Lincosamides activity

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

Lincosamides (lincomycin and clindamycin) are representatives of a very small group of drugs synthesized up of an amino acid bound to an amino sugar. Lincosamides bind with the 50 S ribosomal subunit of bacteria and inhibit protein synthesis. They also inhibit pep-tidyltransferase action. Lincosamides are bacteriostatic antibiotics however, when they reach a certain level in the plasma, they also exhibit bactericidal action against some bacteria. Lincosamides are highly active against anaerobic infections such as Peptococcus, Peptostreptococcus, Actinomyces, Propionibacterium, and Clostridium fringens, a few types of Peptococcus and Clostridium. 

Lincomycin Lincomycin, 6,8-dideoxy-6-fran -(l-methyl-4-propyl-L-2-pyrrolidincar-boxamido)-l-methylthio-D-eryf/2ro-a-D-gfl/flcfo-octopyranoside (32.5.1), is the first lincosamide that has found use in clinical practice, and which was isolated in 1962 from the culture liquid of the activity of the actinomycete Streptomyces lincolnensis [292-295]. 

Similar to macrolides, lincosamides also target the SOS ribosome subunit. More specifically, they inhibit the enzyme peptidyl transferase, which in turn inhibits the activity of ribosomes, preventing the binding of amino acyl-tRNA to the A site on the SOS subunit. That activity blocks the synthesis of proteins. 

Pirlimycin is a lincosamide recently approved by the US Food and Drug Administration for treatment of mastitis in dairy cattle (113, 114). It has excellent activity against Staphylococcus aureus, the principal organism responsible for mastitis in the dairy cow, and is administered as an aqueous gel by intramammary infusion (115). 

Lincosamides. Clindamycin has antibacterial activity similar to that of erythromycin. It exerts a bacteriostatic effect mainly on Gram-positive aerobic, as well as on anaerobic pathogens. Clindamycin is a semisynthetic chloro analogue of lincomycin, which derives from a Streptomyces species. Taken orally, clindamycin is better absorbed than lincomycin, has greater antibacterial ef cacy and is thus preferred. Both penetrate well into bone tissue. 

The lincosamides, lincomycin and clindamycin are active against Grampositive bacteria. Plasmid-mediated inactivation from enzymatic nucleo-tidylation occurs in some staphylococci. Plasmid-encoded enzymes can modify streptogramin A (O-acetyltransferase enzyme) and streptogramin B (hydrolase enzyme involved) in S. aureus [198, 199], There is no evidence that bacteria can circumvent the action of other antibiotics for example, mupirocin is not degraded [200]. 

Currently, one structure of a Irncosamide antibiotic bound to the ribosome is available for analysis [4]. like the macrolide antibiotics, drndamycin binds near the hydrophobic crevice at the entrance to the peptide exit turmel. As with the macrolide carbomycin A, dindamycin interacts not only with the hydrophobic crevice at the entrance to the peptide exit turmd, but also with the active site hydrophobic crevice. The nudeotides that surroimd the clindamydn binding site were previously implicated in binding of lincosamides based on nucleotide protection studies and on the analysis of mutations conferred by resistance (Fig. 4.4). 

Macrolides e.g. erythromycin. Clindamycin, structurally a lincosamide, has a similar action and overlapping antibacterial activity. 

Macrolides inhibit growth of bacteria by inhibiting protein synthesis on ribosomes (17,415,416). Bacterial resistance to macrolides is often accompanied by cross-resistance to lincosamide and streptogramin B antibiotics (MLS-resistance), which can be either inducible or constitutive (417). 14-Membered macrolides generally induce resistance to themselves, whereas 16-membered macrolides do not consequendy, one advantage of the latter is their activity against bacteria which are inducibly resistant to erythromycin. Both 14- and 16-membered macrolides lack activity against constitutively resistant strains (387,388). 

Fernandes, P. B., Baker, W. R., Freiberg, L, A., Hardy, D. J., and McDonald, E. J. (1989). New macrolides active against Streptococcus pyogenes with inducible or constitutive type of macrohde-lincosamide-streptogramin B resistance. Antimicrob. Agents Chemother. 33, 78-81. 

Most of the data on rokitamycin have been published in Japanese and Italian journals. As a propionyl ester of leucomycin, rokitamycin has an antimicrobial spectrum similar to that of erythromycin, it is especially potent against L. pneumophila, M. pneumoniae, and Chlamydia. Like other 16-membered macrolides, it is active against bacteria that are inducibly resistant to erythromycin but inactive against strains that are constitutively resistant to macrolide-lincosamide-streptogramin B antibiotics. 

Lincosamide antibiotic bacteriostatic inhibitor of protein synthesis (50S) active against gram-positive cocci, B fragilis. Tox GI distress, pseudomembranous colitis. 

Bacterial resistance to macrolides results from alterations in ribosomal structure with loss of macrolide binding affinity. The structural alteration very often involves methy-lation of ribosomal RNA and is attributed to enzymatic activity expressed by plasmids. Cross-resistance between macrolides, lincosamides, and streptogramins occurs as a result of these drugs sharing a common binding site on the ribosome. 

As a result of these observations, recommendations have been made to include an incubation step in methods of analysis for lincosamides in liver. " If the aim is to detect lincosamide use, then inclusion of an incubation step is necessary to maximize the possibility of detection. However, as indicated earlier, MRLs, where set, are based on the parent compound only with no reference to the metabolites, either by summation of separate measurements or by conversion to a suitable marker. Thus, inclusion of an incubation step could lead to falsely high residue concentrations and the possibility of samples that fall within the legal limits being reported as non-compliant. As a result, analytically, steps should be taken to minimize enzymatic activity to prevent this reverse metabolism. A long-term solution to this issue might be to include the sulfoxides in the legislation as additional markers in some form. 

Lcclercq R, Nantas L, Soussy C-J, Duval J. Activity of RP59500, a new parenteral semisyn-thetic streptogtamin, against staphylococci with various mechanisms of resistance to mactolide-lincosamide-streptogramin antibiotics. ] Antimicrob Chemother 1992 30(Suppl A 67-75. 

---