Tetracyclines bacterial resistance

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 tetracyclines are no longer used clinically to the same extent as they were in the past because of the increase in bacterial resistance. 

Still among the most frequently prescribed drugs, the antibiotic tetracyclines have decreased in popularity recently due to development of bacterial resistance in the clinic. The search for improved agents goes on. 

Erythromycin has efficacy similar to tetracycline, but it induces higher rates of bacterial resistance. Resistance may be reduced by combination therapy with benzoyl peroxide. Erythromycin can be used for patients who require systemic antibiotics but cannot tolerate tetracyclines, or those who acquire bacterial resistance to tetracyclines. The usual dose is 1 g/day with meals to minimize GI intolerance. 

Much of the debate concerning the use of antibiotics in livestock feeds has centered on bacterial resistance. One of the first observations made early in the 1950s, was that the bacterial count in animal feces increased after a temporary decrease when antibiotics, such as tetracyclines, were fed (12). This was in contrast to the effect of sulfonamides, which reduce the count. Obviously, resistance had occurred because the intestinal bacteria were thriving in the presence of antibiotics. Simultaneously, the growth of the animals was increased. Therefore the resistance in itself was not harmful. 

Speer BS, Shoemaker MB, Salyers AA Bacterial resistance to tetracycline Mechanism, transfer, and clinical significance. Clin Microbiol Rev 1992 5 387. [PMID 1423217]... 

Because of potential toxicity, bacterial resistance, and the availability of other effective drugs (eg, cephalosporins), chloramphenicol is all but obsolete as a systemic drug. It may be considered for treatment of serious rickettsial infections, such as typhus or Rocky Mountain spotted fever, in children for whom tetracyclines are contraindicated, ie, those under 8 years of age. It is an alternative to a b-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

For a review on the mechanism of bacterial resistance to tetracycline antibiotics see D. E. Taylor and A. Chau, Antimicrob. Agents Chemother., 1996, 40, 1. 

Although tetracyclines have been widely nsed antibiotics, their clinical usefulness has declined because of increased bacterial resistance. The resistance is due to a decrease in the bacterial drug concentration caused by an active drug efflux mechanism developed by the bacterial cells. 

Systemic or topical antimicrobial therapy (tetracycline, minocycline, erythromycin, at low dose) is used over months (response begins after 2 months). Bacterial resistance is not a problem benefit is due to suppression of bacterial lipolysis of sebum, which generates inflammatory fatty acids. Raised intracranial pressure with loss of vision has occurred with tetracycline used thus. 

Prolonged treatment with the classical antibacterial tetracyclines results in bacterial resistance and/or... 

Acquired bacterial resistance to the tetracyclines has become widespread in animal populations and has severely reduced the usefulness of these drugs. Resistance to the tetracyclines results from plasmid-mediated mechanisms that prevent the active transport of the drug into the bacterial cell or increase the efflux of drug from the bacterial cell. 

Chopra, I. Roberts, M. (2001) Tetracycline antibiotics mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev, 65,232-260. 

Demeclocycline, tetracycline, oxytetracycline, minocycline, and doxycycline are available in the United States for systemic use. Chlortetracycline and oxytetracycline are used in ophthalmic preparations. Methacycline is not available. Other derivatives are available in other countries. The more lipophilic drugs, minocycline and doxycycline, usually are the most active by weight, followed by tetracycline. Resistance of a bacterial strain to any one member of the class may result in cross-resistance to other tetracyclines. Bacterial strains with tetracycline minimum inhibitory concentrations (MICs) of < 4 pg/mL are considered susceptible... 

Decreased intracellular accumulation is a mechanism of bacterial resistance Elimination is predominantly via biliary excretion The patient should discontinue the tetracycline if she becomes pregnant Vaginal candidiasis may occur during treatment... 

Bacterial resistance to tetracyclines was first reported in 1953, very soon after their discovery (18). Tetracycline resistance is often tramposon or plasmid borne, which results in horizontal transmission of resistance factors between and amor different species. Many nonpachogenic bacteria within the environment carry resistance to tetracyclines, and they are now recognized as an important reservoir in transmission. Resistance factors may reside in this reservoir and then be transferred to pathogenic bacteria, rendering the tetracyclines useless in the control of infection-... 

---