Tetracyclines tolerances

Tetracycline antibiotics have found wide application in animal industries for treatment, preventive maintenance and stimulation of growth of large horned livestock owing to what their residue amounts can be present at milk and meat of animals. Residue amounts of antibiotics are not toxic, however, capable to cause allergic reactions and to promote development of tolerance of the some people pathogenic bacterias. According with the legislative requirements of a number of the European countries it is forbidden to deliver to the population production polluted residual contents of tetracyclines. 

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. 

Trimethoprim-sulfamethoxazole (or trimethoprim alone) is a second-line oral agent that may be used for patients who do not tolerate tetracyclines and erythromycin or in cases of resistance to these antibiotics. The adult dose is usually 800 mg sulfamethoxazole and 160 mg trimethoprim twice daily. 

Methacycline is used for the same indications as other antibiotics of the tetracycline series. In some cases it is tolerated better than tetracyclines. Synonyms of this drug are ron-domycin, methamycin, adramycin, and others. 

Minocycline is nsed for the same indications as other antibiotics of the tetracycline series. In a few cases, it is tolerated worse than other tetracyclines, and in particular, it has an effect on the vestibnlar apparatus. In addition, as seen already from the synthesis scheme, it is mnch more expensive than other tetracyclines, which are synthesized in a purely microbiological manner. Synonyms of this drug are clinocin, minocyn, vectrin, and others. 

There are a number of factors that limit the effectiveness of regimens designed to eradicate H. pylori. The first, antibiotic resistance, is seen with metronidazole and clarithromycin but has not been reported with bismuth, amoxicillin, or tetracycline. Second, mild adverse effects (eg, diarrhea, metallic taste, black stools) do occur in approximately 30% to 50% of patients. Therefore, shorter treatment periods in this group of patients may be better tolerated. 

Treatment of uncomplicated urethral, endocervical, or rectal Chlamydia trachomaticinfections- As an alternative regimen to doxycycline or tetracycline (or if erythromycin is not tolerated), sulfisoxazole 500 mg 4 times/day for 10 days or equivalent sulfonamide course. 

The tetracycline antibiotic minocycline (Minocin) is modestly effective in the treatment of rheumatoid arthritis and is generally well tolerated. Radiographic evidence of its efficacy as a DMARD is lacking, although clinical symptoms do abate. It can be useful in the treatment of early, mild disease. A more detailed description of the pharmacology and chnical uses of minocycline is found in Chapter 47. 

There is little difference in clinical response among the various tetracyclines The selection of an agent, therefore, is based on tolerance, ease of administration, and cost. The restriction of their use in pregnancy and in patients under the age of 8 years apphes to all preparations. 

Malarone is generally well tolerated. Adverse effects include abdominal pain, nausea, vomiting, diarrhea, headache, and rash, and these are more common with the higher dosage required for treatment. Reversible elevations in liver enzymes have been reported. The safety of atovaquone in pregnancy is unknown. Plasma concentrations of atovaquone are decreased about 50% by co-administration of tetracycline or rifampin. 

Tetracyclines are recommended as first-line treatment. When tetracyclines are not tolerated or contraindicated, erythromycin is an alternative. However erythromycin has problems with resistance and gastrointestinal adverse effects. If compliance is a problem, either doxycycline or lymecycline may be prescribed (can be taken once daily with food). Minocycline is second-line treatment (e.g. if oral antibiotic has failed). 

Doxycycline is commonly used for moderate to severe acne vulgaris. It is more effective and produces less resistance than tetracycline. The initial dose is 100 or 200 mg daily, followed by 50 mg daily as a maintenance dose after improvement is seen. Doxycycline maybe given with food, but it is more effective when taken 30 minutes before meals. / Minocycline is also commonly used for moderate to severe acne vulgaris. It is more effective than tetracycline. It is dosed similar to doxycycline (100 mg/day or 50 mg twice daily) and on an indefinite basis in selected patients. Minocycline has the most reported adverse effects of the tetracyclines, some of which may be serious. Trimethoprim-sulfamethoxazole (or trimethoprim alone) is a second-line oral agent that may be used for patients who do not tolerate tetracyclines and erythromycin or in cases of resistance to these antibiotics. The adult dose is usually 800 mg sulfamethoxazole and 160 mg trimethoprim twice daily. Clindamycin use is limited by diarrhea and the risk of pseudomembranous colitis. 

More recently possible roles in supporting pH homeostasis and alkali tolerance have been suggested for TetL, which is a tetracycline efflux protein from Bacillus subtilis, and the multidrug transporter MdfA (71). 

In a comparison between oral artesunate (700 mg over 5 days) plus tetracycline (250 mg at 6-hour intervals) and quinine (600 mg quinine sulfate at 8-hour intervals) for 7 days, artesunate was more effective and better tolerated in uncomplicated malaria (see Table 2) (18). Convulsions occurred in one case. 

In a study of the effect of berberine in acute watery diarrhea, oral doses of 400 mg were well tolerated, except for complaints about its bitter taste and a few instances of transient nausea and abdominal discomfort. However, patients with cholera given tetracycline plus berberine were more ill, suffered longer from diarrhea, and required larger volumes of intravenous fluid than those given tetracycline alone (5). 

Cardiovascular reactions to tetracyclines have often been associated with other symptoms of hypersensitivity, such as urticaria, angioedema, bronchial obstruction, and arterial hypotension (37,56). Such reactions occurred in patients who had tolerated tetracyclines previously and were therefore considered as anaphylactic. 

Eor pregnant women with chlamydial urogenital infections, treatment can reduce the risk of pregnancy complications and transmission to the newborn significantly. Because the use of tetracyclines and fluoroquinolones is contraindicated during pregnancy, erythromycin base and amoxicillin are the recommended drug treatments (see Table 115-8). Some clinicians prefer amoxicillin to erythromycin because of better patient tolerability and, as a resulf improved patient compliance. Patients intolerant of... 

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