Tetracycline-resistant bacteria

Thiatetracyclines contain a sulphur atom at position 6 in the molecule. One derivative, thiacycline, is more active than minocycline against tetracycline-resistant bacteria. Despite toxicity problems affecting its possible clinical use, thiacycline could be the starting point in the development of a new range of important tetracycline-type antibiotics. 

Since patients can rarely be relied upon to take (or be given) medication after fasting, and since itis common experience that doses are omitted more or less frequently the properties of doxycycline make it appear a promising successor to the first generation tetracyclines. This is even more likely since the antibacterial spectrum and activity is at least equal to that of tetracycline, and in the case of certain tetracycline-resistant bacteria doxycycline has (of all derivatives tested) shown the highest activity [35, 41]. 

Halling-Sprensen B., G. Sengelpv, and J. Tjpmelund (2002). Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria. Archives of Environmental Contamination and Toxicology 42 263-271. 

A series of tetracycline derivatives has recently been isolated from species of Dactylosporangium. These compounds, the dactylocyclines (Figure 3.55), are glycosides and have the opposite configuration at C-6 to the natural tetracyclines. Importantly, these compounds are active towards tetracycline-resistant bacteria. 

I 7. A culture of bacteria not resistant to tetracycline develops an infection from a virus that is derived from the lysis of tetracycline-resistant bacteria. Most ol the bacterial progeny of the original culture is found to have become resistant to tetracycline. What phenomenon has occurred ... 

Nelson ML, Park PH, Levy SB. Molecular requirements for the inhibition of the tetracycline antiporc protein and the effect of potent inhibitors on the growth of tetracycline-resistant bacteria. J Med Chem 1994 37 1355-1361. 

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

The practice of incorporating low levels of antibiotics in livestock feeds to promote growth has been particularly controversial. It is feared that this practice will result in development of resistant bacteria in animals, which will in turn be passed on to humans, thus diminishing the effectiveness of antibiotics in treatment of human disease. A petition from the Natural Resources Defense Council to ban such uses of penicillin and tetracyclines recently was denied by the Secretary of Health and Human Services. The controversy therefore is likely to continue. Opinion on the subject is quite polarized, and several points of view are presented in this book. 

The advisability of using certain antibiotics, particularly penicillin and tetracycline, in animal feeds has been questioned because of their use in human medicine. Any use of an antibiotic that is prescribed for humans presents some risks to human health, whether the use is for humans, animals or for other purposes but. the uses also have benefits. Otherwise, they would not persist. Antibiotics are used in animal feeds to increase animal weight, increase efficiency of feed utilization, increase reproductive efficiency and decrease morbidity and mortality. These benefits to animals and animal producers are reflected in decreases in food costs to humans. There are also benefits to human health from use of antibiotics in food animals. By reducing the incidence of animal health problems, use of antibiotics in food animals reduce the transference of animal infections to humans. The contention that the effectiveness of penicillin and tetracycline for use in human medicine is rapidly diminishing as a result of the proliferation of resistant bacteria caused by subtherapeutic use of antibiotics in animal production is not supported by experimental data. Rather, the evidence suggests that a fairly stable level of resistance of the intestinal bacteria in humans has long since been established to penicillin and tetracycline as it has been in animals. 

NRDC used Salmonella Infections as the model to make their estimates of mortality and morbidity rates. They pointed out that these are conservative estimates (underestimates) because resistance also occurs In other pathogenic bacteria that cause human diseases. Some of the resistance In these other pathogens results from the pool of resistant bacteria In animals, which Is ultimately due In large part to subtherapeutlc use of penicillin and the tetracyclines In animal feeds. 

Tigecycline IV unaffected by common tetracycline resistance mechanisms very broad spectrum of activity against grampositive, gram-negative, and anaerobic bacteria nausea and vomiting are the primary toxicities... 

Tetracyclines have been extensively used in animal feeds to enhance growth. This practice has contributed to the spread of tetracycline resistance among enteric bacteria and of plasmids that encode tetracycline resistance genes. 

Neal RJ, Chater KF (1987) Nucleotide sequence analysis reveals similarities between proteins determining methylenomydn A resistance in Streptomyces and tetracycline resistance in eu-bacteria. Gene 58 229-241. 

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