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The history of the tetracyclines involves the collective contributions of thousands of dedicated researchers, scientists, clinicians, and business executives over the course of more than 60 years. Discovered as natural products from actinomycetes soil bacteria, the tetracyclines were first reported in the scientific literature in 1948. They were noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in the late 1940s to the early 1950s. The second-generation semisynthetic analogs and more recent third-generation compounds show the continued evolution of the tetracycline scaffold toward derivatives with increased potency as well as efficacy against tetracycline-resistant bacteria, with improved pharmacokinetic and chemical properties. Their biologic activity against a wide spectrum of microbial pathogens and their uses in mammalian models of inflammation, neurodegeneration, and other biological systems indicate that the tetracyclines will continue to be successful therapeutics in infectious diseases and as potential therapeutics against inflammation-based mammalian cell diseases. [ABSTRACT FROM AUTHOR]

Background. Much has been written recently about the potential hazards versus benefits of antibacterial (biocide)—containing soaps. The purpose of this systematic literature review was to assess the studies that have examined the efficacy of products containing triclosan, compared with that of plain soap, in the community setting, as well as to evaluate findings that address potential hazards of this use—namely, the emergence of antibiotic-resistant bacteria. Methods. The PubMed database was searched for English-language articles, using relevant keyword combinations for articles published between 1980 and 2006. Twenty-seven studies were eventually identified as being relevant to the review. Results. Soaps containing triclosan within the range of concentrations commonly used in the community setting (0.1%–0.45% wt/vol) were no more effective than plain soap at preventing infectious illness symptoms and reducing bacterial levels on the hands. Several laboratory studies demonstrated evidence of triclosan-adapted cross-resistance to antibiotics among different species of bacteria. Conclusions. The lack of an additional health benefit associated with the use of triclosan-containing consumer soaps over regular soap, coupled with laboratory data demonstrating a potential risk of selecting for drug resistance, warrants further evaluation by governmental regulators regarding antibacterial product claims and advertising. Further studies of this issue are encouraged. [ABSTRACT FROM AUTHOR]

We examined whether household use of antibacterial cleaning and hygiene products is an emerging risk factor for carriage of antimicrobial drug-resistant bacteria on hands of household members. Households (N = 224) were randomized to use of antibacterial or nonantibacterial cleaning and hygiene products for 1 year. Logistic regression was used to assess the influence of antibacterial product use in homes. Antibacterial product use did not lead to a significant increase in antimicrobial drug resistance after 1 year (odds ratio 1.33, 95% confidence interval 0.74-2.41), nor did it have an effect on bacterial susceptibility to triclosan. However, more extensive and longer term use of triclosan might provide a suitable environment for emergence of resistant species. Further research on this issue is needed. [ABSTRACT FROM AUTHOR]

The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance-the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Within Nepal, geographic, social, and economic barriers greatly limit access to allopathic health care. The country therefore offered the opportunity to evaluate the effect of antibiotic accessibility (as measured by allopathic medicine consumption) on antibiotic resistance in the normal intestinal flora. The aerobic gram-negative fecal flora of 33–34 healthy adults from each of 3 villages with different access to health care facilities in Kathmandu were examined for antibiotic susceptibility. The frequency of antibiotic resistance decreased significantly with increasing distance from Kathmandu and decreasing population density but did not reflect contact with health care providers or individual medicine consumption. The findings suggest that an individual's overall exposure to antibiotics and antibiotic-resistant bacteria (resulting from close proximity to other community members and to sources of accessible allopathic health care, such as in the vicinity of Kathmandu), has an equal or greater impact on an individual's carriage of antibiotic-resistant bacteria than does direct consumption of antibiotics. [ABSTRACT FROM AUTHOR]

Bacterial resistance presents therapeutic dilemmas to clinicians worldwide. The warnings were there long ago, but too few people heeded them. Thus an emerging problem has grown to a crisis. Resistance is an ecological phenomenon stemming from the response of bacteria to the widespread use of antibiotics and their presence in the environment. While determining the consequences of inaction on the present and future public health, we must work to remedy the lack of action in the past. By improving antibiotic use and decreasing resistance gene frequency at the local levels, we can move towards reversing the resistance problem globally. [ABSTRACT FROM AUTHOR]

