Antibiotics clindamycin

It is important to acknowledge that as we acquire additional experience with known drugs, new uses for existing agents are often identified. For example, it has recently been shown that the combination of the antibacterial antibiotic clindamycin (used clinically for years for its relatively... 

Clindamycin Solutions of clindamycin salts are incompatible with alkaline doses or other drugs that are unstable at low pH. Clindamycin phosphate is not compatible with some rubber packing materials. pH-dependent degradation was reported with clindamycin, and phosphate salt was found to be most stable. Therapy with clindamycin should be stopped if diarrhea or colitis are found. The patient should be treated with other antibiotics. Clindamycin potentiates the actions of neuromuscular-blocking agents, opioids, and the antagonistic action of parasympathomimetics. 

Fig. 11. Eight transient 500 MHz H-NMR spectra of an 11.9 pg (0.027 pmol) sample of the antibiotic clindamycin (7) prepared in 500 pL of CDC13 in a 5 mm NMR tube (top trace) 292 pL in a 4mm tube (middle trace) and 163 pL in a 3 mm tube (bottom trace). All data were acquired using a 500 MHz 5 mm gradient inverse triple resonance Varian Cold-probe . The s/n ratio was measured for each spectrum using a 200 Hz region of representative noise downfield of the anomeric proton resonating at 5.3 ppm. The s/n ratios were 14.4 1, 20.8 1, and 21.5 1 for the 5, 4, and 3mm tubes, respectively.

Drug Interactions - Absorption half-life of the antibiotic, clindamycin, was prolonged in human subjects when a kaolin-pectin antidiarrheal suspension was coadministered, although the extent of absorption remained the same. On the other hand, both the rate and the extent of absorption of digoxin were lower when it was coadministered with the same kaolin-pectin suspension. Physical absorption and alterations in gut transit time appeared to partly explain the findings. 

The low aqueous solubility of the antibiotic clindamycin hydrochloride is responsible for the pain experienced on intramuscular injection. Phosphorylation improves the aqueous solubility from 3 to >150mg/mL and avoids the pain resulting from injection of the parent clindamycin. The phosphorylated drug (Figure 41.13) possesses little or no intrinsic antibacterial activity, but, due to the enzymatic action of phosphatases, it is rapidly converted to the parent drug. The half-life for hydrolysis in vivo is approximately lOmin and only 1-2% of an intravenous dose is eliminated in the urine as unchanged prodrug. " ... 

For the degradation of the antibiotic clindamycin, which is held at pH 4.0 in an aqueous solution, kinetic measurements show that at 343 K the reaction is first-order with a rate constant equal to 2.49 x 10 s . Over the temperature range 320 K to 360 K, the activation energy was found to be 123.3 kJ mol k Calculate the rate constant at 295 K. Since the degradation reaction is first-order, it turns out that the time taken for 1% decomposition turns out to be close to 0.01/A r and this time is independent of the initial concentration of the antibiotic. Hence, is it possible to conclude that if the compound were to be stored at 295 K, it would remain safe for use at the end of an economically acceptable shelf-life ... 

Lincomycin (Lincocin) has been used in the past to treat serious streptococci, pneumococci, and staphylococci infections but has generally been replaced by safer and more effective antibiotics. Clindamycin (Cleocin) is a semisynthetic derivative of lincomycin and has a similar mechanism but is more effective. It is indicated for the treatment of bone and joint infections, pelvic (female) and intraabdominal infections, bacterial septicemia, pneumonia, and skin and soft tissue infections. In a normal dose, lincosamides prevent the growth of bacteria (bacteriostatic). In larger doses, it kills bacteria (bacteriocidal). 

Fig. 13.4 Workflow for a phage-amplification assay using stable-isotope labeled phages to simultaneously determine the presence of Staphylococcus aureus in a sample, as well as the susceptibility of microorganism to two antibiotics—clindamycin and cefoxitin. (Reprinted with permission from Rees et al. (2015), copyright 2015, American Chemical Society)...

The thioglycoside antibiotic clindamycin-2-phosphate 29 has three separate molecules in the crystal, differing mainly in the orientation of the phosphate group and the pyrrolidinyl moiety. Thiosugar glycoside 30 and bis(2,3,4,6-tetra-0-acetyl-P-D-glucopyranosyl)diselenide and disulfide. ... 

Lincomycin. The liacomycias and celesticetins are a small family of antibiotics that have carbohydrate-type stmctures. Clindamycin, a chemical modification of lincomycin, is clinically superior. Antibiotics ia this family inhibit gram-positive aerobic and anaerobic bacteria by interfering with proteia biosyathesis. 

Some antibiotics, such as the tetracyclines, tetracycline (7), doxycycline (78), and minocycline (17), chloramphenicol (79), and clindamycin (23) have modest antimalarial properties, but are slow-acting. 

In recent years, many parent dmgs have been converted to esters to generate so-called prodmgs ia order to overcome some undesirable property such as bitter taste, poor absorption, poor solubiUty, and irritation at site of iajection. For example, antibiotics such as chloramphenicol [56-75-7] and clindamycin [18323-44-9] have been derivatized as their palmitate esters ia order to minimise their bitter taste. 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

Clostridium dijficile, described in older texts as of little significance as a pathogen if present in the gut, may, after therapy with antibiotics such as clindamycin or ampicillin, remain uninhibited, grow and produce toxins which give rise to a serious condition known as pseudomembranous colitis. The organism will usually succumb to vancomycin. 

Employed as the hydrochloride and administered by dilute intravenous injection, vancomycin is indicated in potentially life-threatening infections that cannot be treated with other effective, less toxic, antibiotics. Oral vancomycin is the drug of choice in the treatment of antibiotic-induced pseudomembranous colitis associated with the administration of antibiotics such as clindamycin and lincomycin (section 9.3). 

Fig. 5.14 Miscellaneous antibiotics A, chloramphenicol B, fusidic acid C, lincomycin D, clindamycin E, mupirocin (pseudomonic acid A).

Clindamycin (93 R = H), an antibiotic obtained by chlorinating linco-mycin, is converted by a species of Streptomyces into inactive phosphorus-containing compounds. These have been shown to be nucleoside 5 -phosphates derived from adenosine, cytidine, guanosine, and uridine. 

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. 

Broad-spectrum antibiotic cefotaxime or ceftriaxone (clindamycin for cephalosporin allergy) vancomycin for staphylococcal and resistant pneumococcal organisms... 

Broad intravenous antibiotic coverage for the encapsulated organisms can include ceftriaxone or cefotaxime. For patients with true cephalosporin allergy, clindamycin may be used. If staphylococcal infection is suspected owing to previous history or the patient appears acutely ill, vancomycin should be initiated. Macrolide antibiotics, such as erythromycin and azithromycin, may be initiated if Mycoplasma pneumonia is suspected. While the patient is receiving broad-spectrum antibiotics, their regular use of penicillin for prophylaxis can be suspended. Fever should be controlled with acetaminophen or ibuprofen. Because of the risk of dehydration during infection with fever, increased fluid may be needed.6,27... 

If a patient aspirates his or her oral contents and pneumonia develops, then anaerobes and Streptococcus spp. are the primary pathogens. Antibiotics active against these organisms include penicillin G, ampicillin/sulbactam, clindamycin, and metronidazole. 

In uncomplicated cases, prompt oral antibiotic therapy with amoxicillin or a first-generation cephalosporin halts the progression of lymphangitis. Clindamycin may be used if the patient has a significant (1-lactam allergy. Intravenous antibiotics (penicillinase-stable penicillins, first-generation cephalosporins,... 

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