Immunologic antibiotics

Bacteria produce chromosomady and R-plasmid (resistance factor) mediated P-lactamases. The plasmid-mediated enzymes can cross interspecific and intergeneric boundaries. This transfer of resistance via plasmid transfer between strains and even species has enhanced the problems of P-lactam antibiotic resistance. Many species previously controded by P-lactam antibiotics are now resistant. The chromosomal P-lactamases are species specific, but can be broadly classified by substrate profile, sensitivity to inhibitors, analytical isoelectric focusing, immunological studies, and molecular weight deterrnination. Individual enzymes may inactivate primarily penicillins, cephalosporins, or both, and the substrate specificity predeterrnines the antibiotic resistance of the producing strain. Some P-lactamases are produced only in the presence of the P-lactam antibiotic (inducible) and others are produced continuously (constitutive). 

There are also drugs which by themselves can cause kidney failure. The mechanisms behind drugs negative effects on the kidneys are multiple. Among the most important is diminished blood flow to the kidneys (prerenal failure). Others are immunological damages to the nephrons caused by deposition of autoimmune complexes or direct nephrotoxicity caused by for example, antibiotics. The kidney function can also be damaged by post-renal obstructions, for example, kidney stones, urethral strictures or prostate hyperplasia (Ashley 2004). 

The classical microbial assay approaches to measuring antibiotic residues, diffusion, turbidimetric and acid production were described and the advantages and limitations reviewed. Other systems so discussed and reviewed were the affinity or receptor methods and the immunological approach using ELISA or EMIT assay techniques. The classical systems, in general, could measure antibiotic residues at the fractional ppm to the ppb levels. The potentials of the receptor and immunological assay system were discussed. 

Microbiologically based assay systems invariably measure the active antibiotic(s) or forms of the antibiotic that can be inhibitory to microorganisms. Immunological assays can measure both the active antibiotic as well as microbiologically inactive species. 

Immunological assays measure those moieties that can cause an antigenic response. For the most part, immunological assays should not be interfered with by antibiotics from the other antibiotic families, the specificity of the antibodies being vaguely similar to the specificity of enzyme systems. 

Applications of the immunological systems are limited by the ability to develop suitable antibodies. Most antibiotics are relatively small molecules having molecular weights under 500. 

Medical devices may be assisted in their function by pharmacological, immunological or metabolic means, but as soon as these means are not any more ancillary with respect to the principal purpose of a product, the product becomes a medicinal product. The claims made for a product, in accordance with its method of action may, in this context, represent an important factor for its classification as MD or medicinal product. Examples of MDs incorporating a medicinal substance with ancillary action include catheters coated with heparin or an antibiotic, bone cements containing antibiotic and blood bags containing anticoagulant. ... 

In AD increased S. aureus colonization plays a fundamental role therefore, antistaphylococcal therapy is part of a successful management of the disease. Epidermal lipid deficiencies and barrier dysfunction contribute to enhanced S. aureus attachment to the skin and mediate immunological and inflammatory effects including the release of superantigens, additional exotoxins, and exoenzymes, and perhaps bacterial DNA-triggered mechanisms. Therapeutic possibilities include the use of topical antiseptics in cases of microbial-laden atopic eczema, corticosteroids, and specific antibiotic-antiseptic combinations in cases of localized superinfected atopic eczema and systemic antibiotics in cases of generalized superinfected atopic eczema.48... 

Because a library can contain thousands of different clones, it can be difficult to isolate a clone with DNA of specific interest. This is because the majority of cloned DNAs do not contain a readily selectable genetic marker, such as antibiotic resistance, or lead (as discussed earlier) to the production of a foreign protein. Methods to achieve this have been developed and utilize hybridization, immunochemical, and structural techniques. A specific DNA sequence of only several kilobases can be isolated from a genome containing in excess of 106 kilobases. Hybridization requires a radioactive DNA or RNA molecule (a probe) that is complementary (or partially so) to the sequence of the cloned DNA. Immunologic techniques require that the polypeptides coded by the DNAs of interest are available and have specific antigenic properties that allow detection. Structural analysis can also be used when the other techniques are inapplicable. 

Some antibiotic-related considerations concerning extraction and isolation that should be addressed include (a) the presence of impurities and side products, along with their quantitation and the results of tests assessing their immunologic and toxicologic properties, (b) the development of specific analytical techniques capable of differentiating the product from related antibiotics, and (c) identification of minor active components as well as their levels and respective antimicrobial activities. 

Upon systemic distribution, many drugs evoke skin reactions that are caused on an immunological basis. Moreover, cutaneous injury can also arise from nonimmunological mechanisms. Cutaneous side effects vary in severity from harmless to lethal. Cutaneous reactions are a common form of drug adverse reaction. Nearly half of them are attributed to antibiotics or sulfonamides, and one-third to nonsteroidal anti-inflammatory agents, with many other pharmaceuticals joining the list... 

TSPK is a chronic epithelial keratitis of unknown etiology, suggested to be due to chronic subclinical viral infection in the deep layers of the basal epithelium. Support for this theory includes the protracted coruse of this condition, its tendency to recur, the lack of effect by antibiotics on its clinical course, and lack of bacterial isolation from eyes affected by the condition. The clinical presentation of corneal mononuclear cell infiltrates, the rapid resolution of these infiltrates with topical steroids, and their rapid reappearance if topical steroids are stopped too quickly support the possibility that the primary presentation is a typical immunologic response. 

Many reactions to beta-lactam antibiotics are clearly not immune mediated. These include bleeding disorders, neurotoxicity, and most cases of diarrhea. In addition, many reactions, the pathogenesis of which is still being discussed, clearly depend on the daily and the cumulative dose of beta-lactam antibiotics and hence the duration of treatment. Although the rare, but well-understood, immune hemolysis after penicillin is seen mostly with high-dose and long-term treatment, dose dependency and time dependency point to direct toxicity rather than to immunological mechanisms. Indeed, direct toxic effects of beta-lactam antibiotics on eukaryotic cells and specific interactions with receptor proteins and enzymes have been shown (4) and may underlie particular reactions. 

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