MarR is a regulator of multiple antibiotic resistance in Escherichia coli. It is the prototypical member of the MarR family of regulatory proteins found in bacteria and archaea that play important roles in the development of antibiotic resistance, a global health problem. Here we describe the crystal structure of the MarR protein, determined at a resolution of 2.3 Å. This is the first reported crystal structure of a member of this newly-described protein family. The structure shows MarR as a dimer with each subunit containing a winged-helix DNA binding motif. [ABSTRACT FROM AUTHOR]

The recent entry of products containing antibacterial agents into healthy households has escalated from a few dozen products in the mid-1990s to more than 700 today. Antibacterial products were developed and have been successfully used to prevent transmission of disease-causing microorganisms among patients, particularly in hospitals. They are now being added to products used in healthy households, even though an added health benefit has not been demonstrated. Scientists are concerned that the antibacterial agents will select bacteria resistant to them and cross-resistant to antibiotics. Moreover, if they alter a person's microflora, they may negatively affect the normal maturation of the T helper cell response of the immune system to commensal flora antigens; this change could lead to a greater chance of allergies in children. As with antibiotics, prudent use of these products is urged. Their designated purpose is to protect vulnerable patients. [ABSTRACT FROM AUTHOR]

Antibiotic resistance was once confined primarily to hospitals but is becoming increasingly prevalent in family practice settings, making daily therapeutic decisions more challenging. Recent reports of pediatric deaths and illnesses in communities in the United States have raised concerns about the implications and future of antibiotic resistance. Because 20 percent to 50 percent of antibiotic prescriptions in community settings are believed to be unnecessary, primary care physicians must adjust their prescribing behaviors to ensure that the crisis does not worsen. Clinicians should not accommodate patient demands for unnecessary antibiotics and should take steps to educate patients about the prudent use of these drugs. Prescriptions for targeted-spectrum antibiotics, when appropriate, can help preserve the normal susceptible flora. Antimicrobials intended for the treatment of bacterial infections should not be used to manage viral illnesses. Local resistance trends may be used to guide prescribing decisions. [ABSTRACT FROM AUTHOR]

Discusses the identification of multiple antibiotic resistance (marRAB) operon regulated genes in Escherichia coli. Regulated mapping by the mar operon; Sequencing and gene identification of cloned junctional fragments; Antibiotic susceptibility phenotypes; Expression of mar-regulated gene fusions.

Looks at antimicrobial resistance, focussing on the behavior of bacterial agents. Introduction of resistant bacteria from hospital; Results of studies of emerging resistant bacteria; Results of studies concerning resistance in bacteria.

TetA specified by Tn10 is a class B member of group of related bacterial transport proteins of 12 transmembrane alpha helices that mediate resistance to the antibiotic tetracycline. A tetracycline-divalent metal cation complex is expelled from the cell in exchange for an entering proton. The site(s) where tetracycline binds to this export pump is now known. We found that, when cheated to tetracycline, Fe[sup 2+] cleaved the backbone of TetA predominantly at a single position, glutamine 225 in transmembrane helix 7. The related class D TetA protein from plasmid RA1 was cut at exactly the same position. There was no cleavage with glycylcycline, an analog of tetracycline that does not bind to TetA. The Fe[sup 2 +] -tetracycline complex was not detectably transported by TetA. However, cleavage products of the same size as with Fe[sup 2+] occurred with Co[sup 2+], known to be cotransported with tetracycline. The known substrate Mg[sup 2+] -tetracycline interfered with cleavage by Fe[sup 2+]. These findings suggest that cleavage results from binding at a substrate-specific site. Fe[sup 2+] is known to be able to cleave amide bonds in proteins at distances up to approximately 12 Å. We conclude that the α carbon of glutamine 225 is probably within 12 Å of the position of the Fe[sup 2+] ion in the Fe[sup 2+] -tetracycline complex bound to the protein. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss the society's failure to recognize the potential benefits of antibiotics development. They state that antibiotic discovery and development has almost stop due to the continued underestimation of the implications of antibiotic resistance of bacteria. They also add that a halt in antibiotic development is putting an end to an important infection-control measure.