Lincomycin

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Lincomycin
Lincomycin.svg
Lincomycin molecule ball.png
Clinical data
Trade names Biocine, Lincocin
AHFS/Drugs.com Monograph
MedlinePlus a609005
Routes of
administration 		IM/IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability N/A
Elimination half-life 5.4 ± 1.0 h after IM or IV administration
Excretion Kidney and bile duct
Identifiers
  • (2S,4R)-N-[(1R,2R)-2-Hydroxy-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.005.296 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H34N2O6S
Molar mass 406.54 g·mol−1
3D model (JSmol)
  • O=C(N[C@@H]([C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O)[C@H](O)C)[C@H]2N(C)C[C@H](CCC)C2
  • InChI=1S/C18H34N2O6S/c1-5-6-10-7-11(20(3)8-10)17(25)19-12(9(2)21)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,21-24H,5-8H2,1-4H3,(H,19,25)/t9-,10-,11+,12-,13+,14-,15-,16-,18-/m1/s1 Yes check.svgY
  • Key:OJMMVQQUTAEWLP-KIDUDLJLSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Lincomycin is a lincosamide antibiotic that comes from the actinomycete Streptomyces lincolnensis . [3] A related compound, clindamycin, is derived from lincomycin by using thionyl chloride to replace the 7-hydroxy group with a chlorine atom with inversion of chirality. [4] It was released for medical use in September 1964. [5]

Contents

Uses

Although similar in antibacterial spectrum and mechanism of action to macrolides, lincomycin is also effective against other organisms including actinomycetes and some species of Mycoplasma and Plasmodium .[ citation needed ]

However, because of its adverse effects and toxicity, it is rarely used today and reserved for patients allergic to penicillin or where bacteria have developed resistance.

Clinical pharmacology

Intramuscular administration of a single dose of 600 mg of Lincomycin produces average peak serum levels of 11.6 μg/mL at 60 min, and maintains therapeutic levels for 17 h to 20 h, for most susceptible gram-positive organisms. Urinary excretion after this dose ranges from 1.8% to 24.8% (mean: 17.3%).

A two-hour intravenous infusion of 600 mg of Lincomycin achieves average peak serum levels of 15.9 μg/mL and yields therapeutic levels for 14 h for most susceptible gram-positive organisms. Urinary excretion ranges from 4.9% to 30.3% (mean: 13.8%).

The biological half-life after IM or IV administration is 5.4 ± 1.0 h. The serum half-life of lincomycin may be prolonged in patients with severe impairment of renal function, compared to patients with normal renal function. In patients with abnormal hepatic function, serum half-life may be twofold longer than in patients with normal hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing lincomycin from the serum.

Tissue level studies indicate that bile is an important route of excretion. Significant levels have been demonstrated in the majority of body tissues. Although lincomycin appears to diffuse in the cerebrospinal fluid (CSF), levels of lincomycin in the CSF appear inadequate for the treatment of meningitis.

Biosynthesis

Lincomycin is an antibiotic classified as a member of the lincosamide class, which typically features a L-proline amino acid derivative linked through amide group with an eight-carbon aminothio sugar. [6] The two units 4-propyl-L-proline and the amino-octose, are each synthesized separately, and are then condensed by LmbD protein, and then further postcondensation reactions involving cleaving of mycothiol, deacetylation, and S-methylation finally yield lincomycin.

The biosynthesis of the amino acid moiety of lincomycin, starts with tyrosine which is transformed to 4-propyl-L-proline by the consecutive action of LmbB1, LmbB2, LmbW, LmbA and LmbX proteins. 4-Propyl-L-proline is activated by LmbC and loaded into LmbN, a bifunctional peptidyl carrier protein, and is ready for condensation by LmbD.

The biosynthetic pathway for production of the amino-octose moiety is almost fully elucidated although the order of the steps still needs further research. Condensation through a transaldolase (LmbR) of ribose 5-phosphate (C5) with fructose 6-phosphate or sedoheptulose-7-phosphate (providing a C3 unit) forms the octose (C8). Further transformations involving isomerization (LmbN), 1-phosphorylation (LmbP), 8-dephosphorylation (LmbK), guanosine diphosphate attachment at position 1 (LmbO), 4-epimerization (LmbM), 6-oxidation (LmbL), amination (LmbS), imine reduction (LmbZ) and 8-reduction, are performed to construct the amino-octose unit. LmbT protein exchange GDP by ergothioneine and the condensation with 4-propyl-L-proline and catalysed by LmbD can occur. The amide-linked product between the amino acid and the amino-octose bound to ergothioneine is then the substrate of LmbV, which substitute ergothioneine by mycothiol. The mycothiol moiety is then cleaved by LmbE, and the product is further processed by LmbIH, LmbQ, LmbJ, LmbF and is finally sulphur methylated by LmbG, to afford lincomycin.

