Antibiotic resistance concentration

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). 

Numerous studies confirmed ubiquity of several antibiotics (i.e., ofloxacin, trimethoprim, roxythromycin, and sulfamethoxazole) in sewage influent, though at low ng level [8, 13, 14]. However, even at very low concentrations they can have significant ecotoxicological effects in the aquatic and terrestrial compartment [15, 16]. Indiscriminate or excessive use of antibiotics has been widely blamed for the appearance of so-called super-bugs that are antibiotic-resistant. It is of crucial importance to control their emissions into the environment through more cautious utilization and monitoring outbreaks of dmg-resistant infections. 

The clinical relevance of biocide resistance of antibiotic-resistant staphylococci is, however, unclear. It has been claimed that the resistance of these organisms to cationic-type biocides confers a selective advantage, i.e. survival, when such disinfectants are employed clinically. However, the in-use concentrations are several times higher than those to which the organisms are resistant. 

Phenotypic resistance assays directly measure the ability of HlV-1 to replicate in a cell culture in the presence of different antiretroviral drug concentrations. This process is similar to that used to determine antibiotic resistance and is, therefore, more familiar to most clinicians. The recombinant virus, composed of a virus s reverse transcripfase and protease genes, is inserted into a standard reference strain of virus. The recombinant virus is then tested in vitro for fhe amount of drug needed to inhibit virus replication by 50%, relative to the amount of drug needed to inhibit a reference strain of virus. Phenotypic resistance testing is limited by the fact that it is conducted in vitro and not in vivo. 

Although it is still difficult to establish clear cause effect relationships, it is widely accepted that chemical pollution contributes for antibiotic resistance dissemination [10, 33, 34]. There are evidences that antibiotic resistance increase is related with environmental pollution and anthropic pressures. In this respect, antibiotics seem to be a major, although not the unique, form of pollution, mainly because it is estimated that about 75% of the antibiotics consumed by humans and animals are eliminated as active substances [35, 36]. In the environment, antibiotics can suffer adsorption, photolysis or biodegradation, reaching very low concentrations [37]. Nevertheless, at sub-inhibitory levels, as they are found in the environment, antibiotics can promote several alterations on housekeeping functions of the cells. Apparently, some of these alterations are not associated with antibiotic resistance. Even though, they contribute for the perturbation of the microbial community, leading, eventually, to an overall resistance increase [1, 34, 38]. 

Klugman KP, Capper T. Concentration-dependent killing of antibiotic-resistant pneumococci by the methoxyquinolone moxifloxacin./. Antimicrob. Chemother.,... 

The result suggested that thioridazine was able to eliminate different antibiotic resistances singly or jointly in Escherichia coli strains and Shigella flexneri 6 BDC1 quite efficiently, but had a much weaker effect on Vibrio cholerae (Table 42). The pattern of elimination further indicated that penicillin, ampicillin, and amoxicillin were determined by a single plasmid in these bacteria. It seems that effective elimination depended on the curing concentrations, which were close to the MIC value of thioridazine for any... 

An association between antibiotic resistance and chlorhexidine and QAC resistance in Providencia stuartii and Proteus has been observed, but no evidence of a plasmid link obtained [25, 73, 287,288]. Chlorhexidine hypersensitivity has been noted in ciprofloxacin-resistant variants of Ps. aeruginosa [289] and vancomycin- and gentamicin-resistant strains of E. faecium retained sensitivity to the /usbiguanide [289, 290] and to other biocides [270-272], Anderson et al. [272] studied the inactivation kinetics of VRE and vancomycin-sensitive enterococci (VSE) exposed to environmental disinfectants at concentrations well below (extended dilutions) the recommended use-dilutions and found no differences in susceptibility of VRE and VSE. This type of approach is much more relevant than the widespread usage of MICs to measure responses to biocides. 

Clearly, efflux is a major mechanism of multidrug resistance and several authors [41, 42, 71] are now reconsidering reduced drug accumulation in terms of efflux rather than as cellular impermability. It is, however, pertinent to query whether efflux of biocides is of relevance in relation to the concentrations employed in practice and whether biocides are responsible for selecting antibiotic-resistant strains as has been suggested. Clearly, much future experimentation is needed to establish a direct link between antibiotic and biocide resistances. 

It was precisely this lack of activity towards non-polar substrates that provided an important motivation for the antibacterial and cell localization studies [94]. The cadmium texaphyrin 116 was investigated with regard to photo-activity against a strain of an antibiotic-resistant bacteria (S. aureus). The texaphyrin complex 116 proved to be an effective photosensitizer for the photoinactivation of S. aureus cells, being comparable but somewhat less active than hematoporphyrin at any given concentration tested. 

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