Tetracyclines table

The tetracyclines (Table 3.3) are a group of broad spectrum, orally active antibiotics produced by species of Streptomyces, and several natural and semi-synthetic members are used clinically. They contain a linear tetracyclic skeleton of polyketide origin in which the starter group is malonamyl-CoA (Figure 3.54), i.e. the coenzyme A ester of malonate semi-amide. Thus, in contrast to most acetate-derived compounds, malonate supplies all carbon atoms of the tetracycline skeleton, the starter group as well as the chain extenders. The main features of the pathway (Figure 3.54) were deduced from extensive studies of mutant strains of Streptomyces aureofaciens with genetic blocks... 

The tetracyclines (Table 3.3) are a group of broad spectrum, orally active antibiotics produced by cultures of Streptomyces species. Chlortetracycline isolated from Streptomyces aureofaciens was the first of the group to be discovered, closely followed by oxytetracycline from cultures of S. rimosus. Tetracycline was found as a minor antibiotic in S. aureofaciens, but may be produced in quantity by utilizing a mutant strain blocked in the chlorination step b (Figure 3.54). Similarly, the early C-6 methylation step (included in a) can also be blocked, and such mutants accumulate 6-demethyltetracyclines, e.g. demeclocycline (demethylchlorotetracycline). These reactions can also be inhibited in the normal strain of S. aureofaciens by supplying cultures with either aminopterin (which inhibits C-6 methylation) or mercaptothiazole (which inhibits C-7 chlorination). Oxytetracycline from S. rimosus lacks... 

Tetracyclines (Table 46-1) are inhibitors of bacterial protein synthesis. 

The tetracyclines (Table 1.15) are a large family of antibiotics, the first members of which were derived from the Streptomyces genus of Actinobacteria. Chlortetracycline was isolated from Streptomyces aureofaciens in 1944, and a few years later, oxytetracycline and demeclocycline were... 

The most important polyketides of this type are the tetracyclines (Table 35) and derivatives of glutarimide, e.g., cycloheximide, which both are formed in Strepto-mycetes. 

In the United States, the manufacturers of fermentation-derived tetracyclines (1), (2), and (3) are the Ledede Laboratories, a division of American Cyanamid Co., Charles Pfizer Inc., Bristol Laboratories, and RacheUe Laboratories. There are also several manufacturers abroad. Tetracycline is now sold genetically by many companies. Pfizer s doxycycline (6) and Ledede s minocycline (7), both semisynthetic tetracyclines, are the only members of the group that have increasing sales. Table 1 fists the commercial tetracyclines and the corresponding trade names. 

Table 1. Tetracyclines Used for the Therapy of Infectious Diseases...

Table 2. Classification and Distribution of Tetracycline Resistance Determinants in Microorganisms ...

SUMMARY DRUG TABLE TETRACYCLINES, MACROLIDES AND LINCOSAMIDES... 

The recent synthesis of (—)-tetracycline by Myers and co-workers incorporates a biocatalytic step in the first stage which oxidizes benzoic acid aerobically to an a,f)-dihydroxy derivative in the presence of a whole-cell mutant strain of Alcaligenes eutrophus. Figure 4.61 shows a reduced tree diagram for the synthesis and Table 4.28 summarizes the metrics parameters. 

Table 4.28 Summary of reaction metrics and synthesis tree parameters for tetracycline synthesis plan ranked according to overall kernel (maximum) RME. ...

In some cases, catechins can also act in synergistic mode when used in association with currently used antibiotic molecules (Table 2). EGCG exhibited synergy with /3-lactams. Sudano Roccaro et al. [73] found that this compound is able to reverse tetracycline resistance in Staphylococcus epidermidis and S. aureus isolates. This synergistic interaction has been explained by inhibition of tetracycline efflux pump activity in microbial cells resulting in an... 

Table 37.3 shows the complete table of eight indicator variables for 10 triply substituted tetracyclines [31 ] that have been tested for bacteriostatic activity (1/Z), which is defined here as the ratio of the number of colonies grown with a substituted and with the unsubstituted tetracycline. In this application we have three substitution positions, labelled U, V and W. The number of substituents at the three sites equals 2,3 and 3, respectively. Arbitrarily, we chose the compound with substituents H, NOj and NO2 at the sites U, V and W as the reference compound. This leads to a reduction of the number of indicator variables from eight to five, as shown in Table 37.4. The solution of the Free-Wilson model can be obtained directly by means of multiple regression ...

