Tetracyclines, Macrolides, and Lincosamides

The tetracyclines are a group of anti-infectives composed of natural and semisynthetic compounds. They are useful in select infections when die organism shows sensitivity (see Chap. 7) to the tetracyclines, such as in cholera, Rocky Mountain spotted fever, and typhus. 

The tetracyclines exert their effect by inhibiting bacterial protein syndiesis, which is a process necessary for reproduction of die microorganism. The ultimate effect of diis action is tiiat the bacteria are either destroyed or dieir multiplication rate is slowed. The tetracyclines are bacteriostatic (capable of slowing or retarding die multiplication of bacteria), whereas die macrolides and lincosamides may be bacteriostatic or bactericidal (capable of destroying bacteria). 

These antibiotics are effective in die treatment of infections caused by a wide range of gram-negative and gram-positive microorganisms. The tetracyclines are used in infections caused by Rickettsiae (Rocky Mountain spotted fever, typhus fever, and tick fevers). Tetracyclines are also used in situations in which penicillin is contraindicated, in the treatment of intestinal amebiasis, and in some skin and soft tissue infections. Oral 

SUMMARY DRUG TABLE TETRACYCLINES, MACROLIDES AND LINCOSAMIDES 

GENERIC NAME TRADENAME USES ADVERSE REACTIONS DOSAGE RANGES 

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An ongoing assessment is important during therapy widi die tetracyclines, macrolides, and lincosamides. The nurse should take vital signs every 4 hours or as ordered by die primary health care provider. The nurse must notify the primary health care provider if tiiere are changes in the vital signs, such as a significant drop in blood pressure, an increase in die pulse or respiratory rate, or a sudden increase in temperature. 

ORAL ADMINISTRATION. To control the infectious process or prevent a bacterial infection, the nurse must keep several important things in mind when administering the tetracyclines, macrolides, and lincosamides. 

This chaj)ter discusses three groups of broad-spectrum antibiotics the tetracyclines, tlie macrolid, and the lincosamides. Example of the tetracycline include doxycycline (Vibramycin), minocycline (Minocin), and tetracycline (Sumycin). Examples of the macrohde include azithromycin (Zitliromax), clarithromycin (Biaxin), and erytliromycin (E-Mycin). The lincosamides include clindamycin (Cleocin) and lin-comycin (Lincocin). The Summary Drug Table Tetracyclines, Macrolide, and Lincosamide describe the lyi es of broad-spectrum antibiotics discussed in tliis chapter. 

Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking a tetracycline, macrolide, or lincosamide. 

Figure 1.6 Number of antibiotic prescriptions per 1000 inhabitants per antibiotic anatomical therapeutic chemical (ATC) classification in 13 European countries in 1997. In parentheses are the ATCs used by the WHO. Tet = tetracyclines, Pen = penicillin, Ex-Pen = extended-spectrum penicillins, B-Lac = (3-lactamase-sensitive penicillins. Cep = cephalosporins, TMP = trimethoprim (alone or in combination), Mac + Lin = macrolides and lincosamides, Mac = macrolides, Lin = lincosamides. Ami = aminoglycosides, and Qui = quinolone. The 13 countries are SP = Spain, GR = Greece, BG = Belgium, PR = Prance, PL = Portugal, IT = Italy, PI = Pinland, UK = United Kingdom, DE = Denmark, AU = Austria, GE = Germany, SW = Switzerland, and NL = Netherlands. (Based on data from Molstad et al., 2002.)...

Inhibition of protein synthesis through an action on certain subunits of microbial ribosomes (aminoglycosides, tetracyclines, chlorampenicol and its derivatives, macrolides and lincosamides). Each class of antimicrobial agent attaches to a different receptor site apart from macrolides and lincosamides, which bind to the same site on the 50S subunit of the microbial ribosome. 

Examples of antibiotics that attack bacteria by inhibiting protein synthesis at the ribosomal level include the following tetracycline antibiotics (e.g. chlortetracycline) aminoglycoside antibiotics (e.g. neomycin, streptomycin) macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin) also chloramphenicol, fusidic acid and lincosamides (e.g. clindamycin). 

In 2008, Carretero et al. described a multi-class method for the analysis of 31 antibacterials (including f)-lactams, macrolides, lincosamides, quinolones, sulfonamides, tetracyclines, nitroimidazoles, and trimethoprim) in meat samples by PLE-LC-MS/MS. Meat samples were homogenized and blended with EDTA-washed sand, then extracted with water by applying 1500 psi (Ib/in. ), at 70°C. One extraction cycle was 10 min. A drawback of the method is the large volumes of extracts (40 ml) obtained, which required evaporation to concentrate the extract volume prior to final analysis. This evaporation step considerably increases the time required for sample preparation. The proposed method has been applied to the analysis of 152 samples of cattle and pig tissues, with the presence of quinolones, tetracyclines, and sulfonamides detected in 15% of the samples, although at concentrations below the MRLs. 

Dairy products P-Lactams (12) Sulfonamides (4) Tetracyclines (3) Aminoglycosides (4) Macrolides (5) Lincosamides (I) Novobiocin Spectinomycin Chloramphenicol Raw, commingled, and pasteurized milk None 10... 

As a group, the protein biosynthesis inhibitors comprise the second largest class of antibiotics available for clinical use. Natural product classes of antibiotics that inhibit the protein biosynthesis are aminoglycosides, tetracyclines, chloramphenicol, macrolides, lincosamides, fusidic acid, streptogramins and mupirocin (Fig. 7). 

The chemical nature and related physicochemical properties largely govern the distribution and elimination, which refers to biotransformation (metabolism) and excretion, of antimicrobial agents. The majority of antimicrobial agents are weak organic electrolytes, either weak acids (penicillins, cephalosporins, sulphonamides) or weak bases (aminoglycosides, lincosamides, macrolides, diaminopyrimidines, metronidazole), while fluoroquinolones, tetracyclines and rifampin are amphoteric compounds, and chloramphenicol and its... 

Figure 4 Exemplar structures of various antibiotic classes that bind to either the 505 or the 305 subunit. Macrolides azithromycin (1), oxazolidinones linezolid (2), aminoglycosides Kanamycin A (3), Pleuromutilin (4), phenylpropanoids chloramphenicol (5), lincosamides clindamycin (6), Sparsomycin (7), Anisomycin (8), and tetracycline (9). See Scheme 9 for thiosptrepton (38). Not pictured streptogramins such as quinupristin/dalfopristin.

Notation-. A = aminoglycosides AMP = amphenicols fj-L = P-lactams d-SPE, dispersive SPE FQ = fluoroquinolones IP = ionophores L = lincosamides M = macrolides NMZ = nitroimidazoles P = penicillins PLE = pressurized liquid extraction Q = quinolones S = sulfonamides T = tetracyclines TMP = trimethoprim. This table is adapted from QuEChERS = quick, easy, cheap, effective, rugged, and safe ... 

Penicilhn, the first natural antibiotic, produced by genus Penicillium, discovered in 1928 by Fleming, and sulfonamides, the first chemotherapeutic agents, discovered in the 1930s, start a long list of presently known antibiotics. Beside (3-lactams (penicillins and cephalosporins) and sulfonamides, the list includes aminoglycosides, macrolides, tetracyclines, quinolones, peptides, polyether ionophores, rifamycins, lincosamides, coumarins, nitroheterocycles, amphenicols, and others. 

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