Resistance to tetracyclines

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). 

Resistance to tetracyclines is often caused by the acquisition of genes (e.g. tetO and tetM) coding for so-called ribosome protection proteins. These proteins bind to the ribosome and protect them from tetracycline action. 

Although tetracycline, doxycycline, and minocycline are the most commonly prescribed oral antibiotics for acne, erythromycin and clindamycin are appropriate second-line agents for use when patients cannot tolerate or have developed resistance to tetracycline or its derivatives.3 See Table 62-3 for antibiotic dosing guidelines. 

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. 

Resistance to ampicillin for strains carrying pKMIOl and resistance to tetracycline for strains carrying pAQl ... 

Genes encoding efflux pumps confer resistance to tetracyclines Genes encoding proteins protecting the ribosome from the inhibiting effects of tetracycline... 

The most serious association of antibiotics with salmonellosis was the 1965 outbreak in England of phage type 29 Salmonella typhimurium, resistant to tetracyclines. Six human deaths were attributed to this epidemic. It was traced to "shotgun" treatment of young calves with antibiotics followed by wide dispersal of the calves ( ). Although this epidemic did not involve the use of livestock feeds containing antibiotics, the seriousness of the outbreak led to an inquiry in the UK and a report by the Swann Committee, 1969, into this use. The report of the committee called for a stop to the use of certain common antibiotics in animal feeds in the United Kingdom. 

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

Mechanisms of Resistance. Three distinct biochemical mechanisms of resistance to tetracyclines have been identified. The energy-dependent efflux of antibiotic mediated by resistance proteins located in the bacterial... 

Three mechanisms of resistance to tetracycline have been described (1) decreased intracellular accumulation due to either impaired influx or increased efflux by an active transport protein pump (2) ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome and (3) enzymatic inactivation of tetracyclines. The most important of these is production... 

Ruiz J, Ribera A, Jurado A, Marco F, Vila J (2005) Evidence for a reserpine-affected mechanism of resistance to tetracycline in Neisseria gonorrhoeae. APMIS 113 670-674. 

Correct choice = E. Most strains of streptococci are resistant to tetracycline. ... 

Correct choice = A. Widespread resistance to tetracycline limits the clinical uses of this drug. Deposition of tetracycline in calcifying tissues of the fetus and growing children can occur. The drug has the potential for causing hepatic toxicity in the mother. Dairy foods in the diet decrease absorption because of the formation of nonabsorbable chelates of tetracycline with calcium ions. 

Plasmid- and transposon-mediated resistance to trimethoprim involves a by-pass of the sensitive step by duplication of the chromosomally-encoded dihydrofolate reductase (DHFR) target enzyme [203]. Several trimethoprim-resistant bacterial DHFRs have been identified, resistance ensuing because of altered enzyme target sites [204], Low-level resistance to tetracyclines arises in E. coli as a result of chromosomal mutations leading to loss of the outer membrane porin OmpF through which these drugs normally pass [6, 193],... 

Figure 4.2. Proposed mechanism for tetracycline (TET) uptake and efflux across the bacterial cytoplasmic membrane. Mg, divalent magnesium cation TH2 and TH, protonaled and deproton-ated tetracycline, respectively TH Mg, magnesium-tetracycline chelate complex. Tet proteins confer resistance to tetracycline by mediating expulsion ofTH Mg from the cell in exchange for a...

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. 

Figure 19.4 The R-plasmid features of plasmid Pbr322 the gene conferring resistance to ampicillin (ApR) is inserted into the Pstl site, and that conferring resistance to tetracycline into the BamHI site. Replication is controlled by the ColEl origin.

Topical tetracycline may be nsed as an adjnnctive therapy for chlamydial infections but not for initial treatment of acute bacterial conjunctivitis. Numerous organisms are resistant to tetracycline. 

Wright GD. TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics. 1. Biol. Chem. 2004 279(50) 77. 

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