 pgrnl ), while 22c and 25b each exhibited a fourfold decrease in their MIC... 

Whereas these assays highlighted the use of [(NHC)AgX] complexes as therapeutics against drug-resistant organisms, further studies demonstrated their possible use in multi-drug dosages. The co-administration of the [(NHC) AgX] complexes with a subinhibitory concentration of ciprofloxacin led to... 

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