Spectrum of susceptibility

Lincomycin is a narrow spectrum antibiotic with activity against Gram-positive and cell wall-less bacteria including pathogenic species of Streptococcus, Staphylococcus, and Mycoplasma. [7] Lincomycin is used to treat severe bacterial infections in patients who cannot use penicillin antibiotics. Lincomycin shows weak activity against most Gram-negative bacteria. The following represents susceptibility (MIC) data for a few pathogenic bacteria:

Related Research Articles

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Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is used intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally as a treatment for severe Clostridium difficile colitis. When taken orally it is poorly absorbed.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

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<span class="mw-page-title-main">Aztreonam</span> Chemical compound

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<span class="mw-page-title-main">Ceftazidime</span> Antibiotic medication

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<span class="mw-page-title-main">Cefaclor</span> Chemical compound

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<span class="mw-page-title-main">Tigecycline</span> Chemical compound

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<span class="mw-page-title-main">Cefepime</span> Fourth-generation Cephalosporin Antibiotic

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<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

<span class="mw-page-title-main">Amikacin</span> Antibiotic medication

Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.

<span class="mw-page-title-main">Lincosamides</span> Group of antibiotics

Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.

<span class="mw-page-title-main">Clindamycin/benzoyl peroxide</span> Type of medication

Clindamycin/benzoyl peroxide is a topical gel used for the treatment of acne. It is a fixed-dose combination of clindamycin, as the phosphate, an antibiotic, and benzoyl peroxide, an antiseptic.

<span class="mw-page-title-main">Cefdinir</span> Chemical compound

Cefdinir, sold under the brand name Omnicef among others, is an antibiotic used to treat pneumonia, otitis media, strep throat, and cellulitis. It is a less preferred option for pneumonia, otitis media, and strep throat which may be used in those with a severe allergy to penicillin. It is taken by mouth.

<span class="mw-page-title-main">Enrofloxacin</span> Chemical compound

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<span class="mw-page-title-main">Cefditoren</span> Chemical to treat skin infections

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<span class="mw-page-title-main">Delafloxacin</span> Chemical compound

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<span class="mw-page-title-main">Bottromycin</span> Chemical compound

Bottromycin is a macrocyclic peptide with antibiotic activity. It was first discovered in 1957 as a natural product isolated from Streptomyces bottropensis. It has been shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among other Gram-positive bacteria and mycoplasma. Bottromycin is structurally distinct from both vancomycin, a glycopeptide antibiotic, and methicillin, a beta-lactam antibiotic.

References

  1. ↑ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. ↑ Macleod AJ, Ross HB, Ozere RL, Digout G (November 1964). "Lincomycin: A New Antibiotic Active Against Staphylococci and Other Gram-Positive Cocci: Clinical and Laboratory Studies". Canadian Medical Association Journal. 91 (20): 1056–1060. PMC   1928283 . PMID   14217764.
  4. ↑ Birkenmeyer RD, Kagan F (July 1970). "Lincomycin. XI. Synthesis and structure of clindamycin. A potent antibacterial agent". Journal of Medicinal Chemistry. 13 (4): 616–619. doi:10.1021/jm00298a007. PMID   4916317.
  5. ↑ Duncan IB, Jeans B (September 1965). "Lincomycin in hospital practice". Canadian Medical Association Journal. 93 (13): 685–691. PMC   1928825 . PMID   5828940.
  6. ↑ Janata J, Kamenik Z, Gazak R, Kadlcik S, Najmanova L (March 2018). "Biosynthesis and incorporation of an alkylproline-derivative (APD) precursor into complex natural products". Natural Product Reports. 35 (3): 257–289. doi: 10.1039/c7np00047b . PMID   29517100.
  7. ↑ "Lincocin (Lincomycin HCL): Uses, Dosage, Side Effects, Interactions, Warning".
  8. ↑ "Lincomycin HCl" (PDF). EP Susceptibility and 0.05 - 0.4 Minimum Inhibitory >50 Concentration Range (μg/mL) Concentration (MIC) Data. TOKU-E. 6 January 2020.
  9. ↑ "Lincomycin (Lincocin)". The Antimicrobial Index Knowledgebase. TOKU-E. Archived from the original on 3 March 2016.
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