In the above expression the indicator variable I(X) takes the value 0 or 1, depending upon the absence or presence of the substituent X in a particular compound. The overall result of the regression is not significant at the 0.05 level of probability. This may be due to the unfavorable proportion of the number of compounds to the number of parameters in the regression equation (10 to 6). Only the indicator variable for substituent NHj at position W in the tetracycline molecule reaches significance (p = 0.02). This can be confirmed by looking at Table 37.4... 

Complete indicator table and bacteriostatic activities of 10 triply substituted tetracyclines. The three substitution positions are labeled U, V and W [31]. 

The application of various antibiotics such as rifampicin/tetracycline (63), cefatoxime/trimethoprim (64), or bacteriostatic compounds such as Micropur (Roth, Karlsruhe, Germany) (65) used for root pretreatment or added to collection media is another strategy to prevent biodegradation during root exudate collection. However, depending on dosage and plant species, also phytotoxic effects of antibiotics have been reported (Table 3). Antibiotics in the soil environment... 

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. 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

Table 2 Correlation of Dissolution Rates with Biological Measurements for Tolbutamide and Tetracycline Absorption in Humans... 

Thus, as the pH increases, the dissolution rate of a weak base decreases. Referring to Table 2, we can see that, for the weak acid tolbutamide, the dissolution rate increases as pH is increased, as predicted by Eq. (3). Additionally, for the weak base tetracycline, as predicted by Eq. (4), the dissolution rate decreases as pH is increased. Thus far, the more rapid dissolution of the salt forms of these drugs and the direction of change of the dissolution rate with pH have been accounted for with Eqs. (1) to (4). However, there are six possible dissolution rate... 

For identification of oxytetracycline in pharmaceutical preparations, USP 28 [1] describes Method II under identification of tetracycline <193> (see Table 1), BP 2003 [4] describes a TLC and color test. 

OTC can be well separated from TC, DC, and its impurities by means of capillary electrophoresis [25]. However, the use of CE in the analysis of OTC residues is restricted because of the low concentration sensitivity of this technique [28]. HPLC is by far the most widely used method for the analysis of OTC residues in food and fisheries products. Chromatographic analysis of tetracycline including OTC analysis in foods was reviewed by Oka et al. [65] and MacNeil [72]. HPLC methods for the analysis of OTC are summarized in Table 2. 

Antibiotics shorten the duration of diarrhea, decrease the volume of fluid lost, and shorten the duration of the carrier state (see Table 39-3). A single dose of oral doxycycline is the preferred agent. In children younger than 7 years of age, trimethoprim-sulfamethoxazole, erythromycin, and furazolidone can be used. In areas of high tetracycline resistance, fluoroquinolones are effective. 

Organisms may be considered susceptible if the Minimum Inhibitory Concentration (MIC) is not more than 4.0 yg/ml and intermediate if the MIC is 4.0-12.5 yg/ml (see Table 1). Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations and in a biologically active form. 

Because configurational information can be derived from optical rotatory dispersion and circular dichroism scans, considerable work has been conducted using these techniques to study the tetracyclines (32). The absolute configuration of CTC was determined using optical rotatory dispersion data (33) Spectral curves are presented in Figures 8 and 9. The circular dichroism spectrum is similar to that presented by Mitscher et al. (34), except that the values differ by a factor of about 1.5. In Table 3, data obtained by Mitscher and in FDA laboratories are compared. 

A number of papers have appeared reporting the HPLC separation of CTC from its isomers and/or other tetracyclines. There is not a consensus of opinion as to the most satisfactory approach thus, it appears that at this time one must still verify the optimal system for a particular instrument. Methods found in the literature for CTC are described in Table 6. EDTA is added to prevent the formation of complexes of the tetracyclines with metallic surfaces. 

Macrolide antibiotics (clarithromycin, dehydroerythromycin, etc.) and sulfonamides (sulfamethoxazole, sulfadimethoxine, sulfamethazine, and sulfathi-azole) are the most prevalent antibiotics found in the environment with levels around a few micrograms per liter, whereas fluoroquinolones, tetracyclines, and penicillins have been detected in fewer cases and usually at low concentrations (nanograms per liter) [3,20,23,72]. This result is not surprising, since penicillins are easily hydrolyzed and tetracyclines readily precipitate with cations such as calcium and are accumulated in sewage sludge or sediments. Several reviews have reported the environmental occurrence of different antibiotics in aquatic and soil compartments. Some of these data are detailed in Table 1. 

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